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Retriever100
A Multi-Pronged Intervention to Reduce Readmissions and Readmission Intensity after Radical Cystectomy. OBJECTIVE To develop a multi-pronged, evidence-based protocol to reduce readmission risk and readmission intensity, as represented by the duration of the index readmission, after radical cystectomy. MATERIALS AND METHODS A per-protocol study was performed. The protocol included preoperative nutritional supplementation, early stent removal, and a follow-up phone call within 4-5 days of discharge. The pre-protocol period was from February 1,2020 to July 31,2021 and the post-protocol period was from December 1, 2020 to November 31, 2021. Using multivariate regression models, we compared outcomes among patients treated with radical cystectomy before and after protocol initiation. RESULTS We identified 70 pre-protocol patients and 126 post-protocol patients. After adjusting for age, sex, BMI, and frailty score, there was a significant reduction in 90-day readmission intensity (7 vs 5 days; p=0.048) among post-protocol patients. CONCLUSIONS After implementation of an evidence-based protocol for patients undergoing radical 90-day readmission intensity decreased significantly. This protocol may move the needle forward on reducing readmissions, but a larger randomized trial is needed.
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Retriever101
Dynamic tuning of electrical and chemical synaptic transmission in a network of motion coding retinal neurons. Recently, we demonstrated that gap junction coupling in the population of superior coding ON-OFF directionally selective ganglion cells (DSGCs) genetically labeled in the Hb9::eGFP mouse retina allows the passage of lateral anticipatory signals that help track moving stimuli. Here, we examine the properties of gap junctions in the DSGC network, and address how interactions between electrical and chemical synapses and intrinsic membrane properties contribute to the dynamic tuning of lateral anticipatory signals. When DSGC subtypes coding all four cardinal directions were individually loaded with the gap junction-permeable tracer Neurobiotin, only superior coding DSGCs exhibited homologous coupling. Consistent with these anatomical findings, gap junction-dependent feedback spikelets were only observed in Hb9(+) DSGCs. Recordings from pairs of neighboring Hb9(+) DSGCs revealed that coupling was reciprocal, non-inactivating, and relatively weak, and provided a substrate for an extensive subthreshold excitatory receptive field around each cell. This subthreshold activity appeared to boost coincident light-driven chemical synaptic responses. However, during responses to moving stimuli, gap junction-mediated boosting appeared to be dynamically modulated such that upstream DSGCs primed downstream cells, but not vice versa, giving rise to highly skewed responses in individual cells. We show that the asymmetry in priming arises from a combination of spatially offset GABAergic inhibition and activity-dependent changes in intrinsic membrane properties of DSGCs. Thus, dynamic interactions between electrical and chemical synapses and intrinsic membrane properties allow the network of DSGCs to propagate anticipatory responses most effectively along their preferred direction without leading to runaway excitation.
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Retriever102
Suicides by drug poisoning among the elderly in Sweden 1969-1996. BACKGROUND Previous studies have shown an association between the rates of suicide employing certain types of medications and the availability of those drugs. During recent years, prescription patterns of psychoactive drugs commonly used in suicides have undergone some major changes. This study examines whether altered prescription patterns are associated with changes in the rates of drug-related suicides in the elderly. METHODS An ecological study was performed, in which rates of suicide by drug poisoning were related to prescription sales of different psychotropic drugs, derived from the National Prescription Survey (1987-1996). RESULTS Benzodiazepines were the dominant drug type used by elderly persons who committed suicide by drug poisoning. Rates of suicide using benzodiazepines increased despite decreasing prescription sales. Decreasing tricyclic antidepressant sales and increasing SSRI (selective serotonin reuptake inhibitors) sales were paralleled by decreasing rates of suicides employing antidepressants. The fatality ratio (FR) decreased for the antidepressant group, increased for benzodiazepines and remained more or less unchanged for analgesics among the elderly during the study period. CONCLUSIONS Rates of suicide using benzodiazepines increased in the elderly despite decreasing prescription sales. Benzodiazepines should be prescribed restrictively to this age group.
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Retriever103
Elevated intracellular dCTP levels reduce the induction of GC-->AT transitions in yeast by ethyl methanesulfonate or N-methyl-N'-nitro-N- nitrosoguanidine but increase alkylation-induced GC-->CG transversions. The effect of an increased intracellular dCTP:dTTP ratio on the specificities of ethyl methanesulfonate (EMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) mutagenesis was examined in the yeast Saccharomyces cerevisiae. To do so, we used a dCMP deaminase-deficient (dcd1) strain having a dCTP:dTTP ratio > 77-fold larger than its isogenic wild-type parent under the treatment conditions employed. This DNA precursor imbalance lowered the frequencies of EMS- or MNNG-induced SUP4-o mutations by 75 or 45%, respectively, relative to the corresponding values for the wild-type strain. A total of 405 SUP4-o mutations produced by the alkylating agents in the dcd1 background were characterized by DNA sequencing and the mutational spectra were compared to those for 399 mutations induced in the wild-type parent and 207 mutations that arose spontaneously in the dcd1 strain. Unexpectedly, the frequencies of EMS- and MNNG-induced GC-->AT transitions in the dcd1 strain were found to be reduced by 93 and 68%, respectively, considerably more than the decreases for the overall SUP4-o mutation frequencies. The differences were due mainly to substantial increases in the frequencies of GC-->CG transversions. Although these events were the predominant type of spontaneous substitution in the dcd1 strain, they were more frequent after alkylation treatment and were distributed differently than the spontaneous GC-->CG transversions. Preferences for the EMS- or MNNG-induced GC-->AT transitions to occur at GC sites having the guanine located on the transcribed strand or preceded by a 5' purine, respectively, also were diminished in the dcd1 strain.(ABSTRACT TRUNCATED AT 250 WORDS)
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High-throughput sequencing reveals miRNA effects on the primary and secondary production properties in long-term subcultured Taxus cells. Plant-cell culture technology is a promising alternative for production of high-value secondary metabolites but is limited by the decreased metabolite production after long-term subculture. The goal of this study was to determine the effects of miRNAs on altered gene expression profiles during long-term subculture. Two Taxus cell lines, CA (subcultured for 10 years) and NA (subcultured for 6 months), were high-throughput sequenced at the mRNA and miRNA levels. A total of 265 known (78.87% of 336) and 221 novel (79.78% of 277) miRNAs were differentially expressed. Furthermore, 67.17% of the known differentially expressed (DE) miRNAs (178) and 60.63% of the novel DE-miRNAs (134) were upregulated in NA. A total of 275 inverse-related miRNA/mRNA modules were identified by target prediction analysis. Functional annotation of the targets revealed that the high-ranking miRNA targets were those implicated in primary metabolism and abiotic or biotic signal transduction. For example, various genes for starch metabolism and oxidative phosphorylation were inversely related to the miRNA levels, thereby indicating that miRNAs have important roles in these pathways. Interestingly, only a few genes for secondary metabolism were inversely related to miRNA, thereby indicating that factors other than miRNA are present in the regulatory system. Moreover, miR8154 and miR5298b were upregulated miRNAs that targeted a mass of DE genes. The overexpression of these miRNAs in CA increased the genes of taxol, phenylpropanoid, and flavonoid biosynthesis, thereby suggesting their function as crucial factors that regulate the entire metabolic network during long-term subculture. Our current studies indicated that a positive conversion of production properties from secondary metabolism to primary metabolism occurred in long-term subcultured cells. miRNAs are important regulators in the upregulation of primary metabolism.
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Retriever105
Synthesis, Structure, and Theoretical Calculations on NpO2Br42. The actinide-halogen complexes (AnO2X42-, X = Cl, Br, and I) are the simplest and most representative compounds for studying the bonding nature of actinides with ligands. In this work, we attempted to synthesize the crystals of NpO2X42- (X = Cl, Br, and I). The crystals of NpO2Cl42- and NpO2Br42- were successfully synthesized, in which the structure of NpO2Br42- was obtained for the first time. The crystal of NpO2I42- could not be obtained due to the rapid reduction of Np(VI) to Np(V) by I-. The molecular structures of NpO2Cl42- and NpO2Br42- were characterized by single-crystal X-ray diffraction and infrared, Raman, and UV-Vis-NIR absorption spectroscopy. The complexes of NpO2X42- (X = Cl, Br, and I) were also investigated by density functional theory calculations, and the calculated vibration frequencies and absorption features were comparable to the experimental results. Both the experimental results and theoretical calculations demonstrate the strengthened Np-O bonds and the weakened Np-X bonds across the NpO2X42- series; however, the population analysis on the frontier molecular orbitals (MOs) of NpO2X42- indicates a slight reduction in the Np-O bonding covalency and an enhancement in the Np-X bonding covalency from NpO2Cl42- to NpO2I42-. Results in this work have enriched the crystal database of the AnO2X42- family and provided insights into the bonding nature in the actinide complexes with soft- and hard-donor ligands.
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Retriever106
Intracavitary thrombi in the right heart associated with multiple pulmonary emboli. Report of two patients. Two-dimensional echocardiography identified intracavitary masses in the right heart in two patients presenting with extensive pulmonary embolism. In one, a right ventricular mass was identified which was confirmed at subsequent autopsy to be an organizing thromboembolus. In the second patient, a right atrial mass was identified; it disappeared with thrombolytic therapy which was accompanied by clinical improvement. We demonstrate that intracardiac thrombi associated with pulmonary embolism may be identified noninvasively by two-dimensional echocardiography. We suggest the presence of thrombi may represent a large intravascular thrombus. This recognition may influence therapeutic decisions.
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Atypical response of class IC atrial flutter to adenosine. We report the case of a 67-year-old female with a wide QRS complex tachycardia at 180 bpm. A diagnosis of class IC atrial flutter with aberrant ventricular conduction caused by flecainide therapy was formulated. Intravenous adenosine administration resulted in adequate slowing of the ventricular rate and normalization of QRS complexes. Restoration of sinus rhythm was achieved with intravenous amiodarone. The response to adenosine confirmed the diagnosis of supraventricular tachycardia with aberrant conduction, but the transition from arrhythmia onset to restoration of sinus rhythm showed interesting peculiarities.
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Retriever108
The gas-liquid chromatograph and the electron capture detection in equine drug testing. Three gas-liquid chromatographic (G.L.C.) procedures discussed have been designed around the four "esses" of detection tests--speed, sensitivity, simplicity, and specificity. These techniques are admirably applicable to the very low plasma drug levels encountered in blood testing under pre-race conditions. The methods are equally applicable to post-race testing procedures, where both blood and urine samples are tested. Drugs can only rarely be detected by the electron capture detector (E.C.D.) without a prior derivatization step, which conveys to the drug(s) high electron affinity. Because of broad applicability, two derivatizing agents, heptafluorobutyric (HFBA) and pentafluorpropionic (PFPA) anhydrides are employed. The three techniques, allowing broad coverage of various drug classes are: 1) direct derivatization of drugs to form strongly electron capturing amides and esters. 2) reductive fragmentation of drugs with lithium aluminum hydride to form alcohols, with conversion to ester derivatives. 3) oxidative fragmentation of drugs with potassium dichromate to form derivatizable groups, followed by direct derivatization.
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Retriever109
COVID-19 Vaccine-Related Axillary and Cervical Lymphadenopathy in Patients with Current or Prior Breast Cancer and Other Malignancies: Cross-Sectional Imaging Findings on MRI, CT, and PET-CT. Breast radiologists are increasingly seeing patients with axillary adenopathy related to COVID-19 vaccination. Vaccination can cause levels I-III axillary as well as cervical lymphadenopathy. Appropriate management of vaccine-related adenopathy may vary depending on clinical context. In patients with current or past history of malignancy, vaccine-related adenopathy can be indistinguishable from nodal metastasis. This article presents imaging findings of oncology patients with adenopathy seen in the axilla or neck on cross-sectional imaging (breast MRI, CT, or PET-CT) after COVID-19 vaccination. Management approach and rationale is discussed, along with consideration on strategies to minimize false positives in vaccinated cancer patients. Time interval between vaccination and adenopathy seen on breast MRI, CT, or PET-CT is also reported.
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Retriever110
NESTROFT-A Cost-Effective Mass Screening Tool for the Detection of β-Thalassemia Carrier Status in Anemic Pregnant Women: A Step Toward Reducing the National Disease Burden. Introduction β-Thalassemias are inherited hemoglobinopathies commonly encountered in practice. With chances of a promising cure being rare, the prevention of births with this disorder should assume priority, especially in low-resource countries. This can be achieved by the implementation of a mass screening program that is reliable and, at the same time, cost-effective. Objectives This study focuses on the utility of Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) as a mass screening tool to detect thalassemia carriers. Hematological parameters that may predict carrier status were also evaluated. Materials and Methods Hemoglobin estimation was performed on all consented pregnant women. If the patient was found to have hemoglobin < 11 g/dL, the blood sample was subjected to other routine hematological tests along with peripheral smear examination. NESTROFT was performed using 0.36% saline solution. Confirmation was done using high-performance liquid chromatography (HPLC). Statistical Analysis Data obtained were tabulated using version 21 of the Statistical Package for Social Sciences. Means, standard deviations, and percentages were used to describe the sample. Chi-square test and Students' t test were used to identify differences between the groups. Results Of 441 pregnant women enrolled, 206 were found to be anemic. Nineteen (9.2%) of the anemic pregnant women were detected to be carriers of hemoglobinopathies. Among the hematological parameters, mean red blood cell count and reticulocyte count were higher, while mean corpuscular hemoglobin concentration was lower in carriers. Also, carriers were more likely to present with microcytic hypochromic anemia. NESTROFT showed a sensitivity of 84.21%, specificity of 96.25%, a positive predictive value of 69.56%, and a negative predictive value of 98.36%. A false-positive result was seen in 3.74% of the tests, while a false negative result was seen in 15.78% of the tests. Conclusions NESTROFT (0.36%) can be used as a simple and cost-effective mass screening tool for the detection of carrier status. This should be followed by confirmation using HPLC or hemoglobin electrophoresis.
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Pilot study on preventing anastomotic leakage in stapled gastroesophageal anastomosis. BACKGROUND This study explored how to improve the surgical technique to reduce or avoid anastomotic leakage. METHODS From January 2012 to December 2016, 101 consecutive patients with cancer of the esophagus or gastroesophageal junction underwent stapled gastroesophageal anastomosis. The procedure included creating a tube-type stomach, fixing an inserted anvil, inspecting mucosa-to-mucosa alignment in the lumen under direct vision after firing the stapler, and, if found, manually repairing a rupture of the mucous membrane of the anastomosis. RESULTS A rupture of the mucous membrane of the anastomosis was found in four out of the 101 patients and manually repaired. No postsurgical anastomotic leakage occurred. All patients recovered well and the average postoperative stay was 10.4 days. There was no mortality within 30 days after surgery. CONCLUSION It is critical to inspect the integrality of the luminal mucous membrane of the anastomosis under direct vision in order to prevent anastomotic leakage in surgical resection of esophageal and gastroesophageal junction malignancies.
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Discordance in PD-L1 expression using 22C3 and SP142 assays between primary and metastatic triple-negative breast cancer. AIMS SP142 and 22C3 assays are approved companion diagnostic assays for anti-PD-1/PD-L1 therapy selection in metastatic triple-negative breast cancer (TNBC). The discordance in PD-L1 status between primary and metastatic tumors in the same patient has been poorly characterized. Here, we examined the concordance of PD-L1 status between the two assays and between primary tumors and metastases for each assay. METHODS We retrospectively evaluated tumor samples from 160 patients with TNBC, including 45 patients with paired primary and metastatic tumors. PD-L1 status was assessed using SP142 and 22C3 assays, to determine the immune cell (IC) score, tumor cell (TC) score (SP142 and 22C3), and combined proportion score (CPS: 22C3). RESULTS The concordance of PD-L1 positivity at diagnostic cutoffs for SP142 (IC ≥ 1) and 22C3 (CPS ≥ 10) was substantial (κ = 0.80) in primary tumors and moderate (κ = 0.60) in metastatic tumors. In comparison, between primary and metastatic tumors, the concordance with 22C3 was moderate (κ = 0.50), whereas that with SP142 was poor (κ = -0.03). Among patients who were PD-L1 negative for both assays in primary tumors, 7/30 (23.3%) were PD-L1 positive for both or either 22C3 or SP142 in the metastatic tumors. CONCLUSIONS The inter-assay concordance of PD-L1 positivity at diagnostic cutoffs was substantial in primary tumors and moderate in metastatic tumors. Discordance between PD-L1 status in primary and metastatic tumors was frequently observed, especially with SP142. Some patients with a PD-L1-negative status in primary tumors may still be candidates for immunotherapy, depending on the PD-L1 status in their metastatic tumors.
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Retriever113
Synthesis and antimicrobial studies of chalconyl pregnenolones. An efficient and facile synthesis of 17-chalconyl derivatives of pregnenolone and their evaluation as antimicrobial agents against various microbial strains is reported. The scheme involves the transformation of the starting pregnenolone acetate into pregnenolone, conversion of pregnenolone to the corresponding chalcone derivatives. The compounds 3a-3j showed significant antimicrobial activity against all microbial strains used for testing.
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Retriever114
Control of the Near Infrared Photoluminescence of Locally Functionalized Single-Walled Carbon Nanotubes via Doping by Azacrown-Ether Modification. Doped semiconducting single-walled carbon nanotubes (SWNTs) through local chemical functionalization (lf-SWNTs) show fascinating photoluminescence (PL) that appears with a longer wavelength and enhanced quantum yield compared to the original PL of non-modified SWNTs. In this study, we introduce an azacrown ether moiety at the doped sites of lf-SWNTs (CR-lf-SWNTs), and observe selective PL wavelength shifts depending on different interaction modes of silver ion inclusion and protonation of the amino group in the ring. Interestingly, their different values of the wavelength shifts show a clear correlation with calculated electron density of the nitrogen atom in the azacrown moiety in case of the inclusion form and the protonated form. This newly-observed responsiveness based on molecular interactions is expected to create doped sites that can versatilely control the PL functions based on molecular systems.
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Retriever115
Mechanisms of transcoelomic metastasis in ovarian cancer. Metastasis from epithelial ovarian cancer can occur via the transcoelomic, haematogeneous, or lymphatic route. Of these, transcoelomic metastasis is the most common, and is responsible for the greatest morbidity and mortality in women with this disease. Unfortunately, very little is known about the mechanisms behind this process. This review assesses the current evidence and ideas about the biology of transcoelomic dissemination. The mechanisms of cell detachment, migration, and implantation in transcoelomic metastasis are placed within the context of clinical observations of ovarian cancer to derive a stepwise hypothesis of this process. Evidence for transcoelomic dissemination versus transcoelomic metaplasia in ovarian cancer is presented. Future high throughput microarray studies that compare changes at a genomic and gene expression level between primary ovarian tumours and their peritoneal metastases are hoped to lead to a more conclusive picture of transcoelomic metastasis, and to delineate the key molecular players in this process. These studies might also result in the identification of potential new therapeutic targets in ovarian cancer.
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Retriever116
The scholarship of teaching: implications for nursing faculty. Nursing educators are faced with the dilemma of addressing the scholarship of teaching for promotion and tenure decisions. This article defines the scholarship of teaching and explores the history of the concept. Implications of the relevance of the topic for nursing faculty with suggestions for documenting the scholarship of teaching are discussed.
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Retriever117
Borrelia hermsii causing relapsing Fever and uveitis. PURPOSE To describe a case of uveitis that is associated with Borrelia hermsii relapsing fever. DESIGN Interventional case report. METHODS A 12-year-old boy with two weeks of relapsing fevers 10 days after camping in remote eastern Oregon was examined. Borrelia hermsii immunoglobulin M and G levels were markedly elevated. Intravenous ceftriaxone, followed by four weeks of oral cephuroxime was administered, but the patient developed unilateral floaters and blurred vision in association with anterior and intermediate uveitis. RESULTS Doxycycline was administered for presumed residual infection. Four weeks later, the visual acuity had improved. The anterior chamber was quiet, and topical corticosteroid was tapered successfully. CONCLUSION Although rare, Borrelia hermsii should be included in the list of spirochetal diseases that are associated with uveitis.
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Retriever118
Folic acid dependent hypersarcosinaemia. Hypersarcosinaemia is a rare inborn error of metabolism, caused by a deficiency of the sarcosine dehydrogenase complex with tetrahydrofolate as a formaldehyde acceptor needed for the sarcosine-glycine conversion. Prolonged therapy with folic acid on a hypersarcosinaemic patient resulted in a significant effect on the urinary excretion of sarcosine, leading to the conclusion that the patient has a folic acid dependent hypersarcosinaemia.
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Retriever119
Efficacy of systemic minoxidil and tofacitinib combination in treatment-resistant alopecia universalis. Alopecia areata (AA) is an autoimmune nonscarring alopecic disorder, which presents with varying amounts of hair loss, ranging from focal patchy loss to entire scalp and body hair loss. Treatment of AA is a challenging issue within dermatology practice. Although many treatment options are present, response to medications remains unsatisfactory, especially in severe and recalcitrant cases. In this study, we present a case of treatment-resistant AU, which was successfully treated by the combination of tofacitinib and oral minoxidil.
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Retriever120
Patient and limb outcomes 10 years after endovascular revascularization of the superficial femoral artery for peripheral artery disease: The Boston Femoral Artery Endovascular Revascularization Outcomes (Boston FAROUT) study. BACKGROUND We aimed to describe patient and limb outcomes in the decade after endovascular revascularization for chronic lower-extremity peripheral artery disease (PAD). METHODS We assessed outcomes in patients having endovascular revascularization of the superficial femoral artery in two centers between 2003 and 2011 and followed for a median 9.3 (25-75%: 6.8, 11.1) years. Outcomes included death, myocardial infarction, stroke, repeat limb revascularizations, and amputations. We used competing risks analysis with clustering by patient to determine the hazard ratios (HR) and 95% CI for patients, and procedural characteristics for cause of death, cardiovascular events, and major adverse limb events (MALE). RESULTS There were 253 index limb revascularizations in 202 patients followed for a median 9.3 years. Patients had intensive medical treatment with 90% on statins and 80% on beta-blockers. During follow up there were 57 (28%) cardiovascular deaths and 62 (31%) noncardiovascular deaths. Of the 253 limbs, 227 (90%) were free of MALE over follow up and 93 (37%) had MALE or minor repeat revascularization. In multivariable models, cardiovascular death significantly associated with critical limb ischemia (HR = 3.21, 95% CI = 1.84, 5.61) and noncardiovascular death with chronic kidney disease (HR = 2.69, 95% CI = 1.68, 4.30), and smoking (HR = 2.75, 95% CI = 1.01, 7.52). MALE or minor repeat revascularization associated with critical limb ischemia (HR = 1.43, 95% CI = 0.84, 2.43), smoking (HR = 2.49, 95% CI = 1.26, 4.90), and lesion length > 200 mm (HR = 1.51, 95% CI = 0.98, 2.33). CONCLUSIONS Among patients with intensive medical therapy, the risk of noncardiovascular death was high and similar to cardiovascular death. Endovascular intervention can have acceptable long-term results. Future studies should evaluate strategies to reduce both cardiovascular and noncardiovascular deaths.
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Retriever121
Evidence for genetic heterogeneity in the carbohydrate-deficient glycoprotein syndrome type I (CDG1). We have analyzed a series of polymorphic markers on chromosome 16p13 in 17 families with carbohydrate-deficient glycoprotein syndrome type I (CDG1). First, linkage to the region between D16S406 and D16S500 is confirmed. The telomeric border of the candidate region is now definitively placed proximal to D16S406 by crossovers observed in 2 families. Second, in 1 family with 2 affected siblings, the disease is not linked to chromosome 16p. Genetic heterogeneity has not been previously reported for CDG1, and this observation has implications for prenatal diagnosis. Third, allelic associations suggest that the disease locus is localized close to D16S414/D16S497. This places the region of interest centromeric of its published localization.
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The impact of thiols for insulin secretion. The review summarizes the present state to be known on regulation of insulin secretion. Special attention is drawn on the impact of ion fluxes and the redox state of pancreatic beta-cells stimulated with different secretagogues.
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Retriever123
Association of interleukin-33 gene polymorphisms with susceptibility to late onset Alzheimer's disease: a meta-analysis. The association between interleukin-33 (IL-33) gene polymorphisms and late onset Alzheimer's disease (LOAD) remains controversial in previous studies. Thus, a meta-analysis was conducted to assess the association between the IL-33 polymorphisms (rs11792633 and rs7044343) and LOAD susceptibility. Crude odds ratio (OR) and 95% confidence interval (CI) were used to investigate the relationship strength. Sensitivity analysis was performed, and publication bias was estimated by the Begg's and Egger's tests. Overall, six independent studies involving 2,589 patients and 8,414 control samples met our inclusion criteria and were included in this meta-analysis. The results showed that IL-33 rs11792633 polymorphism had statistically significant correlation with a decreased risk of LOAD in heterozygous comparison model (OR =0.64, 95% CI =0.48-0.83), homozygote comparison model (OR =0.83, 95% CI =0.74-0.93), dominant model (OR =0.78, 95% CI =0.67-0.91), recessive model (OR =0.70, 95% CI =0.59-0.84), and allelic model (OR =0.79, 95% CI =0.69-0.91), which were also validated by stratified subgroup analysis. Additionally, there was an apparent association between the IL-33 rs7044343 variant and LOAD risk under four genetic models for overall population (heterozygous comparison model: OR =0.75, 95% CI =0.63-0.89; dominant model: OR =0.83, 95% CI =0.70-0.98; recessive model: OR =0.80, 95% CI =0.68-0.94; allelic model: OR =0.86, 95% CI =0.79-0.94) as well as Caucasian subgroup. In summary, our meta-analysis implicated that IL-33 gene polymorphisms rs11792633 and rs7044343 were significantly associated with the susceptibility of LOAD.
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Folic Acid Levels During Pregnancy Regulate Trophoblast Invasive Behavior and the Possible Development of Preeclampsia. Background One of the unique features of placentation is its similarity to tumorigenesis yet being very well regulated. It allows rapid proliferation, migration, and invasion of mononuclear trophoblast cells into the maternal uterus and remodeling the maternal vasculature. This pseudomalignant nature of trophoblastic cells is strictly regulated and its importance becomes evident in abnormal pregnancies that are characterized by aberrant trophoblast proliferation/invasion like preeclampsia. In addition to this, the importance of folic acid supplementation during pregnancy is well documented. We aimed to analyze the molecular and epigenetic regulation of the pseudomalignant nature of placentation via folic acid levels. Methods Placental tissue samples were collected from different pregnancies in three different gestational stages. We estimated the impact of folic acid levels on global methylation, LINE1 methylation, and expression of DNMTs in all three gestational stages in pregnant women and preeclampsia pregnancies. We also analyzed the effect of folic acid supplementation on trophoblastic invasion using placental derived cells viz, JEG-3 and HTR-8/SVneo cell line and verified the molecular and epigenetic mechanisms involved in this regulation. Results Development of preeclampsia was observed to be associated with lower folate levels in placental tissue, higher global methylation level, and higher expression of DNMT1and DNMT3A. Folic acid supplementation was found to increase the invasive potential of placental trophoblasts by almost two folds which were associated with the decreased expression of tumor suppressor genes and tissue inhibitors of matrix metalloproteinases; and increased expression of oncogenes, telomerase gene, and matrix metalloproteinases. These folic acid-mediated changes were observed to be regulated by CpG methylation in the case of many genes. Folic acid supplementation was also observed to significantly decrease global methylation in placental trophoblasts related to decreasing expression of DNMT1 and DNMT3A. Conclusion Lower folic acid levels are associated with preeclampsia development and folic acid supplementation regulates the invasive potential of placental trophoblasts as mediated by various epigenetic changes in the placenta suggesting the protective effect of folic acid against preeclampsia.
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Retriever125
Detection of gene-environment interactions in joint segregation and linkage analysis. We compare approaches for analysis of gene-environment (G x E) interaction, using segregation and joint segregation and linkage analyses of a quantitative trait. Analyses of triglyceride levels in a single large pedigree demonstrate the two methods and show evidence for a significant interaction (P=.015 when segregation analysis is used; P=.006 when joint analysis is used) between a codominant major gene and body-mass index. Genotype-specific correlation coefficients, between triglyceride levels and body-mass index, estimated from the joint model are rAA=.72, rAa=.49, and raa=. 20. Several simulation studies indicate that joint segregation and linkage analysis leads to less-biased and more-efficient estimates of a G x E-interaction effect, compared with segregation analysis alone. Depending on the heterozygosity of the marker locus and its proximity to the trait locus, we found joint analysis to be as much as 70% more efficient than segregation analysis, for estimation of a G x E-interaction effect. Over a variety of parameter combinations, joint analysis also led to moderate (5%-10%) increases in power to detect the interaction. On the basis of these results, we suggest the use of combined segregation and linkage analysis for improved estimation of G x E-interaction effects when the underlying trait gene is unmeasured.
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Retriever126
Cemented or uncemented hemiarthroplasty for displaced intracapsular femoral neck fractures. The aim of this study was to establish whether or not to cement the hemiarthroplasty for displaced intracapsular femoral neck fractures in the elderly. Consecutive patients treated by hemiarthroplasty in adjacent hospitals were reviewed. The same monoblock prosthesis was used; in hospital A they were uncemented (121 patients), and in hospital B they were cemented (123 patients). Notes were reviewed retrospectively. Surviving patients (50 and 56 respectively) were assessed prospectively for pain and functional ability using validated scoring systems. Follow-up was 32-36 months. Patient demographics were similar. Fewer of the cemented group had been revised or were awaiting revision ( P=0.036). There was no difference in general complication or mortality rates. There was a highly statistically significant greater deterioration in pain ( P=0.003), walking ability ( P=0.002), use of walking aids ( P=0.003) and activities of daily living ( P=0.009) in the uncemented group. Our findings support the use of cemented hemiarthroplasty in the elderly.
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Retriever127
Ibrutinib, obinutuzumab, idelalisib, and beyond: review of novel and evolving therapies for chronic lymphocytic leukemia. Chronic lymphocytic leukemia (CLL) is a neoplasm resulting from the progressive accumulation of functionally incompetent monoclonal B lymphocytes in the blood, bone marrow, lymph nodes, and spleen. It is the most common leukemia in Western countries and typically occurs in elderly patients. Initial treatment of CLL often includes a first-generation anti-CD20 antibody (rituximab) with chemotherapy and is the current standard of treatment for "younger" old adults (< 70 yrs of age) or older, clinically fit patients. However, because disease progression and drug resistance are inevitable, patients typically die from their disease or treatment-related complications. Improved understanding of the B-cell receptor signaling pathway, which is essential for normal B-cell growth and tumorigenesis, has led to the development of targeted therapies, with improved short-term clinical outcomes. Ibrutinib, obinutuzumab, and idelalisib, three novel agents recently approved by the U.S. Food and Administration for CLL, all have the potential to change the treatment paradigm. In this article, we describe the pathogenesis of CLL and some of its prognostic factors. Emphasis is on the pharmacology, dosing, clinical efficacy, safety, and place of therapy of ibrutinib, obinutuzumab, and idelalisib. Investigational agents that target different parts of the CLL pathogenic pathway are also described.
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Endowing TADF luminophors with AIE properties through adjusting flexible dendrons for highly efficient solution-processed nondoped OLEDs. The amalgamation of thermally activated delayed fluorescence (TADF) and aggregation-induced emission (AIE) properties, termed AIE-TADF, is a promising strategy to design novel robust luminescent materials. Herein, we transform 2,3,4,5,6-penta(9H-carbazol-9-yl)benzonitrile (5CzBN) from an ACQ molecule into an AIEgen by simply decorating the 5CzBN core with alkyl chain-linked spirobifluorene dendrons. By increasing the number of flexible dendrons, these materials can not only show obvious AIE-TADF characteristics and uniform film morphology, but can also exhibit better resistance to isopropyl alcohol, which are beneficial to fully solution-processed OLEDs. Notably, 5CzBN-PSP shows great device efficiency with an external quantum efficiency (EQE), current efficiency and power efficiency of 20.1%, 58.7 cd A-1 and 46.2 lm W-1, respectively and achieved record-breaking efficiency in solution-processed nondoped OLEDs based on AIE emitters. This work demonstrates a general approach to explore new efficient emitters by the marriage of AIE and TADF which could potentially improve their performance in various areas.
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Detection of acute traumatic coagulopathy and massive transfusion requirements by means of rotational thromboelastometry: an international prospective validation study. INTRODUCTION The purpose of this study was to re-evaluate the findings of a smaller cohort study on the functional definition and characteristics of acute traumatic coagulopathy (ATC). We also aimed to identify the threshold values for the most accurate identification of ATC and prediction of massive transfusion (MT) using rotational thromboelastometry (ROTEM) assays. METHODS In this prospective international multicentre cohort study, adult trauma patients who met the local criteria for full trauma team activation from four major trauma centres were included. Blood was collected on arrival to the emergency department and analyzed with laboratory international normalized ratio (INR), fibrinogen concentration and two ROTEM assays (EXTEM and FIBTEM). ATC was defined as laboratory INR >1.2. Transfusion requirements of ≥10 units of packed red blood cells within 24 hours were defined as MT. Performance of the tests were evaluated by receiver operating characteristic curves, and calculation of area under the curve (AUC). Optimal cutoff points were estimated based on Youden index. RESULTS In total, 808 patients were included in the study. Among the ROTEM parameters, the largest AUCs were found for the clot amplitude (CA) 5 value in both the EXTEM and FIBTEM assays. EXTEM CA5 threshold value of ≤37 mm had a detection rate of 66.3% for ATC. An EXTEM CA5 threshold value of ≤40 mm predicted MT in 72.7%. FIBTEM CA5 threshold value of ≤8 mm detected ATC in 67.5%, and a FIBTEM CA5 threshold value ≤9 mm predicted MT in 77.5%. Fibrinogen concentration ≤1.6 g/L detected ATC in 73.6% and a fibrinogen concentration ≤1.90 g/L predicted MT in 77.8%. Patients with either an EXTEM or FIBTEM CA5 below the optimum detection threshold for ATC received significantly more packed red blood cells and plasma. CONCLUSIONS This study confirms previous findings of ROTEM CA5 as a valid marker for ATC and predictor for MT. With optimum threshold for EXTEM CA5 ≤ 40 mm and FIBTEM CA5 ≤ 9 mm, sensitivity is 72.7% and 77.5% respectively. Future investigations should evaluate the role of repeated viscoelastic testing in guiding haemostatic resuscitation in trauma.
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Inhibition of neutrophil infiltration into A549 lung tumors in vitro and in vivo using a CXCR2-specific antagonist is associated with reduced tumor growth. Neutrophils are important innate immune cells that are involved in microbial clearance at sites of infection and in wound healing. The microenvironment of tumors often resembles that of chronic inflammation and increased numbers of neutrophils have been observed in several tumors and, in some cases, these positively correlate with poor prognosis. Neutrophil recruitment into tumors appears to be dependent on chemokines that bind to CXCR1 and CXCR2 expressed by neutrophils. In our study, we used lung adenocarcinoma A549 multicellular tumor spheroids and A549 tumor xenografts along with a CXCR2-specific small molecule inhibitor (AZ10397767) to investigate the recruitment and function of human neutrophils in tumors. We found that A549 spheroids constitutively secrete high levels of CXCL chemokines and that neutrophil recruitment into A549 tumors in vitro and in vivo is largely dependent on CXCR2 activation. AZ10397767 significantly reduced the numbers of infiltrating neutrophils into both in vitro and in vivo tumor models, which was associated with slower growing tumors. Neutrophil infiltration into A549 tumor spheroids increased their size compared to noninfiltrated spheroids and neutrophil-derived factors increased the proliferation of A549 tumor cells and induced endothelial cell tubule formation in vitro. In contrast, we saw no reduction in microvascular density in AZ10397767-treated A549 tumors or in tumors grown in CXCR2(-/-) mice, suggesting that angiogenesis in these tumors is CXCR2-independent. Our data show that neutrophils can contribute to lung tumor growth and that CXCR2 antagonists may be a useful therapeutic agent in the treatment of lung carcinomas.
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Completion thyroidectomy and lateral neck dissection revealed adhesions in the lateral neck compartment after gasless transaxillary endoscopic thyroidectomy: a case report. Background Endoscopic thyroidectomy is effective and safe surgical option for thyroid surgery while providing satisfactory cosmetic results. Gasless transaxillary endoscopic approaches have been reported to achieve endoscopic thyroidectomy in our center. Case Description We present a patient who previously underwent gasless transaxillary endoscopic lobectomy with ipsilateral central neck dissection who underwent open completion thyroidectomy and lateral neck dissection (LND) (reoperation) in our center. The ultrasound test before the first treatment did not reveal abnormal lymph nodes in the central and lateral neck compartments. Further evaluation of the neck lymph nodes was not performed. Meanwhile, this patient did not participate in the originally planned follow-up at the 3- and 6-month visits. At the one-year visit, imaging tests revealed enlarged and suspicious malignant lymph nodes in levels III and IV of the lateral neck compartments. We believed that reoperation was performed for persistent, rather than truly recurrent disease for this patient. During the second surgery, we found that the surface of internal jugular vein (IJV) was significantly adhered to the surrounding fibroadipose tissue and the omohyoid muscle was adhered to the IJV. After carefully dissected the IJV, the dissection of the lateral neck compartment had been performed successfully. Conclusions Exposure of the lateral neck compartment in the gasless transaxillary procedure, especially exposure of the IJV, causes adhesions of the lateral neck compartment and brings difficulties for possible future LND. Gasless transaxillary endoscopic thyroid surgery should be performed in strictly selected patients with adequate preoperative assessment. The IJV should be carefully dissected to avoid IJV injury, and the lateral neck compartment could be dissected successfully during reoperation.
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Anthraquinone analogues with inhibitory activities against influenza a virus from Polygonatum odoratum. Three anthraquinone analogues (1-3) were isolated by phytochemical work on EtOAc-soluble ingredients extracted from the roots of Polygonatum odoratum. The structures of all isolates were elucidated by NMR, MS and CD experiments, of which 1 (polygodoquinone A) was identified as a new anthraquinone derivative. Specifically, 1 represents an unusual structure composed of a naphthoquinone derivative linked to an anthraquinone via a C-C bond. 1-3 exhibited remarkable influenza A virus inhibitory activity with IC50 values of 11.4, 11.0, and 2.3 μM, respectively, which were better than ribavirin as the positive control.
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Insights into the Host-Pathogen Interaction Pathways through RNA-Seq Analysis of Lens culinaris Medik. in Response to Rhizoctonia bataticola Infection. Dry root rot (Rhizoctonia bataticola) is an important disease of lentils (Lens culinaris Medik.).To gain an insight into the molecular aspects of host-pathogen interactions, the RNA-seq approach was used in lentils following inoculation with R.bataticola. The RNA-Seq has generated >450 million high-quality reads (HQRs) and nearly 96.97% were properly aligned to the reference genome. Very high similarity in FPKM (fragments per kilobase of exon per million mapped fragments) values (R > 0.9) among biological replicates showed the consistency of the RNA-Seq results. The study revealed various DEGs (differentially expressed genes) that were associated with changes in phenolic compounds, transcription factors (TFs), antioxidants, receptor kinases, hormone signals which corresponded to the cell wall modification enzymes, defense-related metabolites, and jasmonic acid (JA)/ethylene (ET) pathways. Gene ontology (GO) categorization also showed similar kinds of significantly enriched similar GO terms. Interestingly, of the total unigenes (42,606), 12,648 got assembled and showed significant hit with Rhizoctonia species. String analysis also revealed the role of various disease responsive proteins viz., LRR family proteins, LRR-RLKs, protein kinases, etc. in the host-pathogen interaction. Insilico validation analysis was performed using Genevestigator® and DEGs belonging to six major defense-response groups viz., defense-related enzymes, disease responsive genes, hormones, kinases, PR (pathogenesis related) proteins, and TFs were validated. For the first time some key miRNA targets viz. miR156, miR159, miR167, miR169, and miR482 were identified from the studied transcriptome, which may have some vital role in Rhizoctonia-based responses in lentils. The study has revealed the molecular mechanisms of the lentil/R.bataticola interactions and also provided a theoretical approach for the development of lentil genotypes resistant to R.bataticola.
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Does Dispersion Dominate over H-Bonds in Drug-Surface Interactions? The Case of Silica-Based Materials As Excipients and Drug-Delivery Agents. Amorphous silica is widely employed in pharmaceutical formulations both as a tableting, anticaking agent and as a drug delivery system, whereas MCM-41 mesoporous silica has been recently proposed as an efficient support for the controlled release of drugs. Notwithstanding the relevance of this topic, the atomistic details about the specific interactions between the surfaces of the above materials and drugs and the energetic of adsorption are almost unknown. In this work, we resort to a computational ab initio approach, based on periodic Density Functional Theory (DFT), to study the adsorption behavior of two popular drugs (aspirin and ibuprofen) on two models of an amorphous silica surface characterized by different hydrophilic/hydrophobic properties due to different SiOH surface groups' density. Particular effort was devoted to understand the role of dispersive (vdW) interactions in the adsorption mechanism and their interplay with H-bond interactions. On the hydrophilic silica surface, the H-bond pattern of the Si-OH groups rearranges to comply with the formation of new H-bond interactions triggered by the adsorbed drug. The interaction energy of ibuprofen with the hydrophilic model of the silica surface is computed to be very close to the sublimation energy of the ibuprofen molecular crystal, accounting for the experimental evidence of ibuprofen crystal amorphization induced by the contact with the mesoporous silica material. For both surface models, dispersion interactions play a crucial role in dictating the features of the drug/silica system, and they become dominant for the hydrophobic surface. It was proved that a competition may exist between directional H-bonds and nonspecific dispersion driven interactions, with important structural and energetic consequences for the adsorption. The results of this work emphasize the inadequacy of plain DFT methods to model adsorption processes involving inorganic surfaces and drugs of moderate size, due to the missing term accounting for London dispersion interactions.
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[Obstructive sleep apnea syndrome: an analysis of treatment in 450 patients]. OBJECTIVE To explore the most appropriate treatment through comparing surgery, coblator plasma surgery (CPS) and nasal continuous positive airway pressure (nCPAP) in obstructive sleep apnea syndrome (OSAS). METHOD Four hundred and fifty cases were retrospectively analyzed, 368 patients were operated by uvuloplatopharyngoplasty (UPPP), partial excision of root of tongue and/or partial inferior turbinectomy. CPS were performed in 65 patients and 25 cases were accepted the nCPAP. Among them, 17 were the first selection and 8 were the second selection after operation failure. RESULT The outcomes of near-term (3-6 months) and long-term (1-3 years) in CPAP group are 95.23% and 83.33%, higher than surgery and CPS group. In the near-term result, surgery group is similar to CPS group (86.39% and 78.04%). The long-term effective of surgery group is lower than 50% and become worse with the time passed. And surgery may be accompanied with some dangerous and complications after operation. But the side effect in CPS and nCPAP is very little. CONCLUSION The treatment of OSAS is developing to safety, simple and acceptable. nCPAP and some simple safely surgery are fitted in serious patients. UPPP, CPS and nCPAP have good effect in light and middle patients. The long-term effect of CPS should still be observed in future.
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Differential alterations in plasma colony-stimulating factor concentrations after coronary artery bypass graft surgery with extracorporeal circulation. To determine whether colony-stimulating factor (CSF) might participate to the inflammatory response after cardiac surgery, plasma concentrations of granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF) and GM-CSF were measured in 31 patients undergoing coronary artery bypass graft (CABG) surgery with extracorporeal circulation (ECC). Plasma G-CSF and M-CSF concentrations increased after weaning of ECC, reached maximum value at the sixth post-operative hour, and remained elevated at the 24th post-operative hour. In contrast, plasma GM-CSF levels did not change. Plasma M-CSF, G-CSF and GM-CSF values were not different whether patients developed post-operative complications or not. In conclusion, M-CSF and G-CSF are produced after CABG surgery despite the use of high aprotinin doses in hope to abrogate the inflammatory response. G-CSF and M-CSF might play a role in the inflammatory process often observed after CABG surgery.
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Contraception methods used by women with rheumatoid arthritis and psoriatic arthritis. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are common in women of childbearing age and are often treated with teratogenic medications. In this study, we assessed contraceptive methods in young women with RA or PsA and correlated contraceptive method efficacy with use of concomitant rheumatic medications. We combined the data from several cross-sectional surveys of women under the age of 40 with RA or PsA. Two surveys recruited participants from a clinic setting (RA and PsA Clinic Surveys), and the third survey recruited participants from CreakyJoints.org , an online forum for patients with inflammatory arthritis (CreakyJoints Survey). Of the 164 women included, 138 had RA (67 in RA Clinic Survey, 71 in CreakyJoints Survey) and 26 had PsA (19 in PsA Clinic Survey, 7 in CreakyJoints Survey). Use of specific contraceptive and rheumatic medications were similar between the clinic and online surveys. In the pooled analysis of the Clinic and CreakyJoints survey data, women with RA and PsA reported similar utilization of highly effective contraception methods (31.9% RA, 34.6% PsA) and effective methods (31.2% RA, 30.8% PsA), but different utilization of ineffective methods (35.5% RA, 11.5% PsA) and no methods (1.5% RA, 23.1% PsA), p = 0.0002. These proportions remained similar across subgroups taking methotrexate, anti-TNF biologics, and novel medications. Approximately two thirds of women with RA and PsA reported using effective or highly effective methods of contraception, though women with PsA were more likely to report no methods of contraception.
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Marked Differences in the Submandibular Salivary Proteome between Sardinian Alcohol-Preferring and Sardinian Alcohol-Non Preferring Rats Revealed by an Integrated Top-Down-Bottom-Up Proteomic Platform. Sardinian alcohol-preferring (sP) and Sardinian alcohol-non preferring (sNP) rats have been selectively bred for opposite alcohol preference and consumption. Aiming to verify possible differences at the proteomics level between sP and sNP rats, we investigated the salivary proteome by a a liquid chromatography-mass spectrometry top-down-bottom-up integrated approach. For this purpose, submandibular saliva was collected from alcohol-naive sP and sNP rats under isoprenaline stimulation. A total of 200 peptides and proteins were detected and quantified in the two rat lines, 149 of which were characterized in their naturally occurring structure. The data are available via ProteomeXchange with identifier PXD006997. Surprisingly, sP rats exhibited marked quantitative and qualitative differences with respect to sNP rats, namely higher levels of proteoforms originating from submandibular gland protein C, and from submandibular rat protein 2, as well as those of several unidentified peptides and proteins. sP rats expressed some proteins not detectable in sNP rats such as the glutamine and glutamic acid-rich protein (GRP)-CB. The isoform GRP-B, detectable in both rat lines, was more abundant in sNP rats. The submandibular saliva of sNP rats was also characterized by very high levels of GRP-B proteolytic peptides and rat salivary protein 1. Whether these differences could contribute to the opposite alcohol preference and consumption of sP and sNP rats is currently unknown and requires further investigation.
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Open fetal myelomeningocele repair at a university hospital: surgery and pregnancy outcomes. PURPOSE Myelomeningocele (MMC) is an open neural tube defect that causes great morbidity. Prenatal open repair is the standard treatment; however, there are many complications related to the procedure. This study reports preliminary findings of open in utero repair of MMC in a public tertiary hospital in Brazil and describes factors that could be associated with increased surgical morbidity. METHODS Thirty-nine patients underwent open in utero repair of MMC from October 2015 to August 2019. The Clavien-Dindo classification of surgical complications and a classification system with the preterm definitions of the World Health Organization were used, respectively, for maternal and fetal complications. RESULTS A total of 28 mothers (71.8%) and 31 fetuses (79.5%) experienced at least one minor to major complication. Three mothers (7.7%) had a severe grade 4 complication. Fetal complications grades 3 to 5 occurred in 13 fetuses (33.3%). Gestational age at surgery and at birth were 24.88 ± 1.16 weeks and 33.23 ± 3.68 weeks, respectively. Preterm delivery occurred in 30 patients (76.9%), membrane rupture in 18 patients (46.2%) and chorioamnionitis in 13 patients (33.3%). CONCLUSION Open fetal surgery for MMC was performed at a Brazilian public tertiary care center, resulting in three grade 4 maternal complications. Relevant fetal complications were also present. The use of a standard classification system for complications renders studies more comparable and data more useful for counseling patients. Adjustments of perioperative procedures and long-term follow-up are needed to determine the real benefit of open in utero repair of MMC at our hospital.
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[Energy drink consumption patterns and its adverse effects on adolescent health.] OBJECTIVE Energy drinks generally contain caffeine and other stimulants, commercially aimed at young people. Previous research suggests that its effects on adolescents health are dangerous. The aim of the study was to evaluate the effect of taurine and caffeine consumption from energy drinks on adolescent health and to identify patterns of consumption and, their association with physiological symptoms. METHODS A cross-sectional study of a convenience sample of students (n=135) aged 16 to 17 years was conducted in the State of Hidalgo, Mexico. A self-administered online questionnaire was used from September to November 2020 to report energy drink consumption patterns, perceived effects, and psychophysiological symptoms. The statistical analysis of questionnaire content was made by interjudges evaluation. A concordance index (Cohen-Fleiss Kappa coefficient) was applied for consumption patterns, bivariate correlation tests, Pearson correlation coefficients for levels (very high, moderate, low) of caffeine and taurine were used in the items applied to the target population and Spearmans rho for physiological and psychological effects. RESULTS The participants (mean age: 16 years; 57.8% of women) reported having consumed energy drinks at least once. Only 26.7% of adolescents (n=36) reported that they had never consumed. The average consumption of energy drinks was once per month (24.4%). A statistically significant correlation was found between the consumption of drinks with taurine and the physical effects (tremors and chest pain) and caffeinated beverages with psychophysiological (fatigue, excessive urination, insomnia, and feeling of lack of rest). CONCLUSIONS The study findings indicate associations between energy drink consumption and the presence of adverse psychological and physical symptoms in adolescents.
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Prognostic factors and results of therapy for adult thalamic and brainstem tumors. This report is a retrospective analysis of 83 adults (greater than 16 years of age) with histologically proven or presumed primary neoplasms of the thalamus, hypothalamus, midbrain, pons, and medulla. Patients were treated with combined surgery and postoperative irradiation or with irradiation alone at the Washington University Medical Center (St. Louis, MO) from January 1950 through December 1984. Histologic analysis confirmed the diagnosis of tumor in 21, including nine with well-differentiated astrocytoma, four with astrocytoma with anaplasia, and eight with glioblastoma multiforme. Overall and disease-free survivals at 5 years were 28.7 and 23.2%, respectively. A statistical analysis was performed to ascertain the prognostic importance of the following variables: age, race, gender, duration of symptoms, cranial nerve paresis, primary site, extent of surgery, histology, and irradiation dose. The only factor identified by univariate analysis to be critical for survival was primary location of disease. Patients with supratentorial (thalamus/hypothalamus, midbrain) tumors had a 10-year disease-free survival of 15.4% compared to 29.6% for those with infratentorial (pons, medulla) tumors (P = 0.07). Patients with lesions of the pons had a 5-year disease-free survival of 35.8% compared to 13.8% for those with tumors of the thalamus (P = 0.05). Increasing irradiation dose was not correlated with superior survival. Factors evaluated but established to be insignificant were age (P = 0.27), race (P = 0.63), gender (P = 0.27), duration of symptoms (P = 0.19), cranial nerve paresis (P = 0.71), histologic type (P = 0.16), and extent of surgery (P = 0.94). Follow-up for 13 surviving patients ranged from 2.6 to 28.7 (mean, 12.0) years. Neurologic deficits in surviving patients were absent in 15% (two of 13), mild in 62% (eight of 23), and moderate in 23% (three of 13). One case of brain radionecrosis was identified (6000 cGy, 200 cGy daily).
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Liquid chromatography-linked protein phosphatase bioassay; a highly sensitive marine bioscreen for okadaic acid and related diarrhetic shellfish toxins. Okadaic acid and dinophysistoxin-1 were resolved by liquid chromatography, then identified and quantitated by specific inhibition of both protein phosphatase-1 and -2A (PP1/PP2A) catalytic subunits in a 32P-phosphorylase a phosphatase radioassay. Based on the IC50 for PP2A inhibition (0.2 nM), the procedure has a detection sensitivity of less than 10 pg okadaic acid. Confirmative identification by PP1 inhibition (IC50 = 19 nM) requires 500 pg okadaic acid. Analyses of methanolic extracts from control, "okadaic acid spiked" and suspected diarrhetic mussels showed the bioscreen to be accurate, reproducible and identified okadaic acid/dinophysistoxin-1 in Canadian shellfish for the first time. In addition, a protein phosphatase inhibitor distinct from okadaic acid/dinophysistoxin-1 was identified in diarrhetic mussels with a potency equivalent to 900 ng okadaic acid/g digestive tract. Protein phosphatase inhibition probably underlies the biological activity of okadaic acid as a diarrhetic shellfish toxin and tumour promoter (Cohen, P., Holmes, C. F. B. and Tsukitani, Y. (1990), TIBS 15, 98-102). The liquid chromatography-linked protein phosphatase bioscreen should therefore facilitate identification of novel toxins comprising diarrhetic profiles in infested shellfish.
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The "seeing place": Teaching nurse practitioners about cultural difference through dramatization. BACKGROUND The use of dramatization in health professional education is one method to teach students about implicit bias and cultural difference, yet it has not been widely studied among graduate students of nursing. OBJECTIVES The purpose of this article is to present a qualitative analysis of data regarding doctoral nursing students' responses to a new dramatic exercise as part of a funded project to facilitate cultural learning in a diversity-enhanced nursing curriculum. DESIGN We employed a cross-sectional posttest design with qualitative data collection and hermeneutic analysis. Setting and. PARTICIPANTS Subjects were students from two cohorts in a Doctor of Nursing Practice program at a large metropolitan university in the Midwestern United States (n = 136). METHODS Following a dramatic exercise facilitated by a local theatre group, students debriefed and provided feedback via paper-based surveys collected by their instructor. The research team reviewed and analyzed student feedback with an eye toward new learning or insights around cultural difference. RESULTS Students rated the dramatic exercise highly. Their written feedback provided for a deeper exploration of how they internalized messages about cultural difference. These experiences were thematized in the following way: (a) Awareness is facilitated through integrating nonverbal (kinesthetic) and verbal encounters, (b) Hesitancy to participate in unfamiliar activities creates tension, and (c) Safety is a foundational aspect of learning sensitive issues. CONCLUSION Dramatization of culturally sensitive scenarios for advanced practice nurses can lead to new understanding. Educators who understand the need for thoughtful introduction of dramatization experiences can better prepare nurses for interaction in cross-cultural clinical environments.
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Redetermination of (NH(4))(2)HAsO(4). In comparison with the original determination based on Weissenberg film data [Khan et al. (1970 ▶). Acta Cryst. B26, 1889-1892], the current redetermination of diammonium hydrogenarsenate(V) reveals all atoms with anisotropic displacement parameters and all H atoms localized. This allowed an unambiguous assignment of the hydrogen-bonding pattern, which is similar to that of the isotypic phosphate analogue (NH(4))(2)HPO(4). The structure of the title compound consists of slightly distorted AsO(3)(OH) and NH(4) tetra-hedra, linked into a three-dimensional structure by an extensive network of O-H⋯O and N-H⋯O hydrogen bonds.
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Oncologists experience with second primary cancer screening: current practices and barriers and potential solutions. OBJECTIVES Screening for second primary cancer (SPC) is one of the key components of cancer survivorship care. The aim of the present study was to explore oncologists' experience with promoting second primary cancer screening. METHODS Two focus group interviews were conducted with 12 oncologists of diverse backgrounds. Recurrent issues were identified and placed into thematic categories. RESULTS Most of the oncologists did not consider SPC screening promotion as their responsibility and did not cover it in routine care. All of the study participants had experience with unexpected SPC cases, and they were under emotional tress. There was no systematic manner of providing SPC screening. Oncologists usually prescribe SPC screening in response to patients' requests, and there was no active promotion of SPC screening. Short consultation time, limited knowledge about cancer screening, no established guideline for SPC screening, and disagreement with patients about oncologists' roles were major barriers to its promotion. An institution-based shared care model was suggested as a potential solution for promoting SPC screening given current oncology practices in Korea. CONCLUSION Oncologists could not effectively deal with the occurrence of SPC, and they were not actively promoting SPC screening. Lack of knowledge, limited health care resources, and no established guidelines were major barriers for promoting SPC screening to cancer survivors. More active involvement of oncologists and a systematic approach such as shared-care models would be necessary for promoting SPC screening considering increasing number of cancer survivors who are vulnerable.
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A prediction model of nodal metastasis in cN0 oral squamous cell carcinoma using metabolic and pathological variables. BACKGROUND The efficacy of 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography/Computed Tomography(PET/CT) in evaluating the neck status in clinically node-negative (cN0) oral squamous cell carcinoma(OSCC) patients was still unsatisfying. We tried to develop a prediction model for nodal metastasis in cN0 OSCC patients by using metabolic and pathological variables. METHODS Consecutive cN0 OSCC patients with preoperative 18F-FDG PET/CT, subsequent surgical resection of primary tumor and neck dissection were included. Ninety-five patients who underwent PET/CT scanning in Shanghai ninth people's hospital were identified as training cohort, and another 46 patients who imaged in Shanghai Universal Medical Imaging Diagnostic Center were selected as validation cohort. Nodal-status-related variables in the training cohort were selected by multivariable regression after using the least absolute shrinkage and selection operator (LASSO). A nomogram was constructed with significant variables for the risk prediction of nodal metastasis. Finally, nomogram performance was determined by its discrimination, calibration, and clinical usefulness. RESULTS Nodal maximum standardized uptake value(nodal SUVmax) and pathological T stage were selected as significant variables. A prediction model incorporating the two variables was used to plot a nomogram. The area under the curve was 0.871(Standard Error [SE], 0.035; 95% Confidence Interval [CI], 0.787-0.931) in the training cohort, and 0.809(SE, 0.069; 95% CI, 0.666-0.910) in the validation cohort, with good calibration demonstrated. CONCLUSIONS A prediction model incorporates metabolic and pathological variables has good performance for predicting nodal metastasis in cN0 OSCC patients. However, further studies with large populations are needed to verify our findings.
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The effects of marijuana extract and delta 9-tetrahydrocannabinol on luteal function in the rhesus monkey. The effects of marijuana extract (ME) and delta 9-tetrahydrocannabinol (THC) on corpus luteum function were studied in the rhesus monkey by the use of in vivo and in vitro techniques. THC (2.5 mg/kg) or vehicle (3% Tween 80 in saline) was administered by an intramuscular injection to rhesus monkeys on day 20, 21, or 22 of the menstrual cycle. Progesterone (P) levels were measured at 6-hour intervals for the first 24 hours after treatment. THC caused a significant decrease in P levels during this 24-hour period. This decrease was reversed by the administration of human chorionic gonadotropin (hCG) at 6 hours after THC administration. When THC was administered 2 hours after hCG, it failed to inhibit the expected rise in serum P levels caused by hCG. Direct effects of the drugs on P production were studied with the use of dispersed luteal cells obtained from monkeys on day 21 or 22 of the menstrual cycle. Neither ME nor THC had any effect on basal P production in these in vitro studies. These data suggest that the inhibitory effect of THC on P levels during the luteal phase are not mediated by a direct effect of the drug on ovarian steroid production.
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Improved culture media for piscine hemoflagellates, Cryptobia and Trypanosoma (Kinetoplastida). Increasing the Hepes buffer in minimum essential medium from 25 mM to 100 mM yielded a significantly larger number of Cryptobia salmositica. Cryptobia salmositica (pathogenic and nonpathogenic strains), Cryptobia bullocki, and Trypanosoma danilewskyi did not multiply either in heat-inactivated trout plasma (< or =25%) or in less than 10% fresh trout plasma. Both strains of C. salmositica multiplied better in 10% fresh trout plasma than in 25% heat-inactivated fetal bovine serum. In contrast, C. bullocki and T. danilewskyi multiplied better in 25% fetal bovine serum; 10% fetal bovine serum did not significantly reduce multiplication of C. bullocki. The nonpathogenic vaccine strain of C. salmositica cultured in 10% fresh trout plasma still protected rainbow trout from high parasitemia when challenged with the pathogen.
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A personal COVID-19 dendritic cell vaccine made at point-of-care: Feasibility, safety, and antigen-specific cellular immune responses. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a world-wide pandemic. Internationally, because of availability, accessibility, and distribution issues, there is a need for additional vaccines. This study aimed to: establish the feasibility of personal dendritic cell vaccines to the SARS-CoV-2 spike protein, establish the safety of a single subcutaneous vaccine injection, and determine the antigen-specific immune response following vaccination. In Phase 1, 31 subjects were assigned to one of nine formulations of autologous dendritic cells and lymphocytes (DCL) incubated with 0.10, 0.33, or 1.0 µg of recombinant SARS-CoV-2 spike protein, and admixed with saline or 250 or 500 µg of granulocyte-macrophage colony-stimulating factor (GM-CSF) prior to injection, then assessed for safety and humoral response. In Phase 2, 145 subjects were randomized to one of three formulations defined by incubation with the same three quantities of spike protein without GM-CSF, then assessed for safety and cellular response. Vaccines were successfully manufactured for every subject at point-of-care. Approximately 46.4% of subjects had a grade 1 adverse event (AE); 6.5% had a grade 2 AE. Among 169 evaluable subjects, there were no acute allergic, grade 3 or 4, or serious AE. In Phase 1, anti-receptor binding domain antibodies were increased in 70% of subjects on day-28. In Phase 2, in the 127 subjects who did not have high levels of gamma interferon-producing cells at baseline, 94.4% had increased by day 14 and 96.8% by day 28. Point-of-care personal vaccine manufacturing was feasible. Further development of such subject-specific vaccines is warranted.
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Studies on the synthesis of furanosteroids. I. Viridin models. Alkyne oxazoles of general structure I are transformed directly to furo[2,3-b]phenol derivatives II by a sequence involving intramolecular Diels-Alder/retro-Diels-Alder reaction followed by tautomerization. Suitably functionalized phenols II undergo an intramolecular phenol-dienone-aldol condensation, generating the A,B,E-ring skeleton III characteristic of the viridin (1) class of furanosteroids.
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Parental Choice of Recall Method for HPV Vaccination: A Pragmatic Trial. OBJECTIVES Completion rates for the human papillomavirus vaccine (HPV) series among adolescents remain low. Effectiveness of recall with parents choosing the method (preference-based recall) for increasing HPV series completion is unstudied. Within a cluster-randomized trial, we examined effectiveness of preference-based recall compared with usual care for increasing series completion and the association of recall choices with completion. METHODS All Kaiser Permanente Colorado pediatric practices (n = 7) were randomized to intervention (n = 4) or control (n = 3) by using covariate-constrained randomization. From January to June 2013, parents at intervention practices whose adolescents received HPV 1 were asked the recall method they preferred for subsequent doses and if they also wanted their child reminded. Completion rates were assessed 1 year after HPV 1. RESULTS At intervention practices, 374 (43%) of 867 patients were enrolled; 39% preferred text, 18% e-mail, 9% auto-dialer, and 34% 2-methods; 19% chose to have adolescent also recalled. Intervention adolescents were more likely to complete (63% vs 38%) than were controls (adjusted risk ratio 1.47 [1.38-1.57]) and less likely to be late in completing the series (45% vs 57%, P = .02). Rates of completion were similar between different recall methods, but significantly higher for those preferring e-mail and phone compared withother methods (90% vs 60%. P = .008). Completion rates were similar for adolescents who also received recalls (62%) versus those who did not (63%). CONCLUSIONS Preference-based recall was effective in increasing HPV series completion rates, with point estimates substantially higher than for most published studies of reminder/recall.
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High-Deductible Health Plans and Healthcare Access, Use, and Financial Strain in Those with Chronic Obstructive Pulmonary Disease. Rationale: Medical treatment can improve quality of life and avert exacerbations for those with chronic obstructive pulmonary disease (COPD). High-deductible health plans (HDHPs) can increase exposure to medical costs, and might compromise healthcare access and financial well-being for patients with COPD.Objectives: To examine the association of HDHPs with healthcare access, utilization, and financial strain among individuals with COPD.Methods: We analyzed privately insured adults aged 40-64 years with COPD in the 2011-2017 National Health Interview Survey, which uses Internal Revenue Service-specified thresholds to classify health plans as "high" or "traditional" deductible coverage. We assessed the association between enrollment in an HDHP and indicators of cost-related impediments to care, financial strain, and healthcare utilization, adjusting for potential confounders.Results: Our sample included 803 individuals with an HDHP and 1,334 with a traditional plan. The two groups' demographic and health characteristics were similar. Individuals enrolled in an HDHP more frequently reported delayed or foregone care, cost-related medication nonadherence, medical bill problems, and financial strain. They also more frequently reported out-of-pocket healthcare spending in excess of $5,000 a year. Although the two groups' office visit rates were similar, those enrolled in an HDHP were more likely to report a hospitalization or emergency room visit in the past year.Conclusions: For patients with COPD, enrollment in an HDHP was associated with cost-related barriers to care, financial strain, and more frequent emergency room visits and hospitalizations.
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Imaging Features of Renal Masses to Select Optimal Candidates for Tumor Enucleation Partial Nephrectomy. PURPOSE OF REVIEW The goal of this paper was to critically evaluate preoperative findings that optimally select candidates for renal tumor enucleation partial nephrectomy. RECENT FINDINGS Tumor enucleation has been widely accepted as a management option for patients with chronic kidney disease, hereditary renal cell carcinoma, or multifocal disease. Recent evidence suggests safety and efficacy in the management of routine small renal masses. With recent advances in imaging, the literature for ruling out aggressive renal cell carcinoma and selection for tumor enucleation is robust. As the incidence of renal cell carcinoma rises, partial nephrectomy continues to be the mainstay of treatment for localized renal cell carcinoma. Tumor enucleation maximizes preservation of renal parenchyma without hindering oncologic outcomes. It is important to recognize key tumor radiologic findings which urologists may use to optimize patient selection for tumor enucleation.
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The processing of kinetic contours in the brain. This work investigates whether the brain assigns special cortical areas for the processing of kinetic contours. In human imaging experiments, we compared the brain activity produced in the so-called 'kinetic occipital' area ('KO') when humans perceive shapes generated from kinetic boundaries or from equiluminant colors. 'KO' was activated whenever subjects perceived shapes, no matter how they were derived; it is therefore not specialized for the processing of kinetic contours. The application of independent component analysis (ICA) to imaging data obtained when subjects viewed 22 min of an action movie showed that the time course of activity in 'KO' correlates better with activity in area V3 than with activity in two adjacent areas, V5 and LO. We thus consider 'KO' to be part of the V3 family of areas, and use the terminology of Smith et al. (J Neurosci 18:3816-3830, 1998), to refer to it as area V3B. Recordings from orientation-selective cells in the macaque V3 complex show that the great majority have the same orientational specificity when tested with oriented lines generated from kinetic stimuli or from luminance differences. We conclude that there is no present evidence for a visual area specialized for the processing of kinetic contours in the primate visual brain.
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Barriers and facilitators to implementing evidence-based health innovations in low- and middle-income countries: A systematic literature review. The unsuccessful implementation of health innovations occurs frequently, leading to missed opportunities where improvements could have been made on various aspects of a health system. The purpose of this study is to identify, assess and synthesise the facilitators and barriers to sustainably implementing evidence-based health innovations in a low- and middle-income country (LMIC) context. To identify the LMIC specific facilitators and barriers, a systematic literature review was conducted. 79 studies were analysed, and the implementation barriers and facilitators identified in each study were extracted. The extracted barriers and facilitators were categorised and synthesized into one of seven concepts: context, innovation, relations and networks, institutions, knowledge, actors or resources. There were no substantial variations between the frequency that each concept was identified as a facilitator or barrier to implementation. However, resources, which includes time, human, financial and physical resources, was the most frequently mentioned concept; emphasising the need to focus on the resource situation in LMICs. This study contributes to the growing literature that aims to inform health system planners and evaluators in LMICs on effectively and sustainably implementing evidence-based health innovations.
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Identification of victims from mass grave discovery near Benghazi, Libya. BACKGROUND A mass grave is any site that containing two or more associated corpses, at random or on purpose placed, of people who have died as a result of extra-judicial or random executions, not including those people who have died from armed confrontations or known major catastrophes. CASE PRESENTATION The purpose of this paper is to explain how to reconstruct a biological profile of decomposed or skeletonized bodies and clarify the efforts done by the Libyan scientist after 2011 revolution and to set a reference for other researcher. The alleged location of the grave, as well as the alleged number and identities of the persons buried in the grave were obtained exclusively from witnesses' and relatives' testimonies. CONCLUSION As the testimonies said, the grave was located at the alleged location and seven skeletons were exhumed. Also, the osteological and DNA study made investigators to identify the exhumed skeletons. And the dental analysis support the identification of a seven man alleged to have been buried in the grave, 7 victims were discovered.
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Neurological aspects of areca and betel chewing. Betel quid chewing has been claimed to produce a sense of well-being, euphoria, warm sensation of the body, sweating, salivation, palpitation, heightened alertness and increased capacity to work. These effects suggest that betel quid chewing affects predominantly the central and autonomic nervous systems. Several studies have been conducted to elucidate the central and autonomic effects of betel quid chewing. The results are: (1) betel quid chewing increased the heart rate with onset within 2 minutes, maximal effect within 4-6 minutes and an average duration of 16.8 minutes. The cardio-acceleratory response was more prominent for fresh and occasional chewers than for habitual chewers; (2) betel quid chewing increased the skin temperature with onset and duration similar to a cardio-acceleratory response. The hyperthermic effect was abolished by atropine and partly inhibited by propranolol. (3) Betel quid chewing had no effect on simple reaction time but shortened the choice reaction time. (4) Betel quid chewing produced widespread cortical desynchronization of EEG. (5) Chewing of one or two betel quids attenuated the sympathetic skin response while continued consumption of more than two betel quids affected the RR interval variation. (6) Plasma concentrations of noradrenaline and adrenaline were elevated during betel quid chewing. These studies have confirmed several effects claimed by betel quid users. The effects of betel quid chewing appeared to be habit-related and dose-dependent. Although arecoline has been thought to be responsible for several effects of betel quid chewing, the present data suggest a role also played by sympathetic activation.
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Soluble guanylate cyclase of platelets: function and regulation in normal and pathological states. Chromatography of 105,000 x g supernatants of human and rat platelets on DEAE-cellulose yielded identical elution profiles containing 2 protein fractions (peaks I and II). Only peak II was found to possess guanylate cyclase activity. In the spectrum of the 105,000 x g supernatant of human platelets the absorption maximum was specified at 410 nm (the Soret band) which disappeared from the spectrum of the active protein fraction (peak II) but was detected in the nonactive fraction (peak I). The enzyme preparation was obtained in the heme-deficient form. In the experiments with rat platelets, the Soret band was absent from the corresponding spectra and the enzyme was not activated by sodium nitroprusside; i.e., in soluble guanylate cyclase of rat platelets, unlike the generally accepted notion, the heme is not a prosthetic group of the enzyme. It was shown that carnosine (beta-alanyl-L-histidine), a water-soluble antioxidant, inhibits guanylate cyclase activation by sodium nitroprusside. This inhibitory effect is caused by the interaction of carnosine with the guanylate cyclase heme and can be used for evaluating the degree of saturation of the enzyme with the heme. ADP-induced aggregation of human platelets (donors) is accompanied by a fall in the basal guanylate cyclase activity (with Mg2+) and the enhancement of the enzyme stimulation with sodium nitroprusside, protoporphyrin IX, arachidonic acid and L-arginine with simultaneous cGMP elevation in platelets. A hypothetic scheme of the regulatory role of cGMP in platelet aggregation is proposed. In the experiments with the acute myocardial ischemia of rats, 15 min after the surgery a sharp fall in the platelet guanylate cyclase activity accompanied by a decrease in the enzyme activity in the ischemic zone of the left ventricle of heart took place. The results provided evidence of the high sensitivity of platelet guanylate cyclase to pathological changes occurring in the myocardium at the earliest stages of the development of pathology.
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Upon drug-induced apoptosis in lymphoma cells X-linked inhibitor of apoptosis (XIAP) translocates from the cytosol to the nucleus. The X-linked inhibitor of apoptosis (XIAP) and cellular inhibitor of apoptosis-1 (cIAP-1) are emerging as versatile proteins in programmed cell death with a scope of possible functions reaching far beyond their well known inhibitory effects on caspases. We previously demonstrated that the ability of drugs to modify expression and cleavage of the IAPs are crucial for the synergistic effects achieved by the combinations of different cytotoxic drugs employed to treat malignant lymphomas. In order to more clearly assess the underlying molecular mechanisms, we here evaluated the consequences of drug-induced apoptosis on the localization and aggregation of XIAP and cIAP-1. The influence of drug-induced apoptosis on localization of IAPs was investigated using immunofluorescence microscopy as well as western blot analysis. Apoptosis was induced by chemotherapeutic drugs with different modes of action (bendamustine, cladribine, fludarabine, doxorubicin and mitoxantrone) and assessed by flow-cytometry using Annexin V. We demonstrate that XIAP and cIAP-1 are downregulated and/or cleaved in a dose-dependent manner upon treatment with a variety of anti-cancer drugs. Moreover we provide evidence that in the context of drug-induced apoptosis XIAP, its BIR3-RING cleavage product and cIAP-1 undergo an extensive change of subcellular localization. Immunofluorescence microscopy reveals that XIAP, in contrast to cIAP-1, is located in discrete cytosolic protein aggregates and-upon induction of apoptosis with cytotoxic drugs--redistributes into large nuclear inclusions. This translocation of XIAP and its BIR3-RING cleavage product from the cytosol into the nucleus is confirmed by cell fractionation and western blot analyses. Of note, in this experimental setting putative interaction partners of XIAP-such as Apaf-1, caspase-3 and -7--do not co-localize with XIAP. These results imply a new unknown function of XIAP and its BIR3-RING fragment in the nucleus in the context of drug-induced apoptosis. The localization of cIAP-1 in mitochondria and its liberation from these indicate a profoundly different function of this protein despite its similar modular structure to XIAP.
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Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling. Multiple myeloma (MM) is a hematological cancer causing from accumulated abnormal plasma cells. STAT3 overexpression in MM appears to be mediated by a variety of factors, and it may be associated with an adverse prognosis and play a role in microenvironment-dependent treatment resistance. Unfortunately, MM remains an incurable disease, as relapse is very common. Therefore, there is urgent need to develop new treatment options for MM. Radotinib is a novel anti-cancer drug, currently approved in South Korea for the treatment of chronic myeloid leukemia patients. It is an oral, multitargeted inhibitor of receptor tyrosine kinases, including BCR-ABL, c-KIT, PDGFR, and Src family kinases. However, little is known about the effects of radotinib on multiple myeloma cells. However, little is known about the effects of radotinib on multiple myeloma cells. But even tinip almost not known about the impact of multiple myeloma cells. Moreover, nothing is known about how it affects STAT3 and JAK2. In this study, we analyzed the effect of radotinib on multiple myeloma cells. Herein, Moreover, nothing is known about how it. Moreover, not all is known about how the affects STAT3 and JAK2. We investigated the effect of radotinib on the STAT3 signaling pathway in MM cells, including several MM cell lines and mouse models. So we investigated the effect of radotinib on MM cells, including several MM cell lines and mouse models. Interestingly, radotinib induced apoptosis, and inhibited cell proliferation in MM cells including RPMI-8226, MM.1S, U266B1, and IM-9 cells. Moreover, radotinib treatment significantly increased the number Annexin V-positive cells and G0/G1-phase cells. In addition, radotinib treatment in various MM cells strongly suppressed the activity and expression of STAT3 and JAK2 proteins. We also observed that diverse proteins related to the STAT3 signaling pathway, including c-Myc, Bcl-xL, Mcl-1, cyclin D1 and cyclin D3, were powerfully inhibited by radotinib treatment in MM cells. Furthermore, radotinib significantly suppressed MM cell growth in a xenograft animal model using IM-9 cells. In conclusion, radotinib may play an important role as a candidate agent for MM treatment.
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Uptake of postprandial lipoproteins into bone in vivo: impact on osteoblast function. Dietary lipids and lipophilic vitamins are transported by postprandial lipoproteins and are required for bone metabolism. Despite that, it remains unknown whether bone cells are involved in the uptake of circulating postprandial lipoproteins in vivo. The current study was performed to investigate a putative participation of bone in the systemic postprandial lipoprotein metabolism in mice, to identify potentially involved cell type populations and to analyze whether lipoprotein uptake affects bone function in vivo. As a model for the postprandial state, chylomicron remnants (CR) were injected intravenously into mice. Next to the liver and compared to other organs, bone appeared to be the second most important organ for the clearance of radiolabeled CR particles from the circulation in vivo. In addition, uptake of radiolabeled CR by primary murine osteoblasts and hepatocytes was quantified to be in a similar range in vitro. A complementary approach with fluorescently labeled CR and immunohistochemical staining for apoE proved that intact CR particles were taken up into bone and liver. Electron microscopy localization studies of bone sections revealed CR uptake into sinusoidal endothelial cells, macrophages and osteoblasts. The relative amount of radiolabeled CR uptake into femoral cortical bone, representing predominantly osteoblasts, and bone marrow, representing predominantly non-osteoblast cells, was within the same range. Most importantly, the injection of vitamin K1-enriched CR resulted in an increase of the degree of osteocalcin carboxylation in vivo while total osteocalcin concentrations remained unaffected, giving functional proof that osteoblasts process CR in vivo. In conclusion, here we demonstrate that bone is involved in the postprandial lipoprotein metabolism in mice. Osteoblasts participate in CR clearance from the circulation, which has a direct impact on the secretory function of osteoblasts.
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The autoimmune/inflammatory syndrome induced by adjuvants (ASIA)/Shoenfeld's syndrome: descriptive analysis of 300 patients from the international ASIA syndrome registry. The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is a recently identified condition in which the exposure to an adjuvant leads to an aberrant autoimmune response. We aimed to summarize the results obtained from the ASIA syndrome registry up to December 2016, in a descriptive analysis of 300 cases of ASIA syndrome, with a focus on the adjuvants, the clinical manifestations, and the relationship with other autoimmune diseases. A Web-based registry, based on a multicenter international study, collected clinical and laboratory data in a form of a questionnaire applied to patients with ASIA syndrome. Experts in the disease validated all cases independently. A comparison study regarding type of adjuvants and differences in clinical and laboratory findings was performed. Three hundred patients were analyzed. The mean age at disease onset was 37 years, and the mean duration of time latency between adjuvant stimuli and development of autoimmune conditions was 16.8 months, ranging between 3 days to 5 years. Arthralgia, myalgia, and chronic fatigue were the most frequently reported symptoms. Eighty-nine percent of patients were also diagnosed with another defined rheumatic/autoimmune condition. The most frequent autoimmune disease related to ASIA syndrome was undifferentiated connective tissue disease (UCTD). ASIA syndrome is associated with a high incidence of UCTD and positive anti-nuclear antibodies (ANA) test. Clinical and laboratory features differ from the type of adjuvant used. These findings may contribute to an increased awareness of ASIA syndrome and help physicians to identify patients at a greater risk of autoimmune diseases following the exposure to vaccines and other adjuvants. The ASIA syndrome registry provides a useful tool to systematize this rare condition.
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Determination of copper in biological materials by atomic absorption spectroscopy: a reevaluation of the extinction coefficients for azurin and stellacyanin. A new method for the determination of copper in biological materials by graphite furnace atomic absorption spectroscopy is presented. This new procedure is an extension of the classic method of standard additions, where the analyte concentration is determined in a series of identical samples to which various amounts of metal standard have been added. The concentration of metal in the original sample is determined from an extrapolation of a plot of absorbance versus added analyte. In the new method, the amount of copper is determined by the method of standard additions for different concentrations of the sample under investigation as well. From an extrapolation of the data, the concentration of copper in the absence of interfering matrix is obtained. Studies with fetal bovine serum demonstrate that the new extrapolation technique is precise. Furthermore, considerably more copper is detected than by the classic method of standard additions applied to a nitric acid treated sample. The matrix effects of phosphate, nitrate, albumin, and serum were also examined. Both phosphate and serum, at physiological pH, decrease the detectability of added copper, while nitrate and albumin were without effect. The accuracy of this method has been verified by determining the extinction coefficients of stellacyanin and azurin. The values obtained, 4.33 X 10(3) and 3.75 X 10(3) M-1 cm-1, respectively, are considerably different from those determined by the method of standard additions on nitric acid digests of these proteins, but were close to values previously reported and determined colorimetrically.
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Rethinking the origins of autism: Ida Frye and the unraveling of children's inner world in the Netherlands in the late 1930s. Historiographies on the phenomenon of "autism" display Leo Kanner and Hans Asperger as the great pioneers. The recent controversy on who was first in "discovering" autism urges research into the question of how scientific discoveries relate to processes of academic reflection and social intervention. The Netherlands provide an interesting case in pioneering work in autism, since Dutch experts described autism in children already in the late 1930s, preceding the first publications on autism in children by Kanner and Asperger. This paper examines the Dutch origins of autism by focusing on Ida Frye's contribution to the teamwork at the Paedological Institute in Nijmegen, which resulted in descriptions of children with autism. The theoretical aim of this paper is to underline the importance of the productive interplay between social interventions and scientific efforts concerning the complex inner world of special children.
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Basics of the virology of HIV-1 and its replication. Human immunodeficiency virus is undoubtedly the causative agent of AIDS. The understanding of HIV-1 pathogenesis is essential to develop and maintain antiretroviral treatment and vaccination. Since the first isolation of HIV-1 in cell culture, thousands of publications dealing with HIV and/or AIDS per year were released. In this review we give a basic overview of the virology of HIV-1 including the functions of the different HIV-1 proteins required for effective viral replication. Moreover, we summarize the interactive processes between HIV-1 and its target cells. Finally, the HIV-1 specific immune response and the current status of antiretroviral therapy are briefly described in this review.
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"I Wasn't Gonna Quit, but by Hook or by Crook I was Gonna Find a Way Through for the Kids": A Narrative Inquiry, of Mothers and Practitioners, Exploring the Help-seeking of Mothers' Experiencing Child to Parent Violence. Purpose Child to parent violence is a significant concern that has been researched over the last sixty years. However, little is known about the help-seeking pathways of parents experiencing child to parent violence (CPV). Barriers and enablers to disclosing CPV have been explored, and responses to address CPV have been nominally researched. The mapping of a disclosure to a choice of where to get help has not occurred. This study seeks to map help-seeking pathways of mothers and considers these pathways in regards to the relations within families and sociomaterial conditions. Method This narrative inquiry utilizes response-based practice and Barad's concept 'intra-action' to examine interviews with mothers (n = 11) who experience CPV, and practitioners (n = 19) who work with families experiencing CPV. Results Five help-seeking pathways of mothers are found in this study. Three themes evident across the pathways are explored including: (1) help-seeking within pre-existing relationships; (2) mothers' feelings of fear, shame and judgement entangled with help-seeking; and (3) conditions which enable and hinder help-seeking from family. Conclusions This study finds sociomaterial conditions such as single motherhood and judgement limit help-seeking possibilities. Further, this study finds help-seeking occurs within pre-existing relationships along with the entanglement of CPV with other issues such as intimate partner violence (IPV) and homelessness. This study demonstrates the benefits of employing a response-based approach alongside 'intra-action' within a research and practice context.
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Investigation of a Q fever outbreak in a rural area of The Netherlands. A Q fever outbreak occurred in the southeast of The Netherlands in spring and summer 2007. Risk factors for the acquisition of a recent Coxiella burnetii infection were studied. In total, 696 inhabitants in the cluster area were invited to complete a questionnaire and provide a blood sample for serological testing of IgG and IgM phases I and II antibodies against C. burnetii, in order to recruit seronegative controls for a case-control study. Questionnaires were also sent to 35 previously identified clinical cases. Limited environmental sampling focused on two goat farms in the area. Living in the east of the cluster area, in which a positive goat farm, cattle and small ruminants were situated, smoking and contact with agricultural products were associated with a recent infection. Information leaflets were distributed on a large scale to ruminant farms, including hygiene measures to reduce the risk of spread between animals and to humans.
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Total sympathetic activity and atrial natriuretic factor levels in VVI and DDD pacing with different atrioventricular delays during daily activity and exercise. The purpose of the study was to assess at rest and during exercise total sympathetic activity, as expressed by plasma cyclic AMP (cAMP) blood levels and sinus node activity (SNA), as well as atrial natriuretic factor (ANF) blood levels in VVI and DDD pacing with long and short atrioventricular delays in DDD paced patients suffering from complete heart block. Clinical parameters, such as exercise time, and arterial blood pressure (ABP) were also taken into consideration. Thirteen patients (six males, mean age 65 +/- 2 years), were examined randomly in VVI and DDD pacing with 100 and 150 ms atrioventricular delays (AVD). Plasma cAMP and ANF were measured at rest, at peak exercise and 15 and 30 min after the test. The cAMP at rest remained unchanged whatever the pacing mode or the AVD, but 30 min after exercise, the cAMP levels were statistically lower in DDD pacing with short AVD (100 ms) than in DDD with long AVD (150 ms) or VVI pacing (cAMP DDD/100 ms: 16 +/- 0.8 pmol.ml-1, cAMP DDD/150 ms: 20 +/- 2 pmol.ml-1, P < 0.01, cAMP VVI: 29 pmol.ml-1, P < 0.001). ANF plasma levels at rest were significantly higher in VVI pacing than in DDD modes, with either long or short AVD (ANF DDD/100 ms: 93 +/- 10 pg.ml-1, ANF DDD/150 ms: 100 +/- 13 pg.ml-1, ANF VVI: 150 +/- 16 pg.ml-1, P < 0.001, P < 0.03 respectively compared to VVI).(ABSTRACT TRUNCATED AT 250 WORDS)
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[The effect of glycine on survival after hemorrhagic shock in the rats]. OBJECTIVE To investigate the effect of glycine on survival after hemorrhagic shock in the rats and elucidate the underlying mechanisms. METHODS Wistar rats were bled to establish the shock model and subsequently resuscitated with shed blood and normal saline. Just prior to resuscitation, the rats were divided into three groups: sham group, shock group and shock + glycine group. RESULTS (1) 72 h after resuscitation, the survival rate of shock group decreased to 20%, while the survival rate of shock + glycine group was 77.8%, the difference was significant (P < 0.05). (2) 18 h after resuscitation, pathologic alterations of organs showed, pulmonary edema, leukocyte infiltration in interstitial tissue and cellular degeneration in shock group. Glycine reduced these pathological alterations significantly. (3) 18 h after resuscitation, creatine phosphokinase, transaminases and creatinine were elevated significantly in shock group, while these were elevated slightly in shock + glycine group, the differences were significant (P < 0.01). (4) Increases in intracellular calcium and production of TNF-alpha by isolated Kupffer cells stimulated by endotoxin were elevated significantly by hemorrhagic shock, which were totally prevented by glycine (P < 0.01). CONCLUSION Glycine reduces organ injury and mortality caused by hemorrhagic shock by preventing increase of intracellular calcium and production of TNF-alpha of Kupffer cells and blocking systemic inflammation responses.
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Proline synthesis through PYCR1 is required to support cancer cell proliferation and survival in oxygen-limiting conditions. The demands of cancer cell proliferation alongside an inadequate angiogenic response lead to insufficient oxygen availability in the tumor microenvironment. Within the mitochondria, oxygen is the major electron acceptor for NADH, with the result that the reducing potential produced through tricarboxylic acid (TCA) cycle activity and mitochondrial respiration are functionally linked. As the oxidizing activity of the TCA cycle is required for efficient synthesis of anabolic precursors, tumoral hypoxia could lead to a cessation of proliferation without another means of correcting the redox imbalance. We show that in hypoxic conditions, mitochondrial pyrroline 5-carboxylate reductase 1 (PYCR1) activity is increased, oxidizing NADH with the synthesis of proline as a by-product. We further show that PYCR1 activity is required for the successful maintenance of hypoxic regions by permitting continued TCA cycle activity, and that its loss leads to significantly increased hypoxia in vivo and in 3D culture, resulting in widespread cell death.
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Effects of Short-Term Low-Dose Glucocorticoids for Patients with Mild COVID-19. OBJECTIVES To evaluate the role of short-term low-dose glucocorticoids in mild COVID-19 patients. METHODS We conducted a retrospective, cross-sectional, single-center study in Kunming, China. A total of 33 mild COVID-19 cases were divided into two treatment groups (with and without glucocorticoids, methylprednisolone, were used in this setting), and the absolute value of peripheral blood lymphocyte count; CD3+, CD4+, and CD8+ T cell counts; and the time to achieve negative transformation of a nucleic acid pharyngeal swab were recorded. Peripheral blood lymphocyte and T cell counts were compared between the treatment group and 25 healthy individuals. At the point of time when there was a 50% accumulation conversion rate (positive to negative nucleic acid on pharyngeal swab), and the nucleic acid turned negative in half of the patients in two groups, the peripheral blood lymphocyte and T cell counts were compared between treatment groups. RESULTS The mean cumulative time for the 50% negative conversion rate of the nucleic acid in the pharyngeal swab was 17.7 ± 5.1 days and 13.9 ± 5.4 days in the glucocorticoid group and the nonglucocorticoid group, respectively. The absolute peripheral blood lymphocyte count and the T cell subset count in the glucocorticoid group were lower than those in the nonglucocorticoid group. When the nucleic acid turned negative in half of the patients, the absolute value of peripheral blood lymphocyte count and CD4+ T cells of the glucocorticoid group and the nonglucocorticoid group was not significantly different; the CD3+ and CD8+ T cells in the glucocorticoid group were lower than those in the nonglucocorticoid group. The absolute peripheral blood lymphocyte count, CD3+ T cells, and CD4+ T cells in the glucocorticoid group were lower than those of the healthy group during the whole disease period, and CD8+ T cells returned to normal at 19-21 days of the disease period. There was no significant difference between the nonglucocorticoid group and the healthy group for absolute peripheral blood lymphocyte and CD8+ T cells; moreover, CD3+ T cells and CD4+ T cells were lower in the nonglucocorticoid group than those in the healthy group from the day of admission to the 18th day and returned to normal at the period of 19-21 days. The absolute peripheral lymphocyte count (P = 0.048, effect size d = 0.727) and T cell subset count (CD3: P = 0.042, effect size d = 0.655; CD4: P < 0.01, effect size d = 0.599; and CD8: P = 0.034, effect size d = 0.550) in the nonglucocorticoid group were higher than those in the glucocorticoid group, and the difference between the groups was statistically significant. CONCLUSIONS This study found that the use of short-term, low-dose glucocorticoids does not negatively influence the clinical outcome, without affecting the final clearance of viral nucleic acid in mild COVID-19 patients.
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Inhibiting NAD+-dependent DNA ligase activity with 2-(cyclopentyloxy)-5'-deoxyadenosine (CPOdA) offers a new tool for DNA replication and repair studies in the model archaeon Haloferax volcanii. DNA ligases play an essential role in many aspects of DNA metabolism in all three domains of life. The haloarchaeal organism Haloferax volcanii encodes both ATP- and NAD(+)-dependent DNA ligase enzymes designated LigA and LigN, respectively. Neither LigA nor LigN alone is required for cell viability but they share an essential function, most likely the ligation of Okazaki fragments during chromosome replication. Here we show that 2-(cyclopentyloxy)-5'-deoxyadenosine (referred to as CPOdA), originally developed as a inhibitor of bacterial NAD(+)-dependent DNA ligases, is a potent inhibitor of the growth of Hfx. volcanii cells expressing LigN alone, causing chromosome fragmentation and cell death, while cells expressing LigA are unaffected. Growth inhibition occurs at significantly lower CPOdA concentrations (MIC ≤ 50 ng ml(-1)) than those required for inhibition of bacterial growth (≥2 μg ml(-1)). CPOdA has the potential to become a vital tool in DNA replication and repair studies in this important model organism.
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Removal and recovery of acridine orange from solutions by use of magnetic nanoparticles. Here we report a separation of a cationic dye, acridine orange (AO), by use of magnetic nanoparticles (gamma-Fe(2)O(3)). The particles were showed to capture 98% of the dye within the first 20 min of contact time. The maximum sorption capacity of the magnetic nanoparticles (MNPs) for AO was 59mg/g. The sorption isotherms fit well with the Freundlich model. The sorption kinetics fits well the pseudo-second-order rate equation model. 60-90% dye recovery was achieved by rotary evaporating the dye bearing nanoparticles in acetone. The nanoparticles were recycled for additional dye removal.
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Possible Impact of Vitamin D Status and Supplementation on SARS-CoV-2 Infection Risk and COVID-19 Symptoms in a Cohort of Patients with Inflammatory Bowel Disease. The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (anti-spike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease (p = 0.019), while a VD level higher than 30 ng/mL (p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic.
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Different behavioural patterns induced by the dopamine agonist apomorphine analysed by multivariate statistics. Exploratory behaviour was recorded in an automatic holeboard apparatus measuring activity, locomotion, rearing, hole exploration and corner restricted behaviour. Multivariate statistical methods were used to analyse the results. Low doses of the dopamine agonist apomorphine (0.01-0.1 mg/kg SC) dose-dependently reduced most variables measured, although the pattern of behaviour resembled that of normal animals. High doses of apomorphine (0.2-1.0 mg/kg SC) induced a qualitative change in the pattern of behaviour with a stereotyped locomotion and a reduced mean time of exploration of holes. The described methods for detection and statistical analysis of behaviour differentiates between the behavioural patterns induced by high and low doses of apomorphine and may be useful in finding and analysing patterns of drug induced behaviour related to various mechanisms of action.
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Persistent activation of central amygdala CRF neurons helps drive the immediate fear extinction deficit. Fear extinction is an active learning process whereby previously established conditioned responses to a conditioned stimulus are suppressed. Paradoxically, when extinction training is performed immediately following fear acquisition, the extinction memory is weakened. Here, we demonstrate that corticotrophin-releasing factor (CRF)-expressing neurons in the central amygdala (CeA) antagonize the extinction memory following immediate extinction training. CeA-CRF neurons transition from responding to the unconditioned stimulus to the conditioned stimulus during the acquisition of a fear memory that persists during immediate extinction training, but diminishes during delayed extinction training. Inhibition of CeA-CRF neurons during immediate extinction training is sufficient to promote enhanced extinction memories, and activation of these neurons following delay extinction training is sufficient to reinstate a previously extinguished fear memory. These results demonstrate CeA-CRF neurons are an important substrate for the persistence of fear and have broad implications for the neural basis of persistent negative affective behavioral states.
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Large-scale production of endotoxin-free plasmids for transient expression in mammalian cell culture. Transient expression of recombinant proteins in mammalian cell culture in a 100-L scale requires a large quantity of plasmid that is very labour intensive to achieve with shake flask cultures and commercially available plasmid purification kits. In this paper we describe a process for plasmid production in 100-mg scale. The fermentation is carried out in a 4-L fed-batch culture with a minimal medium. The detection of the end of batch and triggering the exponential (0.1 h(-1)) feed profile was unattended and controlled by Multi-fermenter Control System. A restricted specific growth rate in fed-batch culture increased the specific plasmid yield compared to batch cultures with minimal and rich media. This together with high biomass concentration (68-107 g L(-1) wet weight) achieves high volumetric yields of plasmid (95-277 mg L(-1) depending on the construct). The purification process consisted of alkaline lysis, lysate clarification and ultrafiltration, two-phase extraction with Triton X-114 for endotoxin removal, anion-exchange chromatography as a polishing step, ultrafiltration and sterile filtration. Both fermentation and purification processes were used without optimisation for production of four plasmids yielding from 39 to 163 mg of plasmids with endotoxin content of 2.5 EU mg(-1) or less.
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Permethrin-induced oxidative stress and toxicity and metabolism. A review. Permethrin (PER), the most frequently used synthetic Type I pyrethroid insecticide, is widely used in the world because of its high activity as an insecticide and its low mammalian toxicity. It was originally believed that PER exhibited low toxicity on untargeted animals. However, as its use became more extensive worldwide, increasing evidence suggested that PER might have a variety of toxic effects on animals and humans alike, such as neurotoxicity, immunotoxicity, cardiotoxicity, hepatotoxicity, reproductive, genotoxic, and haematotoxic effects, digestive system toxicity, and cytotoxicity. A growing number of studies indicate that oxidative stress played critical roles in the various toxicities associated with PER. To date, almost no review has addressed the toxicity of PER correlated with oxidative stress. The focus of this article is primarily to summarise advances in the research associated with oxidative stress as a potential mechanism for PER-induced toxicity as well as its metabolism. This review summarises the research conducted over the past decade into the reactive oxygen species (ROS) generation and oxidative stress as a consequence of PER treatments, and ultimately their correlation with the toxicity and the metabolism of PER. The metabolism of PER involves various CYP450 enzymes, alcohol or aldehyde dehydrogenases for oxidation and the carboxylesterases for hydrolysis, through which oxidative stress might occur, and such metabolic factors are also reviewed. The protection of a variety of antioxidants against PER-induced toxicity is also discussed, in order to further understand the role of oxidative stress in PER-induced toxicity. This review will throw new light on the critical roles of oxidative stress in PER-induced toxicity, as well as on the blind spots that still exist in the understanding of PER metabolism, the cellular effects in terms of apoptosis and cell signaling pathways, and finally strategies to help to protect against its oxidative damage.
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Bicycloheptylamine-Doxorubicin Conjugate: Synthesis and Anticancer Activities in σ2 Receptor-Expressing Cell Lines. BACKGROUND Novel bicycloheptylamines were designed and synthesized. These compounds were found to be selective for sigma-2 receptors. These receptors have been found to be up to 10 fold over-expressed in certain cancer cell lines, leading to investigation of possible uses as a biomarker in diagnosis and/or treatment especially in cancers with poor prognosis. OBJECTIVES The aim was to conjugate a novel sigma-2 receptor ligand to doxorubicin to examine anticancer activities, with and without conjugation, and therefore possibilities in drug delivery. METHODS Conjugation was conducted using N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide HCl as a coupling agent. Affinity towards the sigma-2 receptor was tested using ligand-receptor binding studies. Anticancer activities against cancer cell lines were carried out using cell viability assays. Caspase dependency was tested using Z-VAD-FMK, a pan-caspase inhibitor, to begin to investigate mechanisms of action. RESULTS The target compound retained affinity towards the sigma-2 receptor and exhibited potent anticancer activities on cancer cell lines expressing the sigma-2 receptor. The potencies exceeded those of doxorubicin, the lead sigma-2 receptor ligand, as well as non-covalent combination of both drugs. The activity was also found to be caspase-dependent. CONCLUSION The conjugation of target bicycloheptylamines with cytotoxic moieties may yield potent and selective molecules for detection and/or treatment of certain cancers.
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Clinical outcomes following different stenting techniques for coronary bifurcation lesions: a systematic review and network meta-analysis of randomised controlled trials. BACKGROUND Controversy still exists regarding the optimal treatment of coronary bifurcation lesions. AIMS We aimed to analyse the evidence from randomised controlled trials (RCTs) to compare outcomes following different bifurcation stenting techniques. METHODS We systematically searched for RCTs comparing different techniques published up to July 2022. We then conducted a pairwise meta-analysis to compare outcomes between provisional stenting (PS) versus upfront 2-stent techniques. Moreover, we performed a network meta-analysis (NMA) to compare all strategies with each other. The primary endpoint was major adverse cardiac events (MACE). RESULTS Twenty-four RCTs (6,890 patients) analysed PS, T-stenting, double-kissing (DK)-crush, crush, or culotte stenting. The pairwise meta-analysis did not reveal a significant difference between the PS and 2-stent techniques. However, the prespecified sensitivity analysis, which included RCTs exclusively enrolling patients with true bifurcation lesions, showed a lower rate of MACE following 2-stent techniques, and meta-regression indicated that a longer side branch lesion was associated with a greater benefit from the 2-stent strategy, which was the most apparent in RCTs with a mean lesion length >11 mm. NMA revealed that DK-crush was associated with the lowest MACE rate (odds ratio 0.47, 95% confidence interval: 0.36-0.62; p<0.01; PS as a reference). CONCLUSIONS Overall, 2-stent techniques were not significantly better than PS in terms of clinical outcomes. However, the results of the sensitivity analysis suggested that there might be a benefit of a 2-stent approach in selected patients with true bifurcation lesions, especially in the case of long side branch lesions. An NMA revealed that DK-crush was associated with the lowest event rates when compared with other techniques.
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Experimental Studies on Lateral Root Formation in Radish Seedling Roots: II. Analysis of the Dose-Response to Exogenous Auxin. Application of indoleacetic acid (IAA) and other auxins causes cultured radish (Raphanus sativus L. ;Scarlet Globe') seedling root segments to produce an increased frequency (FR, no. cm(-1)) of lateral roots (LR); in the absence of auxin, segments spontaneously form about 6 LR cm(-1). A dose-response study has revealed that the increase in FR follows a biphasic Michaelis-Menten relationship with the medium concentration of the undissociated form of IAA ([IAAH](m)). The fitted curve for phase I has a maximum response level (R(max)) of 5.2 LR per centimeter above the spontaneous FR; the [IAAH](m) giving half-maximal response (C(1/2)) is 21 nanomolar. For phase II, the values for R(max) and C(1/2) are 56 LR per centimeter and 11 micromolar, respectively. The response is variable in the transition concentration region between the two phases; in that region (but not, or much less commonly, at higher or lower [IAAH](m)), LR initiation may resume or continue after the first day. At and above 100 micromolar [IAAH](m), the roots are hyperstimulated and generally fail to respond. The developmental stage of LR formed in medium with very low [IAAH](m) (10 nanomolar) is enhanced compared to LR formed in medium lacking auxin; the stage is diminished at higher auxin levels, in inverse correlation with FR. Trends in the responses to NAA and IBA were similar, but NAA required only 0.03 times the dose of IAA, while IBA required 6 times the dose of IAA. These findings may be of use in a search for possible auxin receptors involved with LR initiation.
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Rationing Rotational Magnet Cochlear Implant Technology in a Single Payer Healthcare System. INTRODUCTION In a publicly funded health care system, fiscally responsible management of any program is required. This is especially pertinent as evolving technology and associated incremental costs, places pressure on device availability within a fixed funding envelope. The application of rotational magnet technology and associated escalating surgical wait times must be justified to patients and the single-payer system. We present a single cochlear implant center's attempt at a rationing schema for magnetic resonance compatible cochlear implantation. Contrasting approaches to rationing care are evaluated and deliberated. METHODS Based on a comparison of magnetic resonance imaging (MRI) rates within the general population to our cochlear implant (CI) cohort, we attempt the development of a decision-making schema that maximizes the number of patients to receive a CI while rationing the distribution of a rotational magnet technology to similarly situated individuals most likely to benefit. RESULTS We elect to provide rotational magnet technology to select patient cohorts. This is based on the dominant imaging needs of these populations and the probability of requiring recurrent imaging studies. We consider this an ethical approach grounded in the egalitarian principle of equality of opportunity within cohorts of patients. CONCLUSION Given finite resources, increasing per unit cost will unavoidably extend wait times for adult patients. Our approach does not afford similar implant devices for all patients, but rather all similarly situated individuals. Therefore, access to a scare medical resource requires program rigor and a formalized policy around candidacy for emergent technology.
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[Metabolism-reproduction interactions in domestic animals]. In farm animals as in human, reproduction is affected by changes in the level of energetic balance. The main factors that link metabolism and reproduction, like insulin, IGFs, glucose, FFA, leptin and NPY, act on hypothalamo-pituitary axis as well as on gonads by directly altering gametogenesis.
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Selected physicochemical properties of amniotic fluid according to week of pregnancy. BACKGROUND A hundred years ago, scientists believed that amniotic fluid is a yellowish hypotonic mixture of foetal urine and maternal transudate with peculiar odour. Current knowledge shows that it represents a dynamic, complex mixture of inorganic and organic compounds. OBJECTIVES Despite modern technological procedures, information is still lacking about the composition and properties of amniotic fluid. We focused on dynamics of selected physical and chemical properties of the amniotic fluid with the increasing gestational week. METHODS The physicochemical characteristics of 89 amniotic fluid samples were determined according to the week of pregnancy. The determination of pH, specific gravity, glucose and nitrites was performed immediately, at room temperature. RESULTS Our results show a significant negative correlation between week of pregnancy and semi-quantitative determined parameters of specific gravity (p < 0.001), pH (p < 0.01) and glucose (p < 0.001) values. Within the whole group of samples (n = 89), 29 % (n = 26) were nitrites positive (N+) and 71 % (n = 63) nitrites negative (N-). CONCLUSION In this study were determined basic parameters of amniotic fluid, which could be related to a wide range of pathological states (Tab. 2, Fig. 1, Ref. 27).
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Positive and Negative Emotion Regulation in Adolescence: Links to Anxiety and Depression. Emotion regulation skills develop substantially across adolescence, a period characterized by emotional challenges and developing regulatory neural circuitry. Adolescence is also a risk period for the new onset of anxiety and depressive disorders, psychopathologies which have long been associated with disruptions in regulation of positive and negative emotions. This paper reviews the current understanding of the role of disrupted emotion regulation in adolescent anxiety and depression, describing findings from self-report, behavioral, peripheral psychophysiological, and neural measures. Self-report studies robustly identified associations between emotion dysregulation and adolescent anxiety and depression. Findings from behavioral and psychophysiological studies are mixed, with some suggestion of specific impairments in reappraisal in anxiety. Results from neuroimaging studies broadly implicate altered functioning of amygdala-prefrontal cortical circuitries, although again, findings are mixed regarding specific patterns of altered neural functioning. Future work may benefit from focusing on designs that contrast effects of specific regulatory strategies, and isolate changes in emotional regulation from emotional reactivity. Approaches to improve treatments based on empirical evidence of disrupted emotion regulation in adolescents are also discussed. Future intervention studies might consider training and measurement of specific strategies in adolescents to better understand the role of emotion regulation as a treatment mechanism.
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Antimycobacterial activity in vitro of pigments isolated from Antarctic bacteria. In this study, we describe the antimycobacterial activity of two pigments, violacein, a purple violet pigment from Janthinobacterium sp. Ant5-2 (J-PVP), and flexirubin, a yellow-orange pigment from Flavobacterium sp. Ant342 (F-YOP). These pigments were isolated from bacterial strains found in the land-locked freshwater lakes of Schirmacher Oasis, East Antarctica. The minimum inhibitory concentrations (MICs) of these pigments for avirulent and virulent mycobacteria were determined by the microplate Alamar Blue Assay (MABA) and Nitrate Reductase Assay (NRA). Results indicated that the MICs of J-PVP and F-YOP were 8.6 and 3.6 μg/ml for avirulent Mycobacterium smegmatis mc²155; 5 and 2.6 μg/ml for avirulent Mycobacterium tuberculosis mc²6230; and 34.4 and 10.8 μg/ml for virulent M. tuberculosis H₃₇Rv, respectively. J-PVP exhibited a ~15 times lower MIC for Mycobacterium sp. than previously reported for violacein pigment from Chromobacterium violaceum, while the antimycobacterial effect of F-YOP remains undocumented. Our results indicate these pigments isolated from Antarctic bacteria might be valuable lead compounds for new antimycobacterial drugs used for chemotherapy of tuberculosis.
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[Feeding behavior, dietary sufficiency and nutritional status in children between 6 and 18 months]. INTRODUCTION Infant feeding has specific qualitative and quantitative characteristics. The influence of parents on food intake is crucial in the development of habits and an adequate nutritional state. OBJECTIVE To evaluate eating behavior, dietary characteristics, and nutritional status of children between 6 to 18 months. SUBJECTS AND METHOD Cross-sectional descriptive study in 199 children. Using convenience sampling, demographic and anthropometric data were recorded for nutritional status, and dietary history, through a 24-hour reminder for dietary behavior and food sufficiency. The Student's t-test and one-way ANOVA were applied for continuous variables and the chi-square test for the categori cal ones. RESULTS 54.8% were women. Regarding nutritional status, 21.1% were overweight and 7.6% obese. 56.8% of the children had meal numbers according to their age. The average energy intake was 652.9 ± 224.2 calories per day. The intake of energy and macronutrients was significantly higher in children not consuming breast milk and aged 12 to 18 months. The energy, lipids, and carbohydrates adequacy in girls was significantly higher than in boys. 83.1% of food consumption was habitual for this age group. CONCLUSION In eating behavior, we observed that 4 out of 10 children have meal numbers higher than suggested for their ages. Regarding dietary sufficiency, there is a higher intake in children with normal nutritional status, without breastfeeding, and between 12 and 18 months. Despite the high prevalence of obesity, it was lower than that observed at the national level.
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Idiopathic scoliosis: relations between the Cobb angle and the dynamical strategies when sitting on a seesaw. The aim of this study was to determine the influence of the severity of the spinal curve on the postural regulation when self-imposed disturbances occur in a seated position in anteroposterior (AP) and mediolateral (ML) orientations. Twelve female adolescents with a right thoracic scoliosis (Cobb = 30.4° ± 9.7) were included in this study. The ground reaction forces (GRF) were studied while the subjects were maintaining their sitting on a seesaw (ML or AP destabilisation). Five conditions were tested: eyes open; with additional loads placed onto the subject's right or left shoulder; or onto the subject's right or left pelvis. We tested the correlation between the Cobb angle and the postural parameters (index of performance and GRF variability) for each condition. When the destabilisation was AP, the Cobb angle was significantly correlated with GRF variability and anterior and concavity index of performance. Two conditions showed higher correlations: stabilisation with the concavity pelvis load (GRF variability) and the open eyes (index of performance). In contrast, whatever the condition tested was, no link was found when the destabilisations were applied in ML direction. The destabilisation in a seated position highlights the influence of the curve severity on the postural organisation. In seated position, the postural control strategies specific to the scoliotic patients were always correlated by severity of curve, especially when the destabilisation is applied in AP directions. This study showed that the unstable seating position can be considered as a pertinent paradigm to help finding a postural clinical index for adolescent idiopathic scoliosis.
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Effect of recombinant human interleukin-3 on haematological recovery from chemotherapy-induced myelosuppression. Patients with non-small-cell lung cancer (NSCLC) were treated with ICE chemotherapy (ifosfamide 2000 mg/m2, days 1-3; carboplatin 300 mg/m2, day 1; etoposide 75 mg/m2, days 1-3) intravenously (i.v.) during the first 3 d of a maximum of four 28 d treatment cycles. Interleukin-3 (IL-3) was administered in cycles 2 and 4 as a daily subcutaneous (s.c.) injection on days 5-18. Cohorts of three patients were treated at dosage levels of 0.5, 1.25, 2.5, 5.0, 10.0 and 15.0 micrograms/kg/d. At 15.0 micrograms/kg/d a 'flu-like' syndrome of myalgias, arthralgias and fatigue was considered dose-limiting. Other toxicities were headache, fever, urticaria, arrhythmia, chills and flushing. Subsequently, nine patients were added to the group receiving 10 micrograms/kg/d. 27 patients received IL-3 after their second course of ICE. At 10 and 15 micrograms/kg/d, IL-3 in cycle 2 was associated with enhanced haematological recovery. Depth of neutrophil nadir and days of neutropenia (ANC < 0.5 x 10(9)/l) were reduced in 9/13 patients and in 8/11 patients, respectively. No effect was seen on platelet nadir or days of thrombocytopenia. IL-3 was well tolerated up to 10 micrograms/kg/d when given as a daily s.c. injection. Results suggest IL-3 as a potential adjunct to chemotherapy, and further studies to explore administration of IL-3 in combination with other cytokines in this setting are warranted.
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Evaluation of the efficacy of ozonated olive oil for controlling the growth of Alternaria alternata and its toxins. Toxigenic fungi infect fruits and vegetables either during harvest or storage and create mycotoxins as secondary metabolites, which pose a serious threat to human and animal health throughout the food chain. Therefore, the objective of this study was to determine the inhibitory effect of OZO against the growth and spore germination of the Alternaria alternata fungal strain. Additionally, evaluation of the synthesis inhibition of Alternaria toxins (ATs), among which are alternariol (AOH), alternariol-9-methyl ether (AME), and tenuazonic acid (TeA) in the potato dextrose broth (PDB) medium and orange fruit after harvest. The results indicated that the inhibition zone was 29.0 ± 1.2 mm at 20 mg/L of OZO. The MIC and MFC values were recorded at 0.186 and 1.57 mg/mL, respectively. In this regard, OZO prevented conidia germination at 98.8% with the treatment of 5 mg/mL. OZO at 20 mg/mL was efficacious in producing a high loss in ATs production in the PDB medium, reaching 73.4, 76, and 67.1% for AOH, AME, and TeA, respectively. In addition, OZO prevents the biosynthesis of AOH and AME during the storage of orange fruits compared with the positive control sample. In contrast, 20 mg/mL reduced TeA accumulation and the appearance of Alternaria brown spot (ABS) in orange. To the best of our knowledge, this is the first report that studies OZO to control ATs in vitro in orange fruits.
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A non-bilaterian perspective on the development and evolution of animal digestive systems. Digestive systems and extracellular digestion are key animal features, but their emergence during early animal evolution is currently poorly understood. As the last common ancestor of non-bilaterian animal groups (sponges, ctenophores, placozoans and cnidarians) dates back to the beginning of animal life, their study and comparison provides important insights into the early evolution of digestive systems and functions. Here, I have compiled an overview of the development and cell biology of digestive tissues in non-bilaterian animals. I will highlight the fundamental differences between extracellular and intracellular digestive processes, and how these are distributed among animals. Cnidarians (e.g. sea anemones, corals, jellyfish), the phylogenetic outgroup of bilaterians (e.g. vertebrates, flies, annelids), occupy a key position to reconstruct the evolution of bilaterian gut evolution. A major focus will therefore lie on the development and cell biology of digestive tissues in cnidarians, especially sea anemones, and how they compare to bilaterian gut tissues. In that context, I will also review how a recent study on the gastrula fate map of the sea anemone Nematostella vectensis challenges our long-standing conceptions on the evolution of cnidarian and bilaterian germ layers and guts.
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Pain in the left ear as the presenting symptom of acute myocardial infarction in a renal transplant recipient. Chest pain is the main presenting symptom in patients with acute myocardial infarction. However, many patients present with atypical symptoms, which may delay proper diagnosis and treatment. We present the first documented case of pain in the left ear as an atypical presentation of acute myocardial infarction 5 days after renal transplantation.
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Neonatal exposure of 17β-estradiol has no effects on mutagenicity of 7,12-dimethylbenz [a] anthracene in reproductive tissues of adult mice. INTRODUCTION Biological studies in animals and epidemiological findings in humans clearly demonstrate that estrogens including 17β-estradiol (E2) are weak carcinogens via both genetic and epigenetic mechanisms. Carcinogenesis analyses have indicated that female mice exposed to E2 as neonates develop more mammary and ovarian tumors when compared to adult exposures. In the present study, Big Blue transgenic mice were used to investigate the effects of E2 on mutagenicity of 7,12-dimethylbenz [a] anthracene (DMBA), a genotoxic carcinogen, in mammary gland and ovary following neonatal exposure. RESULTS DMBA treatment resulted in significant increases in cII mutant frequencies (MFs) in both mammary glands and ovaries, with A:T → T:A transversion as the predominant type of mutation. However, co-exposure to E2 daily for the first 5 days after birth and to DMBA at 6 months of age did not significantly increase cII MFs compared to DMBA treatment alone. Further, there were also no significant differences in mutational spectra between DMBA exposure alone and E2 + DMBA treatment. CONCLUSION These results suggest that early life exposures of mice to estrogens like E2 do not enhance mutagenicity by subsequent exposure to a chemical like DMBA in later life.
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CXCL16 and oxLDL are induced in the onset of diabetic nephropathy. Diabetic nephropathy (DN) is a major cause of end-stage renal failure worldwide. Oxidative stress has been reported to be a major culprit of the disease and increased oxidized low density lipoprotein (oxLDL) immune complexes were found in patients with DN. In this study we present evidence, that CXCL16 is the main receptor in human podocytes mediating the uptake of oxLDL. In contrast, in primary tubular cells CD36 was mainly involved in the uptake of oxLDL. We further demonstrate that oxLDL down-regulated alpha(3)-integrin expression and increased the production of fibronectin in human podocytes. In addition, oxLDL uptake induced the production of reactive oxygen species (ROS) in human podocytes. Inhibition of oxLDL uptake by CXCL16 blocking antibodies abrogated the fibronectin and ROS production and restored alpha(3) integrin expression in human podocytes. Furthermore we present evidence that hyperglycaemic conditions increased CXCL16 and reduced ADAM10 expression in podocytes. Importantly, in streptozotocin-induced diabetic mice an early induction of CXCL16 was accompanied by higher levels of oxLDL. Finally immunofluorescence analysis in biopsies of patients with DN revealed increased glomerular CXCL16 expression, which was paralleled by high levels of oxLDL. In summary, regulation of CXCL16, ADAM10 and oxLDL expression may be an early event in the onset of DN and therefore all three proteins may represent potential new targets for diagnosis and therapeutic intervention in DN.
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Retriever195
[Relations between sinus aspergillosis, primary rhinoliths and dental pathology]. Sinus aspergilloses, which can be classified as aspergillar sinusitis and pseudo-tumoral forms, are probably much more prevalent than would appear form the published literature. Many cases of caseous sinusitus reported since the end of the last century were probably unrecognized aspergillosis infections. In the same way, primary rhinoliths can probably be related to aspergillosis. Many cases of sinus aspergillosis appear to be of dental origin, particularly when radiography detects the presence of dental obturation paste in the sinus opacity: this appearance in the sinus opacity: this appearance is almost pathognomic of the affection. Sinus aspergillosis should be recognized as recovery can be obtained in the majority of cases by simple sinus washouts, without the need for chemotherapy.
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Retriever196
Dose-dependent effects of 1O2 in chloroplasts are determined by its timing and localization of production. In plants, highly reactive singlet oxygen (1O2) is known to inhibit photosynthesis and to damage the cell as a cytotoxin. However, more recent studies have also proposed 1O2 as a signal. In plants under stress, not only 1O2 but also other reactive oxygen species (ROS) are generated simultaneously, thus making it difficult to link a particular response to the release of 1O2 and establish a signaling role for this ROS. This obstacle has been overcome by the identification of conditional mutants of Arabidopsis thaliana that selectively generate 1O2 and trigger various 1O2-mediated responses. In chloroplasts of these mutants, chlorophyll or its biosynthetic intermediates may act as a photosensitizer and generate 1O2. These 1O2-mediated responses are not only dependent on the dosage of 1O2 but also are determined by the timing and suborganellar localization of its production. This spatial- and temporal-dependent variability of 1O2-mediated responses emphasizes the importance of 1O2 as a highly versatile and short-lived signal that acts throughout the life cycle of a plant.
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Pharmacokinetics and Tolerability of a New Hydroxyethyl Starch (HES) Specification [HES (130/0.4)] after Single-Dose Infusion of 6% or 10% Solutions in Healthy Volunteers. OBJECTIVE To investigate the pharmacokinetic profile and tolerability of a single-dose infusion of the new hydroxyethyl starch (HES) specification, HES (130/0.4), 6% and 10% solutions in healthy volunteers. STUDY DESIGN In an open, randomised, single-dose, parallel-group study, 12 healthy volunteers (in each group) received intravenous infusions of 500ml of a new HES specification [HES (130/0.4)] of either 6% or 10% solution within 30 minutes. RESULTS Plasma elimination initially occurred with an alpha half-life of approximately 0.5 to 0.75 hour. A half-life of approximately 12 hours was reported for the terminal phase. Between 60 to 70% of the total plasma elimination was due to renal excretion. The total plasma clearances of 31.4 ml/min and 26.0 ml/min for the 6 and 10% solutions, respectively, were higher than those reported for other HES specifications. The volume of distribution in the central compartment was approximately 5.9L, which roughly corresponded to the blood volume. Single doses of 6% and 10% HES (130/0.4) were well tolerated. CONCLUSION The new HES specification demonstrated favourable pharmacokinetic properties compared with other HES specifications of medium or high molecular weight. No clinically relevant plasma accumulation and related undesired effects on haemostasis are expected to occur under multiple-dose conditions.
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Occupational exposure of health care personnel to hepatitis B and hepatitis C: prevention and surveillance strategies. Ensuring the safety of personnel working in health care environments can be challenging and requires a multifaceted approach to target reductions in occupational exposures to blood-borne pathogens, such as hepatitis B or hepatitis C. This article reviews the epidemiology of occupational exposures to hepatitis B and hepatitis C in health care personnel in hospital settings. The nature and likelihood of risk to health care personnel are evaluated along with estimates of seroconversion risk. The review focuses on prevention programs and available surveillance programs to aid in monitoring and reducing occupational exposures to blood-borne pathogens.
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Revealing the Effect of Skull Deformation on Intracranial Pressure Variation During the Direct Interaction Between Blast Wave and Surrogate Head. Intracranial pressure (ICP) during the interaction between blast wave and the head is a crucial evaluation criterion for blast-induced traumatic brain injury (bTBI). ICP variation is mainly induced by the blast wave transmission and skull deformation. However, how the skull deformation influences the ICP remains unclear, which is meaningful for mitigating bTBI. In this study, both experimental and numerical models are developed to elucidate the effect of skull deformation on ICP variation. Firstly, we performed the shock tube experiment of the high-fidelity surrogate head to measure the ICP, the blast overpressure, and the skull surface strain of specific positions. The results show that the ICP profiles of all measured points show oscillations with positive and negative change, and the variation is consistent with the skull surface strain. Further numerical analysis reveals that when the blast wave reaches the measured point, the peak overpressure transmits directly through the skull to the brain, forming the local positive ICP peak, and the impulse induces the local inward deformation of the skull. As the peak overpressure passes through, the blast impulse impacts the nearby skull supported by the soft and incompressible brain tissue and extrudes the skull outward in the initial position. The inward and outward skull deformation leads to the oscillation of ICP. These numerical analyses agree with experimental results, which explain the appearance of negative and positive ICP peaks and the synchronization of negative ICP with surface strain. The study has implications for medical injury diagnosis and protective equipment design.
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