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Retriever500 | Exogenous melatonin ameliorates hepatic injury in a rat cardiopulmonary bypass model.
Hepatic injury after cardiac surgery was considered to be a consequence of cardiopulmonary bypass (CPB). This study tested the hypothesis that melatonin could attenuate the hepatic injury in a rat CPB model. Male Sprague-Dawley rats were randomly divided into four groups: sham-operation group, control group (given an equal volume of vehicle), low dose melatonin (10 mg/kg) treated group and high dose melatonin (20 mg/kg) treated group. Blood samples were collected at the beginning, at the cessation of CPB, and at 30 min, 1, 2, 3 and 24 h post-operation. Liver samples were harvested at 24 h after operation. The serum indices of the liver enzymes and systemic inflammation, as well as oxidative stress indices and the Ca++-ATPase activity of liver tissues were determined. In the control animals, the indices of liver enzymes, tumor necrosis factor-alpha (TNF-alpha) increased after operation, and liver inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), myeloperoxidase (MPO) increased as well. However, the activities of liver antioxidative enzymes and the concentration of glutathione (GSH) decreased remarkably. Results in melatonin group showed that melatonin reversed all the biochemical changes, but there was no significant difference between the melatonin-treated groups. In addition, histological findings further supported these results. All results indicated that application of exogenous melatonin during operation preserves liver function by reducing oxidative stress and the systemic inflammatory response. | No pos | No neg |
Retriever501 | Factors Influencing the Recurrence Potential of Benign Endometrial Polyps after Hysteroscopic Polypectomy.
BACKGROUND
An endometrial polyp is a frequently encountered gynecologic disease with abnormal uterine bleeding and infertility being the two common presenting problems, and hysteroscopic polypectomy is an effective method to remove them. The postoperative polyp recurrence might result in reappearance of abnormal uterine bleeding or infertility, whereas factors influencing the postoperative recurrence potential have limited data.
METHODS
This case-series report included 168 premenopausal women who suffered from endometrial polyps and underwent hysteroscopic polypectomy. All of them were awaiting a future pregnancy. Office hysteroscopy was done before and after hysteroscopic polypectomy, in which preoperative hysteroscopy examined the number, type, and location of endometrial polyps, and postoperative hysteroscopy checked the polyp recurrence. Surgical indications, either infertility or the presentation of abnormal uterine bleeding, and follow-up duration were recorded.
RESULTS
Seventy-three out of 168 (43%) women had polyp recurrence after hysteroscopic polypectomy. Multivariate logistic regression analysis revealed that more endometrial polyps (P = 0.015) and longer duration of follow-up (P = 0.004) were significantly associated with an increased risk of postoperative polyp recurrence. The type of endometrial polyps was not correlated with polyp recurrence potential, whereas pedunculated type endometrial polyps were closely related to the presentation of abnormal uterine bleeding (P = 0.001).
CONCLUSIONS
A higher number of endometrial polyps and longer follow-up duration are associated with a greater potential of polyp recurrence after hysteroscopic polypectomy. | No pos | No neg |
Retriever502 | Saccharin may act as a tumour promoter by inhibiting metabolic cooperation between cells.
The possible role of saccharin in the carcinogenic process is, at present, still unclear. Carcinogenesis is a complex process involving, in many test systems, initiation and promotion phases. Current evidence favours the hypothesis that initiation is due to a mutagenic event, while promotion (at least the early portion) is the result of epigenetic changes. Although saccharin has been reported to be a weak mutagen in various in vitro test systems and a weak initiator in mouse skin, there is increasing evidence from in vitro, as well as in vivo, studies that it might act as a tumour promoter, rather than as a mutagen. Recently L.P.Y. et al and J.E.T. et al. developed an in vitro assay to detect tumour promoters, which has been independently reported by Murray and Fitzgerald. The assay is based on the principle that phorbol ester-type tumour promoters block 'metabolic cooperation' or a type of cell-cell communication between cells. We report here a series of experiments demonstrating the elimination of metabolic cooperation in the hypoxanthine guanine phosphoribosyltransferase (HGPRT) system in Chinese hamster V79 cells, indicating that saccharin shares properties similar to those of other known promoters. | No pos | No neg |
Retriever503 | Voltage-Dependent Calcium Channels, Calcium Binding Proteins, and Their Interaction in the Pathological Process of Epilepsy.
As an important second messenger, the calcium ion (Ca2+) plays a vital role in normal brain function and in the pathophysiological process of different neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and epilepsy. Ca2+ takes part in the regulation of neuronal excitability, and the imbalance of intracellular Ca2+ is a trigger factor for the occurrence of epilepsy. Several anti-epileptic drugs target voltage-dependent calcium channels (VDCCs). Intracellular Ca2+ levels are mainly controlled by VDCCs located in the plasma membrane, the calcium-binding proteins (CBPs) inside the cytoplasm, calcium channels located on the intracellular calcium store (particular the endoplasmic reticulum/sarcoplasmic reticulum), and the Ca2+-pumps located in the plasma membrane and intracellular calcium store. So far, while many studies have established the relationship between calcium control factors and epilepsy, the mechanism of various Ca2+ regulatory factors in epileptogenesis is still unknown. In this paper, we reviewed the function, distribution, and alteration of VDCCs and CBPs in the central nervous system in the pathological process of epilepsy. The interaction of VDCCs with CBPs in the pathological process of epilepsy was also summarized. We hope this review can provide some clues for better understanding the mechanism of epileptogenesis, and for the development of new anti-epileptic drugs targeting on VDCCs and CBPs. | No pos | No neg |
Retriever504 | A multinational investigation of the impact of subcutaneous sumatriptan. IV: Patient satisfaction.
This report describes the patient satisfaction results from a prospective, sequential, multinational study. The study was conducted to concurrently evaluate the effects of sumatriptan, compared with customary therapy, on clinical parameters, health-related quality of life, productivity and patient satisfaction in adult patients with moderate to severe migraine. Patients treated migraine attacks for 12 weeks with their customary therapy, followed by 24 weeks' treatment with subcutaneous sumatriptan 6 mg. A questionnaire was conducted at the end of each study phase, or retrospectively at the end of the study, to assess patient satisfaction with customary therapy and sumatriptan. Sumatriptan was considered by most patients (67 to 85%) to be dependable and fast-acting, and to have a long duration of effect, allowing a quick return to normal activities. By comparison, 15 to 32% of patients considered that their customary therapy possessed the same attributes. However, customary therapy was considered to be easy/very easy to use by 82% of patients compared with 62% for subcutaneous sumatriptan. 89% of patients indicated that they would use sumatriptan again in the future. This study demonstrates that treatment of migraine attacks with subcutaneous sumatriptan for 24 weeks is associated with greater patient satisfaction as regards specific drug attributes than customary therapy. | No pos | No neg |
Retriever505 | Ocular lateropulsion in Wallenberg's syndrome: a prospective clinical study.
In order to evaluate the occurrence and clinical value of ocular lateropulsion in Wallenberg's syndrome, a prospective study was carried out. Lateropulsion of the horizontal and vertical refixation saccades was a rather regular finding, especially in complete Wallenberg's syndrome. Lateral ocular deviation after elimination of fixation was present in nearly all cases. The tonic lateral vector was always directed to the involved side. It is concluded that ocular lateropulsion is an easily elicited sign with a lateralizing value in lateral bulbar infarction. Further systematic search of ocular lateropulsion in other posterior fossa disorders is needed to determine its topographical significance. | No pos | No neg |
Retriever506 | Preliminary feasibility and effectiveness of a novel community language intervention for preschool children in the United Kingdom.
BACKGROUND
Very young children from lower socioeconomic status (SES) backgrounds often show poorer language development. Whilst there have been attempts to provide early intervention programmes, these sometimes miss the most disadvantaged groups.
AIMS
This report presents preliminary feasibility and effectiveness data for a novel language intervention designed for parents of toddlers in the United Kingdom.
METHODS AND PROCEDURES
In total, 43 UK families of 2-4-year-olds were recruited to the study, half of whom completed an 8-week course (Tots Talking) focussed on parent interaction, and half of whom acted as wait-list controls.
RESULTS AND OUTCOMES
Results suggest that such programmes are feasible for families with 86% staying in the intervention. In addition, greater changes in underlying communication skills such as joint attention and gesture were evident compared to wait-list controls.
CONCLUSIONS AND IMPLICATIONS
We conclude that pre-verbal skills may be more important to measure as initial outcomes than language or vocabulary change in this population.
WHAT THIS PAPER ADDS
What is already known on the subject Children from lower socioeconomic status (SES) backgrounds are at higher risk of communication difficulties and there is a need for community intervention programmes for very young children. What this study adds This study suggests that such programmes can be feasible and effective, but that very early/basic communicative skills (such as joint attention) may be boosted first rather than language or vocabulary. What are the clinical implications of this work? Children's centres and other community services could feasibly run short parent facing courses emphasising contingent communication in low SES families and other diverse groups. These may be more successful run with younger preschoolers. Joint attention may be a better focus of intervention before expecting vocabulary or language change. Community health professionals may find this information useful in referring and supporting families in need. | No pos | No neg |
Retriever507 | Evaluation of plasma von Willebrand factor as a biomarker for acute arterial damage in rats.
Plasma von Willebrand factor (vWF) was evaluated as a potential biomarker of acute arterial damage in rats after a vasotoxic dose of the dopaminergic vasodilator, fenoldopam (FP). Male Sprague-Dawley rats were given FP or isotonic saline by subcutaneous injection, and plasma vWF was measured at 2, 6, and 24 hours after challenge. Mean plasma vWF values increased in FP-treated rats compared to controls at 2 hours (167 vs 122%; p < 0.05) and 6 hours postdose (172 vs 130%; p < 0.01) but were comparable to control values after 24 hours. Mesenteric arterial lesions were observed microscopically in all FP-treated rats 24 hours postdose but were not present in rats at 1, 2, 4, 6, or 8 hours after FP challenge. Further, plasma vWF concentrations increased in saline-treated rats after only the minimal perturbation of repeated venipuncture. These results indicate an early, minimal, and transient release of vWF that precedes the onset of morphologically evident vascular damage. The minimal increases in plasma vWF concentrations were of limited predictive value, may be more reflective of an acute-phase reactant response, and were not considered a reliable biomarker of acute FP-induced arterial damage in the rat. | No pos | No neg |
Retriever508 | Management of hemorrhagic pseudoaneurysmal arteriovenous fistula of the sphenopalatine artery.
n-Butyl cyanoacrylate (n-BCA) embolization of a hemorrhagic pseudoaneurysmal arteriovenous fistula of the sphenopalatine artery in a patient with paranasal sinus squamous cell carcinoma treated with regional surgery and radiation has, to our knowledge, not been previously reported. | No pos | No neg |
Retriever509 | Pre-COVID-19 fear conditioning responses predict COVID-19-related anxiety: evidence from an exploratory study.
BACKGROUND AND OBJECTIVES
Fear conditioning represents the prevailing model by which organisms acquire novel threat contingencies. However, little work has been devoted to linking laboratory measures of fear conditioning to the development of real-world threat responses. To fill this gap, the present study explored whether individual differences in a laboratory-based fear conditioning measure could predict levels of COVID-19-related anxiety and avoidance assessed during the first month of the pandemic.
DESIGN AND METHOD
Forty-eight undergraduate students who had previously participated in two fear conditioning experiments prior to COVID-19 completed a survey assessing COVID-19 anxiety and avoidance. The fear conditioning experiment involved learning to discriminate between a shape contingently associated with mild electric shock (CS+) and two other shapes that were not (CS-).
RESULTS
Increased subjective anxiety to our laboratory CS+ prior to the pandemic predicted heightened COVID-19 anxiety. Follow-up analyses revealed that participants with high COVID-19 anxiety exhibited increased anxiety to CS+ during the final experimental block relative to participants with low COVID-19 anxiety.
CONCLUSIONS
Findings from this exploratory study tentatively implicate fear conditioning in the development of real-world fear responses and underscore the importance of investigating laboratory fear conditioning as a predictor of anxiety responses to real-world threats. | No pos | No neg |
Retriever510 | Continuous absorption and emission of light by the heteronuclear rare gas (ArXe)+ and (KrXe)+ ions.
Studies of radiative transitions between ground and charge transfer excited terms of heteronuclear rare-gas (ArXe)+ and (KrXe)+ ions with small and moderate dissociation energies (D0 ArXe =179 and D0 KrXe =389 meV) are reported. Potential energy curves and dipole transition matrix elements are evaluated using ab initio calculations based on the CASSCF method followed by the NEVPT2 treatment and perturbative description of relativistic effects as implemented in the ORCA suite. We develop an efficient approach for the calculations of Boltzmann-averaged cross sections, rate constants, and absorption and emission coefficients associated with the integral contributions of bound-bound and bound-free transitions from a manifold of rovibrational states of the (RgXe)+ ion. A similar approach is used for the description of the free-free and free-bound transitions between different electronic terms of a quasimolecular (RgXe)+ ion temporarily formed during a collision of Ar or Kr atoms with Xe+ ions. Our method is based on the quantal version of the theory of non-adiabatic transitions in molecular and quasimolecular systems combined with the approximation of a quasicontinuum for rovibrational energy levels. This allowed us to obtain a semianalytic expression for the integral absorption properties particularly relevant at elevated temperatures. We perform a comprehensive analysis of the identified radiative processes in local thermodynamic equilibrium plasmas of rare gas Rg/Xe mixtures containing both atomic, Xe+, and molecular, RgXe+, ions and determine their role in the formation of the absorption and emission spectra in a wide range of wavelengths and gas temperatures. The results obtained are in good agreement with the available experimental data. | No pos | No neg |
Retriever511 | COVID-Somnia: A Multicentric Study on Sleep Disturbances During the COVID-19 Pandemic With Spatial Mapping of Hotspots.
Objective The purpose of this study was to document sleep quality and assess its sociodemographic, behavioral (i.e., tobacco use, alcohol use, and screen time), and mental-health-related indicators (i.e., anxiety and depression) in adults aged 30-59 years across three states of India, and to geo-locate state and district-level findings of sleep quality during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Methods From October 2020 to April 2021, residents (aged 30-59 years) of Kerala, Madhya Pradesh, and Delhi completed a web-based survey that included sociodemographic and behavioral factors, clinical history of COVID-19, and mental health screening instruments for anxiety and depression, namely the Generalized Anxiety Disorder 2-item (GAD-2) and Patient Health Questionnaire-2 (PHQ-2). The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the quality of sleep. Average PSQI scores were geo-mapped. Results Of the 694 participants who responded, 647 completed the PSQI. The mean (SD) global PSQI score was 5.99 (3.2), with approximately 54% of participants reporting poor sleep quality (PSQI Score>5). Eight hotspot districts with severe sleep disturbances (mean score PSQI>6.5) were identified. Multivariable logistic regression analysis showed that compared to Madhya Pradesh, participants from Kerala and Delhi had 62% and 33% lower chances of having poor sleep quality, respectively. Those who screened positive for anxiety had higher odds of having poor sleep quality (adjusted odds ratio {aOR}=2.4, P=0.006*). Conclusion Overall, sleep quality was poor during the early stages of the COVID-19 pandemic (October 2020-April 2021), especially among those who reported high levels of anxiety. Among the three included states, there were differences in sleep quality. | No pos | No neg |
Retriever512 | Genetic and biochemical studies of hepatic carcinoma in the Egyptian population.
BACKGROUND
Hepatocellular carcinoma (HCC), a deadly malignancy of the liver, is considered the third leading reason behind cancer deaths. It is more frequent in men than in women of ages above 50. Liver disease, leading to liver cirrhosis (LC), is mostly caused by alcoholism abuse, reaction diseases of the liver, or viral hepatitis B or C infection. Interleukin-6 (IL-6) is considered an effective pro-inflammatory cytokine, which plays a crucial role in the host defense mechanism. Its level is higher in HCC patients than in LC cases, indicating that tumor cells increase the production of cytokines. The X-ray repair cross-complementing group 1 (XRCC1) gene is a major DNA repair gene. It acts as a scaffold of various activities that are concerned in the repairing method by interacting with components of base excision repair. This study aims to measure the serum concentrations of IL6 and C-reactive protein (CRP) and investigate whether XRCC1 Arg194Trp and Arg399Gln polymorphisms are related to HCC disease.
MATERIALS AND METHODS
Whole-blood DNA was extracted from 123 HCC patients and 123 healthy volunteers. Tetra-primer amplification refractory mutation system was performed in the detection of XRCC1 Arg399Gln and Arg194Trp polymorphisms.
RESULTS
Serum concentration levels of IL-6 and CRP are significantly higher in patients with HCC than in control subjects. The allelic and genotype frequency distributions of XRCC1 (Arg399Gln and Arg194Trp) are significantly increased in HCC cases compared to healthy volunteers.
CONCLUSION
Arg/Gln, Arg/Trp, Gln/Gln, and Trp/Trp genotypes are associated with higher risk HCC than the Arg/Arg genotype. | No pos | No neg |
Retriever513 | Ethnic Variation in Satisfaction and Appearance Concerns in Adolescents With Idiopathic Scoliosis Undergoing Posterior Spinal Fusion With Instrumentation.
STUDY DESIGN
Cohort analysis.
OBJECTIVE
Document satisfaction with management and appearance concerns in children of different ethnicity who underwent spinal fusion/instrumentation for adolescent idiopathic scoliosis (AIS).
SUMMARY OF BACKGROUND DATA
Scoliosis Research Society Questionnaire (SRS-30) outcomes in AIS indicate a link between appearance and satisfaction as well as ethnic variation in appearance domain. Exploration of these findings in the Scoliosis Appearance Questionnaire (SAQ) will allow better understanding of ethnic variation in appearance concerns.
METHODS
Children with AIS who underwent posterior-only operations and completed the SAQ's question 31 were identified. Univariate logistic regression of SAQ questions 12-30 was used to assess relationships with ethnicity.
RESULTS
1,977 children [boys: 281, girls: 1,290, unspecified: 406; average age 15.1 ± 2.0 years preoperatively and 817 children (boys: 113, girls: 569, unspecified: 135; average age 15.1 ± 2.0 years) at 2 years' follow-up met inclusion criteria. The majority were Caucasian (57.3%). Few were Hispanic (3.4%). Preoperatively, the largest percentage of patients in each ethnic group answered "very true" to "wanting to be more even." Preoperatively, Asians were least likely to be concerned about evenness of shoulders, hips, waist, ribs, and chest in back (p < .05); however, they expressed greatest concern about height (p < .05). African Americans and Hispanics were more likely to be concerned about breast evenness and anterior chest and looking better in clothes (p < .05). African Americans were most concerned about overall evenness and evenness of shoulders, hips, waist, ribs, posterior chest, leg length, and looking more attractive (p < .05). Surgical scar was most important postoperatively for all ethnicities. African Americans and Hispanics were more self-conscious about scar (p < .05). African Americans were most likely to want to be more even and have more even shoulders, hips, waist, leg lengths, ribs, breasts, and chest postoperatively.
CONCLUSIONS
Ethnicity influenced appearance concerns in pre- and postoperative SAQ evaluation. Ethnic variation in appearance concerns should be taken into account and differentiated when counseling patients about AIS and surgical correction.
LEVEL OF EVIDENCE
Level III. | No pos | No neg |
Retriever514 | Liners for waste containment constructed with class F and C fly ashes.
Hydraulic conductivity of a Class F fly ash containing residual organic carbon was evaluated in this study using laboratory and field tests. Compacted specimens of the Class F fly ash mixed with various materials (sand, Class C fly ash, and bottom ash) were prepared in the laboratory at various water contents and different compactive efforts. Hydraulic conductivity of the compacted specimens was measured using flexible-wall permeameters. A test pad was constructed to determine whether a low hydraulic conductivity liner could be constructed with Class F fly ash mixtures. Sealed double-ring infiltrometers and two-stage borehole permeameters were used to measure the field hydraulic conductivity of the test pad. Specimens were also removed from the test pad for hydraulic conductivity testing in the laboratory. Results of the study showed that mixtures of Class F and Class C fly ashes along with coarse aggregate can be compacted to hydraulic conductivities needed for landfill liners provided compaction is wet of optimum water content. The field tests showed that constructing a fly ash liner with hydraulic conductivities similar to those found in the laboratory is challenging, and requires careful attention to factors that result in cracks and permeable interlift regions that result in high field hydraulic conductivity. Leachate collected from the base of the test pad also showed that metal leaching must be considered when designing a liner with fly ash. | No pos | No neg |
Retriever515 | MiR-29b level-mediated regulation of Klotho methylation via DNMT3A targeting in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by chronic bronchitis and emphysema. Cigarette smoke extract (CSE) is the predominant cause of COPD. This study aimed to investigate the effects of miR-29b and their underlying mechanisms in a COPD cell model. MiR-29b and DNMT3A expression in lung tissue samples (taken at least 5 cm away from the tumor lesion) of NSCLC cases with smoking (n = 30), without smoking (n = 30), and with COPD (with smoking) (n = 30) was researched by qRT-PCR. A medium containing 10 % CSE was employed to induce murine alveolar macrophage MH-S cells to establish COPD cells. 5-Aza-cdr (5-AZA-2'-deoxycytidine) was used to block DNMT3A. The relationship and interaction between miR-29b and DNMT3A were validated through the dual luciferase reporter assay. The expression levels of macrophage M1 polarization marker proteins iNOS and TNF-α, DNMT3A, and Klotho protein were monitored using western blotting. The methylation levels of the miR-29b precursor gene and Klotho promoter were detected by quantitative methylation-specific PCR (MS-qPCR). The levels of IL-1β, IL-6, and TNF-α in cell culture medium were detected via ELISA. It was found that the expression of miR-29b was downregulated, as a result of increased DNA methylation, and that of DNMT3A was upregulated in the lung tissues of NSCLC cases with COPD (with smoking). DNMT3A expression was negatively correlated with miR-29b expression in the lung tissues of NSCLC cases with COPD (with smoking). In addition, miR-29b expression was distinctly downregulated in CSE-induced MH-S cells and inhibited CSE-induced M1 polarization and inflammation. Importantly, DNMT3A was identified as a direct target gene of miR-29b. MiR-29b is negatively regulated by DNMT3A-mediated DNA methylation. Moreover, Klotho expression was downregulated and the Klotho promoter methylation level was increased in lung tissues of NSCLC cases with COPD (with smoking). The negative feedback between miR-29b and DNMT3A modulates CSE-induced M1 polarization and inflammation in macrophages as well as Klotho promoter methylation in CSE-mediated MH-S. Collectively, these findings indicate that the miR-29b level in COPD controls Klotho methylation via DNMT3, which maybe a promising target for the treatment of COPD. | No pos | No neg |
Retriever516 | Low molecular weight heparin decreases rebound ischemia in unstable angina or non-Q-wave myocardial infarction: the Canadian ESSENCE ST segment monitoring substudy.
OBJECTIVES
The goal of this study was to determine whether enoxaparin was more effective than heparin in reducing recurrent ischemic episodes.
BACKGROUND
Continuous ST segment monitoring is a simple tool for assessment of ischemia and identifies patients with a worse prognosis. Little is known about the impact of low molecular weight heparin on ST segment shift.
METHODS
Patients were randomized to receive enoxaparin or heparin (mean 3.4 days). Three-lead ST segment monitoring was performed for the first 48 h (n = 220) and an additional 48 h (n = 174) after intravenous study drug discontinuation (mean 1.9 days later).
RESULTS
During initial monitoring, ischemia rates were similar among the heparin and enoxaparin groups (27.2% vs. 22.6%, p = 0.44); however, the time to first ischemic episode was earlier among heparin-treated patients (11 +/- 11 vs. 25 +/- 18 min, p = 0.001). After drug discontinuation, ischemic episodes occurred more frequently (44.6% vs. 25.6%, p = 0.009), and the total ischemic duration was greater among heparin patients (18 +/- 39 vs. 5 +/- 12 min/24 h, p = 0.005). Recurrent ischemia occurred more frequently after discontinuation in the heparin (46% vs. 31%, p = 0.043), but not the enoxaparin, group (18.4% vs. 25%, p = 0.33). Regardless of treatment, patients with ischemia were more likely to die or experience (re)infarction at one year (18.4% vs. 8.3%, p = 0.023).
CONCLUSIONS
ST segment shift occurs frequently in unstable angina/non-Q-wave myocardial infarction despite antithrombotic therapy and is associated with worse one-year prognosis. Enoxaparin is a more effective antithrombotic treatment than unfractionated heparin and leads to greater prevention of rebound ischemia. | No pos | No neg |
Retriever517 | Denaturation maps of DNA: experimental and theoretical maps of phiX174 DNA.
A formaldehyde denaturation map of the replicative form of phiX174 DNA is obtained. The RFI DNA was converted into a linear state by restriction endonuclease pst I which introduces into this DNA a single double-stranded break. The map has four clear-cut peaks. Their positions excellently correlate with the peak positions on the map of equilibrium denaturation theoretically obtained earlier from the known nucleotide sequence of phiX174 DNA. The sequence is also used for a calculation of the maps of smoothed AT-content. The maxima on these maps correlate well with the peaks on the denaturation maps. To reveal the causes of a good correlation between the experimental formaldehyde and theoretical equilibrium denaturation maps, the theoretical formaldehyde denaturation maps are calculated for different conditions (temperature, formaldehyde concentration) using the detailed theory of DNA interaction with formaldehyde developed earlier. | No pos | No neg |
Retriever518 | Ion channels. Preventing artifacts and reducing errors in single-channel analysis.
The power of single-channel analysis techniques has rapidly expanded during the past few years, giving investigators increased ability to identify models and estimate parameters while reducing error and artifacts. At present, however, there is no single best method, as even the most advanced techniques have various limitations which depend on the experimental data and models being examined. Consequently, for the examined models and experimental data, the most critical part of single-channel analysis is to estimate errors and evaluate the ability of the methods used to discriminate among possible gating mechanisms. The magnitudes of the errors and the ability to identify models and estimate parameters depend on the models being examined as well as the experimental conditions and data. Consequently, the evaluation of the errors associated with each method needs to be repeated when the experimental data and examined models change. | No pos | No neg |
Retriever519 | GABAA and GABAB receptors differentially regulate synaptic transmission in the auditory thalamo-amygdala pathway: an in vivo microiontophoretic study and a model.
Stimulation of the medical geniculate body elicits extracellular single unit responses in the lateral nucleus of the amygdala that are dependent upon glutamatergic neurotransmission [Li et al. (1995) Exp. Brain Res., 105-87-100]. In the present study, we examined the contribution of inhibitory amino acid transmission to these excitatory responses. Antagonists of GABAA or GABAB receptors were delivered microiontophoretically to cells activated by stimulation of the medial geniculate body. Blockade of GABAA receptors with bicuculline resulted in a pronounced increase in evoked short latency unit responses (4-8 ms). In some cases, cells that were not responsive to the stimulation became responsive in the presence of bicuculline. In contrast, delivery of GABAB antagonists, Phaclofen or 2-OH-saclofen, did not affect these short-latency responses. Using paired-pulse stimulation, both short (< 30 ms) and longer (> 50 ms) latency inhibitory processes were revealed. GABAA blockade eliminated the short latency inhibition and GABAB blockade eliminated the longer latency inhibition in most cells. These results suggest that the activation of GABAA and GABAB receptors differentially regulate glutamatergic synaptic transmission in the auditory thalamo-amygdala pathway. Moreover, our findings suggest that at least part of this regulation is via a feedforward mechanism. We tested the sufficiency of feedforward inhibition to account for the data using a simple computational model that incorporates the results presented here. | No pos | No neg |
Retriever520 | Mid-term results following arthroscopic capsular release in patients with primary and secondary adhesive shoulder capsulitis.
PURPOSE
The purpose of this study was to assess the effectiveness of arthroscopic capsular release carried out for refractory cases of both primary and secondary adhesive shoulder capsulitis that were not responsive to at least 6 months of prior conservative therapy.
METHODS
Arthroscopic 360-degree capsular release was performed on 167 patients (173 shoulders) with adhesive shoulder capsulitis. Ninety-one shoulders (52.6%) had primary and 82 shoulders (47.4%) secondary adhesive capsulitis. The median follow-up period was 36 months (range 14-67 months).
RESULTS
All patients were evaluated according to the constant score. Both groups (primary and secondary adhesive capsulitis) experienced a significant improvement for all ranges of motion immediately postoperative, as well as at the time of follow-up. The median preoperative constant score was 41 (range 18-61) points and increased significantly to a median of 83 (range 27-100) at the time of follow-up. In the group of primary adhesive capsulitis, median preoperative score was 42 points (range 19-58) and increased to 85 points (range 36-100) at follow-up. In the group of secondary adhesive capsulitis, the preoperative mean increased from 41 points (range 18-61) to 74 points (range 27-100) at the time of the follow-up. The constant score component for pain and the visual analogue scale (VAS) score were also significantly increased.
CONCLUSION
Arthroscopic capsular release in patients with primary and secondary adhesive shoulder capsulitis represents a valuable therapeutic choice with minimal complications, to effectively reduce pain and improve movement in all planes of motion.
LEVEL OF EVIDENCE
Therapeutic retrospective case series study, Level IV. | No pos | No neg |
Retriever521 | Investigation of the Physicochemical and Biological Stability of the Adalimumab Biosimilar CT-P17.
INTRODUCTION
CT-P17 (Celltrion, Inc., Incheon, Republic of Korea) is a biosimilar of reference adalimumab (Humira®; AbbVie Inc., North Chicago, IL, USA), which has recently received regulatory approval from the European Medicines Agency.
METHODS
This analysis was designed to evaluate the stability profile of CT-P17 compared with reference adalimumab and the currently licensed adalimumab biosimilars ABP 501 (Amjevita®/Amgevita®; Amgen Inc., Thousand Oaks, CA, USA) and SB5 (Imraldi®; Biogen Inc., Cambridge, MA, USA) when stored at low temperature (5 °C) or room temperature (25 °C) with 60% relative humidity for up to 28 days.
RESULTS
Multiple orthogonal and complementary tests demonstrated that CT-P17 was stable for 28 days under all tested conditions, as well as for protein concentrations tested (50 vs 100 mg/mL), type of delivery device (autoinjector vs prefilled syringe), and manufacturing date (recently manufactured vs aged for 17 months). There were slight differences among products in terms of charge variants, oxidation level, purity, and number of subvisible particles; however, overall, the quality of each product was maintained over 28 days.
CONCLUSION
Our data suggest that CT-P17 may be used without any significant loss of stability when stored at 5 °C or 25 °C with 60% relative humidity for up to 28 days, and was not impacted by protein concentration tested and delivery device. Comparative stability data suggest that the appropriate maximum storage period for CT-P17 may be up to 28 days at room temperature with 60% relative humidity. | No pos | No neg |
Retriever522 | Gestational Exposure to Phthalates and Social Responsiveness Scores in Children Using Quantile Regression: The EARLI and HOME Studies.
Linear regression is often used to estimate associations between chemical exposures and neurodevelopment at the mean of the outcome. However, the potential effect of chemicals may be greater among individuals at the 'tails' of outcome distributions. Here, we investigated distributional effects on the associations between gestational phthalate exposure and child Autism Spectrum Disorder (ASD)-related behaviors using quantile regression. We harmonized data from the Early Autism Risk Longitudinal Investigation (EARLI) (n = 140) Study, an enriched-risk cohort of mothers who had a child with ASD, and the Health Outcomes and Measures of the Environment (HOME) Study (n = 276), a general population cohort. We measured concentrations of 9 phthalate metabolites in urine samples collected twice during pregnancy. Caregivers reported children's ASD-related behaviors using the Social Responsiveness Scale (SRS) at age 3-8 years; higher scores indicate more ASD-related behaviors. In EARLI, associations between phthalate concentrations and SRS scores were predominately inverse or null across SRS score quantiles. In HOME, positive associations of mono-n-butyl phthalate, monobenzyl phthalate, mono-isobutyl phthalate, and di-2-ethylhexyl phthalate concentrations with SRS scores increased in strength from the median to 95th percentile of SRS scores. These results suggest associations between phthalate concentrations and SRS scores may be stronger in individuals with higher SRS scores. | No pos | No neg |
Retriever523 | MMP-12 siRNA improves the homeostasis of the small intestine and metabolic dysfunction in high-fat diet feeding-induced obese mice.
The changes of small intestinal homeostasis have been recognized to contribute essentially to the obese development. However, the core small intestinal regulator which mediates over-nutrient impacts on the homeostasis of the small intestines remains elusive. Here, we identify the MMP-12 as such a responsive factor in mouse small intestines. Taking advantages of the nano delivery system, we demonstrate that small intestine-specific MMP-12 knockdown alleviates high-fat diet feeding-induced metabolic disorders and improves intestinal homeostasis in mice, including a significant decrease in lipid transportation, bile acid reabsorption, and inflammation. In parallel, the small intestinal integrity is recovered and the gut microbiota composition is reversed towards that under normal diet feeding. Mechanistically, MMP-12, differing from its traditional elastolytic function, acts as a transcriptional factor to activate Fabp4 transcription through epigenetic modification. In translational medicine, clinical applications of our nanosystem and therapeutic interventions targeting MMP-12 will benefit patients with obesity and associated diseases. | No pos | No neg |
Retriever524 | [Follow-up of 60 children with ulcerative colitis and Crohn disease].
The clinical courses of 60 children suffering from ulcerative Colitis (UC, n = 21) and Crohn's disease (CD, n = 39) were investigated over a period of 8.7 and 5.1 years respectively. At the time of diagnosis all UC-patients showed mucohemorrhagic feces. Relapses often occurred after emotional stress and in 81% of all patients during the winter season. Typical late complications were arthritis (6/21), osteoporosis (6/21), allergic diseases (8/21) and diabetes mellitus (2/21). However, the psychosomatic development appeared normal in at least 17/21 of these patients. Generally the courses in children with CD were more serious. Despite intensive therapy 15/39 children developed an intestinal stenosis which was followed by bowel resection in 11 of them. Further complications were fistulas (6/39), abscess-formations (4/39) and osteoporosis (12/39) due to steroid therapy. Only 12/39 showed a significant catch-up growth. Interviews and psychological tests revealed that CD-patients were introverted with strong connections to their families. Equally they longed for approval and social contact with their contemporaries. | No pos | No neg |
Retriever525 | Parameters influencing the course of passive drug loading into lipid nanoemulsions.
Passive drug loading can be used to effectively identify suitable colloidal lipid carrier systems for poorly water-soluble drugs. This method comprises incubation of preformed carrier systems with drug powder and subsequent determination of the resulting drug load of the carrier particles. Until now, the passive loading mechanism is unknown, which complicates reliable routine use. In this work, the influence of drug characteristics on the course of passive loading was investigated systematically varying drug surface area and drug solubility. Fenofibrate and flufenamic acid were used as model drugs; the carrier system was a trimyristin nanodispersion. Loading progress was analyzed by UV spectroscopy or by a novel method based on differential scanning calorimetry. While increasing drug solubility by micelle incorporation did not speed up passive loading, a large drug surface area and high water solubility were key parameters for fast loading. Since both factors are crucial in drug dissolution as described by the Noyes-Whitney equation, these findings point to a dissolution-diffusion-based passive loading mechanism. Accordingly, passive loading also occurred when drug and carrier particles were separated by a dialysis membrane. Knowledge of the loading mechanism allows optimizing the conditions for future passive loading studies and assessing the limitations of the method. | No pos | No neg |
Retriever526 | Extradural morphine: influence of adrenaline admixture.
The influence of the addition of adrenaline on extradural morphine analgesia and pharmacokinetics was investigated in a double-blind study. Morphine 2 mg was administered to 14 patients undergoing thoracotomy. In addition, adrenaline 50 micrograms added to the extradural solution, was administered to half of the patients, selected randomly. Morphine concentrations in serial plasma and cerebrospinal fluid (CSF) samples were measured. Postoperative analgesia was estimated by determining the requirement for additional analgesics. Following extradural administration of plain morphine, the peak morphine concentrations in CSF were 22 +/- 5 (SEM) times those in plasma; during the elimination phase the CSF concentrations exceeded those in plasma by about 150 times. The area under the concentration v. time curve (AUC) was 162 +/- 27 (SEM) times larger in CSF than in plasma. The admixture of adrenaline with the extradural morphine increased the individual variability in CSF and plasma concentrations. However, compared with the plain morphine group, adrenaline did not significantly increase the concentrations of morphine in CSF, nor were the morphine concentrations in plasma significantly decreased. The duration of analgesia was related to the amount of morphine in CSF, that is AUC (P less than 0.05) and peak concentrations of morphine in CSF (P less than 0.05). | No pos | No neg |
Retriever527 | Evaluating Patient Perspectives of Provider Professionalism on Twitter in an Academic Obstetrics and Gynecology Clinic: Patient Survey.
BACKGROUND
One-third of Americans use social media websites as a source of health care information. Twitter, a microblogging site that allows users to place 280-character posts-or tweets-on the Web, is emerging as an important social media platform for health care. However, most guidelines on medical professionalism on social media are based on expert opinion.
OBJECTIVE
This study sought to examine if provider Twitter profiles with educational tweets were viewed as more professional than profiles with personal tweets or a mixture of the two, and to determine the impact of provider gender on perceptions of professionalism in an academic obstetrics and gynecology clinic.
METHODS
This study randomized obstetrics and gynecology patients at the University of Michigan Von Voigtlander Clinic to view one of six medical provider Twitter profiles, which differed in provider gender and the nature of tweets. Each participant answered 10 questions about their perception of the provider's professionalism based on the Twitter profile content.
RESULTS
The provider profiles with educational tweets alone received higher mean professionalism scores than profiles with personal tweets. Specifically, the female and male provider profiles with exclusively educational tweets had the highest and second highest overall mean professionalism ratings at 4.24 and 3.85, respectively. In addition, the female provider profiles received higher mean professionalism ratings than male provider profiles with the same content. The female profile with mixed content received a mean professionalism rating of 3.38 compared to 3.24 for the male mixed-content profile, and the female profile with only personal content received a mean professionalism rating of 3.68 compared to 2.68 for the exclusively personal male provider profile.
CONCLUSIONS
This study showed that in our obstetrics and gynecology clinic, patients perceived providers with educational profiles as more professional than those with a mixture of educational and personal tweets or only personal tweets. It also showed that our patient population perceived the female provider with educational tweets to be the most professional. This study will help inform the development of evidence-based guidelines for social media use in medicine as it adds to the growing body of literature examining professionalism and social media. | No pos | No neg |
Retriever528 | Syrian hamster female protein: analysis of female protein primary structure and gene expression.
The concentration in plasma of the female protein (FP) of the golden Syrian hamster is regulated by sex steroids and by mediators of the acute-phase response to tissue injury or inflammation. A complementary DNA (cDNA) clone corresponding to FP was isolated from a hamster liver cDNA library and used to determine the nucleotide sequence and derived amino acid sequence of native FP. The primary sequence of FP is 69 percent identical to human serum amyloid P component and 50 percent identical to human C-reactive protein. Evidence showed that sex-limited and acute-phase control of the FP gene is pretranslational. The FP protein is thus a useful model for investigating dual regulation of expression of a single gene. | No pos | No neg |
Retriever529 | Implementation of a Multimodal Analgesia Protocol Among Outpatient Neurosurgical Patients Undergoing Spine Surgery to Improve Patient Outcomes.
PURPOSE
This quality improvement project implemented an evidence-based multimodal analgesia protocol among patients undergoing outpatient spine surgery in an attempt to decrease postoperative opioid requirements, postoperative pain scores, and facility and postanesthesia care unit length of stay (LOS).
DESIGN
Two independent samples were compared with a preimplementation and postimplementation design. There were 37 patients in the preimplementation group and 36 patients in the postimplementation group.
METHODS
Data were collected by a retrospective chart review of neurosurgical patients undergoing spine surgery and included postoperative opioid requirements, postoperative pain scores, facility and postanesthesia care unit LOS, and the number of protocol components implemented on each patient.
FINDINGS
Intraoperative and postoperative by mouth opioid requirements were significantly decreased postimplementation. Postoperative opioid requirements decreased, and postimplementation pain scores were reduced across all time points. LOS did not significantly change.
CONCLUSIONS
This multimodal analgesia protocol significantly decreased opioid consumption among neurosurgical patients at this surgery center. | No pos | No neg |
Retriever530 | Skin disease of penis and male genitalia is linked to atopy and circumcision: caseload in a male genital dermatology clinic.
BACKGROUND/OBJECTIVES
Male genital dermatoses are a common and underappreciated cause of morbidity. Its prevalence and the characteristics of patients presenting with these conditions are poorly understood. The aim of the study was to ascertain which dermatoses were referred to the Male Genital Dermatology Clinic in Melbourne, Australia and to determine whether circumcision and atopy are associated with male genital skin disease.
METHOD
This was a retrospective review of 331 new patients who attended the clinic from 2004 to 2012. Descriptive statistics were obtained to determine the frequency of diagnoses made in the clinic and to record the proportions of circumcised and atopic patients.
RESULTS
The most common primary diagnoses were irritant contact dermatitis (n = 67), dysaesthesia (n = 60), psoriasis (n = 31), lichen sclerosus (n = 28), unknown (n = 19), genital warts (n = 18), normal anatomic variant (n = 17), other infection (n = 17), eczema (n = 16) and lichen planus (n = 16). For the 10 most commonly observed conditions, more than 70% of patients were uncircumcised and more than 69% of these patients had a history of atopy.
CONCLUSIONS
The diagnoses made were described, including their associations with non-circumcision and atopy. Several of these observations have not been recognised before in the literature. We discuss lessons learned in the management of male genital disease and its psychosocial impact. | No pos | No neg |
Retriever531 | "Leg spring" characteristics and the aerobic demand of running.
PURPOSE
By applying a simple, linear mass-spring model to running, the normalized leg spring stiffness (Kleg), the normalized effective vertical stiffness (Kvert), and the mass-specific mechanical power output of the spring (Psp) were determined and correlated with aerobic demand. The purpose of the study was to determine whether leg spring characteristics explain any of the interindividual variability observed in aerobic demand at a given submaximal running speed.
METHODS
Recreational runners (N = 16) ran on a treadmill at 3.35 m x s(-1) for physiological measures and overground for biomechanical measures. The latter included a sagittal plane video record of the running motion and ground reaction data.
RESULTS
We found no relationship between the aerobic demand of running and Kleg (r = -0.18), an inverse relationship between aerobic demand and Kvert (r = -0.48), and a positive correlation between aerobic demand and Psp (r = 0.45).
CONCLUSIONS
The inverse relationship between Kvert and aerobic demand indicates that less economical runners possess a more compliant running style during ground contact. This running style may place greater force demands on extensor musculature. | No pos | No neg |
Retriever532 | Subchondral route for nutrition to articular cartilage in the rabbit. Measurement of diffusion with hydrogen gas in vivo.
The route of nutrients going to articular cartilage was studied by determining the diffusion of hydrogen molecules from the subchondral circulation to the articular cartilage in rabbits. In all immature animals there was diffusion of hydrogen from subchondral bone into articular cartilage, while in the older immature animals the results were variable. None of the mature animals showed any diffusion of hydrogen into articular cartilage. The rate of diffusion of hydrogen was significantly lower in the articular cartilage than in the subchondral bone in the immature animals while the concentrations of hydrogen in the articular cartilage were only fractions of those in the subchondral bone at the same instant. Histologically, the deep layers of immature cartilage are penetrated extensively by vascular buds from the ossified portion of the epiphysis, while in adults the articular cartilage is separated from subchondral vascular spaces by an end-plate of bone. Blood vessels penetrating into the basilar layer of articular cartilage in immature animals appear to play an important role in the nutrition of articular cartilage coming from the subchondral region. | No pos | No neg |
Retriever533 | The Role of miRNA in the Diagnosis, Prognosis, and Treatment of Osteosarcoma.
Osteosarcoma (OS) is one of the most common malignant tumors derived from mesenchymal tissue and is highly invasive, mainly in children and adolescents. Treatment of OS is mostly based on standard treatment options, including aggressive surgical resection, systemic chemotherapy, and targeted radiation therapy, but the 5-year survival rate is still low. MicroRNA (miRNA) is a highly conserved type of endogenous nonprotein-encoding RNA, about 19-25 nucleotides in length, whose transcription process is independent of other genes. Generally, miRNAs play a role in regulating cell proliferation, differentiation, apoptosis, and development by binding to the 3' untranslated region of target mRNAs, whereby they can degrade or induce translational silencing. Although miRNAs play a regulatory role in various metabolic processes, they are not translated into proteins. Several studies have shown that miRNAs play an important role in the diagnosis, treatment, and prognosis of OS. Herein, the authors describe new advances in the diagnosis, prognosis, and treatment of miRNAs in OS. | No pos | No neg |
Retriever534 | Effect of Tityus serrulatus scorpion venom on the rabbit isolated corpus cavernosum and the involvement of NANC nitrergic nerve fibres.
1. The effect of Tityus serrulatus scorpion venom and its toxin components on the rabbit isolated corpus cavernosum was investigated by use of a bioassay cascade. 2. Tityus serrulatus venom (3-100 microg), acetylcholine (ACh; 0.3-30 nmol) and glyceryl trinitrate (GTN; 0.5-10 nmol) dose-dependently relaxed rabbit isolated corpus cavernosum preparations precontracted with noradrenaline (3 microM). The selective soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-alquinoxalin-1-one] (ODQ; 30 microM) increased the basal tone of the rabbit isolated corpus cavernosum and abolished the relaxations induced by the agents mentioned above. Methylene blue (30 microM) also inhibited the relaxations induced by Tityus serrulatus venom but, in contrast to ODQ, the inhibition was irreversible. 3. The non-selective NO synthase (NOS) inhibitors Nomega-nitro-L-arginine methyl ester (L-NAME; 10 microM) and NG-iminoethyl-L-ornithine (L-NIO; 30 microM) also increased the tone of the rabbit isolated corpus cavernosum and markedly reduced both ACh- and Tityus serrulatus venom-induced relaxations without affecting those evoked by GTN. The inhibitory effect was reversed by infusion of L-arginine (300 microM), but not D-arginine (300 microM). The neuronal NOS inhibitor 1-(2-trifluoromethylphenyl) imidazole (TRIM, 100 microM) did not affect either the tone of the rabbit isolated corpus cavernosum or the relaxations induced by ACh, bradykinin (Bk), Tityus serrulatus venom and GTN. TRIM was approximately 1,000 times less potent than L-NAME in inhibiting rabbit cerebellar NOS in vitro, as measured by the conversion of [3H]-L-arginine to [3H]-L-citrulline. 4. The protease inhibitor aprotinin (Trasylol; 10 microg ml[-1]) and the bradykinin B2 receptor antagonist Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7, Oic8]-BK; 50 nM) did not affect the rabbit isolated corpus cavernosum relaxations induced by Tityus serrulatus venom. The ATP-dependent K+ channel antagonist glibenclamide (10 microm) and the Ca2+-activated K+ channel antagonists apamin (0.1 microM) and charybdotoxin (0.1 microM) also failed to affect the venom-induced relaxations. Similarly, the K+ channel blocker tetraethylammonium (TEA; 10 microM) had no effect on the venom-induced relaxations. 5. Capsaicin (3 and 10 nmol) relaxed the rabbit isolated corpus cavernosum in a dose-dependent and non-tachyphylactic manner. Ruthenium red (30 microM), an inhibitor of capsaicin-induced responses, markedly reduced the relaxations caused by capsaicin, but failed to affect those induced by Tityus serrulatus venom. L-NAME (10 microM) had no effect on the capsaicin-induced relaxations of the rabbit isolated corpus cavernosum. 6. The sodium channel blocker tetrodotoxin (TTX; 1 microM) abolished the relaxations of the rabbit isolated corpus cavernosum induced by Tityus serrulatus venom without affecting those evoked by capsaicin, ACh and GTN. Tetrodotoxin (1 microM) also promptly reversed the response to the venom when infused during the relaxation phase. 7. The bioassay cascade of the toxin components purified from Tityus serrulatus venom revealed that only fractions X, XI and XII caused dose-dependent relaxations of the rabbit isolated corpus cavernosum and these were markedly reduced by either TTX (1 microM) or L-NAME (10 microM). 8. Our results indicate that Tityus serrulatus scorpion venom (and the active fractions X, XI and XII) relaxes rabbit corpus cavernosum via the release of NO. This release is specifically triggered by the activation of capsaicin-insensitive cavernosal non-adrenergic non-cholinergic (NANC) fibres, that may possibly be nitrergic neurones. Tityus serrulatus venom may therefore provide an important tool for understanding further the mechanism of NANC nitrergic nerve activation. | No pos | No neg |
Retriever535 | Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease.
Alzheimer's disease is an irreversible, progressive neurodegenerative disorder. Various therapeutic approaches are being used to improve the cholinergic neurotransmission, but their role in AD pathogenesis is still unknown. Although, an increase in tau protein concentration in CSF has been described in AD, but several issues remains unclear. Extensive and accurate analysis of CSF could be helpful to define presence of tau proteins in physiological conditions, or released during the progression of neurodegenerative disease. The amyloid cascade hypothesis postulates that the neurodegeneration in AD caused by abnormal accumulation of amyloid beta (Aβ) plaques in various areas of the brain. The amyloid hypothesis has continued to gain support over the last two decades, particularly from genetic studies. Therefore, current research progress in several areas of therapies shall provide an effective treatment to cure this devastating disease. This review critically evaluates general biochemical and physiological functions of Aβ directed therapeutics and their relevance. | No pos | No neg |
Retriever536 | The left hemiblocks: significance, prognosis and treatment.
This review article is concerned with the concept of left hemiblocks and analyses their significance, prognosis and treatment. It first stresses that the left bundle branch is not sensu stricto a bifascicular structure since it generally is either fanlike, or trifascicular. The anatomical situation, however, remains compatible with the physiological concept of the hemiblocks. The electrocardiographic features of left anterior and posterior hemiblocks are described. A histopathological investigation clearly demonstrates that both are signs of left bundle branch disease, often degenerative in nature and more widely spread than expected from the electrocardiographic terminology. The association of a left hemiblock with right bundle branch block is frequently considered as sign of poor prognosis. This is true in the setting of acute myocardial infarction where it accompanies large infarcts. In chronic cases, the prognosis is primarily influenced by the underlying pathology. Patients with partial bilateral bundle branch block should be investigated and, if needed, paced when they have symptoms, a PR interval which lengthens with the course of time, or signs of cardiomyopathy, or large anterior infarction. Asymptomatic individuals with apparent primary disease of the conducting system are neither studied, nor considered for prophylactic pacing. | No pos | No neg |
Retriever537 | Impact of socioeconomic position and distance on mental health care utilization: a nationwide Danish follow-up study.
PURPOSE
To determine the impact of socioeconomic position (SEP) and distance to provider on outpatient mental health care utilization among incident users of antidepressants.
METHOD
A nationwide register-based cohort study of 50,374 person-years.
RESULTS
Persons in low SEP were more likely to have outpatient psychiatrist contacts [odds ratio (OR) 1.25; confidence interval (CI) 1.17-1.34], but less likely to consult a co-payed psychologist (OR 0.49; CI 0.46-0.53) and to get mental health service from a GP (MHS-GP) (OR 0.81; CI 0.77-0.86) compared to persons in high SEP after adjusting for socio-demographics, comorbidity and car ownership. Furthermore, persons in low SEP who had contact to any of these therapists tended to have lower rates of visits compared to those in high SEP. When distance to services increased by 5 km, the rate of visits to outpatient psychiatrist tended to decrease by 5% in the lowest income group (IRR 0.95; CI 0.94-0.95) and 1% in the highest (IRR 0.99; CI 0.99-1.00). Likewise, contact to psychologists decreased by 11% in the lowest income group (IRR 0.89; CI 0.85-0.94), whereas rate of visits did not interact.
CONCLUSION
Patients in low SEP have relatively lower utilization of mental health services even when services are free at delivery; co-payment and distance to provider aggravate the disparities in utilization between patients in high SEP and patients in low SEP. | No pos | No neg |
Retriever538 | [Histological aspect of urinary schistosomiasis in Togo: results of a cohort of 192 cases].
The high prevalence of urinary schistosomiasis in Togo and its late management often lead to sequels. This study takes stock of these cancerous and non-cancerous lesions observed on histological pieces in the pathology laboratory of the Teaching Hospital of Lome in 10 years. We find 28.1 % of malignant tumor lesions, dominated by urothelial carcinoma. | No pos | No neg |
Retriever539 | Virtual Clinical Simulation for Training Amongst Undergraduate Medical Students: A Pilot Randomised Trial (VIRTUE-Pilot).
BACKGROUND
Clinical virtual simulators are promising new technologies that might facilitate teaching clinical skills.
OBJECTIVE
This study aimed to assess whether a virtual reality simulator might facilitate learning and improve adherence to current clinical guidelines.
METHODOLOGY
A double-masked randomised trial was undertaken among fourth-year medical students at Universidad Andres Bello, Chile. Participants were randomised to a clinical virtual simulator (Body Interact®, Body Interact Inc., Austin, TX) or a small-group discussion session on the management of myocardial infarction. Main outcomes included performance in an objective structured clinical examination (OSCE) and adherence to clinical recommendations. Analyses were undertaken under the intention to treat principle by an independent statistician.
RESULTS
Fifty students volunteered to participate. Most were female (30 students, 58.8%) and had a mean age of 23.0±2.7 years. Thirty-two participants (62.8%) had used virtual reality platforms before. Students allocated to the simulator showed better OSCE scores (mean difference: 2.8 points; 95% confidence interval (CI): -3.2 to +8.7 points, p=0.14) and were faster to implement diagnostic and therapeutic interventions, but not in a statistically significant way.
DISCUSSION
Academic performance was slightly improved by the use the simulator, although the overall effect was smaller than expected.
CONCLUSION
This study examined the influence of a clinical virtual simulator on the academic performance and guideline adherence of undergraduate medical students, with small group discussions as a point of comparison. The findings revealed that there were no statistically significant distinctions between the two methods, potentially attributed to the selection of the comparator and the relatively brief intervention period. | No pos | No neg |
Retriever540 | Effect of simulated gastric fluid and bile on survival of Vibrio vulnificus and Vibrio vulnificus phage.
Bacteria and phages may be exposed to acid conditions in the stomach and to bile in the intestine. Survival of three strains of Vibrio vulnificus and three strains of its phages was examined at 37 degrees C after exposure to simulated gastric fluid at pH 3 to 4 or to 0, 1, and 2% bile in broth or buffer. Mean D-values (decimal reduction times) at pH 4 and 3 were 3.3 and 1.3 min for V. vulnificus and 97.8 and 0.7 min for its phages. No V. vulnificus survivors were found at pH 2.0. There were few survival differences among strains of V. vulnificus or its phages. Numbers of V. vulnificus increased 1 log in tryptic soy broth containing 1 or 2% bile after 3 h. Numbers of V. vulnificus and its phages remained constant in phosphate-buffered saline regardless of bile concentrations up to 3 h. Those V. vulnificus bacteria and phages that survive stomach acidity may proliferate in the small intestine, since they are resistant to bile. | No pos | No neg |
Retriever541 | The time course of acclimation to the stress of triose phosphate use limitation.
Triose phosphate utilisation (TPU) limits the maximum rate at which plants can photosynthesise. However, TPU is almost never found to be limiting photosynthesis under ambient conditions for plants. This, along with previous results showing adaptability of TPU at low temperature, suggest that TPU capacity is regulated to be just above the photosynthetic rate achievable under the prevailing conditions. A set of experiments were performed to study the adaptability of TPU capacity when plants are acclimated to elevated CO2 concentrations. Plants held at 1500 ppm CO2 were initially TPU limited. After 30 h they no longer exhibited TPU limitations but they did not elevate their TPU capacity. Instead, the maximum rates of carboxylation and electron transport declined. A timecourse of regulatory responses was established. A step increase of CO2 first caused PSI to be oxidised but after 40 s both PSI and PSII had excess electrons as a result of acceptor-side limitations. Electron flow to PSI slowed and the proton motive force increased. Eventually, non-photochemical quenching reduced electron flow sufficiently to balance the TPU limitation. Over several minutes rubisco deactivated contributing to regulation of metabolism to overcome the TPU limitation. | No pos | No neg |
Retriever542 | Biologically active derivatives of fatty acids: prostaglandins, thromboxanes, and endoperoxides.
The causal role assigned to the E and F prostaglandins in inflammatory processes, implied by the antiinflammatory action of prostaglandin synthetase inhibitors, is not consistent with the findings reported here that a compound (MK-447) capable of increasing levels of these prostaglandins is antiinflammatory in classical animal models of acute inflammation. That both MK-447 and prostaglandin synthetase inhibitors depress the enzymatic formation of PGG2 from arachidonic acid suggests that this endoperoxide plays a pivotal role in acute inflammation. However, in view of the intermediate nature of PGG2, it seems likely that such a pivotal role for this substance is a function of its ability to be converted to other inflammatory mediators. Possible candidates for a causal role are thromboxane A2 (TXA2) prostacyclin (PGI2), both of which derive from PGG2. However, direct evidence is presented to show that an oxygen equivalent released in the enzymatic conversion of PGG2 to PGH2 is a prime factor in inflammation. | No pos | No neg |
Retriever543 | Protection against fatal Pseudomonas aeruginosa pneumonia in mice after nasal immunization with a live, attenuated aroA deletion mutant.
Studies of immunity to Pseudomonas aeruginosa have indicated that a variety of potential immunogens can elicit protection in animal models, utilizing both antibody- and cell-mediated immune effectors for protection. To attempt to optimize delivery of multiple protective antigens and elicit a broad range of immune effectors, we produced an aroA deletion mutant of the P. aeruginosa serogroup O2/O5 strain PAO1, designated PAO1deltaaroA. Previously, we reported that this strain elicits high levels of opsonic antibody directed against many serogroup O2/O5 strains after nasal immunization of mice and rabbits. Here, we assessed the protective efficacy of immunization with PAO1deltaaroA against acute fatal pneumonia in mice. After active immunization, high levels of protection were achieved against an ExoU-expressing cytotoxic variant of the parental strain PAO1 at doses up to 1,000-fold greater than the 50% lethal dose. Significant protection against PAO1 and two of four other serogroup O2/O5 strains was also found, but there was no protection against serogroup-heterologous strains. The serogroup O2/O5 strains not protected against were killed in opsonophagocytic assays as efficiently as the strains with which protection was seen, indicating a lack of correlation of protection and opsonic killing within the serogroup. In passive immunization experiments using challenge with wild-type PAO1 or other noncytotoxic members of the O2/O5 serogroup, there was no protection despite the presence of high levels of opsonic antibody in the mouse sera. However, passive immunization did prevent mortality from pneumonia due to the cytotoxic PAO1 variant at low-challenge doses. These data suggest that a combination of humoral and cellular immunity is required for protection against P. aeruginosa lung infections, that such immunity can be elicited by using aroA deletion mutants, and that a multivalent P. aeruginosa vaccine composed of aroA deletion mutants of multiple serogroups holds significant promise. | No pos | No neg |
Retriever544 | Insights into methyltransferase specificity and bioactivity of derivatives of the antibiotic plantazolicin.
Peptide antibiotics represent a class of conformationally constrained natural products of growing pharmaceutical interest. Plantazolicin (PZN) is a linear, polyheterocyclic natural product with highly selective and potent activity against the anthrax-causing bacterium, Bacillus anthracis. The bioactivity of PZN is contingent on dimethylation of its N-terminal Arg residue by an S-adenosylmethionine-dependent methyltransferase. Here, we explore the substrate tolerances of two homologous PZN methyltransferases by carrying out kinetic analyses of the enzymes against a synthetic panel of truncated PZN analogs containing the N-terminal Arg residue. X-ray cocrystal structures of the PZN methyltransferases with each of these heterocycle-containing substrates provide a rationale for understanding the strict substrate specificity of these enzymes. Kinetic studies of structure-guided, site-specific variants allowed for the assignment of residues governing catalysis and substrate scope. Microbiological testing further revealed that upon dimethylation of the N-terminal Arg, a pentaheterocyclized PZN analog retained potent anti-B. anthracis activity, nearly equal to that of full-length PZN. These studies may be useful in the biosynthetic engineering of natural product analogs with different bioactivity profiles, as demonstrated by our identification of a truncated plantazolicin derivative that is active against methicillin-resistant Staphylococcus aureus (MRSA). | No pos | No neg |
Retriever545 | Ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay for simultaneous quantifications of CZ48, lactone-stabilized camptothecin, and camptothecin and their pharmacokinetic and biliary evaluations in rats.
CZ48, a prodrug of camptothecin (CPT), has a broad spectrum of antitumor activity against various types of human tumors without severe toxicity in preclinical human tumor-xenografted mouse models, which facilitates further preclinical and clinical pharmacokinetic (PK) evaluations of CZ48. In this study, a UHPLC-MS/MS method was developed and validated to simultaneously quantify CZ48 and CPT in rat plasma and bile. Detection was performed using the API 3200 Q Trap triple quadrupole mass spectrometer in a positive ion mode. Chromatographic separation was achieved on Waters ACQUITY UPLC BEH Shield RP18 column with a gradient elution at a flow rate of 0.45 ml/min, using mobile phases of 0.1% acetic acid in water (A) and 0.1% acetic acid in acetonitrile (B). The method was linear at the concentration ranges of 0.98 (LLOQ) -1000 ng/ml of CZ48 and CPT in rat plasma and 3.9 (LLOQ) -1000 ng/ml in bile. Intra- and inter-day accuracy and precision values did not deviate by more than 6.57% and 10.15% for CZ48 and CPT, respectively, in plasma, and 12.09% and 13.48% in bile. Extraction recoveries of CZ48 were 90.18-95.42% from plasma and 86.51 -91.66% from bile. The recoveries of CPT were 91.56-97.06% from plasma and 84.89-89.15% from bile. No significant matrix effects were observed in plasma and bile within 14.00% and 16.19%, respectively. CZ48 and CPT in plasma were stable after extraction process and different storage conditions, including bench-top, processed sample in autosampler, three cycles of freeze and thaw, and long-term (3 month) stability at -80 °C. The application of the validated method was demonstrated by a PK study after an intravenous dose of CZ48 in rats. | No pos | No neg |
Retriever546 | The frequency of coronary heart disease and myocardial infarction in rheumatoid arthritis patients.
The authors studied the frequency of coronary heart disease (CHD) and myocardial infarction (MI) in 500 rheumatoid arthritis (RA) patients (116 men and 384 women). Almost 75% RA patients received 15.0-50.0 g of acetylsalicylic acid (ASA) monthly for above 4 years. The authors did not find significant differences in the frequency of CHD risk factors in the group of RA patients and in the Polish population of similar age. The authors noted only 2 cases of MI and 2 cases of CHD in 500 RA patients. All these patients received ASA irregularly and in small doses. The morbidity coefficient analysis showed that MI is 3-times less frequent in RA patients than in the Polish population. The authors suppose that long-term ASA treatment is one of the factors reducing the risk of CHD and MI probably by inhibition of the platelet function. | No pos | No neg |
Retriever547 | Bystander CPR, ventricular fibrillation, and survival in witnessed, unmonitored out-of-hospital cardiac arrest.
STUDY OBJECTIVE
To assess whether bystander CPR (BCPR) on collapse affects initial rhythm and outcome in patients with witnessed, unmonitored out-of-hospital cardiac arrest (OHCA).
DESIGN
Prospective cohort study. Student's t test, the chi 2 test, and logistic regression were used for analysis.
SETTING
Suburban emergency medical service (EMS) system.
PARTICIPANTS
Patients 19 years or older with witnessed OHCA of presumed cardiac origin who experienced cardiac arrest before EMS arrival between July 1989 and July 1993.
RESULTS
Of 722 patients who met the entry criteria, 153 received BCPR. Patients who received BCPR were younger than those who did not: 62.5 +/- 15.4 years versus 66.8 +/- 15.1 years (P < .01). We found no differences in basic or advanced life support response intervals or in frequency of AED use. More patients initially had ventricular fibrillation (VF) in the BCPR group: 80.9% versus 61.4% (P < .01). The interval to definitive care for ventricular tachycardia (VT)/VF was longer for the BCPR group (8.59 +/- 5.3 versus 7.45 +/- 4.7 minutes; P < .05). The percentage of patients discharged alive who were initially in VT/VF was higher in the BCPR group: 18.3% versus 8.4% (P < .001). In a multivariate model, BCPR is a significant predictor for VT/VF and live discharge with adjusted ORs of 2.7 (95% CI, 1.7 to 4.4) and 2.4 (95% CI, 1.5 to 4.0), respectively. For those patients in VT/VF, BCPR predicted live discharge from hospital with an adjusted OR of 2.1 (95% CI, 1.2 to 3.6).
CONCLUSION
Patients who receive BCPR are more often found in VT/VF and have an increased rate of live discharge, with controls for age and response and definitive care intervals. For VT/VF patients, BCPR is associated with an increased rate of live discharge. | No pos | No neg |
Retriever548 | Long-term disappearance of previous chromosomal abnormalities in myelodysplastic syndromes treated with low dose cytosine arabinoside and granulocyte/macrophage-colony stimulating factor.
Most therapies for elderly patients with myelodysplastic syndromes offer few short responses and little improvement in survival. We describe two patients who, after several cycles of low dose cytosine arabinoside and GM-CSF, achieved and maintained complete remission and became transfusion independent. Previous chromosomal abnormalities also disappeared and karyotype remains normal. | No pos | No neg |
Retriever549 | T-regulatory cells and programmed death 1+ T cells contribute to effector T-cell dysfunction in patients with chronic obstructive pulmonary disease.
RATIONALE
Previous studies from our laboratory have shown that peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD) prone to exacerbations with nontypeable Haemophilus influenzae have impaired responses to lipoprotein P6. We hypothesized that an underlying immunosuppressive network could be responsible for the defective antibacterial immunity observed in these patients. We evaluated T regulatory cells (Tregs), myeloid-derived suppressor cells (MDSC), and exhausted T effector cells (programmed death 1 [PD-1](+)) in patients with COPD, because these cells are known to play a pivotal role in suppressing immune responses.
OBJECTIVES
We performed an in-depth characterization of Tregs, T effector cells, and MDSC in COPD and correlated their levels and function with disease severity.
METHODS
Treg, effector T cell, and MDSC frequency from patients with COPD and healthy subjects' PBMCs were analyzed by flow cytometry. Treg immunosuppressive capacity was measured by in vitro suppression assay. The frequency of interferon-γ producing T cells and T-cell proliferation were measured after blocking CTLA-4 and PD-1. Plasma proinflammatory and immunosuppressive cytokine levels were measured.
MEASUREMENTS AND MAIN RESULTS
Significantly increased levels of Tregs, MDSC, and PD-1(+) exhausted effector T cells were present in patients with COPD compared with healthy subjects. Tregs from patients with COPD suppressed P6-specific T-cell proliferation to a greater extent than Tregs from healthy subjects. Plasma levels of Treg-generated cytokines, IL-10, and transforming growth factor-β were elevated. Blockade of CTLA-4 resulted in significant augmentation of T-cell IFN-γ production in patients with COPD.
CONCLUSIONS
Functionally suppressive Tregs, MDSCs, and exhausted PD-1(+) T cells contribute to effector T-cell dysfunction in COPD. | No pos | No neg |
Retriever550 | Oxygenation properties of extracellular giant hemoglobin from Oligobrachia mashikoi.
Oxygenation properties of hemoglobin (Hb) from Oligobrachia mashikoi were extensively investigated. Compared to human Hb, Oligobrachia Hb showed a high oxygen affinity (P(50)=1.4 mmHg), low cooperativity (n =1.4), and a small Bohr effect (deltaH(+)=-0.28) at pH 7.4 in the presence of minimum salts. Addition of NaCl caused no change in the oxygenation properties of Oligobrachia Hb, indicating that Na(+) and Cl(-) had no effect. Mg(2+) and Ca(2+) remarkably increased the oxygen affinity and cooperativity. The dependence of the oxygen affinity on Ca(2+) concentration indicated that ca. 0.6 Ca(2+) per heme is bound to the protein moiety upon oxygen binding. CO(2) and a polyanion, inositol hexaphosphate, showed a null effect on the oxygenation properties. Thus, unlike the vertebrate Hbs, but like the annelid extracellular Hbs, the oxygen binding properties of Oligobrachia Hb are regulated by divalent cations which preferentially bind to the oxy form. | No pos | No neg |
Retriever551 | Syntheses and crystal structure of 4-[(pyridin-3-yl)diazen-yl]morpholine and 1-[(pyridin-3-yl)diazen-yl]-1,2,3,4-tetra-hydro-quinoline.
Two new heterocyclic 1,2,3-triazenes were synthesized by diazo-tation of 3-amino-pyridine following respectively by coupling with morpholine or 1,2,3,4-tetra-hydro-quinoline. 4-[(Pyridin-3-yl)diazen-yl]morpholine (I), C9H12N4O, has monoclinic P21/c symmetry at 100 K, while 1-[(pyridin-3-yl)diazen-yl]-1,2,3,4-tetra-hydro-quinoline (II), C14H14N4, has monoclinic P21/n symmetry at 100 K. These 1,2,3-triazene derivatives were synthesized by the organic medium method by coupling reactions of 3-amino-pyridine with morpholine and 1,2,3,4-tetra-hydro-quinoline, respectively, and characterized by 1H NMR, 13C NMR, IR, mass spectrometry, and single-crystal X-ray diffraction. The mol-ecule of compound I consists of pyridine and morpholine rings connected by an azo moiety (-N=N-). In the mol-ecule of II, the pyridine ring and the 1,2,3,4-tetra-hydro-quinoline unit are also connected by an azo moiety. The double- and single-bond distances in the triazene chain are comparable for the two compounds. In both crystal structures, the mol-ecules are connected by C-H⋯N inter-actions, forming infinite chains for I and layers parallel to the bc plane for II. | No pos | No neg |
Retriever552 | Prevention of donor-specific T-cell unresponsiveness after buffy-coat-depleted blood transfusion.
The immunosuppressive effect of blood transfusions has been demonstrated in several clinical studies. The effect is probably mediated by HLA-class-II-bearing donor leucocytes, because results from laboratory tests show specific down-regulation of the recipient's T-Cell response after administration of blood from donors sharing one HLA haplotype with the recipient. In the present study we evaluated the immunosuppressive potential of buffy-coat-depleted red cell transfusions in patients waiting for renal transplantation, by measuring the frequency of cytotoxic precursor T cells before and after transfusion. The buffy coat was removed from whole blood by the Optipress system and resulted in > 97% depletion of lymphocytes and monocytes. A single transfusion of HLA-haplotype-matched buffy-coat-depleted red cells induced donor-specific down-regulation of T-cell responses in only two of 14 patients. Since HLA-class-II-bearing cells are also involved in the induction of anti-HLA antibodies, we evaluated retrospectively the incident of HLA alloimmunization after a single transfusion of buffy-coat-depleted red cells. No anti-HLA antibodies were found in 140 patients at risk for primary immunization. We conclude that the poor immunological responses found after a single transfusion of HLA-haplotype-matched buffy-coat-depleted red cells is due to the small number of residual HLA-class-II-bearing donor cells. This blood component should not be used for induction of immunosuppression. | No pos | No neg |
Retriever553 | [Cellular responses by cytokines--gene regulation in the IFN system].
Interferon (IFNs), as a class of antiviral cytokines, are also known as "negative growth regulators," they inhibit the growth of a variety of normal and malignant cells. Normally, Type I IFNs (i.e. IFN-alpha, -beta) are not induced, but viruses and a number of other cytokines transiently activate the IFN genes. In order to elucidate the molecular mechanisms of cellular responses by viruses and cytokines, we have identified two nuclear factors, IRF-1 and IRF-2, both bind to the regulatory cis-elements of IFN and IFN-responsive genes. The genes encoding IRF-1 and IRF-2, have been cloned and extensively characterized. The IRF cDNA expression studies in factor-negative cells have revealed IRF-1 and IRF-2 to function as transcriptional activator and repressor, respectively. In normal cells, the IRF genes are subject to induction through stimuli such as viruses and cytokines including IFNs per se. The findings provide evidence for the presence of an elaborate network of cytokines system wherein the IRFs play a crucial role for the cytokine-mediated cellular responses. | No pos | No neg |
Retriever554 | Tailor-made ultra-crystalline, high molecular weight poly(ε-caprolactone) films with improved oxygen gas barrier and optical properties: a facile and scalable approach.
The work presents a facile and scalable approach for fabricating tailor-made ultra-crystalline, high molecular weight biodegradable polymer poly(ε-caprolactone) [PCL] through ring-opening polymerization. Linear homopolymer of PCL were fabricated by tuning the molar ratio of monomer: initiator: catalyst in associated with organometallic catalyst (tin octoate) and a non-toxic and structurally symmetric initiator ethylene glycol (EG). High molecular weight PCL homopolymer formation with molecular weight higher than 90,000 Da was examined by FTIR, NMR and GPC. The ultra-crystalline characteristics (percent crystallinity, %Xc >70%) and unique crystal morphology of PCL were thoroughly scrutinized using DSC, XRD, HRTEM, SAED patterns and POM analysis. The developed protocol for the solvent-free technology allows high conversion ~99% at lowest possible reaction time of 1 h suggesting it a cost effective process, which is scalable to larger volume (5000 mL) without compromising the final product properties. The fabricated ultra-crystalline, high molecular weight PCL films showed good oxygen barrier property (~197 cm3 mm-1 day-1), surface free energy (133.7 mN/m) and optical transparency, recommending its niche in envisioned applications like low temperature flexible packaging and biomedical field. | No pos | No neg |
Retriever555 | Fetal heart rate monitoring practices at a public hospital in Northern Uganda - what health workers document, do and say.
Background: In Uganda, perinatal mortality is 38 per 1000 pregnancies. One-third of these deaths are due to birth asphyxia. Adequate fetal heart rate (FHR) monitoring during labor may detect birth asphyxia but little is known about monitoring practices in low resource settings.Objective: To explore FHR monitoring practices among health workers at a public hospital in Northern Uganda.Methods: A sequential explanatory mixed methods study was conducted by reviewing 251 maternal records and conducting 11 interviews and two focus group discussions with health workers complemented by observations of 42 women in labor until delivery. Quantitative data were summarized using frequencies and percentages. Content analysis was used for qualitative data.Results: FHR was assessed in 235/251 (93.6%) of records at admission. Health workers documented the FHR at least once in 175/228 (76.8%) of cases during the first stage of labor compared to observed 17/25 (68.0%) cases. Median intervals between FHR monitoring were 30 (IQR 30-120) minutes in patients' records versus 139 (IQR 87-662) minutes according to observations. Observations suggested no monitoring of FHR during the second stage of labor but records indicated monitoring in 3.2% of cases. Reported barriers to adequate FHR monitoring were inadequate number of staff and monitoring devices, institutional challenges such as few beds, documentation problems and perceived non-compliant women not reporting for repeated checks during the first stage of labor. Health workers demonstrated knowledge of national FHR monitoring guidelines and acknowledged that practice was different.Conclusions: When compared to national and international guidelines, FHR monitoring is sub-optimal in the studied setting. Approximately one in four women was not monitored during the first stage of labor. Barriers to appropriate FHR monitoring included shortage of staff and devices, institutional challenges and mother's negative attitudes. These barriers need to be addressed in order to reduce neonatal mortality. | No pos | No neg |
Retriever556 | A Novel Cobalt(II) Coordination Complex Constructed from H2Pyri and 4,4'-Bipy: Synthesis, Characterization and Bioactivity.
The new complex of {[Co(4,4'-Bipy)(H2O)4]·(Pyri) · 3H2O}n (4,4'-Bipy = 4,4'-bipyridyl, H2Pyri = 3,5- Pyridinedicarboxylic acid) was synthesized and characterized by IR, element analysis and X-ray single-crystal diffraction. The binding of the complex with extracted HeLa cells DNA was investigated by UV and fluorescence spectrum. Gel electrophoresis assay demonstrated the ability of the complex cleaving the extracted HC-DNA. The complex exhibited a higher cytotoxicity against tumor cells in vitro. Furthermore, the apoptotic tests indicated the complex had an apoptotic effect on HeLa cells. | No pos | No neg |
Retriever557 | Functional role and signal-induced modulation of proteins recognizing the conserved TCATTT-containing promoter elements in the murine IL-5 and GM-CSF genes in T lymphocytes.
The TCATTT-containing element extending from -61 to -41 of the mouse IL-5 gene is highly conserved in the corresponding region of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene and has been previously shown to be involved in regulating inducible GM-CSF gene expression. By using stable transfection assays in the mouse Th2 clone D10.G4.1, we show that the TCATTT-containing element is also involved in the regulation of inducible IL-5 gene expression. The mouse IL-5 and GM-CSF homologues of this element were found by gel shift analysis to form DNA-nuclear protein complexes of similar electrophoretic mobility under conditions in which expression of these genes is induced. However, comparative studies using extracts of D10.G4.1 cells treated with the cellular activators Con A and PMA and the inhibitors cycloheximide and cyclosporin A indicated that the binding activities to the conserved elements in the IL-5 and GM-CSF genes (designated NF-IL-5A and NF-GM-CSFA, respectively) are regulated by different signaling pathways. In addition, NF-IL-5A is not induced in the Th1 clone HDK-1 which does not express the IL-5 gene. The strong correlation between the signal-dependent and cell-specific modulation of IL-5 and GM-CSF gene expression patterns and the binding activities of NF-IL-5A and NF-GM-CSFA suggests that these nuclear proteins are involved in the transduction of T cell activation signals to the transcriptional machinery of these genes through their interactions with their respective TCATTT-containing elements. | No pos | No neg |
Retriever558 | Natural product-inspired esters and amides of ferulic and caffeic acid as dual inhibitors of HIV-1 reverse transcriptase.
Using an HIV-1 Reverse Transcriptase (RT)-associated RNase H inhibition assay as lead, bioguided fractionation of the dichloromethane extract of the Ocimum sanctum leaves led to the isolation of five triterpenes (1-5) along with three 3-methoxy-4-hydroxy phenyl derivatives (6-8). The structure of this isolates were determined by 1D and 2D NMR experiments as well as ESI-MS. Tetradecyl ferulate (8) showed an interesting RNase H IC50 value of 12.4 μM and due to the synthetic accessibility of this secondary metabolite, a structure-activity relationship study was carried out. A series of esters and amides of ferulic and caffeic acids were synthesized and, among all, the most active was N-oleylcaffeamide displaying a strong inhibitory activity towards both RT-associated functions, ribonuclease H and DNA polymerase. Molecular modeling studies together with Yonetani-Theorell analysis, demonstrated that N-oleylcaffeamide is able to bind both two allosteric site located one close to the NNRTI binding pocket and the other close to RNase H catalytic site. | No pos | No neg |
Retriever559 | Design of internal quality control for reference value studies.
Internal quality control should assure that the desired quality goals are achieved during reference value studies. Quality goals are often stated in the form of allowable limits of error, such as an allowable total error or an allowable bias. For reference value studies, it may be more appropriate to utilize a goal for allowable bias. In either case, it is possible to calculate a metric in the form of the critical systematic error that can be used to guide selection or design of the internal quality control procedure. A graphical tool, called the critical-error graph, facilitates the selection by superimposing the calculated critical systematic error on the power curves of different control rules and numbers of control measurements. Examples are provided to illustrate the calculation of the critical systematic error from both an allowable total error goal and an allowable bias goal, using figures from an extensive tabulation of available total error and bias goals. | No pos | No neg |
Retriever560 | Hydrophobic nature of the active site of mandelate racemase.
Mandelate racemase (EC 5.1.2.2) from Pseudomonas putida catalyzes the interconversion of the two enantiomers of mandelic acid with remarkable proficiency, stabilizing the altered substrate in the transition state by approximately 26 kcal/mol. We have used a series of substrate analogues (glycolates) and intermediate analogues (hydroxamates) to evaluate the contribution of the hydrophobic cavity within the enzyme's active site to ligand binding. Free energy changes accompanying binding of glycolate derivatives correlated well with the hydrophobic substituent constant pi and the van der Waals surface areas of the ligands. The observed dependence of the apparent binding free energy on surface area of the ligand was -30 +/- 5 cal mol(-1) A(-2) at 25 degrees C. Free energy changes accompanying binding of hydroxamate derivatives also correlated well with pi values and the van der Waals surface areas of the ligands, giving a slightly greater free energy dependence equal to -41 +/- 3 cal mol(-1) A(-2) at 25 degrees C. Surprisingly, mandelate racemase exhibited a binding affinity for the intermediate analogue benzohydroxamate that was 2 orders of magnitude greater than that predicted solely on the basis of hydrophobic interactions. This suggests that there are additional specific interactions that stabilize the altered substrate in the transition state. Mandelate racemase was competitively inhibited by (R,S)-1-naphthylglycolate (apparent K(i) = 1.9 +/- 0.1 mM) and (R,S)-2-naphthylglycolate (apparent K(i) = 0.52 +/- 0.03 mM), demonstrating the plasticity of the hydrophobic pocket. Both (R)- (K(m) = 0.46 +/- 0.06 mM, k(cat) = 33 +/- 1 s(-1)) and (S)-2-naphthylglycolate (K(m) = 0.41 +/- 0.03 mM, k(cat) = 25 +/- 1 s(-1)) were shown to be alternative substrates for mandelate racemase. These kinetic results demonstrate that no major steric restrictions are imposed on the binding of this bulkier substrate in the ground state but that steric factors appear to impair transition state/intermediate stabilization. 2-Naphthohydroxamate was identified as a competitive inhibitor of mandelate racemase, binding with an affinity (K(i) = 57 +/- 18 microM) that was reduced relative to that observed for benzohydroxamate and that was in accord with the approximately 10-fold reduction in the value of k(cat)/K(m) for the racemization of 2-naphthylglycolate. These findings indicate that, for mandelate racemase, steric constraints within the hydrophobic cavity of the enzyme-intermediate complex are more stringent than those in the enzyme-substrate complex. | No pos | No neg |
Retriever561 | An insight into the sialome of Anopheles funestus reveals an emerging pattern in anopheline salivary protein families.
Anopheles funestus, together with Anopheles gambiae, is responsible for most malaria transmission in sub-Saharan Africa, but little is known about molecular aspects of its biology. To investigate the salivary repertoire of this mosquito, we randomly sequenced 916 clones from a salivary-gland cDNA library from adult female F1 offspring of field-caught An. funestus. Thirty-three protein sequences, mostly full-length transcripts, are predicted to be secreted salivary proteins. We additionally describe 25 full-length housekeeping-associated transcripts. In accumulating mosquito sialotranscriptome information--which includes An. gambiae, Anopheles stephensi, Anopheles darlingi, Aedes aegypti, Aedes albopictus, Culex pipiens quinquefasciatus, and now An. funestus--a pattern is emerging. First, ubiquitous protein families are recruited for a salivary role, such as members of the antigen-5 family and enzymes of nucleotide and carbohydrate catabolism. Second, a group of protein families exclusive to blood-feeding Nematocera includes the abundantly expressed D7 proteins also found in sand flies and Culicoides. A third group of proteins, only found in Culicidae, includes the 30 kDa allergen family and several mucins. Finally, 10 protein and peptide families, five of them multigenic, are exclusive to anophelines. Among these proteins may reside good epidemiological markers to measure human exposure to anopheline species such as An. funestus and An. gambiae. | No pos | No neg |
Retriever562 | Soft-tissue coverage of complex dorsal hand and finger defects using the turnover adipofascial flap.
Complex hand wounds with exposed tendon or bone often require free tissue transfer. We report results in 13 patients with complex dorsal hand or digital wounds who underwent soft-tissue reconstruction using a turnover adipofascial flap and skin grafting over a 35-month period. The mean patient age was 44 years. Mechanism of injury included the following: three gunshot, four degloving, one table saw, three chain saw, one thumb avulsion, and one crush. Flap sizes varied from 2 × 4 to 10 × 18 cm, involving the dorsum of the hand in four patients, thumb in two patients, index finger in one patient, long finger in three patients, long and ring fingers in one patient, and web space in two patients. Skin graft survival was 100% in 12 patients. One patient died of sepsis from unrelated medical conditions. All fractures were healed at follow-up, and there were no donor site complications. The adipofascial flap is a good alternative to free tissue transfer for the coverage of complex dorsal hand and finger soft-tissue defects and is associated with technical ease, good cosmetic results, and minimal donor site morbidity. | No pos | No neg |
Retriever563 | Depression and randomized, controlled trials: problems and solutions.
Research into what works in depression is in trouble. All treatments appear equally effective and what happens in research trials does not seem to translate into clinical practice or, to put it another way, clinical practice is not reflected in randomized controlled trials. We run the risk of designing cosmetic trials with no real relationship to clinical services that only serve to demonstrate that new treatments are effective in artificial settings. This article outlines possible reasons for this, which include how depression is diagnosed, how people are recruited into trials, the design of trials and how outcomes are assessed. The solutions to these problems involve changing how patients are recruited, considering other trial designs and using different outcome measures. | No pos | No neg |
Retriever564 | Validation of Brief Multidimensional Spirituality/Religiousness Inventory (BMMRS) in Italian Adult Participants and in Participants with Medical Diseases.
This study aimed at assessing the reliability and construct validity of Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS) on Italian sample.
SAMPLE
353 Italian participants: 58.9% affected by different diseases and 41.1% healthy subjects. The results of descriptive statistics of internal consistency reliabilities (Chronbach's coefficient) of the BMMRS revealed a remarkable consistency and reliability of different scales DSE, SpC, SC, CSC, VB, SPY-WELL and a good Inter-Class Correlations ≥70 maintaining a good stability of the measures over the time. BMMRS is a useful inventory for the evaluation of the principal spiritual dimensions. | No pos | No neg |
Retriever565 | [Treatment of acute cholecystitis in the elderly: urgent surgery versus medical therapy and surgery delay].
INTRODUCTION
Acute cholecystitis in elderly patients is a frequent disease characterized by a high mortality rate and serious complications. The choice between emergency surgery or conservative therapy in addition to delayed surgery is a controversial issue.
PATIENTS AND METHODS
Retrospective cohort study over patients aged 70 years or older undergoing acute cholecystitis treatment between 2003 and 2009. Epidemiological, clinical,diagnostic, surgical and cost-effectiveness parameters were analysed.
STATISTICAL METHOD
We use Chi squared test, Student's t test and ANOVA. A level of p < 0.05 was accepted as significant.
RESULTS
During the six-year period studied 173 episodes of acute cholecystitis were treated on 147 patients (52% females), with an average age of 80.6 years (maximum 101). In 103 episodes (77 patients) medical treatment was taken, 31 of them undergone elective surgery by means of 100% laparoscopic approach, 6,4% conversion rate, 9,6% morbidity in absence of mortality. In other 85 patients emergency surgery was performed, 78.5% of them through laparoscopy approach with a conversion rate of 19.7%, 53% morbidity and 3,5% mortality.
CONCLUSIONS
Taking into account all variables, emergency surgery and medical treatment followed by elective cholecistectomy get similar outcomes, making better progress those who underwent early laparoscopic cholecystectomy. | No pos | No neg |
Retriever566 | Ex vivo stimulation of cytomegalovirus (CMV)-specific T cells using CMV pp65-modified dendritic cells as stimulators.
Cytomegalovirus (CMV) infection is a dangerous complication in immunosuppressed individuals such as allogeneic stem cell transplant patients. CMV disease can be prevented by the early post-transplant transfer of donor-derived, CMV-directed, T cells. Fast and cost efficient methods to generate CMV-specific T cells are, therefore, warranted. The current study utilized peptide-pulsed and adenovirus-transduced dendritic cells (DC) to generate CMV-restricted T cells. After one stimulation with CMV pp65495-503 peptide-pulsed DC and three re-stimulations with peptide-pulsed monocytes, virtually all T cells were CD8+, expressed the relevant T cell receptor and exhibited high peptide-specific lytic activity. After only one stimulation, pp65495-503-restricted T cells could be sorted to a purity of higher than 95% and expanded up to 1000-fold in 2 weeks. This technique may prove useful for the rapid generation of large quantities of specific cytolytic T lymphocytes (CTL) for cell therapy. DC transduced with an adenoviral vector encoding the full-length pp65 protein (Adpp65) were able to simultaneously expand CTL against multiple epitopes of pp65. In addition, they activated CMV-specific CD4+ T-helper cells. This approach would stimulate multiple-epitope populations of pp65-specific T cells and could be made available to patients of any human leucocyte antigen (HLA) haplotype. DC transduced with adenoviral vectors to express full-length antigens may prove to be potent vaccines against viral pathogens and cancer. | No pos | No neg |
Retriever567 | Engraftment after infusion of CD34+ marrow cells in patients with breast cancer or neuroblastoma.
The CD34 antigen is expressed by 1% to 4% of human and baboon marrow cells, including virtually all hematopoietic progenitors detectable by in vitro assays. Previous work from our laboratory has shown that CD34+ marrow cells can engraft lethally irradiated baboons. Because the CD34 antigen has not been detected on most solid tumors, positive selection of CD34+ cells may be used to provide marrow cells capable of engraftment, but depleted of tumor cells. In seven patients with stage IV breast cancer and two patients with stage IV neuroblastoma, 2.5 to 17.5 x 10(9) marrow cells were separated by immunoadsorption with the anti-CD34 antibody 12-8 and 50 to 260 x 10(6) positively selected cells were recovered that were 64 +/- 16% (range 35% to 92%) CD34+. The patients received 1.0 to 5.2 x 10(6) CD34-enriched cells/kg after marrow ablative therapy. Six patients engrafted, achieving granulocyte counts of greater than 500/mm3 at 34 +/- 10 (range 21 to 47) days and platelets counts of greater than 20,000/mm3 at 46 +/- 14 (range 28 to 66) days posttransplant. Five of these patients showed durable engraftment until the time of death 82 to 386 days posttransplant. One patient failed to sustain engraftment associated with metastatic marrow disease. Three patients died at days 14, 14, and 17 posttransplant, two of whom had evidence of early engraftment. These studies suggest that CD34+ marrow cells are capable of reconstituting hematopoiesis in humans. | No pos | No neg |
Retriever568 | Functional and structural neural alterations in Internet gaming disorder: A systematic review and meta-analysis.
This meta-analytic study aimed to identify the common and specific neural alterations in Internet gaming disorder (IGD) across different domains and modalities. Two separate meta-analyses for functional neural activation and gray-matter volume were conducted. Sub-meta-analyses for the domains of reward, cold-executive, and hot-executive functions were also performed, respectively. IGD subjects, compared with healthy controls, showed: (1) hyperactivation in the anterior and posterior cingulate cortices, caudate, posterior inferior frontal gyrus (IFG), which were mainly associated with studies measuring reward and cold-executive functions; and, (2) hypoactivation in the anterior IFG in relation to hot-executive function, the posterior insula, somatomotor and somatosensory cortices in relation to reward function. Furthermore, IGD subjects showed reduced gray-matter volume in the anterior cingulate, orbitofrontal, dorsolateral prefrontal, and premotor cortices. These findings suggest that IGD is associated with both functional and structural neural alterations in fronto-striatal and fronto-cingulate regions. Moreover, multi-domain assessments capture different aspects of neural alterations in IGD, which may be helpful for developing effective interventions targeting specific functions. | No pos | No neg |
Retriever569 | Outcomes after transcatheter aortic valve replacement in older patients.
BACKGROUND
The prevalence of aortic valve stenosis is increasing due to the continuously growing geriatric population. Data on procedural success and mortality of very old patients are sparse, raising the question of when this population may be deemed as "too old even for transcatheter aortic valve replacement (TAVR)." We, therefore, sought to evaluate the influence of age on outcome after TAVR and the impact of direct implantation.
METHODS
The data of 394 consecutive patients undergoing TF-TAVR were analyzed. Patients were divided into four age groups: ≤75 (group 1, n = 28), 76-80 (group 2, n = 107), 81-85 (group 3, n = 148), and >85 (group 4, n = 111) years. Direct implantation was performed when possible according to current recommendations. Survival was evaluated by Kaplan-Meier analysis.
RESULTS
Mortality at 30 days and 1 year was not significantly different between the four age groups (3.6 vs. 6.7 vs. 5.4 vs. 2.7% and 7.6 vs. 17 vs. 14.5 vs. 13%m respectively, log-rank p = 0.59). Direct implantation without balloon aortic valvuloplasty was more frequently performed on patients aged >85 vs. ≤85 years (33.3 vs. 14.1%, p < 0.001). the incidence of procedural complications frequently associated with advanced age (stroke, vascular complications) was not significantly increased in group 4.
CONCLUSION
Outcome after TF-TAVR is comparable among different age cohorts, even in very old patients. Direct implantation simplifies the procedure and could therefore play a role in reducing the incidence of peri-interventional complications in patients of advanced age. | No pos | No neg |
Retriever570 | Bioinformatic prediction and experimental verification of sRNAs in the haloarchaeon Haloferax volcanii.
Recently a small-scale RNomics study led to the experimental identification of 21 intergenic and 18 antisense sRNA genes in the haloarchaeon Haloferax volcanii. To broaden the knowledge about sRNAs in haloarchaea, two bioinformatic approaches were used to predict sRNA genes in the genome of H. volcanii. More than 120 putative intergenic sRNA genes were identified by these comparative genomic approaches. The expression of 61 of the predicted genes was analyzed using DNA microarrays, and 37 were found to be expressed under at least one of three conditions tested. Using the results of Northern blot analyses and of a high throughput sequencing study the number of expressed genes was raised to 54 and the small size was verified for 26 predicted sRNAs. An analysis of the coding capacity revealed that the set of predicted sRNAs most likely does not encode proteins or peptides. In two cases it turned out that the predictions had not identified bona fide sRNAs but conserved regions in UTRs of large protein-encoding transcripts. Taken together, the combination of bioinformatic prediction and experimental verification has more than tripled the number of known haloarchaeal sRNAs, underscoring the importance of regulatory RNAs in the third domain of life, the archaea. Further analyses of the biological functions of selected sRNAs, including the construction of deletion mutants, are currently under way. | No pos | No neg |
Retriever571 | Abi, Sra1, and Kette control the stability and localization of SCAR/WAVE to regulate the formation of actin-based protrusions.
BACKGROUND
In animal cells, GTPase signaling pathways are thought to generate cellular protrusions by modulating the activity of downstream actin-regulatory proteins. Although the molecular events linking activation of a GTPase to the formation of an actin-based process with a characteristic morphology are incompletely understood, Rac-GTP is thought to promote the activation of SCAR/WAVE, whereas Cdc42 is thought to initiate the formation of filopodia through WASP. SCAR and WASP then activate the Arp2/3 complex to nucleate the formation of new actin filaments, which through polymerization exert a protrusive force on the membrane.
RESULTS
Using RNAi to screen for genes regulating cell form in an adherent Drosophila cell line, we identified a set of genes, including Abi/E3B1, that are absolutely required for the formation of dynamic protrusions. These genes delineate a pathway from Cdc42 and Rac to SCAR and the Arp2/3 complex. Efforts to place Abi in this signaling hierarchy revealed that Abi and two components of a recently identified SCAR complex, Sra1 (p140/PIR121/CYFIP) and Kette (Nap1/Hem), protect SCAR from proteasome-mediated degradation and are critical for SCAR localization and for the generation of Arp2/3-dependent protrusions.
CONCLUSIONS
In Drosophila cells, SCAR is regulated by Abi, Kette, and Sra1, components of a conserved regulatory SCAR complex. By controlling the stability, localization, and function of SCAR, these proteins may help to ensure that Arp2/3 activation and the generation of actin-based protrusions remain strictly dependant on local GTPase signaling. | No pos | No neg |
Retriever572 | The skin fungus-induced Th1- and Th2-related cytokine, chemokine and prostaglandin E2 production in peripheral blood mononuclear cells from patients with atopic dermatitis and psoriasis vulgaris.
BACKGROUND
It is suggested that skin fungi may be involved in the development of atopic dermatitis (AD) and psoriasis vulgaris (PV).
OBJECTIVE
We studied skin fungus-induced Th1- or Th2-related cytokine, chemokine and prostaglandin E2 (PGE2) secretion in peripheral blood mononuclear cells (PBMC) from patients with AD and PV and normal subjects.
METHODS
PBMC were cultured with the extracts of Malassezia furfur (MF), Candida albicans (CA) and Trichophyton rubrum (TR). The cytokine, chemokine and PGE2 amounts in the supernatants were measured by enzyme-linked immunosorbent assays.
RESULTS
MF induced IL-4 and macrophage-derived chemokine (MDC) secretion in AD patients, while induced IFN-gamma and interferon-inducible protein of 10 kDa (IP-10) secretion in PV patients, however, did not induce either secretion in normal subjects. CA induced IL-4, MDC, IFN-gamma and IP-10 secretion in AD and PV patients and normal subjects. In AD patients, the magnitude of IL-4 and MDC responses to CA was higher than that to MF. Compared with PV patients and normal subjects, the magnitude of IL-4 and MDC responses to CA was higher while that of IFN-gamma and IP-10 responses to CA was lower in AD patients. TR induced moderate IL-4 and MDC secretion only in AD patients. The three fungi induced higher levels of PGE2 secretion in AD patients than in PV patients and normal subjects. Cyclooxygenase-2 inhibitor NS-398 suppressed PGE2 responses to MF, CA and TR, and partially suppressed IL-4 and MDC responses to MF, CA and TR, while enhanced IFN-gamma and IP-10 responses to CA in AD patients, and these effects of NS-398 were reversed by cyclic AMP analogue.
CONCLUSION
AD patients manifest Th2-skewed responses to MF, CA and TR, which may be partially attributable to the enhanced PGE2 responses to these fungi. PV patients manifest Th1-skewed responses to MF. | No pos | No neg |
Retriever573 | Spatial genome organization during T-cell differentiation.
The spatial organization of genomes within the mammalian cell nucleus is non-random. The functional relevance of spatial genome organization might be in influencing gene expression programs as cells undergo changes during development and differentiation. To gain insight into the plasticity of genomes in space and time and to correlate the activity of specific genes with their nuclear position, we systematically analyzed the spatial genome organization in differentiating mouse T-cells. We find significant global reorganization of centromeres, chromosomes and gene loci during the differentiation process. Centromeres were repositioned from a preferentially internal distribution in undifferentiated cells to a preferentially peripheral position in differentiated CD4+ and CD8+ cells. Chromosome 6, containing the differentially expressed T-cell markers CD4 and CD8, underwent differential changes in position depending on whether cells differentiated into CD4+ or CD8+ thymocytes. Similarly, the two marker loci CD4 and CD8 showed distinct behavior in their position relative to the chromosome 6 centromere at various stages of differentiation. Our results demonstrate that significant spatial genome reorganization occurs during differentiation and indicate that the relationship between dynamic genome topology and single gene regulation is highly complex. | No pos | No neg |
Retriever574 | First line crizotinib in anaplastic lymphoma kinase (ALK) rearranged squamous cell lung cancer.
Recently the superiority of Crizotinib to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC has been demonstrated. We report of a 36-year-old never smoker with advanced squamous cell carcinoma, presenting with a left lower lobe lesion, N3 nodal disease and multiple metastases (pleura, adrenal, muscle, bone). Despite squamous histology we decided on molecular testing. IHC for ALK was positive and confirmatory fluorescent in situ hybridization showed translocation of ALK. Although there is little evidence on ALK rearrangements in squamous NSCLC we decided on first line treatment with Crizotinib (250 mg twice daily). Eight and twelve weeks after treatment initiation a whole-body FDG fusion PET/CT scan showed dramatic tumor response with little remaining metabolic uptake in the left lobe and a single bone lesion. This evidence raises the question whether ALK testing should be done in never smokers with squamous NSCLC in the absence of oncogenic driver mutations. To our knowledge, this the first report of first line treatment of full squamous ALK-positive NSCLC with crizotinib. | No pos | No neg |
Retriever575 | Bioelectricity generation, contaminant removal and bacterial community distribution as affected by substrate material size and aquatic macrophyte in constructed wetland-microbial fuel cell.
Integrating microbial fuel cell with constructed wetland (CW-MFC) is a novel way to harvest bioelectricity during wastewater treatment. In this study, the bioelectricity generation, containment removal and microbial community distribution in CW-MFC as affected by substrate material sizes and aquatic macrophyte were investigated. The planted CW-MFC with larger filler size showed a significant promotion of the relative abundance of electrochemically active bacteria (beta-Proteobacteria), which might result in the increase of bioelectricity generation in CW-MFC (8.91mWm-2). Additionally, a sharp decrease of voltage was observed in unplanted CW-MFC with smaller filler size in Cycle eight. However, the peak COD (86.7%) and NO3-N (87.1%) removal efficiencies were observed in planted CW-MFC with smaller filler size, which was strongly related to the biodiversity of microorganisms. Generally, the acclimation of exoelectrogens as dominant microbes in the anode chamber of planted CW-MFC with larger filler size could promote the bioelectricity generation during wastewater treatment. | No pos | No neg |
Retriever576 | [Polish doctors in the Cieszyn of Silesia on the threshold of the 19th and 20th centuries (until 1920)].
The Polish medical profession in the Cieszyn part of Silesia (the powiats of Bielsko, Cieszyn, Frysztat and Frydek) began to take shape in the second half of the 19th century. The doctors either came from the local, peasant population, or were migrants, mainly from western Małopolska. Because of the influx of Germans and Czechs, in search of employment, to the ethnically Polish Cieszyn part of Silesia, the proportion of the Polish population in this area fell from 74.5% in 1880 to 68.5% in 1910. The local population became progressively German or Czech. Out of about 30 Polish doctors belonging to the Polish community, only a dozen or so were still active by 1920. The doctors not only satisfied the Polish community's medical needs, but also their cultural, educational, political, economic and sports needs. In 1919, the Polish medical profession provided a medical bulwark against the Czech aggression and took part in preparations for the plebiscite in the Cieszyn part of Silesia. Following the partition of this region in 1920, those Polish doctors living in the part annexed to Czechoslovakia moved to Poland. Three Polish doctors remained in Zaolzie, and they began to reestablish a Polish medical group for the 100.000-strong Polish ethnic minority in the Zaolzie part of Czechoslovakia. | No pos | No neg |
Retriever577 | Unraveling the human bone microenvironment beyond the classical extracellular matrix proteins: a human bone protein library.
A characteristic feature of bone, differentiating it from other connective tissues, is the mineralized extracellular matrix (ECM). Mineral accounts for the majority of the bone tissue volume, being the remainder organic material mostly derived from collagen. This, and the fact that only a limited number of noncollagenous ECM proteins are described, provides a limited view of the bone tissue composition and bone metabolism, the more so considering the increasing understanding of ECM significance for cellular form and function. For this reason, we set out to analyze and extensively characterize the human bone proteome using large-scale mass spectrometry-based methods. Bone samples of four individuals were analyzed identifying 3038 unique proteins. A total of 1213 of these were present in at least 3 out of 4 bone samples. For quantification purposes, we were limited to noncollagenous proteins (NCPs) and we could quantify 1051 NCPs. Most classical bone matrix proteins mentioned in literature were detected but were not among the highly abundant ones. Gene ontology analyses identified high-abundance groups of proteins with a functional link to mineralization and mineral metabolism such as transporters, pyrophosphatase activity, and Ca(2+)-dependent phospholipid binding proteins. ECM proteins were as well overrepresented together with nucleosome and antioxidant activity proteins, which have not been extensively characterized as being important for bone. In conclusion, our data clearly demonstrates that human bone tissue is a reservoir of a wide variety of proteins. In addition to the classical osteoblast-derived ECM, we have identified many proteins from different sources and of unknown function in bone. Thus, this study represents an informative library of bone proteins forming a source for novel bone formation modulators as well as biomarkers for bone diseases such as osteoporosis. | No pos | No neg |
Retriever578 | War’s long shadow: masculinity, medicine, and the gendered politics of trauma, 1914-1939.
War is an inherently traumatizing experience, and during the First World War more than 15,000 Canadian soldiers were diagnosed with some form of war-related psychological wounds. Many more went unrecognized. Yet the very act of seeking an escape from the battlefield or applying for a postwar pension for psychological traumas transgressed masculine norms that required men to be aggressive, self-reliant, and un-emotional. Using newly available archival records, contemporary medical periodicals, doctors' notes, and patient interview transcripts, this paper examines two crises that arose from this conflict between idealized masculinity and the emotional reality of war trauma. The first came on the battlefield in 1916 when, in some cases, almost half the soldiers evacuated from the front were said to be suffering from emotional breakdowns. The second came later, during the Great Depression, when a significant number of veterans began to seek compensation for their psychological injuries. In both crises, doctors working in the service of the state constructed trauma as evidence of deviance, in order to parry a larger challenge to masculine ideals. In creating this link between war trauma and deviance, they reinforced a residual conception of welfare that used tests of morals and means to determine who was deserving or undeserving of state assistance. At a time when the Canadian welfare state was being transformed in response to the needs of veterans and their families, doctors' denial that "real men" could legitimately exhibit psychosomatic symptoms in combat meant that thousands of legitimately traumatized veterans were left uncompensated by the state and were constructed as inferior, feminized men. | No pos | No neg |
Retriever579 | Treatment of diabetic ulcers.
Diabetic ulcers are chronic wounds that are the result of repetitive trauma in the insensate foot. The presence of infection and peripheral vascular disease makes the treatment of these wounds demanding and requires a multidisciplinary approach. The main principles of the management include adherence to the principles of good wound care, such as aggressive debridement of all non-viable tissue, adequate off-loading of pressure, prompt treatment of infection and moist wound dressings. Over the last decade, new therapeutic modalities, including growth factors and living skin equivalents, have been available to the practicing physicians. Judicious use of advanced wound care products may provide the best means of treating these challenging wounds in an efficient and cost-effective way. | No pos | No neg |
Retriever580 | Solid-phase nano-extraction and laser-excited time-resolved Shpol'skii spectroscopy for the analysis of polycyclic aromatic hydrocarbons in drinking water samples.
A unique method for screening polycyclic aromatic hydrocarbons in drinking water samples is reported. Water samples (500 microl) are mixed and centrifuged with 950 microl of a commercial solution of 20 nm gold nanoparticles for pollutants extraction. The precipitate is treated with 2 microl of 1-pentanethiol and 48 microl of n-octane, and the supernatant is then analyzed via laser-excited time-resolved Shpol'skii spectroscopy. Fifteen priority pollutants are directly determined at liquid helium temperature (4.2 K) with the aid of a cryogenic fiber-optic probe. Unambiguous pollutant determination is carried out via spectral and lifetime analysis. Limits of detection are at the parts-per-trillion level. Analytical recoveries are similar to those obtained via high-performance liquid chromatography. The simplicity of the experimental procedure, use of microliters of organic solvent, short analysis time, selectivity, and excellent analytical figures of merit demonstrate the advantages of this environmentally friendly approach for routine analysis of numerous samples. | No pos | No neg |
Retriever581 | Frequencies of pyrethroid resistance-associated mutations of Vssc1 and CYP6D1 in field populations of Musca domestica L. in Turkey.
House flies were collected from 16 different provinces in the Aegean and Mediterranean regions of Turkey, and the frequencies of pyrethroid resistance-associated mutations in Vssc1 and CYP6D1 in these field-collected populations were studied. Although there is no organized resistance management program for house fly control in Turkey, it is known that different groups of insecticides, including pyrethroids, are used. The frequencies of both Vssc1 and CYP6D1 alleles were weighted toward the susceptibles, with Vssc1-susceptible alleles having higher frequencies in both regions (0.75 in Aegean and 0.69 in Mediterranean populations) than CYP6D1-susceptible alleles (0.65 in Aegean and 0.56 in Mediterranean populations). The frequencies of kdr-his alleles were higher than the frequencies of kdr alleles in these populations. While the frequencies of kdr-his alleles were close to each other in the Aegean (0.23) and Mediterranean (0.17) populations, the frequencies of kdr alleles remarkably differed in these two regions, with values of 0.02 and 0.14, respectively. In contrast to Europe, Asia, and the U.S.A., no super-kdr allele was detected in the samples from both regions. We identified six and eight different Vssc1+CYP6D1 genotype classes in the Aegean and Mediterranean regions, respectively. The three most common genotype classes in the regions were susceptible Vssc1 with heterozygous CYP6D1v1 (29%), sus/kdr-his1 with heterozygous CYP6D1v1 (23%), and susceptible Vssc1 with CYP6D1 (22%). The total frequencies of these three most common genotype classes (approximately 75%) obtained in our study were very close to the value obtained in Florida in a previous study, which was related by the similarity of temperature patterns between Florida and the corresponding regions of Turkey. This may reflect the lack of overwintering fitness cost associated with resistance alleles in both climates. | No pos | No neg |
Retriever582 | [The practice of development and implementation of quality management systems in medical laboratories. The GOST R ISO 15189-2009 "medical laboratories. The detailed requirements to quality and competence". Particular difficulties of global nature].
The article discusses the methodological issues related to the implementation of international principles of standardization in the format of GOST R ISO 9001-2008 "Quality management systems. Requirements", GOST R ISO 15189-2009 "Medical laboratories. The detailed requirements to quality and competence" and GOST R ISO 18113.1-5 "Medical items for diagnostics in vitro. Information provided by manufacturer (marking)". This approach legibly assigns the responsibility concerning the support of metrological correctness of laboratory measurements. The lacking of both full-value public and sectorial normative documentation and coordinated positions of Rosstandard and Minzdrav of Russia on functioning of medical laboratories is noted. | No pos | No neg |
Retriever583 | Muscle pathology grade for facioscapulohumeral muscular dystrophy biopsies.
INTRODUCTION
As we move toward planning for clinical trials in facioscapulohumeral muscular dystrophy (FSHD), a better understanding of the clinical relationship with morphological changes in FSHD muscle biopsies will be important for stratifying patients and understanding post-therapeutic changes in muscle.
METHODS
We performed a prospective cross-sectional study of quadriceps muscle biopsies in 74 genetically confirmed FSHD participants (64 with FSHD type 1 and 10 with FSHD type 2). We compared a 12-point muscle pathology grade to genetic mutation, disease severity score, and quantitative myometry.
RESULTS
Pathology grade had moderate correlations with genetic mutation (rho = -0.45, P < 0.001), clinical severity score (rho = 0.53, P < 0.001), disease duration (rho = 0.31, P = 0.03), and quantitative myometry (rho = -0.47, P < 0.001). We found no difference in the frequency of inflammation between FSHD types 1 and 2.
CONCLUSIONS
The pathology grade of quadriceps muscle may be a useful marker of disease activity in FSHD, and it may have a role in stratification for future clinical trials. | No pos | No neg |
Retriever584 | Fluoroquinolones in animal health.
The fluoroquinolones are a series of synthetic antibacterial agents that are undergoing extensive investigation for both human and veterinary use in the treatment of a variety of bacterial infections. These agents work through the inhibition of DNA gyrase, interfering with the supercoiling of bacterial chromosomal material. As a result, these agents are rapidly bactericidal primarily against gram-negative bacteria, mycoplasma, and some gram-positive bacteria, with most having little to no activity against group D streptococci and obligate anaerobic bacteria. Resistance develops slowly and is almost always chromosomal and not plasmid-mediated. However, development of resistance to the fluoroquinolones and transfer of that resistance among animal and human pathogens have become a hotly debated issue among microbiologists. The fluoroquinolones are a current antimicrobial class whose use in veterinary medicine is being scrutinized. From a pharmacokinetic perspective, these agents are variably but well absorbed from the gastrointestinal tract and almost completely absorbed from parenteral injection sites, and they are well distributed to various tissues in the body. The fluoroquinolones are metabolized and renally excreted, with many of them having approximately equal excretion by the hepatic and the renal excretory systems. The primary toxicity observed at therapeutic doses involves the gastrointestinal system and phototoxicity, although at higher doses central nervous system toxicity and ocular cataracts are observed. Administration to immature animals may result in erosive arthropathies at weight-bearing joints, and administration of high doses to pregnant animals results in maternotoxicity and occasionally embryonic death. The fluoroquinolones are approved for indications such as urinary tract infections and soft tissue infections in dogs and cats and colibacillosis in poultry. Approval for bovine respiratory disease in the United States is being sought. Other indications for which the fluoroquinolones have been used in animal health include deep-seated infections, prostatitis, and other bacterial infections resistant to standard antimicrobial therapy. | No pos | No neg |
Retriever585 | Tumor idiotype vaccines. VI. Synergistic anti-tumor effects with combined "internal image" anti-idiotypes and chemotherapy.
Anti-Id antibodies that have biologic activity as stimulators of specific immunity have been used in experimental vaccines and tumor protection models. However, very little is known about the therapeutic potential of anti-Id antibodies in animals and men. In this study we explored the combination of anti-Id and chemotherapy in a murine tumor system for which we had previously generated protective anti-Id mAb. First, we investigated various protocols by using a protective anti-Id in active immunization. Mice preimmunized before tumor transfer and challenged again after tumor survived significantly longer. Next, we explored the use of soluble anti-Id as immunostimulator in tumor-bearing mice. Although this treatment did not induce long-term survival, it significantly increased survival time. Interestingly, this anti-Id effect was dose dependent, whereby large and small doses had no effect. Finally, stimulatory anti-Id therapy and cyclophosphamide (Cy) treatment was combined. Tumor bearing mice were given a single dose of Cy followed by different doses of soluble anti-Id. The optimal effect on tumor growth and survival was achieved with 80 mg/kg Cy and 10 micrograms/mouse of anti-Id, where 80% of mice survived longer than 100 days. These results provide guidelines for developing clinical protocols for cancer patients by using combination therapy of anti-Id and chemotherapy. | No pos | No neg |
Retriever586 | Trends in Diabetes Treatment and Monitoring among Medicare Beneficiaries.
BACKGROUND
Diabetes is a costly and common condition, but little is known about recent trends in diabetes management among Medicare beneficiaries.
OBJECTIVE
To evaluate the use of diabetes medications and testing supplies among Medicare beneficiaries.
DESIGN/SETTING
Retrospective cohort analysis of Medicare claims from 2007 to 2014.
PARTICIPANTS
Traditional Medicare beneficiaries with a diagnosis of diabetes in the current or any prior year.
MAIN MEASURES
We analyzed choices of first diabetes medication for those new to medication and patterns of adding medications. We also examined the use of testing supplies, use of statins and ACE inhibitors/angiotensin receptor blockers, and spending.
KEY RESULTS
Diagnosed diabetes increased from 28.7% to 30.2% of beneficiaries from 2007 to 2014. The use of metformin as the most commonly prescribed first medication increased from 50.2% in 2007 to 70.2% in 2014, whereas long-acting sulfonylureas decreased from 16.6% to 8.2%. The use of thiazolidinediones fell considerably, while the use of new diabetes medication classes increased. Among patients prescribed insulin, long-acting insulin as the first choice increased substantially, from 38.9% to 56.8%, but short-acting or combination regimens remained common, particularly among older or sicker beneficiaries. Prescriptions of testing supplies for more than once-daily testing were also common. The mean total cost of diabetes medications per patient increased over the period due to the increasing use of high-cost drugs, particularly by those patients with costs above the 90th percentile of spending, although the median costs decreased for both medications and testing supplies.
CONCLUSIONS
The use of metformin and long-acting insulin have increased substantially among elderly Medicare patients with diabetes, but a substantial subgroup continues to receive costly and complex treatment regimens. | No pos | No neg |
Retriever587 | CT evaluations of focal liver reactions following stereotactic body radiotherapy for small hepatocellular carcinoma with cirrhosis: relationship between imaging appearance and baseline liver function.
This study aimed to assess the imaging appearances of focal liver reactions following stereotactic body radiotherapy (SBRT) for small hepatocellular carcinoma (HCC) and to examine relationships between imaging appearance and baseline liver function. We retrospectively studied 50 lesions in 47 patients treated with SBRT (30-40 Gy in 5 fractions) for HCC, who were followed up for more than 6 months. After SBRT, all patients underwent regular follow-ups with blood tests and dynamic CT scans. At a median follow-up of 18.1 months (range 6.2-43.7 months), all lesions but one were controlled. 3 density patterns describing focal normal liver reactions around HCC tumours were identified in pre-contrast, arterial and portal-venous phase scans: iso/iso/iso in 4 patients (Type A), low/iso/iso in 8 patients (Type B) and low/iso (or high)/high in 38 patients (Type C). Imaging changes in the normal liver surrounding the treated HCC began at a median of 3 months after SBRT, peaked at a median of 6 months and disappeared 9 months later. Liver function, as assessed by the Child-Pugh classification, was the only factor that differed significantly between reactions to treatment showing "non-enhanced" (Type A and B) and "enhanced" (Type C) appearances in CT. Hence, liver tissue with preserved function is more likely to be well enhanced in the delayed phase of a dynamic contrast-enhanced CT scan. The CT appearances of normal liver seen in reaction to the treatment of an HCC by SBRT were therefore related to background liver function and should not be misread as recurrence of HCC. | No pos | No neg |
Retriever588 | [Comparison of treatments in patients with inoperable stage IV advanced esophageal cancer].
BACKGROUND/AIMS
The aim of this study was to compare palliative treatments such as chemotherapy, chemoradiotherapy or radiotherapy with best supportive care in patients with inoperable advanced esophageal cancer.
METHODS
A total of 67 patients with inoperable advanced esophageal cancer visiting Kosin University Gospel Hospital between January 2000 and July 2010 were included in a retrospective analysis. Patients were categorized as having palliative treatment or best supportive care to compare their prognosis.
RESULTS
The median survival was 6.4 months in 67 patients. There was significant difference in median survival between the palliative and best supportive treatment (9.8 months vs. 4.5 months, p=0.01). The patients who underwent palliative treatment had superior 1-year and 3-year overall survival rate than those with best supportive treatment (27%, 10% vs. 5%, 5%, respectively). The 1-year and 3-year overall survival rate of palliative treatment was 18% (1-year overall survival rate) in chemotherapy, 33% (1-year overall survival rate) in radiotherapy, 45% and 9% in concurrent chemoradiotherapy, and 20% and 20% in sequential chemoradiotherapy, respectively.
CONCLUSIONS
These results may suggest that palliative treatments are more effective than best supportive care. Further prospective studies are still needed to elucidate beneficial effect of palliative treatments on inoperable advanced esophageal cancer. | No pos | No neg |
Retriever589 | [Effect of ginger-processing on the contents of guanosine in Pinelliae rhizoma (banxia)].
OBJECTIVE
To compare the guanosine contents in various products of Pinellia Rhizoma processed by different amounts of ginger and alum.
METHOD
Using the technology of HPLC.
RESULT
The guanosine contents in the two products of Pinellia Rhizoma processed in line with the pharmacopoeial method and orthogonal method respectively are very close to each other and change every little as compared with raw Pinellia Rhizoma. But the contents in the products of Pinelliae Rhizoma processed in other ways (digged in alum solution or in ginger Juice decocted with ginger juice, etc.) are much less than those of raw Pinellia Rhizoma.
CONCLUSION
There are no obvious differences in guanosine contents between Pinellia Rhizoma processed by orthogonal technology and Pinellia Rhizoma processed by pharmacopoeial method. Processing technology has considerable influence on the water soluble components of Pinellia Phizoma. | No pos | No neg |
Retriever590 | The use of tapered plastic luer connectors in neonatal extracorporeal membrane oxygenation.
Tapered luer connectors can split, crack, and leak under certain clinical conditions. The purpose of this study was to analyze the causes of these failures and suggest methods of managing the problem. Experience is related to the use of plastic luers in neonatal extracorporeal membrane oxygenation; however, the guidelines suggested may have some application in the general intensive care population. | No pos | No neg |
Retriever591 | Substrates for sulfate reduction and methane production in intertidal sediments.
The activity of and potential substrates for methane-producing bacteria and sulfate-reducing bacteria were examined in marsh, estuary, and beach intertidal sediments. Slow rates of methane production were detected in all sediments, although rates of sulfate reduction were 100- to 1,000-fold higher. After sulfate was depleted in sediments, the rates of methane production sharply increased. The addition of methylamine stimulated methanogenesis in the presence of sulfate, and [C]methylamine was rapidly converted to CH(4) and CO(2) in freshly collected marsh sediment. Acetate, hydrogen, or methionine additions did not stimulate methanogenesis. [methyl-C]methionine and [2-C]acetate were converted to CO(2) and not to CH(4) in fresh sediment. No reduction of CO(2) to CH(4) occurred in fresh sediment. Molybdate, an inhibitor of sulfate reduction, inhibited [2-C]acetate metabolism by 98.5%. Fluoracetate, an inhibitor of acetate metabolism, inhibited sulfate reduction by 61%. These results suggest that acetate is a major electron donor for sulfate reduction in marine sediments. In the presence of high concentrations of sulfate, methane may be derived from novel substrates such as methylamine. | No pos | No neg |
Retriever592 | Denitrification performance and mechanism of denitrification biofilm reactor based on carbon-nitrate counter-diffusional.
This study researched denitrification performance and mechanism of denitrification biofilm reactor with different HRTs and carbon sources dosages. Experimental group (EG) had better nitrate and COD removal performance than control group (CG) with different HRTs or carbon doses, and the maximum nitrate-to-nitrite transformation ratio (NTR) of them reached 7.91 ± 1.60% and 17.50 ± 1.92%, respectively. Because organic carbon sources were added to the carrier's interior in EG, forming high local concentrations in biofilms and counter-diffusional with nitrate. By contrast, carbon sources and nitrate were provided from the aqueous phase in CG. Thus, the EG system has more active regions of the biofilm than CG. In addition, EG had higher proportions of microorganisms and enzymes related to denitrification and carbon metabolism. The most dominant phylum, genus, and species were Proteobacteria, Thaurea, and Thauera_sp._27, respectively. The transcript of acetyl-CoA synthetase (K01895) and denitrification (M00529) was mainly originated from unclassified_g__Pseudomonas and unclassified_g__Thauera, respectively. | No pos | No neg |
Retriever593 | Human Oral Mucosal Stem Cells Reduce Anastomotic Leak in an Animal Model of Colonic Surgery.
BACKGROUND
Anastomotic leak is regarded as one of the most feared complications of bowel surgery; avoiding leaks is a major priority. Attempts to reduce or eliminate leaks have included alternate anastomotic techniques. Human oral mucosa stem cells (hOMSC) are self-renewing and expandable cells derived from buccal mucosa. Studies have shown that hOMSC can accelerate tissue regeneration and wound healing. The objective of this study was to evaluate whether hOMSC can decrease anastomotic leak rates in a murine model of colon surgery.
METHODS
Two experiments were performed. In the first study, mice underwent colonic anastomosis using five interrupted sutures. hOMSC (n = 7) or normal saline (NS; n = 17) was injected into the colon wall at the site of the anastomosis. To evaluate whether hOMSC can impact anastomotic healing, the model was stressed by repeating the first experiment, reducing the number of sutures used for the construction of the anastomosis from five to four. Either hOMSC (n = 8) or NS (n = 20) was injected at the anastomosis. All mice that survived were sacrificed on postoperative day 7. Anastomotic leak rate, mortality, daily weight, and daily wellness scores were compared.
RESULTS
In the five-suture anastomosis, there were no differences in anastomotic leak rate, mortality, or daily weight. Mice that received hOMSC had significantly higher wellness scores on postoperative day 2 (p < 0.05). In the four-suture anastomosis, there was a significant decrease in leak rate (70% [NS] vs. 25% [hOMSC], p = 0.029) and higher wellness scores in mice that received hOMSC (p < 0.05).
CONCLUSION
Our study suggests that injecting hOMSC at the colonic anastomosis can potentially reduce anastomotic leak and improve postoperative wellness in a murine model of colon surgery. | No pos | No neg |
Retriever594 | Age-Dependent Functional and Numerical Responses of Neoseiulus cucumeris (Acari: Phytoseiidae) on Two-Spotted Spider Mite (Acari: Tetranychidae).
The age-specific functional and numerical responses of Neoseiulus cucumeris Oudemans (Mesostigmata: Phytoseiidae) on eggs of the two-spotted spider mite, Tetranychus urticae Koch (Prostigmata: Tetranychidae), were assessed in the laboratory using bean leaf discs. Densities of 2, 4, 8, 16, 32, 64, and 128 prey were provided to 4- (protonymph), 6- (deutonymph), 8-, 13-, 18-, 23-, 28-, 33-, and 40-d-old N. cucumeris individuals. The functional response of 28- and 40-d-old N. cucumeris fitted type II, whereas the other ages displayed a type III functional response. The longest handling time observed at the age of 4 d was 0.515 h, whereas the shortest handling time and highest value of maximum attack rate (T/Th) were associated with the age of the 28-d-old treatment (0.261 h and 91.95 prey/d, respectively). The numerical response of N. cucumeris showed a significant increase with increasing prey density, but its rate gradually decreased at higher densities. Therefore, the efficiency of conversion of ingested food was relatively higher at low two-spotted spider mite densities, whereas it was reduced at high two-spotted spider mite densities. The stronger functional response and predation capacity of N. cucumeris on two-spotted spider mite eggs indicated the high potential of this predatory mite as an effective biological control agent against two-spotted spider mite especially at its early and middle ages and also when higher prey densities are present. | No pos | No neg |
Retriever595 | KMT2C knockout generates ASD-like behaviors in mice.
Neurodevelopmental disorders have been associated with genetic mutations that affect cellular function, including chromatin regulation and epigenetic modifications. Recent studies in humans have identified mutations in KMT2C, an enzyme responsible for modifying histone tails and depositing H3K4me1 and H3K4me3, as being associated with Kleefstra syndrome 2 and autism spectrum disorder (ASD). However, the precise role of KMT2C mutations in brain disorders remains poorly understood. Here we employed CRISPR/Cas9 gene editing to analyze the effects of KMT2C brain specific knockout on animal behavior. Knocking out KMT2C expression in cortical neurons and the mouse brain resulted in decreased KMT2C levels. Importantly, KMT2C brain specific knockout animals exhibited repetitive behaviors, social deficits, and intellectual disability resembling ASD. Our findings shed light on the involvement of KMT2C in neurodevelopmental processes and establish a valuable model for elucidating the cellular and molecular mechanisms underlying KMT2C mutations and their relationship to Kleefstra syndrome 2 and ASD. | No pos | No neg |
Retriever596 | Comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes.
The comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes was evaluated in rats at a dose of 6 mg/kg i.v. Doxorubicin was entrapped in cardiolipin liposomes by using 11.2 mumol of drug, 5.6 mumol of cardiolipin, 28.5 mumol of phosphatidylcholine, 19.5 mumol of cholesterol, and 11.1 mumol of stearylamine. The peak plasma concentration with free doxorubicin at 5 min was 1.7 micrograms/ml which was reduced to 0.3 micrograms/ml by 1 h. With cardiolipin liposomes, the peak plasma concentration of doxorubicin achieved at 5 min was 20.9 micrograms/ml. The plasma levels of doxorubicin decreased gradually and by 1 h the drug concentration in plasma was 10 micrograms/ml. The plasma levels of free doxorubicin and doxorubicin entrapped in liposomes were fitted to a 3-compartment computer model. The terminal half-life with free doxorubicin in plasma was 17.3 h whereas it was 69.3 h with drug entrapped in liposomes. The area under the plasma concentration curve with liposomal doxorubicin was 81.4 micrograms X h X ml-1 compared to 1.95 micrograms X h X ml-1 observed with free doxorubicin. The steady state volume of distribution with free doxorubicin was about 23-fold higher than liposomal doxorubicin. The terminal half-life with free doxorubicin in cardiac tissue was 17.9 h compared to 12.6 h with drug encapsulated in liposomes. The terminal half-lives in liver and spleen following administration of liposomal doxorubicin were 15- and 2.3-fold higher, respectively, compared to free drug; furthermore, the concentration X time values of liposomal doxorubicin in liver were 26-fold higher and in spleen 6-fold higher than the free drug. Free doxorubicin and doxorubicin entrapped in liposomes demonstrated 17 and 20% excretion in bile of the injected dose, respectively, in rats. The present studies demonstrate that liposomal encapsulation of doxorubicin significantly alters its pharmacokinetics in plasma and tissues compared to free drug. | No pos | No neg |
Retriever597 | Kinetics of MHC-CD8 interaction at the T cell membrane.
CD8 plays an important role in facilitating TCR-MHC interaction, promoting Ag recognition, and initiating T cell activation. MHC-CD8 binding kinetics have been measured in three dimensions by surface plasmon resonance technique using purified molecules. However, CD8 is a membrane-anchored, signaling kinase-linked, and TCR-associated molecule whose function depends on the cell membrane environment. Purified molecules lack their linkage to the membrane, which precludes interactions with other structures of the cell as well as signaling. Furthermore, three-dimensional binding in the fluid phase is biologically and physically distinct from two-dimensional binding across apposing cell membranes. As a first step toward characterizing the molecular interactions between T cells and APCs, we used a micropipette adhesion frequency assay to measure the adhesion kinetics of single mouse T cells interacting with single human RBCs coated with MHC. Using anti-TCR mAb we isolated and characterized the specific two-dimensional MHC-CD8 binding from the trimolecular TCR-MHC-CD8 interaction. The TCR-independent MHC-CD8 interaction has a very low affinity that depends on the MHC alleles, but not on the peptide complexed to the MHC and whether CD8 is an alphaalpha homodimer or an alphabeta heterodimer. Surprisingly, MHC-CD8 binding affinity varies with T cells from different TCR transgenic mice and these affinity differences were abolished by treatment with cholesterol oxidase to disrupt membrane rafts. These data highlight the relevance and importance of two-dimensional analysis of T cells and APCs and indicate that membrane rafts play an important role in modulating the affinity of cell-cell interactions. | No pos | No neg |
Retriever598 | Unilateral hydrocephalus in paediatric patients, a trial of endoscopic fenestration.
Two uncommon cases of unilateral, asymmetrical hydrocephalus secondary to membranous occlusion of foramen of monro are described. Both the cases presented with clinical features of raised intracranial pressure and their cranial computerized scans (CT) revealed asymmetrical dilatation of lateral ventricles with displacement of septum pellucidum towards the side of smaller ventricle. Neuroendoscopic fenestration of septum pellucidum and foramen of monro was tried in both the cases, which remained successful in first, while the second case required unilateral ventriculoperitoneal shunt, due to failed endoscopic negotiation of narrowed foramen of monro and intraoperative bleeding during endoscopic intervention. | No pos | No neg |
Retriever599 | Astragalosides Supplementation Enhances Intrinsic Muscle Repair Capacity Following Eccentric Exercise-Induced Injury.
Astragalosides have been shown to enhance endurance exercise capacity in vivo and promote muscular hypertrophy in vitro. However, it remains unknown whether astragalosides supplementation can alter inflammatory response and enhance muscle recovery after damage in humans. We therefore aimed to evaluate the effect of astragalosides supplementation on muscle's intrinsic capacity to regenerate and repair itself after exercise-induced damage. Using a randomized double-blind placebo-controlled cross-over design, eleven male participants underwent 7 days of astragalosides supplementation (in total containing 4 mg of astragalosides per day) or a placebo control, following an eccentric exercise protocol. Serum blood samples and variables related to muscle function were collected prior to and immediately following the muscle damage protocol and also at 2 h, and 1, 2, 3, 5, and 7 days of the recovery period, to assess the pro-inflammatory cytokine response, the secretion of muscle regenerative factors, and muscular strength. Astragalosides supplementation reduced biomarkers of skeletal muscle damage (serum CK, LDH, and Mb), when compared to the placebo, at 1, 2, and 3 days following the muscle damage protocol. Astragalosides supplementation suppressed the secretion of IL-6 and TNF-α, whilst increasing the release of IGF-1 during the initial stages of muscle recovery. Furthermore, following astragaloside supplementation, muscular strength returned to baseline 2 days earlier than the placebo. Astragalosides supplementation shortens the duration of inflammation, enhances the regeneration process and restores muscle strength following eccentric exercise-induced injury. | No pos | No neg |
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