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Retriever200
Brain imaging in drug R&D. Magnetic resonance imaging (MRI), used as a clinical diagnostic tool since the early 1980s, is rapidly gaining traction as an integral part of the drug development process. Brain imaging research spans a wide area, covering both structure and function, and ranging from the physics and physiology associated with novel acquisition techniques, to the development of sophisticated image processing algorithms. This paper briefly describes two methods on either end of this spectrum: the "pipeline" framework for the fully automated morphometric analysis of brain imaging data, and molecular MRI, which holds promise for the non-invasive detection of molecular targets of new pharmacological compounds. The potential use of these technologies is illustrated by examples of their applications in multiple sclerosis, Alzheimer's disease, and oncology.
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Retriever201
Urea electrolysis: direct hydrogen production from urine. A new technology has been developed that accomplishes the direct conversion of urine and urea to pure hydrogen via electrochemical oxidation with an inexpensive nickel catalyst.
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Retriever202
[Evaluation of the BD Phoenix ID Yeast System for the Species Identification of Clinical Yeast-Like Organisms]. Most fungi isolated from patients with deep-seated mycosis are yeast-like organisms such as Candida and Cryptococcus. As their respective susceptibilities to antifungal agents can vary depending on the species, rapid identification is important for the administration of appropriate antifungal therapy. The aim of this study was to evaluate the performance of a new automated identification panel, Phoenix Yeast ID (Becton, Dickinson Diagnostics, USA) as well as the time required for identification. The identification results of 106 isolates generated by this system were then compared with those of the API 20C AUX system (SYSMEX bioMérieux Co., Ltd. Japan). Among the 106 isolates, the identification agreement between the two yeast panels was 97/106 (91.5%). Of the 9 (8.5%) discrepant identifications, 5 identification using the Phoenix Yeast ID system and 1 identification using the API 20C AUX system agreed with the genotypic identification. Genotypic identification did not agree with the Phoenix Yeast ID or API 20C AUX findings for the remaining 3 discrepant identifications. Approximately 60% of the C. albicans, C. tropicalis, and C. parapsilosis isolates were identified within 4 hours. In total, about 90% of the 4 major Candida sp. (C. albicans, C. tropicalis and C. glabrata) were identified within 8 hours. In conclusion, the Phoenix Yeast ID findings agreed well with the API 20C AUX findings. Genotypic identification of the discrepant identifications confirmed most of the Phoenix Yeast ID panel identifications. As approximately 80% of the major Candida sp. could be identified within 8 hours using the Phoenix Yeast ID identification system, our results suggest that this system is a clinically useful addition to commercially available yeast identification panels. The Phoenix Yeast ID system showed excellent concordance with genotypic identification for the classification of organisms with discrepant API 20C AUX findings.
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Retriever203
Regulation of gene expression in astrocytes by excitatory amino acids. We have studied the effect of excitatory amino acids on the expression of mRNA for the immediate early genes c-fos, c-jun, jun-B, and NGF-1A in isolated cortical astrocytes. The expression of the different genes was induced by 100 microM kainate, quisqualate, AMPA and high concentrations of K+ (140 mM). NMDA did not induce the expression of any of the genes studied. The effect of quisqualate stimulation was not inhibited by the antagonist CNQX or by withdrawal of external Ca2+. In contrast the kainate effect was abolished by CNQX but not by the removal of external Ca2+. However, elevated K+ induced c-fos only when calcium was present in the external medium. These findings suggest that type-1 astrocytes lack NMDA receptors and that the induction of genes by quisqualate and kainate is in part independent of the presence of calcium in the external medium and may be mediated through second messenger pathways.
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Retinopathy of Prematurity Screening of Preterm Infants With Icteric Vitreous. Purpose: To present 2 cases of premature newborns with hyperbilirubinemia and retinopathy of prematurity (ROP) who could not be examined properly to assess for disease progression because of vitreous opacification in the setting of an icteric vitreous and frail health status. Methods: The cases and their findings were analyzed. Results: Given the sickness of the neonates and examination difficulty, intravitreal bevacizumab was administered in both eyes to prevent disease progression. During subsequent examinations, the patients remained stable until discharge from the neonatal intensive care unit and were followed in the outpatient clinic without complication. Conclusions: The ROP and vitreous opacification in our cases were thought to be caused by hyperbilirubinemia. Because of vitreous opacification, these patients could not be properly examined for ROP. Treatment with an intravitreal antivascular endothelial growth factor injection might be considered to delay disease development until the newborn is healthier and able to be examined.
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Integrated Module of Multidimensional Omics for Peripheral Biomarkers (iMORE) in patients with major depressive disorder: rationale and design of a prospective multicentre cohort study. INTRODUCTION Major depressive disorder (MDD) represents a worldwide burden on healthcare and the response to antidepressants remains limited. Systems biology approaches have been used to explore the precision therapy. However, no reliable biomarker clinically exists for prognostic prediction at present. The objectives of the Integrated Module of Multidimensional Omics for Peripheral Biomarkers (iMORE) study are to predict the efficacy of antidepressants by integrating multidimensional omics and performing validation in a real-world setting. As secondary aims, a series of potential biomarkers are explored for biological subtypes. METHODS AND ANALYSIS iMore is an observational cohort study in patients with MDD with a multistage design in China. The study is performed by three mental health centres comprising an observation phase and a validation phase. A total of 200 patients with MDD and 100 healthy controls were enrolled. The protocol-specified antidepressants are selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Clinical visits (baseline, 4 and 8 weeks) include psychiatric rating scales for symptom assessment and biospecimen collection for multiomics analysis. Participants are divided into responders and non-responders based on treatment response (>50% reduction in Montgomery-Asberg Depression Rating Scale). Antidepressants' responses are predicted and biomarkers are explored using supervised learning approach by integration of metabolites, cytokines, gut microbiomes and immunophenotypic cells. The accuracy of the prediction models constructed is verified in an independent validation phase. ETHICS AND DISSEMINATION The study was approved by the ethics committee of Shanghai Mental Health Center (approval number 2020-87). All participants need to sign a written consent for the study entry. Study findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT04518592.
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Controllable Synthesis of Surface Pt-Rich Bimetallic AuPt Nanocatalysts for Selective Hydrogenation Reactions. Bimetallic nanocatalysts, with efficient and controllable catalytic performance, have a promising application in chemical production. In this study, surface Pt-rich bimetallic AuPt nanoparticles with different Pt/Au ratios were prepared and tested in selective hydrogenation reactions of substituted nitroaromatics. Au nanoparticles were first prepared with n-butyllithium as a rapid reducer, which were further used as seeds in the slow growth process of Pt atoms. Because of the employed sequential reduction method and the following atom diffusion, surface Pt-rich bimetallic AuPt nanoparticles were obtained. Compared with the uniform AuPt alloy nanocatalysts synthesized by the co-reduction method with n-butyllithium as the reducer and monometallic Pt nanocatalysts, the obtained surface Pt-rich AuPt bimetallic nanocatalysts presented an enhanced catalytic selectivity or activity. The performance enhancement is assigned to the optimized Au/Pt interaction in the surface Pt-rich bimetallic nanostructures. This work demonstrates that the optimization of the stoichiometry and construction of bimetallic materials is a feasible method to synthesize controllable and efficient nanocatalysts.
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Retriever207
Impaired grasping in a patient with optic ataxia: primary visuomotor deficit or secondary consequence of misreaching? Optic ataxia is defined as a spatial impairment of visually guided reaching, but it is typically accompanied by other visuomotor difficulties, notably a failure to scale the handgrip appropriately while reaching to grasp an object. This impaired grasping might reflect a primary visuomotor deficit, or it might be a secondary effect arising from the spatial uncertainty associated with poor reaching. To distinguish between these possibilities, we used a new paradigm to tease apart the proximal and distal components of prehension movements. In the "far" condition objects were placed 30 cm from the hand so that subjects had to make a reaching movement to grasp them, whereas in the "close" condition objects were placed adjacent to the hand, thereby removing the need for a reaching movement. Stimulus eccentricity was held constant. We tested a patient with optic ataxia (M.H.), whose misreaching affects only his right hand within the right visual hemifield. M.H. showed a clear impairment in grip scaling, but only when using his right hand to grasp objects in the right visual hemifield. Critically, this grip-scaling impairment was absent in M.H. in the "close" condition. These data suggest that M.H.'s grip scaling is impaired as a secondary consequence of making inaccurate reaching movements, and not because of any intrinsic visuomotor impairment of grasping. We suggest that primary misgrasping is not a core symptom of the optic ataxia syndrome, and that patients will show a primary deficit only when their lesion extends anteriorly within the intraparietal sulcus to include area aIPS.
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Retriever208
Preclinical Evaluation of ADVM-022, a Novel Gene Therapy Approach to Treating Wet Age-Related Macular Degeneration. Inhibition of vascular endothelial growth factor, a key contributor to the choroidal neovascularization associated with wet age-related macular degeneration, is the mode of action of several approved therapies, including aflibercept, which requires frequent intravitreal injections to provide clinical benefit. Lack of compliance with the dosing schedule may result in recurrence of active wet macular degeneration, leading to irreversible vision impairment. Gene therapy providing sustained anti-vascular endothelial growth factor levels in the retina following a single injection could drastically reduce the treatment burden and improve visual outcomes. ADVM-022, an adeno-associated virus vector encoding aflibercept, is optimized for intravitreal delivery and strong protein expression. Here, we report the long-term expression and efficacy of ADVM-022-derived aflibercept in a laser-induced choroidal neovascularization model in non-human primates. Intravitreal administration of ADVM-022 was well tolerated and resulted in sustained aflibercept levels. In addition, ADVM-022 administration 13 months before lasering prevented the occurrence of clinically relevant choroidal neovascularization lesions, similar to animals that received a bolus of intravitreal aflibercept (standard of care) at the time of lesioning. These results demonstrate that a single intravitreal administration of ADVM-022 may provide a safe and effective long-term treatment option for wet macular degeneration and may ultimately improve patients' visual outcomes.
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Retriever209
Automated determination of angiotensin-converting enzyme in serum. This is an adaptation of the Fujirebio "ACEcolor" kit for automated measurement of angiotensin-converting enzyme (EC 3.4.15.1) in serum with the Cobas Fara centrifugal analyzer. The linear range extends to an activity of 110 U/L. Results obtained by the present method and by the manual method were identical, and correlated closely (r = 0.983) with those by Cushman's modified method. The reference interval for 77 adult blood-bank donors was 9-25 U/L (mean 17, SD 4 U/L). Within-run and between-run CVs are 1.7 and 4.0%, respectively. The present method permits rapid, precise, and economical measurement of the enzyme and allows users of a Cobas Fara centrifugal analyzer to introduce a fully automated assay for angiotensin-converting enzyme into their clinical laboratory.
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Retriever210
Structural characteristics of the alloantigens determined by the major histocompatibility complex of the guinea pig. The GPLA B and Ia (I region-associated) antigens are the products of genes found in the guinea pig major histocompatibility complex. Because of their importance in immune response phenomena, a structural study of these antigens was undertaken. [3H]leucine and [3H]fucose were internally incorporated into guinea pig lymph node cells. The GPLA B and Ia antigens were solubilized by the nonionic detergent Nonidet P-40, purified by affinity chromatography using an adsorbent column of lentil lectin, isolated by immunoprecipitation, and examined by discontinuous polyacrylamide-sodium dodecyl sulfate gel electrophoresis. The GPLA antigens B.1, B.2, B.3, and B.4, were shown to be glycoproteins of mol wt 40,000 daltons and to be noncovalently associated with a 12,000 dalton protein. The molecules bearing B.2 and B.3 in a B.2/B.3 heterozygote are shown to be separable, suggesting the antigenic determinant is a primary gene product. In addition, a new GPLA determinant, S, which resembles the B antigen in that it is found on a molecule of approximately 40,000 daltons, was studied. In a B.2/B.3 S+ animal the molecule bearing antigen S was shown to be independent of those bearing B.2 and B.3, providing evidence that the genes determining B and S are at separate loci. The Ia-bearing molecules identified by anti-Ia.2,4 are glycoproteins of mol wt 58,000 daltons which are composed of two subunits of 33,000 and 25,000 daltons, respectively, linked by disulfide bonds. The Ia-bearing molecules are independent of GPLA-bearing molecules, indicating different loci determining these antigens. By all criteria, the guinea pig GPLA B antigens appear homologous to the murine H-2D and H-2K antigens, while the guinea pig Ia antigens appear homologous to the Ia antigens of the mouse.
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Retriever211
Factors associated with the instability of nitrate-insensitive proton transport by maize root microsomes. Proton transport catalyzed by the nitrate-insensitive, vanadate-sensitive H(+)-ATPase in microsomes from maize (Zea mays L.) roots washed with 0.25 molar KI decreased as a function of time at 0 to 4 degrees C. The rate of proton transport was approximately one-half of that by freshly isolated microsomes after 6 to 18 hours of cold storage. The decrease in proton transport coincided with losses in membrane phosphatidylcholine and was not associated with a change in vanadate-sensitive ATP hydrolysis. A technique based on a protocol developed for the reconstitution of Neurospora crassa plasma membrane H(+)-ATPase (DS Perlin, K Kasamo, RJ Brooker, CW Slayman 1984 J Biol Chem 259: 7884-7892) was employed to restore proton transport activity to maize microsomes. These results indicated that the decline in proton transport by maize root membranes during cold storage was not due to degradation of the protein moiety of the H(+)-ATPase, but was due to the loss of phospholipids.
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Retriever212
Iridoid glycoside sequestration by two aposematicPenstemon-feeding geometrid larvae. The iridoid glycoside catalpol was found to be sequestered by larvae ofMeris alticola feeding onPenstemon virgatus and by larvae ofNeoterpes graefiaria which utilizeP. barbatus. The strikingly similar larval patterns of these two ennomine geometrids were previously considered to be disruptive, but predator-based Mullerian mimicry is equally likely to be involved. The cryptic adult moths generally contain only small amounts of catalpol, having left most of the bitter iridoid in the pupal case and in the meconium excreted after eclosion. OneNeoterpes female did contain considerable catalpol in the abdomen, presumably in the eggs.
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Retriever213
Protein/peptide transduction in metanephric explant culture. While gene targeting methods have largely supplanted cell/explant culture models for studying developmental processes, they have not eliminated the need for or value of such approaches in the investigator's technical arsenal. Explant culture models, such as those devised for the metanephric kidney and its progenitors, remain invaluable as tools for screening regulatory factors involved in tissue induction or in the inhibition of progenitor specification. Thus, some factors capable of inducing tissue condensations or nephronic tubule formation in explants of metanephric mesenchyme have been identified through direct treatment of cultures rather than lengthy genetic engineering in animals. Unfortunately, renal progenitors are largely refractory to most contemporary methods for gene manipulation, including transfection and viral transduction, so the applications of explant culture have been rather limited. However, methods for protein or peptide transduction offer greatly improved efficiencies for uptake and expression/regulation of proteins within cells and tissues. Biologically active TAT- or penetratin-fusion proteins/peptides are readily taken up by most cells in metanephric explants or monolayer cultured cells (Plisov et al., J Am Soc Nephrol 16:1632-1644, 2005; Osafune et al., Development 133:151-161, 2006; Wang et al., Cell Signal 22:1717-1726, 2010; Tanigawa, Dev Biol 352:58-69, 2011), allowing a direct functional evaluation of theoretically any protein, including biologically active enzymes and transcription factors, or any targeted interactive domain within a protein.
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Retriever214
On the nature of surface roughness with application to contact mechanics, sealing, rubber friction and adhesion. Surface roughness has a huge impact on many important phenomena. The most important property of rough surfaces is the surface roughness power spectrum C(q). We present surface roughness power spectra of many surfaces of practical importance, obtained from the surface height profile measured using optical methods and the atomic force microscope. We show how the power spectrum determines the contact area between two solids. We also present applications to sealing, rubber friction and adhesion for rough surfaces, where the power spectrum enters as an important input.
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Retriever215
Immunogenicity and reactogenicity of inactivated SARS-CoV-2 vaccines in healthy adults. Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly pathogenic to humans and has caused the ongoing coronavirus disease 2019 (COVID-19) pandemic. Vaccines are one of the efficient ways to prevent the viral infection. After COVID-19 vaccination, the monitoring of the dynamic change in neutralizing antibodies is necessary to determine booster requirements. Methods We estimated the effectiveness of the inactivated vaccines by monitoring dynamic SARS-CoV-2 neutralizing antibodies for over 2 years. Additionally, we also investigated the activation of T lymphocytes (CD3+ T cells) after three doses of the inactivated vaccine. Result The results showed that the rate of reduction of SARS-CoV-2 neutralizing antibody levels gradually showed after each booster dose. The IgG/IgM level at 9 months after the third vaccination were significantly higher than those at 6 months after the second dose (p<0.0001). The expression of CD25+T cell in 18-35 age group was significantly higher than that in the other groups. Nine months after the third dose (the time of last blood sample collection), the expression of CD25+T cell in the 18-35 age group was significantly higher than that at 6 months after the second dose. CD25+T cell in the 18-35 years old group was significantly higher than 6 months after the second vaccination. Conclusion CD25, a late activation marker of lymphocytes and high-activity memory T cell subgroup, exhibited higher levels at the later stages after vaccination. COVID-19 booster vaccination in older adults and regular testing of SARS-CoV-2 neutralizing antibodies are recommended. Booster doses should be administered if the antibody level falls below the 30% inhibition rate.
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Retriever216
Dwyer osteotomy for treatment of calcaneal varus. Treatment of varus deformity of the rearfoot is satisfactorily corrected with a lateral closing wedge osteotomy of the calcaneus. Whether the condition being treated is club foot, pes cavus deformity, or calcaneal varus alone, statistics show the varus component is consistently resolved with this osteotomy approach. A case report of calcaneal varus is presented, including a postoperative complication with resolution.
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Retriever217
A rare case of recurrent hydatid cyst of the spleen: A case report. Cystic echinococcosis (CE), or hydatid disease, is a parasitic infection caused by Echinococcus granulosus endemic to areas with considerable pastoral farming and animal husbandry. Typical presentations include hydatid cyst formation in the liver, lungs, brain, kidneys, or bones. An isolated splenic hydatid cyst is an extremely rare occurrence, accounting for only 0.5%-4% worldwide incidence rates, and recurrent cases are even more infrequent. Globalization, cross-border travel, and altered immigration patterns over time have shifted some of the burden of CE from the developing to the developed world, making the diagnosis challenging for these nonendemic areas. Judicious use of imaging modalities for prompt diagnosis and effective intervention is necessary to treat the initial disease and prevent a recurrence. Herein, we present the case of a 13-year-old male with recurrent isolated splenic hydatid cyst. The patient presented with chronic and nonradiating pain in his left hypochondrium. Physical examination revealed splenomegaly. Ultrasonography showed multiple cysts. Computerized tomography (CT) scan showed cystic lesions in splenic parenchyma with numerous internal enhancing septae. Surgical evacuation was performed for the management of disease.
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Retriever218
Catechol activation in rat rostral ventrolateral medulla after systemic isocapnic metabolic acidosis. The catechol signal recorded using in vivo voltammetry within the rat rostral ventrolateral medulla (RVLM) can be interpreted as a catechol-specific index of the integrated activity of RVLM adrenergic barosensitive bulbospinal and nonbulbospinal neurons. To test the hypothesis that systemic acidosis leads to the activation of RVLM adrenergic neurons, the RVLM catechol signal was observed in rats after mild systemic acidosis (pH 7.20-7.25 for 30 min) induced by 1 M HCl under halothane anesthesia, controlled mechanical ventilation, and continuous infusion of Ringer lactate. Particular attention was paid to ensure that changes in mean arterial pressure (MAP) were <15 mmHg during HCl challenge. Saline administration was not associated with any significant change in all considered variables (n = 5). Mild isocapnic systemic acidosis was associated with an increase in catechol signal (n = 5), irrespective of carotid sinus nerve section (n = 5). In keeping with the aim of the study, there were minor (<15 mmHg) but significant changes in MAP among saline, intact, and deafferented groups. Changes in heart rate were not significant. In conclusion, a catechol activation is observed in the RVLM when arterial pressure is maintained during isocapnic systemic metabolic acidosis. This catechol activation appears primarily centrally mediated. Therefore, adrenergic RVLM neurons may relay inputs from the central respiratory generator to the sympathetic system and/or act as chemosensors for H+ next to the surface of the ventrolateral medulla.
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Retriever219
[The Italian Registry of Vascular Access]. The Vascular Access Study Group of Italian Society of Nephrology has designed a National Register in order to create an archive that collects the data on vascular accesses more detailed than the mere indication of arteriovenous fistula with native vessels, prosthetic fistula and central venous catheter. The obstacles to such a project are represented by the absence of "uniformity" in the name of the arterovenous fistula, the difficulty in increasing the daily work of dialysis centers with another registry and finally by privacy concerns. In order to standardize the vascular accesses name the Study Group proposal is to eliminate any denomination and adopt a code-descriptive system, indicating the seat of the anastomosis (1/3 distal, middle and proximal forearm, arm or lower limb), the limb (if dominant or non-dominant), the vessels involved, the type of anastomosis and the number of interventions that the pt has undergone including the last one. In this way, uniformity and universality are guaranteed. Every aspect scribed will be a cell of a data base and can used to statistical analysis. The study group has set up a software (Gev@) in order to facilitate data storage. The software is based on a form compiled at the end of each surgical procedure. The form will then be archived in digital format thereby generating automatically the data base. The advantage of this system, is represented by the possibility of turning a routine medical procedure, namely the recording of a surgical procedure, in a data base exportable for the creation of the register. As regards the issue of privacy will be obtained the patient's consent to the processing of data and the register will be stored and managed according to the regulations in terms of privacy. In the coming months, after a time of testing, the software will be available to each italian dialisys center.
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Retriever220
Early-stage pathogenic sequence of jaw osteoradionecrosis in vivo. The mechanism underlying jaw osteoradionecrosis (ORN) is not fully understood, particularly in the early stages. To investigate bone and vessel pathogenesis in the early stages of jaw ORN, we generated a mandibular ORN model in miniature pigs (minipigs) by applying a combination of single-dose 25-Gy irradiation (IR) and tooth extraction. We studied 6 ORN model minipigs and 6 control, non-irradiated minipigs. We measured dynamic morphological changes, bone-remodeling-associated gene expression, sphingomyelinase activity, and local blood flow. Bone remodeling, including bone resorption and new bone formation, was observed within 15 days post-IR. Later, an ORN-related imbalance in bone metabolism gradually occurred, with loss of bone regeneration capacity, collagen collapse, and microvascular obliteration. Within 24 hrs post-IR, sphingomyelinase significantly increased in irradiated tissues. At 1 wk post-IR, local blood flow increased, but at 15 days post-IR, it significantly decreased to 50% below normal levels. This study provided details of the sequential occurrences in early-stage ORN in a large animal model. Our results suggested that reduced local blood flow and consequent hypovascularity may have caused an imbalance in bone remodeling. This suggested that microvessel damage may play a key role in the initiation of ORN.
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Retriever221
Developing An Analytic Approach to Understanding the Patient Care Experience. The amount of data available to health-care institutions regarding the patient care experience has grown tremendously. Purposeful approaches to condensing, interpreting, and disseminating these data are becoming necessary to further understand how clinical and operational constructs relate to patient satisfaction with their care, identify areas for improvement, and accurately measure the impact of initiatives designed to improve the patient experience. We set out to develop an analytic reporting tool deeply rooted in the patient voice that would compile patient experience data obtained throughout the medical center.
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Retriever222
Changes in permafrost extent and active layer thickness in the Northern Hemisphere from 1969 to 2018. Understanding the evolutions of the permafrost extent and active layer thickness (ALT) in the Northern Hemisphere (NH) are critical for global carbon flux simulation, climate change prediction, and engineering risk assessment. The temporal change characteristics of the permafrost extent and ALT for the NH have not been studied. We used the Kudryavtsev method, integrating a 0.5° × 0.5° spatial resolution of air temperature, soil texture, snow depth, vegetation type, soil volume moisture content, and organic content to simulate the changes of permafrost extent and ALT in the NH from 1969 to 2018. The results indicated that permafrost extent decreased from 23.25 × 106 km2 (average from 1969 to 1973) to 21.64 × 106 km2 (average from 2014 to 2018), with a linear rate of -0.023 × 106 km2/a. Siberia had the highest degradation rate of 0.014 × 106 km2/a, followed by Alaska, Mongolian Plateau, Qinghai-Tibet Plateau, Northern Canada, and Greenland, with linear rates of -0.012 × 106, -0.005 × 106, -0.004 × 106, -0.0014 × 106, and - 0.0004× 106 km2/a, respectively. The average ALT in the NH increased at a linear rate of 0.0086 m/a. Alaska and Mongolian Plateau had the highest thickening rate of 0.024 m/a, followed by Qinghai-Tibet Plateau, Siberia, Northern Canada, and Greenland, which had linear rates of 0.009, 0.008, 0.0072, and 0.003 m/a, respectively. The uncertainty of the results could be attributed to the inaccurate forcing data and limitations of the Kudryavtsev model.
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Retriever223
Improvements of Developed Graphite Based Composite Anti-Aging Agent on Thermal Aging Properties of Asphalt. To reduce the thermal-oxidative aging of asphalt and the release amount of harmful volatiles during the construction of asphalt pavement, a new composite anti-aging agent was developed. Since the volatiles were mainly released from saturates and aromatics during the thermal-oxidative aging of asphalt, expanded graphite (EG) was selected as a stabilizing agent to load magnesium hydroxide (MH) and calcium carbonate (CaCO3) nanoparticles for preparing the anti-aging agents of saturates and aromatics, respectively. Thermal stability and volatile constituents released from saturates and aromatics before and after the thermal-oxidative aging were characterized using the isothermal Thermogravimetry/Differential Scanning Calorimetry-Fourier Transform Infrared Spectrometer test (TG/DSC-FTIR test). Test results indicate that anti-aging agents of EG/MH and EG/CaCO3 effectively inhibit the volatilization of light components in asphalt and improve the thermal stability of saturates and aromatics. Then, the proportions of EG, MH, and CaCO3 added in the developed composite anti-aging agent of EG/MH/CaCO3 are 2:1:3 by weight. EG/MH/CaCO3 plays a synergetic effect on inhibiting the thermal-oxidative aging of asphalt, and reduces the release amount of harmful volatiles during the thermal-oxidative aging after EG/MH/CaCO3 is added into asphalt at the proposed content of 10 wt.%. EG plays a synergistic role with MH and CaCO3 nanoparticles to prevent the chain reactions, inhibiting the thermal-oxidative aging of asphalt.
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Retriever224
Ten-year results of a bone-preserving low-modulus composite total hip replacement stem. A cementless composite femoral stem was developed with the aim of reducing bone loss secondary to stress shielding. Thirty-one stems were implanted in 27 patients, combined with a cementless acetabular component with polyethylene bearing surface in 30 cases and a bipolar head in 1 case. Patients were followed-up annually with clinical and radiographic evaluation. Fourteen hips underwent dual X-ray absorptiometry (DEXA) scans to monitor postoperative bone mineral density around the stem. The mean follow-up was 10.1 years. The mean Harris hip score improved from 57 to 92. To date, no stem has required revision. All stems are radiographically stable. Acetabular component revision has been required in 8 cases; 3 for liner dissociation and 5 for polyethylene wear. Radiographs and DEXA scans have shown some improvement in bone mineral density (BMD) between the 2 and 5-year follow-up. A cohort of patients displayed improvement in radiographic appearance and BMD in Gruen zone 7. This stem shows evidence of proximal bone preservation and has excellent results at medium to long-term follow-up. The limiting factor in our cohort of patients has been the polyethylene bearing surface.
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Effect of opioid dependence or abuse on opioid utilization after shoulder arthroplasty. AIM To examine whether opioid dependence or abuse has an effect on opioid utilization after anatomic or reverse total shoulder arthroplasty (TSA). METHODS All anatomic TSA (ICD-9 81.80) and reverse shoulder arthroplasty (RSA) (ICD-9 81.88) procedures from 2007 to 2015 were queried from within the Humana claims database utilizing the PearlDiver supercomputer (Colorado Springs, CO). Study groups were formed based on the presence or absence of a previous history of opioid dependence (ICD-9 304.00 and 304.03) or abuse (ICD-9 305.50 and 305.53). Opioid utilization among the groups was tracked monthly up to 1 year post-operatively utilizing National Drug Codes. A secondary analysis was performed to determine risk factors for pre-operative opioid dependence or abuse. RESULTS Two percent of TSA (157 out of 7838) and 3% of RSA (206 out of 6920) patients had a history of opioid dependence or abuse. For both TSA and RSA, opioid utilization was significantly higher in opioid dependent patients at all post-operative intervals (P < 0.01) although the incidence of opioid use among groups was similar within the first post-operative month. After TSA, opioid dependent patients were over twice as likely to fill opioid prescriptions during the post-operative months 1-12. Following RSA, opioid dependent patients were over 3 times as likely to utilize opioids from months 3-12. Age less than 65 years, history of mood disorder, and history of chronic pain were significant risk factors for pre-operative opioid dependence/abuse in patients who underwent TSA or RSA. CONCLUSION Following shoulder arthroplasty, opioid use between opioid-dependent and non-dependent patients is similar within the first post-operative month but is greater among opioid-dependent patients from months 2-12.
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Associations of social environment, socioeconomic position and social mobility with immune response in young adults: the Jerusalem Perinatal Family Follow-Up Study. OBJECTIVES Immune response to cytomegalovirus (CMV) impacts adult chronic disease. This study investigates associations of childhood and adulthood social environment, socioeconomic position (SEP) and social mobility with CMV response in young adults. DESIGN Historical prospective study design. SETTING Subcohort of all 17 003 births to residents of Jerusalem between 1974 and 1976. PARTICIPANTS Participants included 1319 young adults born in Jerusalem with extensive archival and follow-up data, including childhood and adulthood SEP-related factors and anti-CMV IgG titre levels and seroprevalence measured at age 32. MAIN EXPOSURE AND OUTCOME MEASURES Principal component analysis was used to transform correlated social environment and SEP-related variables at two time points (childhood and adulthood) into two major scores reflecting household (eg, number of siblings/children, religiosity) and socioeconomic (eg, occupation, education) components. Based on these components, social mobility variables were created. Linear and Poisson regression models were used to investigate associations of components and mobility with anti-CMV IgG titre level and seroprevalence, adjusted for confounders. RESULTS Lower levels of household and socioeconomic components in either childhood or adulthood were associated with higher anti-CMV IgG titre level and seropositivity at age 32. Compared with individuals with stable favourable components, anti-CMV IgG titre level and risk for seropositivity were higher in stable unfavourable household and socioeconomic components (household: β=3.23, P<0.001; relative risk (RR)=1.21, P<0.001; socioeconomic: β=2.20, P=0.001; RR=1.14, P=0.01), downward household mobility (β=4.32, P<0.001; RR=1.26, P<0.001) and upward socioeconomic mobility (β=1.37, P=0.04; RR=1.19, P<0.001). Among seropositive individuals, associations between household components and mobility with anti-CMV IgG titre level were maintained and associations between socioeconomic components and mobility with anti-CMV IgG titre level were attenuated. CONCLUSIONS Our study provides evidence that accumulating low SEP from childhood through adulthood and social mobility may compromise immune response in young adulthood.
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A practical guide to nonvascular thoracic magnetic resonance imaging. There is increasing perception that thoracic magnetic resonance imaging (MRI) is underutilized. Various obstacles to implementation and utilization of thoracic MRI can be overcome with continuous updating, improvement, and standardization of thoracic MRI protocols, close collaboration with MRI technologists, continued education of MRI technologists, radiologists, and referring health care providers, and incorporation of MRI training into thoracic imaging fellowship programs. The purpose of this article is to share the author's experience in developing a successful nonvascular thoracic MRI practice, discuss the fundamentals of nonvascular thoracic MRI, and provide a "how-to" manual for its performance.
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Localized gastroesophageal adenocarcinoma in the elderly: is age a factor associated with suboptimal treatment? INTRODUCTION Gastroesophageal adenocarcinoma is relatively common in elderly patients as the incidence increases with age. However, the optimal treatment approach is not well established in this group of patients. The aim of this study is to review our experience for localized gastroesophageal adenocarcinoma in patients aged ≥ 80 years and to assess association between patient characteristics, clinical factors and overall survival in order to optimize the therapeutic approaches for this population. METHODS AND MATERIALS patients ≥ 80 years old treated for localized gastroesophageal adenocarcinoma were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were applied to assess the association between patient characteristics and overall survival (OS). Factors that were significant in the multivariate model were included in the final reduced model. RESULTS 127 patients ≥ 80 years old, were included in this study with median age of 83 years. The median follow-up time was 3.2 years, and median OS was 2.5 years (95% CI: 2.0-3.1 years). Independent prognostic factors for OS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) (p=0.003), baseline clinical stage (p=0.01), and surgery (p=0.001). ECOG PS, tumor location, baseline stage, tumor grade and surgery were included in the final reduced model. CONCLUSION Surgical treatment, can improve survival in elderly patients. Therapeutic decisions should be based on the patients' general condition rather that age alone.
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Genetic diversity of Alternaria species associated with black point in wheat grains. The genus Alternaria is a widely distributed major plant pathogen that can act as a saprophyte in plant debris. Fungi of this genus frequently infect cereal crops and cause such diseases as black point and wheat leaf blight, which decrease the yield and quality of cereal products. A total of 25 Alternaria sp. isolates were collected from germ grains of various wheat cultivars from different geographic regions in Kazakhstan. We investigated the genetic relationships of the main Alternaria species related to black point disease of wheat in Kazakhstan, using the inter-primer binding site (iPBS) DNA profiling technique. We used 25 retrotransposon-based iPBS primers to identify the differences among and within Alternaria species populations, and analyzed the variation using clustering (UPGMA) and statistical approaches (AMOVA). Isolates of Alternaria species clustered into two main genetic groups, with species of A.alternata and A.tennuissima forming one cluster, and isolates of A. infectoria forming another. The genetic diversity found using retrotransposon profiles was strongly correlated with geographic data. Overall, the iPBS fingerprinting technique is highly informative and useful for the evaluation of genetic diversity and relationships of Alternaria species.
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A novel dextran hydrogel linking trans-ferulic acid for the stabilization and transdermal delivery of vitamin E. Long-term exposure of the skin to UV light causes degenerative effects, which can be minimized by using antioxidant formulations. The major challenge in this regard is that a significant amount of antioxidant should reach at the site for effective photoprotection. However, barrier properties of the skin limit their use. In the present study, vitamin E (alpha-tocopherol) was loaded into a dextran hydrogel containing ferulic moieties, covalently linked, to improve its topical delivery, and also to increase its relative poor stability, which is due to direct exposure to UV light. Methacrylic groups were first introduced onto the dextran polymer backbones, then the obtained methacrylated dextran was copolymerized with aminoethyl methacrylate, and subsequently esterificated with trans-ferulic acid. The new biopolymer was characterized by Fourier transform infrared spectroscopy. The values of content of phenolic groups were determined. Its ability in inhibiting lipid peroxidation in rat liver microsomal membranes induced in vitro by a source of free radicals, that is tert-butyl hydroperoxide, was studied. Hydrogel was also characterized for swelling behaviour, vitamin E loading efficiency, release, and deposition on the rabbit skin. Additionally, vitamin E deposition was compared through hydrogels, respectively, containing and not containing trans-ferulic acid. The results showed that ferulate hydrogel was a more effective carrier in protecting vitamin E from photodegradation than hydrogel without antioxidant moieties. Then antioxidant hydrogel could be of potential use for cosmetic and pharmaceutical purposes as carrier of vitamin E that is an antioxidant that reduces erythema, photoaging, photocarcinogenesis, edema, and skin hypersensitivity associated with exposure to ultraviolet B (UVB) radiation, because of its protective effects.
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The Wolf method applied to the liquid-vapor interface of water. The Wolf method for the calculation of electrostatic interactions is applied in a liquid phase and at the liquid-vapor interface of water and its results are compared with those from the Ewald sums method. Molecular dynamics simulations are performed to calculate the radial distribution functions at room temperature. The interface simulations are used to obtain the coexisting densities and surface tension along the coexistence curve. The water model is a flexible version of the extended simple point charge model. The Wolf method gives good structural results, fair coexistence densities, and poor surface tensions as compared with those obtained using the Ewald sums method.
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Gay, lesbian and bisexual health care issues and medical curricula. The authors respond to Nancy Robb's account of the inadequacy of medical school curricula in addressing health care issues relevant to gay, lesbian and bisexual people (see page 765 of this issue) by proposing a framework for curriculum reform. This framework supports the development of knowledge, attitudes and skills necessary to the provision of sensitive and comprehensive care for these patient groups through four types of learning experiences: didactic instruction, small-group discussions, simulated patient encounters, and supervised encounters with real patients. Equally important is the attitudinal context in which learning takes place. Without fostering a supportive and accepting environment for education about gay, lesbian and bisexual health care issues, medical schools cannot ensure that future physicians will be equipped to provide appropriate care for all members of society.
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Birnavirus precursor polyprotein is processed in Escherichia coli by its own virus-encoded polypeptide. The cDNA fragment of the large RNA segment of infectious bursal disease virus 002-73, when expressed in Escherichia coli, produces precursor polyprotein (N-VP2-VP4-VP3-C), most of which is then processed to generate constituent polypeptides. Using cDNA fragments containing site-specific mutations and two monoclonal antibodies that are specific to VP2 and VP3 of mature virus particles, we demonstrated that the VP4 protein is involved in processing of the precursor polyprotein to generate VP2 and VP3 and excluded the possibility of internal initiation for the generation of VP3.
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Evidence for two types of P2-purinoceptor in longitudinal muscle of the rabbit portal vein. The actions of ATP, 2-methylthioATP, alpha, beta-methyleneATP, beta, gamma-methyleneATP, adenosine and non-adrenergic, non-cholinergic inhibitory nerve stimulation were compared on the ergotamine-contracted longitudinal muscle of the isolated rabbit portal vein with the vessel endothelium either intact or removed by mechanical rubbing. Non-adrenergic, non-cholinergic inhibitory nerve stimulation produced frequency-dependent relaxations. The purines (except alpha, beta-methyleneATP) also caused relaxation with the following potency order: 2-methylthioATP greater than ATP greater than beta, gamma-methyleneATP = adenosine. 8-Phenyltheophylline, a potent P1-purinoceptor antagonist, antagonised relaxations to adenosine but not those to ATP indicating that ATP and its analogues act directly via a P2-purinoceptor and not via a P1-purinoceptor after breakdown to adenosine. alpha, beta-MethyleneATP produced contractions which were not maintained and was tachyphylactic. The contractions were unaffected by tetrodotoxin and therefore unlikely to be due to release of a contractile substance from a neuronal source following initiation of an action potential. Removal of the endothelium did not affect the actions of non-adrenergic, non-cholinergic inhibitory nerve stimulation, ATP, alpha, beta-methyleneATP, beta, gamma-methyleneATP or adenosine. Thus purine action does not have an endothelium-dependent component in the rabbit portal vein longitudinal muscle. The results indicate the possibility that there may be more than one type of P2-purinoceptor in this tissue.
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Normal vascular development in mice deficient in endothelial NO synthase: possible role of neuronal NO synthase. PURPOSE Nitric oxide formation by nitric oxide synthase (NOS) has been implicated in vascular injury and retinal neovascularization during oxygen-induced retinopathy. However, the role of NOS in normal retinal vascular development and growth has not been studied. The purpose of these experiments was to characterize the expression of NOS in relation to vascular development and to determine the effect of deleting endothelial NOS (eNOS) on this process. METHODS Retinal vascular development was analyzed in 150 eNOS+/+ and eNOS-/- mice ranging from 1 day to 6 months old by using a combination of morphometric and biochemical approaches. The pattern of vascular development was analyzed in retinal tissue sections and whole-mount preparations labeled with fluorescein-conjugated Griffonia simplicifolia lectin. Analysis of vascular density and arterial diameter were performed with the lectin-labeled whole-mounts using computer-assisted morphometry. NO production was quantified by measuring retinal levels of nitrate/nitrite accumulation using the Greiss reaction. Western blotting techniques with isoform-specific NOS antibodies were used to evaluate differences in levels of NOS protein expression. Retinal distribution of nNOS was characterized using nNOS immunocytochemistry and NADPH diaphorase histochemistry. RESULTS These analyses showed that the rate and pattern of retinal vascular development in eNOS-/- mice were comparable with those in wild-type control mice. Measurement of vascular density showed no significant differences between the two strains. The amount of NO production in the eNOS-/- retina was also equivalent to that in the eNOS+/+ retina. Analysis of nNOS expression within the eNOS+/+ and eNOS-/- mice showed similar levels of total nNOS protein in the two strains. Inducible NOS was not detected in either strain. Studies of nNOS distribution showed intense labeling of the deep capillary plexus in the eNOS-/- retina. This was not seen in the wild-type retinas. The number of neuronal cells showing NADPH-diaphorase activity was also significantly increased in the eNOS-/- mice. CONCLUSIONS Development of the retinal vasculature occurs normally without eNOS. The observations of similar levels of NO production, perivascular redistribution of nNOS and increased numbers of NADPH-diaphorase reactive neurons in the eNOS-/- retinas suggest that increases in vascular-associated nNOS activity compensate for the eNOS deficiency in the developing mutant retina.
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Cross-Sectional Survey of Smoking Patterns During the COVID-19 Pandemic in a Tobacco Cessation and Lung Cancer Screening Program. Background: Coronavirus disease 2019 (COVID-19) produces a wide array of deleterious consequences, some of which are unintended. Data are sparse on whether, and if so, how, current cigarette smoking habits are affected by COVID-19. We describe changes to smoking habits and their correlates during the COVID-19 pandemic among participants in a tobacco cessation and lung cancer screening program. Methods: Between June and October 2020, we conducted a cross-sectional survey of a convenience sample of 150 participants in a lung cancer screening and tobacco cessation program. The survey consisted of 3 parts: (1) changes in tobacco use, (2) impact and coping strategies toward COVID-19, and (3) COVID-19 exposure and use of protective measures. Demographic variables included age, sex, race/ethnicity, and marital status. Results: All 150 participants who were contacted agreed to participate in this cross-sectional survey. The statistically significant correlates of increased tobacco use were high uncertainty about the future (P<0.001), loneliness because of social distancing or self-isolating (P<0.001), anger or frustration with how the pandemic has disrupted daily life (P<0.001), boredom resulting from inability to work or engage in regular daily activities/routines (P<0.001), desire to cope using alcohol or drugs (P=0.002), sadness or feelings of hopelessness (P=0.003), and worry or fear about challenges to securing basic needs such as groceries or medication (P<0.001). In contrast, those who smoked less were more likely to practice social distancing (P=0.002) and use protective measures (P=0.005). Conclusion: Among those who decreased or stopped smoking, correlates included greater use of protective measures for COVID-19, including social distancing and testing. These data may aid healthcare providers to identify and provide counsel to cigarette smokers at greater risks for increasing tobacco consumption during stresses such as COVID-19.
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Identification of liver proteins and their roles associated with carbon tetrachloride-induced hepatotoxicity. Carbon tetrachloride (CCl(4)) is a common hepatotoxin used in experimental models to elicit liver injury. To identify the proteins involved in CCl(4)-induced hepatotoxicity, two-dimensional gel electrophoresis was employed followed by mass spectrometry - mass spectrometry (MS/MS) to study the differentially expressed proteins during CCl(4) exposure in the Fischer 344 rat liver proteome for 5 weeks. Ten spots with notable changes between the Control and CCl(4) groups were successfully identified. Among them, four proteins with significant up-regulation, namely calcium-binding protein 1, protein disulfide isomerase, mitochondrial aldehyde dehydrogenase precursor, and, glutathione-S-transferase mu1 and six proteins with significant down-regulation, namely catechol-O-methyltransferase, hemoglobin-alpha-2-chain, hemopexin precursor, methionine sulfoxide reductase A, catalase and carbonic anhydrase 3, were identified. The data indicates that CCl(4) causes hepatotoxicity by depleting oxygen radical scavengers in the hepatocytes. In this rat model, we profiled hepatic proteome alterations in response to CCl(4) intoxication. The findings should facilitate understanding of the mechanism of CCl(4)-induced liver injury.
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Crystal nucleation as the ordering of multiple order parameters. Nucleation is an activated process in which the system has to overcome a free energy barrier in order for a first-order phase transition between the metastable and the stable phases to take place. In the liquid-to-solid transition, the process occurs between phases of different symmetry, and it is thus inherently a multi-dimensional process, in which all symmetries are broken at the transition. In this Focus Article, we consider some recent studies which highlight the multi-dimensional nature of the nucleation process. Even for a single-component system, the formation of solid crystals from the metastable melt involves fluctuations of two (or more) order parameters, often associated with the decoupling of positional and orientational symmetry breaking. In other words, we need at least two order parameters to describe the free-energy of a system including its liquid and crystalline states. This decoupling occurs naturally for asymmetric particles or directional interactions, focusing here on the case of water, but we will show that it also affects spherically symmetric interacting particles, such as the hard-sphere system. We will show how the treatment of nucleation as a multi-dimensional process has shed new light on the process of polymorph selection, on the effect of external fields on the nucleation process and on glass-forming ability.
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Triptolide directly inhibits dCTP pyrophosphatase. Triptolide is a potent natural product, with documented antiproliferative, immunosuppressive, anti-inflammatory, antifertility, and antipolycystic kidney disease effects. Despite a wealth of knowledge about the biology of this compound, direct intracellular target proteins have remained elusive. We synthesized a biotinylated photoaffinity derivative of triptolide, and used it to identify dCTP pyrophosphatase 1 (DCTPP1) as a triptolide-interacting protein. Free triptolide interacts directly with recombinant DCTPP1, and inhibits the enzymatic activity of this protein. Triptolide is thus the first dCTP pyrophosphatase inhibitor identified, and DCTPP1 is a biophysically validated target of triptolide.
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Functional characterization of the human translocator protein (18kDa) gene promoter in human breast cancer cell lines. The translocator protein (18kDa; TSPO) is a mitochondrial drug- and cholesterol-binding protein that has been implicated in several processes, including steroidogenesis, cell proliferation, and apoptosis. Expression of the human TSPO gene is elevated in several cancers. To understand the molecular mechanisms that regulate TSPO expression in human breast cancer cells, the TSPO promoter was identified, cloned, and functionally characterized in poor-in-TSPO hormone-dependent, non-aggressive MCF-7 cells and rich-in-TSPO hormone-independent, aggressive, and metastatic MDA-MB-231 breast cancer cells. RNA ligase-mediated 5'-rapid amplification of cDNA ends analysis indicated transcription initiated at multiple sites downstream of a GC-rich promoter that lacks functional TATA and CCAAT boxes. Deletion analysis indicated that the region from -121 to +66, which contains five putative regulatory sites known as GC boxes, was sufficient to induce reporter activity up to 24-fold in MCF-7 and nearly 120-fold in MDA-MB-231 cells. Electrophoretic mobility shift and chromatin immunoprecipitation assays indicated that Sp1, Sp3 and Sp4 bind to these GC boxes in vitro and to the endogenous TSPO promoter. Silencing of Sp1, Sp3 and Sp4 gene expression reduced TSPO levels. In addition, TSPO expression was epigenetically regulated at one or more of the identified GC boxes. Disruption of the sequence downstream of the main start site of TSPO differentially regulated TSPO promoter activity in MCF-7 and MDA-MB-231 cells, indicating that essential elements contribute to its differential expression in these cells. Taken together, these experiments constitute the first in-depth functional analysis of the human TSPO gene promoter and its transcriptional regulation.
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Theoretical and experimental revision of surface acoustic waves on the (100) plane of silicon. The phase velocity dispersion of the surface acoustic waves on a basal plane of Si(100) has been calculated in the whole range of the azimuthal angle of propagation. We present a detailed description of the calculations. These calculations are compared with the experimental data obtained by a laser acoustic method. Our data convincingly demonstrate the existence of a gap in the spectrum of the phase velocities. The gap means that in a definite range of the phase velocities the SAWs are absent in the whole interval of the azimuthal angles. There is an excellent coincidence between the numerical and experimental data.
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Dynamics of the size distribution of CdTe quantum dot ensembles during growth in liquid and crystalline phases. We recently reported that the growth rate of colloidal CdTe nanoparticles decreases by orders of magnitude when the particles undergo a phase transition from liquid to crystal. The dynamics of nanoparticle growth are dominated by this factor rather than the size dependence of the chemical potential. Herein we discuss how the phase transition affects the size distribution and photoluminescence quantum efficiency of the nanoparticles. We suggest that the absorption linewidth is a better monitor of size distribution than the photoluminescence linewidth because the photoluminescence quantum efficiency, which affects the latter via energy transfer, varies substantially with reaction time. We find that the size distribution broadens in the early stages of growth possibly because of inhomogeneities in the phase transition radius or because particles nucleated at later times coalesce with nanocrystals. The quantum efficiency is enhanced when tellurium is depleted in the reaction solution, giving a cadmium-enriched surface. Batches with high initial tellurium and cadmium concentrations show a substantial amount of delayed nucleation, lower quantum efficiency and some anisotropic growth.
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[Preoperative perspective versus postoperative functional assessment of surgery in chronic mitral regurgitation]. Thirty patients with chronic pure mitral regurgitation who underwent mitral valve replacement during 1981 to 1986 were evaluated for pre- and one year postoperative left ventricular function using two dimensional echogram. Indicators in their evaluation were DdI, DsI, MassI and systolic and diastolic R/Th. Postoperatively, patients (n = 7) were placed in a group of abnormal responses if even one of these indicators of left ventricular function became worse than preoperative performance, patients in this group were symptomatic and two subsequently died. The postoperative FS and mVcf data fort this group were significantly lower than the patients with normal response group (n = 23). These two groups could not be differentiated by preoperative assessments of either DdI, MassI, systolic/diastolic T/Th or normalized systolic/diastolic peak velocity. However, a combination of normalized systolic peak velocity lower than 1.70 and diastolic peak velocity lower than 2.20 of left ventricular wall motion proved to be good predictors of postoperative results.
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Top-down modulation of shape and roughness discrimination in active touch by covert attention. Due to limitations in perceptual processing, information relevant to momentary task goals is selected from the vast amount of available sensory information by top-down mechanisms (e.g. attention) that can increase perceptual performance. We investigated how covert attention affects perception of 3D objects in active touch. In our experiment, participants simultaneously explored the shape and roughness of two objects in sequence, and were told afterwards to compare the two objects with regard to one of the two features. To direct the focus of covert attention to the different features we manipulated the expectation of a shape or roughness judgment by varying the frequency of trials for each task (20%, 50%, 80%), then we measured discrimination thresholds. We found higher discrimination thresholds for both shape and roughness perception when the task was unexpected, compared to the conditions in which the task was expected (or both tasks were expected equally). Our results suggest that active touch perception is modulated by expectations about the task. This implies that despite fundamental differences, active and passive touch are affected by feature selective covert attention in a similar way.
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Cavernous malformations of the hypothalamus: a single-institution series of 12 cases and review of the literature. OBJECTIVE There remains a paucity of literature on hypothalamic cavernous malformations (HCMs). Here, the authors present the largest series of HCMs to date and review the literature to gain additional insight into this rare disease subset. METHODS A prospectively managed database was retrospectively reviewed for patients diagnosed with symptomatic HCM and treated surgically between 1987 and 2019. Data gathered included demographics, presenting signs, radiological measurements, surgical approach, and postoperative events. Functional outcome was measured using the modified Rankin Scale (mRS) and Glasgow Outcome Scale-Extended (GOSE) pre- and postoperatively. A PRISMA guideline systematic review of HCM in the literature was performed. RESULTS Our cohort study consisted of 12 patients with symptomatic, and radiographically confirmed, HCM treated with microsurgery by the senior author (G.K.S.). An additional 16 surgically or conservatively managed patients were also identified from the literature, and the authors analyzed the data of all 28 patients (with 54% of patients being male; mean age 39 ± 16 years, range 10-68 years). Patients harboring HCMs most commonly presented with headache (16/28, 57%), short-term memory impairment (11/28, 39%), and gait disturbance (8/28, 32%). Radiographically, lesions most commonly involved the mammillary region (18/23, 78%), the tuberal/infundibulum region (13/23, 57%), and the preoptic/lamina terminalis region (12/23, 52%), with a mean diameter of 2.5 ± 1.4 cm (range 0.8-7 cm) at presentation. Acute hemorrhage was identified in 96% (23/24) of patients on presentation, with 96% (23/24) intraparenchymal and 29% (7/24) intraventricular. Of 24 patients who were managed surgically, gross-total resection (GTR) was achieved in 88% (21/24) of cases. There were no reports of perioperative infarction or mortality. With a mean follow-up period of 41 months (range 0.5-309 months), 77% (20/26) of patients experienced functional improvement, while 12% (3/26) had no change, and 12% (3/26) experienced increased disability. In our cohort of 12 patients, 83% (10/12) continued to report symptoms at the last follow-up (mean 4.8 years, range 0.1-25.7 years). However, there was a significant improvement in mRS score noted after surgery (mean 1.4 vs 3.1, p = 0.0026) and a trend toward improvement in GOSE score (mean 6.3 vs 5.1, p = 0.09). CONCLUSIONS Hemorrhage from HCMs can cause a symptomatic mass effect on adjacent eloquent structures. While patients are unlikely to be deficit free following surgery, GTR allows for functional improvement and reduces recurrent hemorrhage rates. Microsurgery remains a viable option for symptomatic HCMs in experienced hands.
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Phagocytic acitivity of bovine leukocytes during pregnancy. The phagocytic competence, measured as the total number of polymorphonuclear leukocytes per mm3 which phagocytosed Staphylococcus aureus, strain 321, in vitro, was determined in eight cows during complete pregnancies. Such leukocytes are referred to as "Active PMN'S". There was a gradual decline in the number of these cells from conception to a minimum between the 16th and 20th weeks of pregnancy, followed by a steady increase to the cessation of lactation when a marked drop occurred, after which there was an increase to a maximun during the second week prepartum. From this maximum there was a rapid decrease to an absolute minimum during the first week after parturition. From the second week postpartum there was a gradual increase to conception. The correlation coefficient (r) of number of active PMN'S with time before conception was -0.474 )p-0.01). There were significant differences (p=0.01) in numbers of active PMNS Among the eight cows. It was found that the cows fell into two groups, one whose members had, overall, significantly more active PMNs (p=0.001) than those in the second group. The between cow differences may have been due to 1) age, since the cows with the highest numbers of circulating active PMNs were younger than those in the other group of 2) the combined stress of pregnancy and lactation, as those cows which were both pregnant and milking had the lowest numbers of active PMNs.
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Obligatory separation of hormone binding and biological response curves in systems dependent upon secondary mediators of hormone action. A mathematical model is presented that describes the effects of hormone concentration on receptor saturation and biological response in systems dependent upon the generation of a secondary mediator such as cyclic AMP. The analysis makes the following assumptions: (i) the binding of hormone to its receptor is a reversible, second-order reaction; (ii) the concentration of mediator that is generated is directly proportional to the number of membrane binding sites occupied by hormone; and (iii) the binding of the mediator with its intracellular receptor to generate an effector complex is also second-order and results in a proportionate biological response. It follows from this treatment that the hormone concentration required for half-maximal biological response is formally lower than that required for half-maximal receptor saturation and that the difference between these two concentrations will depend upon the ratio of total mediator generated at full receptor occupancy to the dissociation constant of the mediator with its receptor. Without invoking concepts of negative cooperativity, this model offers a simple explanation for discrepancies between receptor occupancy and biological response curves that are often observed. Moreover, the mathematical form of the predicted biological response curves conforms to the shape of the response curves observed experimentally in a wide variety of systems.
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Subcellular spatially resolved gene neighborhood networks in single cells. Image-based spatial omics methods such as fluorescence in situ hybridization (FISH) generate molecular profiles of single cells at single-molecule resolution. Current spatial transcriptomics methods focus on the distribution of single genes. However, the spatial proximity of RNA transcripts can play an important role in cellular function. We demonstrate a spatially resolved gene neighborhood network (spaGNN) pipeline for the analysis of subcellular gene proximity relationships. In spaGNN, machine-learning-based clustering of subcellular spatial transcriptomics data yields subcellular density classes of multiplexed transcript features. The nearest-neighbor analysis produces heterogeneous gene proximity maps in distinct subcellular regions. We illustrate the cell-type-distinguishing capability of spaGNN using multiplexed error-robust FISH data of fibroblast and U2-OS cells and sequential FISH data of mesenchymal stem cells (MSCs), revealing tissue-source-specific MSC transcriptomics and spatial distribution characteristics. Overall, the spaGNN approach expands the spatial features that can be used for cell-type classification tasks.
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Hollow CoFe₂O₄ nanospheres as a high capacity anode material for lithium ion batteries. Hollow structured CoFe₂O₄ nanospheres were synthesized by a hydrothermal method. The uniform hollow nanosphere architecture of the as-prepared CoFe₂O₄ has been confirmed by field emission scanning electron microscopy and transmission electron microscopy analysis, which give an outer diameter of 200-300 nm and a wall thickness of about 100 nm. CoFe₂O₄ nanospheres exhibited a high reversible capacity of 1266 mA h g⁻¹ with an excellent capacity retention of 93.6% over 50 cycles and an improved rate capability. CoFe₂O₄ could be a promising high capacity anode material for lithium ion batteries.
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The power of women's and men's Social Networks to catalyse normative and behavioural change: evaluation of an intervention addressing Unmet need for Family Planning in Benin. BACKGROUND In Benin, despite good knowledge and availability, modern contraceptive prevalence remains relatively low, and the unmet need for family planning is relatively high. This is partly due to insufficient attention to socio-normative barriers that influence need and method use. Applying social network theory, Tékponon Jikuagou (TJ) aims to reduce socio-normative barriers preventing modern contraceptive use in rural Benin. After community identification, TJ trains influential network actors who encourage critical dialogue about unmet need, family planning, gender, and other social norms within their networks, complemented by radio and services linkages. This paper evaluates TJ's effectiveness and how intervention components affect intermediate and primary FP outcomes. METHODS We report findings from pre/post-intervention cross-sectional research with a comparison group conducted at baseline with 1,043 women and 1,030 men, and 14 months later at endline with 1,046 women and 1,045 men. Using sex-stratified models, we assessed balance across intervention and comparison groups on background characteristics using Pearson's chi-square tests of independence; performed bivariate tests of independence to assess differences between baseline to endline on intermediate outcomes and primary FP outcomes; used logistic regression to examine the effect of intervention components on intermediate and primary FP outcomes. RESULTS Statistically significant improvements in primary outcomes: women's intentions to use modern contraception, achieve met need, and reduce perceived met need. The fourth primary outcome, actual use, showed substantial gains, although not statistically significant. Men's achievement of met FP need and reduced perceived met need were also statistically significant. Assessing intermediate outcomes at individual, couple, normative-network levels, TJ led to statistically significant increases in couple and network communication on fertility desires and family planning use and self-efficacy and confidence to access services. Both women and men showed significant shifts in the acceptability of discussing FP in public. Results for other indicators of norms change were inconsistent. CONCLUSIONS An easy-to-implement, short-duration, gender-equitable social network intervention with a limited set of network actors, TJ effectively decreases social and normative barriers preventing women and men from seeking and using FP services. Results support the broader use of innovative social and behaviour change strategies that diffuse family planning ideas through social networks, diminish normative and communication barriers, and catalyse modern family planning use.
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Inducing factors and deformation mechanism of the Zhangjiacitang landslide in the Three Gorges Reservoir Area. Landslides are the most widely distributed geological hazards in the Three Gorges Reservoir Area (TGRA). Understanding the deformation mechanism and evolution of landslides is of great significance for their prevention and control. In this study, we focused on the Zhangjiacitang landslide, a typical bank landslide in the TGRA. We analyzed the relationship between landslide deformation and water level fluctuations and rainfall, based on accumulated displacement monitoring data, to clarify their triggering factors and deformation mechanism. The results show that the Zhangjiacitang landslide is a large-scale accumulation landslide. Under the influence of cyclic water level fluctuations and periodic rainfall, the accumulated displacement-time curve shows a "stepped" characteristic. Heavy rainfall emerged as the primary factor influencing the deformation of the Zhangjiacitang landslide, leading to substantial deformation throughout different periods. The deformation of the landslide exhibited a positive correlation with the intensity of rainfall. In contrast, the impact of water level changes on the landslide deformation was more intricate. A rapid water level drop (> 0.3 m/d) tended to intensify the landslide deformation, while the slow water level drop period (< 0.3 m/d) did not exhibit such an effect. This study emphasizes the need for closely monitoring the landslide status during heavy rainfall periods and rapid water level decline periods. The findings of this study provide a certain reference for landslide monitoring, early warning, prevention and control in the TGRA.
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Socioeconomic determinants of infant growth: The Perspective Cohort Study of Thai Children. AIM The present study is based on the Prospective Cohort Study of Thai Children (PCTC), and focuses on socioeconomic factors including maternal age, maternal education, living with parents, family size, family income, locality, and sex that affect the growth outcomes of infants at 1 year of age. METHODS Data was collected among 3679 pairs of mothers and infants in the PCTC cohort in rural and urban locations during 2001-2002. Data collection was performed by interviewing mothers in their 7th to 8th month of pregnancy using family profile questionnaires. The anthropometric measures including weight, length, and head circumference of the infants were later collected at 1 year of age at home. RESULTS The results show the effects of family socioeconomic status maternal education, living with parents, family size, family income, locality, and sex on their weight (R(2) = 14.2%, P < 0.001) and length (R(2) = 8.7%, P < 0.001) at 1 year of age. The findings suggest that maternal age, maternal education, living with parents, family size, family income, locality, and sex predict infant head circumference (R(2) = 16.8%, P < 0.001) at 1 year of age. CONCLUSION Infants' growth, including weight, height, and head circumference, are affected by family socioeconomic status factors. It is recommended that the effect of maternal age on growth and development of children among those in the PCTC cohort is examined in the future.
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Surgical Aspects of Corpus Callosotomy. Corpus callosotomy (CC) is one of the options in epilepsy surgeries to palliate patient seizures, and is typically applied for drop attacks. The mechanisms of seizure palliation involve disrupting the propagation of epileptic activity to the contralateral side of the brain. This review article focuses on the surgical aspects of CC. As a variations of CC, anterior two-thirds, posterior one-third, and total callosotomy are described with intraoperative photographs. As less-invasive surgical variations, recent progress in endoscopic CC, and CC without craniotomy, is described. CC remains acceptable under the low prevalence of complications, and surgeons should make the maximum effort to minimize the complication rate.
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APOE-related frequency of cognitive and noncognitive symptoms in dementia. Although memory disorders and the aphaso-apraxo-agnosic syndrome are the most relevant clinical symptoms in dementia, behavioral changes, mood-related disturbances and sleep disorders are the major cause of institutionalization and caregiver concern. In the present study we have investigated the frequency and progression of cognitive and noncognitive symptoms in Alzheimer's disease (AD) as well as the APOE-related frequency of clinical symptoms in dementia. Memory decline (100%), aphasia (94%), apraxia (99%), agnosia (94%) and motor dysfunction (90%) appeared in practically all cases with mild (GDS-3), moderate (GDS 3-4) and severe (GDS 6-7) dementia. The most frequent noncognitive symptoms include anxiety (76%), depression (68%), behavioral changes (67%), psychotic symptoms (43%), sleep disorders (43%), incontinence (23%) and cerebrovascular symptoms (75%). Anxiety, depression, behavioral changes, psychotic symptoms, motor dysfunction and cognitive deterioration paralleled the severity of dementia, increasing their frequency from mild to severe dementia. The most important sleep disorders were irregular sleep-wake pattern (67%) and insomnia (47%). Disorientation (90%) and drug administration (88%) appeared to be the most important factors in causing sleep disorders in dementia. Disorientation, agitation and motor disorders were slightly more frequent in patients with APOE-4/4, while anxiety and sleep disorders appeared more frequently in APOE-3/4. Behavioral changes and psychotic symptoms did not show any clear association with specific APOE subtypes. In conclusion, our results suggest that noncognitive symptoms are very important clinical events in the disease progression and in decision making for therapeutic intervention and institutionalization. Furthermore, it is likely that some brain dysfunctions leading to particular clinical symptoms might be associated with specific AD genotypes.
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The growth-promoting effect of KGF on limbal epithelial cells is mediated by upregulation of DeltaNp63alpha through the p38 pathway. Corneal epithelial stem cells are thought to reside in the limbus, the transition zoon between cornea and conjunctiva. Keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF) are two paracrine factors that regulate the proliferation, migration and differentiation of the limbal epithelial cells; however, the underlying mechanisms are still poorly understood. In an ex vivo limbal explant culture, we found that KGF is a more potent growth stimulator for the epithelial outgrowth than HGF. Immunofluorescence studies of the epithelial outgrowth from cells treated with HGF or KGF showed similar expression patterns of keratin-3 and keratin-14. Interestingly, p63 was highly expressed in KGF-treated limbal epithelial sheets but not in those treated with HGF. Kinase inhibitor studies showed that induction of DeltaNp63alpha expression by KGF is mediated via the p38 pathway. The effect of KGF on limbal epithelial outgrowth was significantly reduced when endogenous DeltaNp63alpha was suppressed, suggesting that KGF-induced limbal epithelial outgrowth is dependent on the expression of DeltaNp63alpha. Our findings strongly suggest that limbal keratocytes regulate limbal epithelial cell growth and differentiation through a KGF paracrine loop, with DeltaNp63alpha expression as one of the downstream targets.
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Whispering gallery modes in a single silica microparticle attached to an optical microfiber and their application for highly sensitive displacement sensing. A compact and relatively stable structure is experimentally demonstrated to excite whispering gallery modes (WGMs) in a single chemically fabricated silica microparticles with a diameter of around 10.6 μm attached to an optical microfiber. The resonance dip with an extinction ratio of 14 dB and Q factor of around 300 has been achieved. Based on the WGMs in this structure, an in-line fiber-optic displacement sensor is presented with a high sensitivity of 33 dB/mm and a measurement range of over 400 μm. The measurement resolution of this displacement sensor can reach to ~10 μm. The good reversibility and repeatability are also verified. This work offers a scheme to observe the WGMs in a single silica microparticles and demonstrates their application for in-line highly-sensitive displacement sensing.
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"Action potentials" in Neurospora crassa, a mycelial fungus. Occasional spontaneous "action potentials" are found in mature hyphae of the fungus Neurospora crassa. They can arise either from low-level sinusoidal oscillations of the membrane potential or from a linear slow depolarization which accelerates into a rapid upstroke at a voltage 5-20 mV depolarized from the normal resting potential (near-180 mV). The "action potentials" are long-lasting, 1-2 min and at the peak reach a membrane potential near-40 mV. A 2-to 8-fold increase of membrane conductance accompanies the main depolarization, but a slight decrease of membrane conductance occurs during the slow depolarization. Two plausible mechanisms for the phenomenon are (a) periodic increases of membrane permeability to inorganic ions, particularly H+ or Cl- and (b) periodic decreases in activity of the major electrogenic pump (H+) or the Neurospora membrane, coupled with a nonlinear (inverse signoid) current-boltage relationship. Identification of action potential-like disturbances in fungi means that such behavior has now been found in all major biologic taxa which have been probed with suitable electrodes. As yet there is no obvious function for the events in fungi.
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Special prognostic phenomenon for patients with mid-range ejection fraction heart failure: a systematic review and meta-analysis. BACKGROUND Clinical features and outcomes of heart failure (HF) with mid-range ejection fraction (HFmrEF) remain controversial. Thus, we systematically reviewed literatures of clinical research to assess and analyze characteristics and prognosis of patients with HFmrEF. METHODS PubMed, Embase, and Web of Science were searched for cohort studies up to April 23, 2019. Clinical features and multivariate adjusted hazard ratios (HRs) of endpoints of short-term all-cause mortality (SAM), long-term all-cause mortality (LAM), long-term cardiovascular death (LCD) and long-term HF rehospitalization (LHR) among patients with HFmrEF and HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF) were well addressed. The primary outcome was LAM. RESULTS Totally 19 studies were included in this study with 164,678 patients enrolled. The follow-up time of LAM was 3.6 ± 2.5 years. HRs of LAM, SAM, LCD, LHR indicated that the risks of patients with HFmrEF were higher than HFpEF patients but lower than HFrEF patients, as for LAM, HFmrEF:HFpEF (reference) HR: 1.07, 95% confidence interval (CI): 1.00-1.15 (I = 63%, P = 0.0005); HFmrEF:HFrEF (reference) HR: 0.80, 95% CI: 0.73-0.88 (I = 70%, P < 0.0001). However, HFmrEF patients had the lowest rate in LAM (30.94%), SAM (2.73%), LCD (17.45%), LHR (26.36%) compared with the other two groups. CONCLUSIONS This systematic review and meta-analysis compared features and prognosis between patients with HFmrEF and HFpEF, HFrEF by HRs. There appeared a special "separation phenomenon" showing rates of endpoints were inconsistent with their hazards in patients with HFmrEF compared with HFpEF patients.
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Medical decision making for the incompetent patient. In America competent adult patients have a right to refuse unwanted medical treatments. For incompetent patients who have made no advance directive, the family ordinarily makes decisions about medical treatments. But in many healthcare facilities, problems arise in choosing a surrogate to make decisions for an incompetent patient and in working with that surrogate. Concrete, step-by-step procedures for resolving conflict are needed. Every effort should be made to have competent patients fill out advance directives or indicate their treatment preferences in the event of loss of competence. Family members may not override decisions made by competent patients, but anyone closely involved with the patients' care may question their competence. The physician generally assesses the patients' competence, but sometimes the courts are involved. The physician may be the appropriate person to choose a surrogate for a patient with limited competence or to make decisions for a totally incompetent patient. The surrogate may be a relative, close friend, physician who knows the patient well, or someone provided by the hospital or government. Treatment decisions are made within the surrogate-patient-physician triad. When different value judgments about the proper treatment conflict, the surrogate may have to mediate to restore physician-patient communication, or institutional proceedings through the ethics committee may be needed to resolve disputes quickly, amicably, and at low cost. As a last resort, the case may be referred to the courts.
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Structure-activity relationships of aryloxyalkanoic acid hydroxyamides as potent inhibitors of histone deacetylase. Syntheses of aryloxyalkanoic acid hydroxyamides are described, all of which are potent inhibitors of histone deacetylase, some being more potent in vitro than trichostatin A (IC(50)=3 nM). Variation of the substituents on the benzene ring as well as fusion of a second ring have marked effects on potency, in vitro IC(50) values down to 1 nM being obtained.
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Diagnostic Accuracy of Synovial Neopterin, TNF-α and Presepsin in Periprosthetic Joint Infection: A Prospective Study. BACKGROUND Due to the lack of specificity of conventional diagnostic tools, the prediction of periprosthetic joint infections (PJI) remains challenging. The purpose of this study was to evaluate the accuracy of synovial fluid neopterin, presepsin, and TNF-α as diagnostic parameters and to compare it to the biomarkers recommended in the 2018 definition of periprosthetic hip and knee infection. METHODS Between August 2018 and July 2019, a prospective cohort study was conducted in 80 patients with painful hip, shoulder, and knee arthroplasty. In addition to medical history, clinical and laboratory data were gathered. PJI was diagnosed based on the 2018 definition of periprosthetic hip and knee infection. Synovial joint fluid was analyzed for biomarker measurement using standard quantitative enzyme immunoassay kits. RESULTS Fifty-three patients (66%) were classified as the aseptic group and twenty-seven patients (34%) as the PJI group. The mean levels of synovial fluid neopterin were significantly higher (p < 0.01) in the PJI group than those in the aseptic group (aseptic 8.3 ± 6.9 vs. PJI 20.9 ± 21.4 nmol/L). The average values of synovial fluid TNF-α and presepsin were not significantly higher in the PJI group than those in the aseptic group (presepsin: aseptic 0.13 ± 0.19 vs. PJI 0.11 ± 0.32 ng/mL, p = 0.08; TNF-α: aseptic 6.6 ± 7.3 vs. PJI 46.3 ± 123.2 pg/mL, p = 0.17). Synovial fluid neopterin was 59% specific and 74% sensitive with a cut-off value of 7.2 nmol/L. The sensitivity and specificity of synovial fluid TNF-α were 63 and 51% with a cut-off value of 3.9 pg/mL. Synovial fluid presepsin was 51% specific and 29% sensitive with a cut-off value above 0.06 ng/mL. CONCLUSION Synovial fluid neopterin appears to a reliable diagnostic marker for detection of PJI. In contrast, synovial fluid TNF-α and presepsin are not suitable to exclude or diagnose PJI.
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Subcutaneous recombinant-human-erythropoietin prevents chemotherapy-related anemia in patients with advanced cancer. Nineteen patients with advanced cancer were randomly allocated to receive: (i) rhEpo 150 UI/kg subcutanously three times/week starting 24 hours after the completion of cisplatin- or carboplatin-based chemotherapy; or (ii) normal saline. There were 17 patients with advanced head and neck carcinoma and 2 patients with small cell lung cancer. Patients were monitored for hemoglobin level, hematocrit, WBC, PLT and reticulocytes. Patients who received rhEpo overall showed a 7.2 +/- 6.3% mean increase in Hb level over their pretreatment values, while control patients had a 26.4 +/- 12% decrease. This difference was statistically significant (p<0.001). No patients in the rhEpo group required transfusion, while 4 patients in the control group received packed red cell transfusion. No significant side-effects attributable to rhEpo were recorded, but 1 patient showed a transitory increase in PLT count. In conclusion, subcutaneous rhEpo may be safely administered to patients with advanced cancer and effectively prevents cisplatin- or carboplatin-related anemia.
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Feasibility and efficacy of pairing fecal immunochemical testing with mammography for increasing colorectal cancer screening among uninsured Latinas in northern Manhattan. OBJECTIVES We evaluated the feasibility and efficacy of a program to promote colorectal cancer screening (CRC) among uninsured Latinas receiving mammography through a cancer screening clinic in northern Manhattan. METHODS Between August 2009 and March 2010, unscreened, average CRC risk, uninsured Latinas, aged 50-64 years, undergoing mammography received a screening recommendation, education, and fecal immunochemical test (FIT). Socio-demographic information and level of acculturation was collected. Screening compliance was assessed. RESULTS Of 651 Latinas evaluated, 210 were eligible and, of these, 94% (n=197) consented to participate; 441 were excluded because they were up-to-date with CRC screening (n=130), < 50 (n=285) or >64 (n=26) years of age. After intervention, 177 (90%) completed FIT. Within 2 weeks, 87% completed the FIT, and 69% did so with no reminder calls. Acculturation was significantly lower among screeners (p=0.014). Compared with non-screeners, screeners were more likely to be foreign-born (p=0.009), to speak only Spanish (p=0.043), and to prefer to read (p=0.037), and think (p=0.015) in Spanish. CONCLUSION This study suggests that pairing CRC education and screening with mammography is both feasible and efficacious.
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Effectiveness and cost-effectiveness of first BCG vaccination against tuberculosis in school-age children without previous tuberculin test (BCG-REVAC trial): a cluster-randomised trial. BACKGROUND Neonatal BCG vaccination is part of routine vaccination schedules in many developing countries; vaccination at school age has not been assessed in trials in low-income and middle-income countries. Catch-up BCG vaccination of school-age children who missed neonatal BCG vaccination could be indicated if it confers protection and is cost-effective. We did a cluster-randomised trial (BCG REVAC) to estimate the effectiveness (efficacy given in routine settings) of school-age vaccination. METHODS We assessed the effectiveness of BCG vaccination in school-age children (aged 7-14 years) with unknown tuberculin status who did not receive neonatal BCG vaccination (subpopulation of the BCG REVAC cluster-randomised trial), between July, 1997, and June, 2006, in Salvador, Brazil, and between January, 1999, and December, 2007, in Manaus, Brazil. 763 schools were randomly assigned into BCG vaccination group or a not-vaccinated control group. Neither allocation nor intervention was concealed. Incidence of tuberculosis was the primary outcome. Cases were identified via the Brazilian Tuberculosis Control Programme. Study staff were masked to vaccination status when identified cases were linked to the study population. We estimated cost-effectiveness in Salvador by comparison of the cost for vaccination to prevent one case of tuberculosis (censored at 9 years) with the average cost of treating one case of tuberculosis. Analysis of all included children was by intention to treat. For calculation of the incidence rate we used generalised estimating equations and correlated observations over time. FINDINGS We randomly assigned 20,622 children from 385 schools to the BCG vaccination group and 18,507 children from 365 schools to the control group. The crude incidence of tuberculosis was 54·9 (95% CI 45·3-66·7) per 100,000 person-years in the BCG vaccination group and 72·7 (62·8-86·8) per 100,000 person-years in the control group. The overall vaccine effectiveness of a first BCG vaccination at school age was 25% (3-43%). In Salvador, where vaccine effectiveness was 34% (8-53%), vaccination of 381 children would prevent one case of tuberculosis and was cheaper than treatment. The frequency of adverse events was very low with only one axillary lymphadenitis and one ulcer greater than 1 cm in 11,980 BCG vaccinations. INTERPRETATION Vaccination of school-age children without previous tuberculin testing can reduce the incidence of tuberculosis and could reduce the costs of tuberculosis control. Restriction of BCG vaccination to the first year of life is not in the best interests of the public nor of programmes for tuberculosis control. FUNDING UK Department for International Development, National Health Foundation.
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Sero-epidemiology of hepatitis E virus (HEV) in urban and rural children of North India. OBJECTIVE To estimate the prevalence of anti-HEV IgG and IgM antibodies to ORF3 peptide of Hepatitis E virus genome in an age stratified urban and rural population of children. DESIGN Cross sectional survey. SETTING Pediatric out-patient clinics in a tertiary hospital and a rural dispensary. METHODS Study subjects between 6 months and 10 years with minor, non-hepatic illnesses were recruited for the study from March to December 1996. Baseline demographic details, drinking water source, sewage disposal methods, reasons for attending the hospital, histories of parenteral exposure in the past 12 months and acute hepatitis in the subjects and the family in the previous six months were obtained. Serum anti-HEV IgG antibodies were screened in all subjects, and in those who were positive, anti-HEV IgM antibodies were assayed as an indicator of recent infection. Serum aminotransferase (ALT) was estimated in those who were anti-HEV IgM antibody positive. RESULT Out of 2160 subjects recruited, 2070 samples could be screened for anti-HEV IgG antibodies. In the urban population (n = 1065) anti-HEV IgG antibodies were detected in 306 subjects (28.7%; 95% CI 26.0-31.6) and of these 131 (42.8%; 95%CI 37.2-48.6) were anti-HEV IgM antibody positive. Amongst 1005 rural children, anti-HEV IgG antibodies were present in 239 (23.8%; 95% CI 21.1-26.4) and IgM antibodies in 113 (47.3%; 95% CI 40.9-53.7) children. The antibodies were present since the first year of age till 10 years of age and, increased with advancing age. Serum transaminases were raised in 7.5% (9/120) and 5.5% (5/88) of subjects with anti-HEV IgM antibodies in urban and rural centers respectively. Overall the seroprevalence of IgG antibodies against HEV were significantly more in urban as compared to that in rural subjects (p = 0.011). However, proportion of children with anti-HEV IgG carrying IgM antibodies was similar in the two study groups (p = 0.298). A model for estimating expected prevalence of anti-HEV IgG antibodies was developed. The observed antibody prevalence in both urban and rural subjects at each age interval after 48 months was less as compared to the expected levels and this gap increased with advancing age categories. It appeared that there was a decay of HEV antibodies with time. CONCLUSIONS Children are susceptible to HEV infection since early infancy. The probability of exposure to HEV during childhood was higher in urban than rural population. Seropositivity to HEV antibodies increased by over 2 times beyond 4 years of age as compared to younger age. Anti-HEV IgG antibodies appear to wean off with increasing age.
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Intracellular accommodation of microbes by plants: a common developmental program for symbiosis and disease? Plant cells engage in mutualistic and parasitic endosymbioses with a wide variety of microorganisms, ranging from Gram-negative (Rhizobium, Nostoc) and Gram-positive bacteria (Frankia), to oomycetes (Phytophthora), Chytridiomycetes, Zygomycetes (arbuscular mycorrhizal fungi) and true fungi (Erysiphe, ascomycete; Puccinia, basidiomycete). Endosymbiosis is characterised by the 'symbiosome', a compartment within host cells in which the symbiotic microorganism is either partially or completely enclosed by a host-derived membrane. The analysis of plant mutants indicates that the genetic requirements for the interaction with rhizobia and arbuscular mycorrhiza fungi are partially overlapping. The extent to which plants use similar or identical developmental programs for the intracellular accommodation of different microorganisms is, however, not clear. For example, plant cells actively weaken their cell wall to facilitate bacterial colonisation, whereas penetration by fungal symbionts appears not to be assisted in this manner. Moreover, different transport requirements are imposed on the symbiotic interface of different interactions indicating that additional system-specific components are likely to exist.
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Impact of new-onset diabetes on clinical outcomes after ST segment-elevated myocardial infarction. Objective. Patients with diabetes have higher mortality rate than patients without diabetes after ST-segment elevated myocardial infarction (STEMI). Prognosis of patients with new onset diabetes (NOD) after STEMI remains unclear. The aim of this study was to evaluate the prognosis of patients with NOD compared to that of patients without NOD after STEMI. Design. This study was a retrospective observational study. We enrolled 901 STEMI patients. Patients were divided into diabetic and non-diabetic groups at index admission. Non-diabetic group was divided into NOD and non-NOD groups. Kaplan-Meier analysis and Cox's proportional hazard regression models were used to compare major adverse cardiac events (MACE) free survival rate and hazard ratio for MACE between NOD and non-NOD groups. Results. Mean follow-up period was 59 ± 28 months. Diabetes group had higher MACE than non-diabetes group (p = .038). However, MACE was not different between NOD and non-NOD groups (p = 1.000). After 1:2 propensity score matching, incidence of MACE was not different between the two groups. In Kaplan-Meier survival curves, MACE-free survival rates were not statistically different between NOD and non-NOD groups either (p = .244). Adjusted hazard ratios of NOD for MACE, all-cause of death, recurrent myocardial infarction, and target vessel revascularization were 0.697 (95% confidence interval [CI]: 0.362-1.345, p = .282), 0.625 (95% CI: 0.179-2.183, p = .461), 0.794 (95% CI: 0.223-2.835, p = .723), and 0.506 (95% CI: 0.196-1.303, p = .158), respectively. Conclusion. This retrospective observational study with a limited statistical power did not show a different prognosis in patients with and without NOD.
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Occupational risk of Lyme disease in endemic areas of New York State. Although Lyme disease (LD) is the most common tick-borne disease in the United States, little is known about the frequency of and risk factors for infection with Borrelia burgdorferi in occupational groups. In 1986, we recruited primarily outdoor workers from six employee groups in southeastern New York where LD is endemic. Of 414 participants who completed questionnaires and had blood samples tested for antibodies against B. burgdorferi by ELISA and Western immunoblot, 27 (6.5%) were seropositive, but only 14 of the 27 reported previous symptoms of LD. Persons who spent more than 30 hours per week outdoors during leisure were 2.5 times more likely to be seropositive than those who did not (p = .02). Those with a history of outdoor employment were twice as likely to be seropositive as those without such a history, although this finding was not statistically significant (p = .70). However, the seroprevalence rate for the employees was 5.9 times higher than the rate for a comparison group of anonymous blood donors from the same region of New York (p less than .001). These results suggest that there was a relatively high rate of seropositivity for the employee groups and that infection was frequently asymptomatic and associated with outdoor exposure.
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A Retrospective Evaluation of Secondary Wound Healing for Extraction of the Maxillary First Molar in Dogs. Oral surgery and exodontia can present challenges in veterinary patients, with a particular area of challenge being extraction and closure of the maxillary first molar (M1) in dogs. This retrospective assessment evaluated patients that had the maxillary first molar extracted with placement of a cruciate suture across the alveolus to achieve partial closure and secure the blood clot. Patients that had teeth extracted adjacent to M1 (maxillary fourth premolar [PM4] or second molar [M2]) were excluded from the study. Three groups of patients were assessed: Group A - at the time of extraction of M1, both the maxillary PM4 and M2 were still present in the oral cavity. Group B - at the time of M1extraction only PM4 or M2 was present, but not both. The tissue was completely intact at the location of the missing tooth. Group C - at the time of M1 extraction neither PM4 or M2 were present, but tissue in these locations was intact. In a three-and-a half-year time period (2015-2018), 179 dogs with 213 solitary M1 extractions were performed. Of these 213 extraction sites, 127 sites (60%) had follow up examination within a two-week postoperative period. Of these 127 sites, 126 (99.2%) appeared appropriately healed without complication. The results of this retrospective evaluation demonstrate that primary closure of a maxillary first molar extraction site may not be required for appropriate soft tissue wound healing in canine patients.
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Deliberate burns in Nigerians. Eleven cases of deliberate burns in Nigerians were studied. Three major reasons for burning were recognized. Ignorance was identified as a factor in the aetiology of some of these avoidable burns. Primary prevention of the burns and the secondary prevention of their complications are outlined. The management of the patients is discussed.
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Evaluation of different laboratory tests and activity indices reflecting the inflammatory activity of Crohn's disease. In a prospective study we compared the usefulness of various laboratory tests (albumin, alpha-1-proteinase inhibitor (A1PI), cholinesterase (CHE), C-reactive protein, erythrocyte sedimentation rate, hematocrit) and activity indices (CDAI, VHAI) in relation to the disease activity by endoscopic criteria. Except for hematocrit highly significant differences (p less than 0.0005) of the mean values of all test results were found for patients without or with slight mucosal lesions compared with patients with severe inflammation of the mucosa. Further analysis of the data indicates the highest test efficiency (84%), sensitivity (80%), and specificity (88.6%) for CHE. CHE showed good correlations to all other tests; the highest correlation was found between CHE and VHAI (r = -0.78). We suggest that a suppression of CHE synthesis mediated by endotoxins and cytokines rather than an increased intestinal loss explains the decreased CHE in severe Crohn's disease. It is concluded from the data that CHE is a useful test to assess the inflammatory activity of Crohn's disease.
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Facilitating factors and barriers to kangaroo mother care utilisation in low- and middle-income countries: A scoping review. BACKGROUND Kangaroo mother care (KMC) has been widely adopted in low-and middle-income countries (LMICs) to minimise low birthweight infants' (LBWIs) adverse outcomes. However, the burden of neonatal and child mortality remains disproportionately high in LMICs. AIM Thus, this scoping review sought to map evidence on the barriers, challenges and facilitators of KMC utilisation by parents of LBWIs (parent of low birthweight infant [PLBWI]) in LMICs. METHODS We searched for studies conducted in LMICs and published in English between January 1990 and August 2020 from SciELO, Google Scholar, JSTOR, LILACS, Academic search complete, PubMed, CINAHL with full text, and Medline databases. We adopted Arksey and O'Malley's framework for conducting scoping reviews. Potential studies were exported to Endnote X7 reference management software for abstract and full article screening. Two independent reviewers did a parallel abstract and full article screening using a standardised form. The results were analysed using thematic content analysis. RESULTS We generated 22 040 studies and after duplicate removal, 42 studies were eligible for full-text screening and 22 studies, most form sub-Saharan Africa, were included in the content analysis. Eight themes emerged from the analysis: access, buy-in, co-ordination and collaboration, medical issues, motivation, social support-gender obligation and empowerment, time and timing and traditional/cultural norms. CONCLUSION Identifying factors affecting KMC may optimise KMC utilisation. Additional studies aiming at identifying influencing factors that affect KMC utilisation amongst PLBWIs' in LMICs need to be conducted to provide evidence-based strategies to enhance practice, inform policy and decision-makers in KMC utilisation amongst the PLBWIs in LMICs and beyond.
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ZFP57 regulation of transposable elements and gene expression within and beyond imprinted domains. BACKGROUND KRAB zinc finger proteins (KZFPs) represent one of the largest families of DNA-binding proteins in vertebrate genomes and appear to have evolved to silence transposable elements (TEs) including endogenous retroviruses through sequence-specific targeting of repressive chromatin states. ZFP57 is required to maintain the post-fertilization DNA methylation memory of parental origin at genomic imprints. Here we conduct RNA-seq and ChIP-seq analyses in normal and ZFP57 mutant mouse ES cells to understand the relative importance of ZFP57 at imprints, unique and repetitive regions of the genome. RESULTS Over 80% of ZFP57 targets are TEs, however, ZFP57 is not essential for their repression. The remaining targets lie within unique imprinted and non-imprinted sequences. Though the loss of ZFP57 influences imprinted genes as expected, the majority of unique gene targets lose H3K9me3 with little effect on DNA methylation and very few exhibit alterations in expression. Comparison of ZFP57 mutants with DNA methyltransferase-deleted ES cells (TKO) identifies a remarkably similar pattern of H3K9me3 loss across the genome. These data define regions where H3K9me3 is secondary to DNA methylation and we propose that ZFP57 is the principal if not sole methylation-sensitive KZFP in mouse ES cells. Finally, we examine dynamics of DNA and H3K9 methylation during pre-implantation development and show that sites bound by ZFP57 in ES cells maintain DNA methylation and H3K9me3 at imprints and at non-imprinted regions on the maternally inherited chromosome throughout preimplantation development. CONCLUSION Our analyses suggest the evolution of a rare DNA methylation-sensitive KZFP that is not essential for repeat silencing, but whose primary function is to maintain DNA methylation and repressive histone marks at germline-derived imprinting control regions.
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Plasmonic-enhanced efficiency of AlGaN-based deep ultraviolet LED by graphene/Al nanoparticles/graphene hybrid structure. The AlGaN-based deep ultraviolet light-emitting diode (DUV LED) has advantages of environmentally friendly materials, tunable emission wavelength, and easy miniaturization. However, the light extraction efficiency (LEE) of an AlGaN-based DUV LED is low, which hinders its applications. Here, we design a graphene/Al nanoparticles/graphene (Gra/Al NPs/Gra) hybrid plasmonic structure, where the strong resonant coupling of local surface plasmons (LSPs) induces a 2.9-times enhancement for the LEE of the DUV LED according to the photoluminescence (PL). The dewetting of Al NPs on a graphene layer by annealing is optimized, resulting in better formation and uniform distribution. The near-field coupling of Gra/Al NPs/Gra is enhanced via charge transfer among graphene and Al NPs. In addition, the skin depth increment results in more excitons being coupled out of multiple quantum wells (MQWs). An enhanced mechanism is proposed, revealing that the Gra/metal NPs/Gra offers a reliable strategy for improving the optoelectronic device performance, which might trigger the advances of LEDs and lasers with high brightness and power density.
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Dissociation between metabolic and contractile responses during intermittent isometric exercise in man. This study examines the temporal changes in high-energy phosphate and metabolic levels, and in force-generating capacity, during and after voluntary submaximal repetitive isometric exercise (RIE). Eight male subjects performed one-legged RIE with the knee extensors at 40% maximum voluntary contraction (MVC) target force (duty cycle: 6 s contraction, 4 s rest) in a 48 cm bore whole body 1.5 T superconducting magnet. Phosphocreatine (PCr), inorganic phosphate (P(i)), ATP and pH were measured every 9 s. Force-generating capacity was repeatedly measured using MVC force and electrically stimulated contractions (sequential train of impulses of 1-100 Hz). During RIE, MVC declined gradually by 56 +/- 5% (mean +/- S.E.M.). Electrically stimulated force also declined, with a disproportionally large drop in low-frequency force, seen as a decline from 0.76 +/- 0.02 to 0.33 +/- 0.02 in 20:50 Hz force ratio. The PCr decline during RIE was 65 +/- 9%, in most subjects seen as a rapid initial drop followed by less or no further decline to exhaustion. pH declined in parallel by 0.18 +/- 0.04 units, whilst ATP levels remained unchanged throughout the exercise. PCr, P(i) and pH recovered to near control values within 5 min of exhaustion. Force, however, was not fully restored after 30 min recovery. The results support the hypothesis that fatigue from submaximal RIE is unrelated to changes in P(i) and H+ levels. The decline in 20:50 Hz force ratio implies that fatigue may be associated with excitation-contraction coupling impairment. No sudden changes were observed in mechanical or metabolic factors at exhaustion. Exhaustion was probably not caused by lack of substrates for ATP resynthesis, since pH had decreased only marginally.
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Microbacterium protaetiae sp. nov., isolated from gut of larva of Protaetia brevitarsis seulensis. A Gram-stain-positive, strictly aerobic, polar flagellated, short rod-shaped bacterium, designated DFW100M-13T, was isolated from gut of the larva of Protaetia brevitarsis seulensis collected from Wanju-gun, South Korea. The growth range of NaCl concentration was 0-3 % (w/v) (optimally 0 % (w/v)), the temperature range for growth was 10-40 °C (optimally 28-30 °C), and the pH range for growth was pH 6.0-9.0 (optimally pH 7.0-8.0). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain DFW100M-13T had a high sequence similarity to members of the genus Microbacterium, having the highest similarity with Microbacterium luticocti DSM 19459T (97.7 %), Microbacterium rhizosphaerae CHO1T (97.1 %), and Microbacterium immunditiarum SK 18T (97.0 %), and formed a distinct lineage with Microbacterium luticocti DSM 19459T within the genus Microbacterium. A phylogenetic tree based on house-keeping genes also showed the result similar to the 16S rRNA gene-based tree. The main respiratory quinone (>10 %) was MK-11, MK-12 and MK-10, and the predominant cellular fatty acids (>10 %) were iso-C16 : 0, anteiso-C17 : 0 and anteiso-C15 : 0. The polar lipids were composed of diphosphatidylglycerol, phosphatidylglycerol, an inidentified glycolipid and an unidnetified lipid. The peptidoglycan type was supposed to be the B2ß with amino acids d-alanine, d-glutamic acid, glycine, l-homoserine and d-ornithine. The genomic DNA G+C content was 68.0 mol%. Based on the polyphasic taxonomic data, strain DFW100M-13T is considered to represent a novel species, for which the name Microbacterium protaetiae sp. nov. is proposed. The type strain is DFW100M-13T (=KACC 19323T=NBRC 113120T).
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Role of antioxidants in the protection against oxidative stress in cattle--trace elements and enzymatic mechanisms (Part 3). The most important enzymatic mechanisms which protect an organism against oxidative stress are superoxide dismutase (SOD), peroxidase (Px), e.g. glutathione peroxidase (GSH-Px) and ascorbate peroxidase, catalase and glutathione reductase. Their activity depends on many trace elements. Enzymatic mechanisms, functioning under physiological conditions, prevent the spread of free radical reactions. New and reoccurring metabolic and infectious diseases of cattle emerge when there is a disproportion in the balance between reactive oxygen species and antioxidative enzymatic barrier.
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Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease. Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning. We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation. These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.
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Gene expression profiling in C57BL/6J and A/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background. BACKGROUND We performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL/6J and A/J. The selected brain areas are implicated in neurobehavioral traits while these mouse strains are known to differ widely in behavior. Consequently, we hypothesized that comparing gene expression profiles for specific brain regions in these strains might provide insight into the molecular mechanisms of human neuropsychiatric traits. We performed a whole-genome gene expression experiment and applied a systems biology approach using weighted gene co-expression network analysis. RESULTS We were able to identify modules of co-expressed genes that distinguish a strain or brain region. Analysis of the networks that are most informative for hippocampus and amygdala revealed enrichment in neurologically, genetically and psychologically related pathways. Close examination of the strain-specific gene expression profiles, however, revealed no functional relevance but a significant enrichment of single nucleotide polymorphisms in the probe sequences used for array hybridization. This artifact was not observed for the modules of co-expressed genes that distinguish amygdala and hippocampus. CONCLUSIONS The brain-region specific modules were found to be independent of genetic background and are therefore likely to represent biologically relevant molecular networks that can be studied to complement our knowledge about pathways in neuropsychiatric disease.
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Applications of ammonium formate-catalytic transfer hydrogenation. Part V (1). Transfer hydrogenolysis of peptides containing p-chlorophenylalanine as a convenient method for preparation of deuterium labeled peptides. Dehalogenation of chlorine bound to aromatic nuclei has been achieved using ammonium formate-catalytic transfer hydrogenation (AF-CTH) techniques. The use of deuterated ammonium formate as the transfer agent in the CTH process when performed in a deuterated solvent medium results in the predominant formation of the labeled product. Thus, ND+4 DCOO(-)-CTH of [D-Ala2, p-ClPhe4]-Leu-enkephalin in 80% CD3COOD/D2O yielded [D-Ala2, Phe (4D)4]-Leu-enkephalin. Levels of D-incorporation were measured by fast atom bombardment-mass spectrometry (FAB-MS) and/or by 13C n.m.r. spectroscopy. Using D-labeled and unlabeled ammonium formate in stoichiometrically similar reactions, it was concluded that the hydrogenation exhibited a primary kinetic isotope effect. Reactant and product concentrations were determined by amino acid analysis and reversed phase HPLC.
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Modelling the efficiency of codon-tRNA interactions based on codon usage bias. The tRNA adaptation index (tAI) is a widely used measure of the efficiency by which a coding sequence is recognized by the intra-cellular tRNA pool. This index includes among others weights that represent wobble interactions between codons and tRNA molecules. Currently, these weights are based only on the gene expression in Saccharomyces cerevisiae. However, the efficiencies of the different codon-tRNA interactions are expected to vary among different organisms. In this study, we suggest a new approach for adjusting the tAI weights to any target model organism without the need for gene expression measurements. Our method is based on optimizing the correlation between the tAI and a measure of codon usage bias. Here, we show that in non-fungal the new tAI weights predict protein abundance significantly better than the traditional tAI weights. The unique tRNA-codon adaptation weights computed for 100 different organisms exhibit a significant correlation with evolutionary distance. The reported results demonstrate the usefulness of the new measure in future genomic studies.
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Risk factors for female breast cancer. A hospital-based case-control study in Madras, India. Five hundred and thirty-one histologically confirmed breast carcinoma cases examined from 1983 to 1986 inclusive at the Cancer Institute (WIA), Madras, India, were matched for age, socioeconomic class and menopausal status with an equal number of controls. Cancer patients without diseases in breast, gynaecological organs or endocrine glands were used as controls. Risk factors for breast cancer were analyzed separately in the premenopausal and the postmenopausal groups. In neither group was there significant association between age at menarche and breast cancer risk. Single women had higher risk than married women. Nulliparity was found to be a risk factor in premenopausal women only. The relative risk increased with age at marriage and age at first birth. A three-fold risk was noted in both pre- and postmenopausal groups when the interval between age at first birth and menarche was more than 12 years and also in women who attained menopause between the age of 44-49.
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+331G/A variant in the progesterone receptor gene, postmenopausal hormone use and risk of breast cancer. A functional promoter polymorphism in the progesterone receptor (PR) gene previously has been associated with an increased risk of postmenopausal breast cancer. Whether the relationship between genetic variation in PR and risk of breast cancer is modified by postmenopausal hormone (PMH) use is unknown. Thus, we conducted a case-control study nested within the prospective Nurses' Health Study to evaluate if the risk of breast cancer associated with having the +331 A risk allele was modified by PMH use. Genotyping of this SNP was available for 1,664 postmenopausal breast cancer cases and 2,391 controls. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer. Women who were carriers of 1 or both variant A alleles had a 31% increased risk of developing breast cancer (95% CI 1.04-1.65). PMH use significantly modified the association between the +331G/A polymorphism and risk (p-interaction <0.05). Among never users of PMH, women who were variant carriers had a significantly increased risk of breast cancer compared to those with the wild-type genotype (OR = 2.57; 95% CI 1.64-4.02). The +331G/A polymorphism was not associated with breast cancer risk among past (OR = 1.23; 95% CI 0.77-1.97) or current (OR = 1.14; 95% CI 0.84-1.56) PMH users. The data from this large prospective study provide evidence for a 2-fold increased risk of developing postmenopausal breast cancer among never users of PMH with the +331G/A SNP. This finding adds to the evidence that the PR has an important etiologic role in breast cancer and should be evaluated in future studies.
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Trisomy 13 syndrome and neural tube defects. Abnormalities of the CNS, such as arhinencephaly or holoprosencephaly, are common findings in trisomy 13 syndrome. However, neural tube defects (NTDs) are rarely reported. A review of 267 patients in the literature on reported CNS developmental defects in trisomy 13 syndrome showed only 6 patients with lumbosacral NTDs. No case of encephalocele or anencephaly was found. We report on 3 patients with spina bifida from the records of 34 necropsies of karyotyped trisomy 13 syndrome, which were found among 403,710 births.
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Severe hypermagnesemia presenting with abnormal electrocardiographic findings similar to those of hyperkalemia in a child undergoing peritoneal dialysis. In this report, we present a pediatric case of severe symptomatic hypermagnesemia resulting from the use of magnesium oxide as a laxative in a child undergoing continuous cyclic peritoneal dialysis for end-stage renal disease. The patient showed abnormal electrocardiography (ECG) findings, such as tall T waves, a widened QRS complex, and irregular conduction, which were initially misdiagnosed as hyperkalemia; later, the correct diagnosis of hypermagnesemia was obtained. Emergent hemodialysis successfully returned the serum magnesium concentration to normal without complications. When abnormal ECG changes are detected in patients with renal failure, hypermagnesemia should be considered.
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On the role of volume transmission and receptor-receptor interactions in social behaviour: focus on central catecholamine and oxytocin neurons. This article is focused on understanding the mechanisms for the interactions between the central catecholamine (CA) and oxytocin (OXY) neurons and their relevance for brain function especially social behaviour in the field of pair bonding. Such a topic is analysed under two perspectives namely the intercellular communication modes between CA and OXT neurons and the molecular integrative mechanisms at the plasma membrane level between their respective decoding systems. As a matter of fact, recent observations strongly indicate a major role of volume transmission and receptor-receptor interactions in the CA/OXT neuron interplay in the brain control of social behaviour and pair bonding. This article is part of a Special Issue entitled: Brain Integration.
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Shave biopsy technique and hemostasis pearl. Nurse practitioners (NPs) are frequently called on to assess and diagnose patients presenting with suspicious or aggravated skin lesions. Performing shave biopsies and removing small neoplasms can be within the scope of a general NP. We offer a thorough review of shave biopsy methods, including required materials, photographic documentation, blade preparation and orientation, and hemostasis techniques. Diagnostic considerations when choosing a shave versus other biopsy techniques are reviewed as is the removal of lesions in cosmetically sensitive areas. Finally, a unique tip to diminish intraprocedure bleeding using aluminum chloride before procedure initiation is presented.
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Impact of structure and morphology on charge transport in semiconducting oligomeric thin-film devices. We investigated various thin-film morphologies of vacuum-deposited highly luminescent 2,5-di-n-octyloxy-1,4-bis[4'-(styryl)styryl]benzene (Ooct-OPV5) in a typical light-emitting-diode device structure. Important modifications in the thin-film morphology and structure were obtained by changing the substrate temperature in the range 23-90 degrees C. Structural analysis by X-ray and electron diffraction provided clear evidence for polymorphism in evaporated thin films of Ooct-OPV5. Concomitantly, the hole mobility in the corresponding devices was determined by transient electroluminescence measurements. We demonstrate that the substrate temperature T(sub) is a key parameter that controls the hole mobility of the devices. Increasing T(sub) between 23 and 84 degrees C results in a progressive increase of the zero-field hole mobility from 10(-6) to 10(-4) cm(2) V(-1) s(-1). The increase in hole mobility is correlated to the average grain size in the thin films. In addition, we give evidence for the existence of a peculiar growth mode in the bulk crystal structure of Ooct-OPV5, whereby the (a,b) and (b,c) planes can grow in a homoepitaxial manner.
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Follow-up of patients diagnosed with and treated for tuberculosis in Brazil: financial burden on the household. OBJECTIVE To evaluate the implications of the proportion of annual family income spent in the pre- and post-diagnosis periods in tuberculosis patients followed for after at least one year after completing tuberculosis treatment in Brazil. METHODS This was a cross-sectional study of tuberculosis patients followed for at least one year after completing tuberculosis treatment in five Brazilian capitals (one in each region of the country). RESULTS A total of 62 patients were included in the analysis. The overall average cost of tuberculosis was 283.84 Brazilian reals (R$) in the pre-diagnosis period and R$4,161.86 in the post-diagnosis period. After the costs of tuberculosis disease, 71% of the patients became unemployed, with an overall increase in unemployment; in addition, the number of patients living in nonpoverty decreased by 5%, the number of patients living in poverty increased by 6%, and the number of patients living in extreme poverty increased by 5%. The largest proportion of annual household income to cover the total costs of tuberculosis was for the extremely poor (i.e., 40.37% vs. 11.43% for the less poor). CONCLUSIONS Policies to mitigate catastrophic costs should include interventions planned by the health care system and social protection measures for tuberculosis patients with lower incomes in order to eliminate the global tuberculosis epidemic by 2035-a WHO goal in line with the United Nations Sustainable Development Goals.
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Intentional Subtotal Resection of Vestibular Schwannoma: A Reexamination. Background  Treatment of vestibular schwannomas (VS) remains controversial. Historical surgical series prioritized gross total resections (GTR); however, near total resections (NTR) and intentional subtotal resections (STR) aiming at improving cranial nerve outcomes are becoming more popular. Objective  The main purpose of this article is to assess the tumor control and facial nerve outcomes in VS patients treated with STR or NTR. Methods  VS patients undergoing STR or NTR at our institution between 1984 and 2016 were retrospectively reviewed. Patient demographics, extent of tumor resection, facial nerve injury, tumor recurrence, and need for Gamma Knife radiosurgery were analyzed. Facial nerve outcomes were quantified using House-Brackmann (HB) scores. Tumor regrowth was defined by the San Francisco criteria. Results  Four-hundred fifty-seven VS resections were performed in a 32-year period. Sixty cases met inclusion criteria. The mean (range) follow-up duration was 30.9 (12-103) months. The STR cohort ( n  = 33) demonstrated regrowth in 12 patients (36.3%) at an average of 23.6 months. The NTR cohort ( n  = 27) did not experience tumor recurrence. Risk of tumor recurrence was positively correlated with preoperative tumor size ( p  = 0.002), size of residual tumor ( p  < 0.001), and STR ( p  < 0.001). Facial nerve outcomes of HB1-2 were observed in the majority of patients in both cohorts (74.1% NTR, 56% STR), though NTR was associated with a higher likelihood of facial nerve recovery ( p  = 0.003). Conclusion  GTR remains the gold standard as long as facial nerve outcomes remain acceptable. NTR achieved superior tumor control and higher likelihood of facial nerve recovery compared with STR.
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Lineage skewing and genome instability underlie marrow failure in a zebrafish model of GATA2 deficiency. Inherited bone marrow failure associated with heterozygous mutations in GATA2 predisposes toward hematological malignancies, but the mechanisms remain poorly understood. Here, we investigate the mechanistic basis of marrow failure in a zebrafish model of GATA2 deficiency. Single-cell transcriptomics and chromatin accessibility assays reveal that loss of gata2a leads to skewing toward the erythroid lineage at the expense of myeloid cells, associated with loss of cebpa expression and decreased PU.1 and CEBPA transcription factor accessibility in hematopoietic stem and progenitor cells (HSPCs). Furthermore, gata2a mutants show impaired expression of npm1a, the zebrafish NPM1 ortholog. Progressive loss of npm1a in HSPCs is associated with elevated levels of DNA damage in gata2a mutants. Thus, Gata2a maintains myeloid lineage priming through cebpa and protects against genome instability and marrow failure by maintaining expression of npm1a. Our results establish a potential mechanism underlying bone marrow failure in GATA2 deficiency.
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Effects of motor cortex and single muscle stimulation on neurons of the lateral vestibular nucleus in the rat. The neuronal responses to stimulation of motor cortical sites and of forelimb single muscles were studied in the lateral vestibular nucleus of anaesthetized rats. Of the 228 neurons tested for response to stimulation of contralateral motor cortex, 63% responded to cortical sites controlling extensor muscles and 30% to those controlling flexors. The corresponding figures for responders to ipsilateral stimulation were 34 and 21%. Vestibulospinal units responded to cortical sites controlling extensor and flexor muscles whereas the remaining lateral vestibular nucleus neurons, very reactive to cortical sites controlling extensor muscles, responded little to contralateral and not at all to ipsilateral cortical sites controlling flexor muscles. The effects evoked by contralateral cortical sites controlling extensors varied, those induced by cortical sites controlling flexors were inhibitory in 77% of cases. The responses to ipsilateral motor cortex stimulation differed not so much by cortical sites controlling extensor or flexor muscles as by whether the neuron was in the dorsal or ventral zone of the lateral vestibular nucleus: mixed in the former, all inhibitory in the latter. Of the lateral vestibular nucleus units tested for response to stimulation of ipsilateral or contralateral forelimb distal muscles, only 11% responded. All the vestibulospinal units responsive to muscle stimulation lay in the dorsal zone of the nucleus. The remainder, dorsal or ventral, were not responsive to contralateral muscles. Single lateral vestibular nucleus cells influenced both by ipsilateral muscle and by contralateral motor cortex made up 24% of the pool, vestibulospinal and non-vestibulospinal. They fell into three groups: responsive to one or both structures but responding more strongly to combined stimulation; responsive to each of the two structures but showing a response to combined stimulation not significantly different from that evoked by the cortex alone; responsive only to combined stimulation. The lateral vestibular nucleus units included in these three groups accounted for 29% of those tested for response to extensor muscles and cortical sites controlling extensors and 15% of those tested for response to flexor muscles and cortical sites controlling flexors. Twenty-five per cent of the vestibulospinal neurons responded both to contralateral muscles and to ipsilateral motor cortex stimulation but none of the non-vestibulospinal neurons responded to both. All the responders to both were in the dorsal zone of the lateral vestibular nucleus and responded to extensor stimuli, always in the same way. These results indicate that motor cortex output exerts a major influence on lateral vestibular nucleus discharges, while the muscle afferents have a modulatory influence on the lateral vestibular nucleus responses to cortex.(ABSTRACT TRUNCATED AT 400 WORDS)
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Course of the masseteric nerve in masseter muscle. The masseter muscle is often exploited by plastic and reconstructive surgeons in transposition operations to correct facial palsy. In benign masseteric hypertrophy, a neurectomy induces atrophy of the muscle and therefore a slender face. A clear understanding of the course of the masseteric nerve is essential in maneuvering the masseter muscle. Detailed dissection was performed on 48 head halves of Korean cadavers, and the inside of each masseter muscle was explored under the microscope with x10 magnification. The masseteric nerve ran anteriorly and inferiorly between the deep and the middle layers. The nerve was observed at 33+/-5.6 mm from the inferior border of the muscle on the anterior third vertical line of the masseter muscle and at 47+/-5.5 mm in the posterior third. The closest distance between the main nerve and the gonion was 32+/-4.1 mm. Approximately two thirds (69.6%) of the masseteric nerve intersected the artery. The safe limit is within 47 mm from the inferior border of the muscle on the posterior third vertical line and within radial 32 mm from the gonion.
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Graft reconditioning with nitric oxide gas in rat liver transplantation from cardiac death donors. BACKGROUND Liver transplant outcomes using grafts donated after cardiac death (DCD) remain poor. METHODS We investigated the effects of ex vivo reconditioning of DCD grafts with venous systemic oxygen persufflation using nitric oxide gas (VSOP-NO) in rat liver transplants. Orthotopic liver transplants were performed in Lewis rats, using DCD grafts prepared using static cold storage alone (group-control) or reconditioning using VSOP-NO during cold storage (group-VSOP-NO). Experiment I: In a 30-min warm ischemia model, graft damage and hepatic expression of inflammatory cytokines, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and endothelin-1 (ET-1) were examined, and histologic analysis was performed 2, 6, 24, and 72 hr after transplantation. Experiment II: In a 60-min warm ischemia model, grafts were evaluated 2 hr after transplantation (6 rats/group), and survival was assessed (7 rats/group). RESULTS Experiment I: Group-VSOP-NO had lower alanine aminotransferase (ALT) (P<0.001), hyaluronic acid (P<0.05), and malondialdehyde (MDA) (P<0.001), hepatic interleukin-6 expression (IL-6) (P<0.05), and hepatic tumor necrosis factor-alpha (TNF-α) expression (P<0.001). Hepatic eNOS expression (P<0.001) was upregulated, whereas hepatic iNOS (P<0.01) and ET-1 (P<0.001) expressions were downregulated. The damage of hepatocyte and sinusoidal endothelial cells (SECs) were lower in group-VSOP-NO.Experiment II: VSOP-NO decreased ET-1 and 8-hydroxy-2'deoxyguanosine (8-OHdG) expression and improved survival after transplantation by 71.4% (P<0.01). CONCLUSION These results suggest that VSOP-NO effectively reconditions warm ischemia-damaged grafts, presumably by decreasing ET-1 upregulation and oxidative damage.
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Histologic study of pulp capping using chlorhexidine in dogs. This histological study was conducted to compare the pulp reactions to chlorhexidine and calcium hydroxide. Twenty permanent premolar teeth of beagle dogs were mechanically exposed under aseptic conditions. The pulp was then capped with one of the following: chlorhexidine 0.2% on the left side and calcium hydroxide (dycal) on the right side of the same dog. Maxillary second premolars were extracted from each dog three weeks after the pulp capping procedure. Maxillary third premolars and mandibular first premolars were extracted at 6 weeks and 9 weeks respectively. The mandibular second premolars were extracted three months after the pulp capping procedure. The specimens were fixed in 10% formalin and decalcified in 5% formic acid. Serial sections, 7 microns thick, were prepared and stained with hematoxylin and eosin. Teeth treated with chlorhexidine or with calcium hydroxide were well tolerated by the dental pulp at 3 and 6-week intervals. Pulps treated showed satisfactory pulp reaction and the odontoblastic layer appeared to be normal and in its configuration. Inflammatory response was not present at the 6-week time interval. At nine weeks, the inflammatory response was severe in those teeth treated with calcium hydroxide. There were no remarkable histological differences among the treatment groups at 12 and 15 weeks. These specimens showed complete loss of pulpal architecture. Regressive changes were seen and microscopic specimens revealed presence of spaces and intertwining bundles of films in the pulp.
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Immunologic cross-reactivity between respiratory chemical sensitizers: reactive dyes and cyanuric chloride. BACKGROUND CyCl is a low molecular weight reactive chemical used as an intermediate in the production of plastics, herbicides, pharmaceuticals, and fiber-reactive dyes. It is a potent inducer of specific IgE antibody. The CyCl functionality is a structural component of monochlorotriazine and dichlorotriazine dyes. OBJECTIVE We have investigated the immunologic cross-reactivity between cyanuric chloride (CyCl) and reactive dyes and it was hypothesized that this moiety might be a dye epitope and that it might stimulate an allergic antibody response in dye-exposed workers. METHODS To test this hypothesis, we have used sera with IgE antibodies to CyCl and also sera from dye-exposed workers who have IgE antibodies to Procion Orange MX2R, an azo dye containing the dichlorotriazine group. As a control group we have used dye-exposed workers with IgE antibody to Remazol Black B, a diazo dye containing the vinyl sulfone-reactive group. RESULTS Using RAST and RAST inhibitions, we identified negligible cross-reactivity between CyCl and dichlorotriazine dye. CONCLUSION The results of this study imply that the allergenic moiety on the dye residue resides in the chromophore rather than in the common structural component of CyCl and dichlorotriazine dyes.
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PTSD symptom changes in refugees. Extreme traumatic events such as a threatened death or serious injury are common experiences for refugees, many of whom display levels of Post-traumatic Stress Disorder (PTSD). Our preliminary investigation of 19 refugees examined whether acceptance of an individual application for Convention Refugee status is a factor in recovery from PTSD. Based on the traumatic experiences identified with the Harvard Trauma Questionnaire, differential rates of recovery from PTSD and generalized distress were prospectively compared in refugees who had either received acceptance in their application for refugee status (n=10) or had been denied status (n=9). PTSD was diagnosed according to criteria outlined in the DSM-IV and distress was measured with the Brief Symptom Inventory. Unique to this study was the assessment of the refugee Claimant prior to his or her individual appearance before the Immigration and Refugee Board in Canada. The data support the hypothesis that a positive outcome for the hearing would significantly relate to a reduced DSM-IV PTSD symptom count and to a reduced generalized distress. Participants who received a positive hearing outcome showed significant recovery relative to those who were denied refugee status. Notwithstanding the small paper size, the results are discussed in terms of how the promise of future freedom from persecution combines with making actual disclosures before the Immigration and Refugee Board to start the process of rehabilitation.
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DNA-damage response associated with occupational exposure, age and chronic inflammation in workers in the automotive industry. The evaluation of genome integrity in populations occupationally exposed to combine industrial factors is of medical importance. In the present study, the DNA-damage response was estimated by means of the alkaline comet assay in a sizeable cohort of volunteers recruited among workers in the automotive industry. For this purpose, freshly collected lymphocytes were treated with hydrogen peroxide (100μM, 1min, 4°C) in vitro, and the levels of basal and H(2)O(2)-induced DNA damage, and the kinetics and efficiency of DNA repair were measured during a 180-min interval after exposure. The parameters studied in the total cohort of workers were in a range of values prescribed for healthy adult residents of Belarus. Based on the 95th percentiles, individuals possessing enhanced cellular sensitivity to DNA damage were present in different groups, but the frequency was significantly higher among elderly persons and among individuals with chronic inflammatory diseases. The results indicate that the inter-individual variations in DNA-damage response should be taken into account to estimate adequately the environmental genotoxic effects and to identify individuals with an enhanced DNA-damage response due to the influence of some external factors or intrinsic properties of the organism. Underling mechanisms need to be further explored.
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Fetal Alcohol Programming of Subsequent Alcohol Affinity: A Review Based on Preclinical, Clinical and Epidemiological Studies. The anatomo-physiological disruptions inherent to different categories of the Fetal Alcohol Spectrum Disorder do not encompass all the negative consequences derived from intrauterine ethanol (EtOH) exposure. Preclinical, clinical and epidemiological studies show that prenatal EtOH exposure also results in early programming of alcohol affinity. This affinity has been addressed through the examination of how EtOH prenatally exposed organisms recognize and prefer the drug's chemosensory cues and their predisposition to exhibit heightened voluntary EtOH intake during infancy and adolescence. In altricial species these processes are determined by the interaction of at least three factors during stages equivalent to the 2nd and 3rd human gestational trimester: (i) fetal processing of the drug's olfactory and gustatory attributes present in the prenatal milieu; (ii) EtOH's recruitment of central reinforcing effects that also imply progressive sensitization to the drug's motivational properties; and (iii) an associative learning process involving the prior two factors. This Pavlovian learning phenomenon is dependent upon the recruitment of the opioid system and studies also indicate a significant role of EtOH's principal metabolite (acetaldehyde, ACD) which is rapidly generated in the brain via the catalase system. The central and rapid accumulation of this metabolite represents a major factor involved in the process of fetal alcohol programming. According to recent investigations, it appears that ACD exerts early positive reinforcing consequences and antianxiety effects (negative reinforcement). Finally, this review also acknowledges human clinical and epidemiological studies indicating that moderate and binge-like drinking episodes during gestation result in neonatal recognition of EtOH's chemosensory properties coupled with a preference towards these cues. As a whole, the studies under discussion emphasize the notion that even subteratogenic EtOH exposure during fetal life seizes early functional sensory and learning capabilities that pathologically shape subsequent physiological and behavioral reactivity towards the drug.
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