Unique and interactive effects of parental neglect, school connectedness, and trait self-control on mobile short-form video dependence among Chinese left-behind adolescents.
Mobile short-form video is becoming increasingly popular among Chinese adolescents. Mobile short-form video dependence has become a pressing issue in Chinese adolescents, especially in left-behind adolescents. Previous studies, however, have focused on general mobile phone dependence and neglected specific types of mobile phone dependence. Few studies have explored the environmental and individual predictors of mobile short-form video dependence. Based on theoretical and empirical evidence, the present study examined the unique and interactive effects of parental neglect, school connectedness, and trait self-control on mobile short-form video dependence among Chinese left-behind adolescents. A total of 618 left-behind adolescents between 11 and 15 years of age completed the anonymous self-report survey. The PROCESS macro for SPSS was applied for data analysis. Parental neglect was positively associated with mobile short-form video dependence, whereas school connectedness and trait self-control were negatively associated with mobile short-form video dependence in left-behind adolescents. Examination of the two-way interactions indicated that school connectedness and trait self-control could buffer the association between parental neglect and left-behind adolescents' mobile short-form video dependence. However, self-control could not moderate the association between school connectedness and mobile short-form video dependence. In addition, the three-way interaction of parental neglect, school connectedness, and trait self-control showed a significant effect on mobile short-form video dependence. The moderating role of school connectedness was stronger for left-behind adolescents with low trait self-control than for those with high trait self-control, and the moderating role of trait self-control was stronger for left-behind adolescents with low school connectedness than for those with high school connectedness. The findings contribute significantly to revealing the complex mechanisms of mobile short-form video dependence and providing comprehensive and specific practical suggestions for the prevention and intervention of mobile short-form video dependence among left-behind adolescents.


Comprehensive Genetic Testing for Pediatric Hypertrophic Cardiomyopathy Reveals Clinical Management Opportunities and Syndromic Conditions.
Hypertrophic cardiomyopathy (HCM) has historically been diagnosed phenotypically. Through genetic testing, identification of a molecular diagnosis (MolDx) is increasingly common but the impact on pediatric patients is unknown. This was a retrospective study of next-generation sequencing data for 602 pediatric patients with a clinician-reported history of HCM. Diagnostic yield was stratified by gene and self-reported race/ethnicity. A MolDx of HCM was identified in 242 (40%) individuals. Sarcomeric genes were the highest yielding, but pathogenic and/or likely pathogenic (P/LP) variants in syndromic genes were found in 36% of individuals with a MolDx, often in patients without documented clinical suspicion for a genetic syndrome. Among all MolDx, 73% were in genes with established clinical management recommendations and 2.9% were in genes that conferred eligibility for clinical trial enrollment. Black patients were the least likely to receive a MolDx. In the current era, genetic testing can impact management of HCM, beyond diagnostics or prognostics, through disease-specific guidelines or clinical trial eligibility. Genetic testing frequently can help identify syndromes in patients for whom syndromes may not be suspected. These findings highlight the importance of pursuing broad genetic testing, independent of suspicion based on phenotype. Lower rates of MolDx in Black patients may contribute to health inequities. Further research is needed evaluating the genetics of HCM in underrepresented/underserved populations. Additionally, research related to the impact of genetic testing on clinical management of other diseases is warranted.


Ethyl glucoside in human urine following dietary exposure: detection by 1H NMR spectroscopy as a result of metabonomic screening of humans.
Metabonomic screening of human urine samples using 1H NMR spectroscopy has revealed the presence of signals resulting from the excretion of ethyl glucoside. Experiments in volunteers have demonstrated that this ethyl glucoside results from dietary exposure to the compound, which is present in beverages such as rice wine and sake, rather than representing a new route for the metabolism of ethanol by humans. The limited studies undertaken in volunteers indicate that ethyl glucoside has a longer biological half life than ethanol itself. The potential problems associated with using this glucoside metabolite as a marker of ethanol consumption are considered.


Triaging of pleural effusion cytology specimens for ancillary flow cytometric analysis.
There are no established criteria in selecting pleural effusion (PE) specimens for flow cytometric analysis (FCA). FCA on effusion specimens may be ordered by a clinician or a cytopathologist. In an effort to improve lab test utilization, this retrospective study aims to identify characteristics of PE specimens on which the addition of FCA has high diagnostic yield. We identified consecutive cases of PE cytology specimens on which FCA was performed over a 5-year period (2014-2019). Patient demographic data and history, FCA diagnosis, cytologic diagnosis, cellular quantity and composition, and peripheral blood cell counts were collected. Chi-square, Mann-Whitney U, and t tests were used when appropriate with a significance level of P < 0.05. We identified 164 FCA cases corresponding to 142 patients (age: 19-90 years; male:female 2:1). The majority of cases had no abnormality by cytologic examination, whereas others were obviously malignant due to non-hematologic malignancy. Most (119 of 164, 73%) had negative immunophenotypic studies by FCA. Forty-five of 164 (27%) FCA cases were positive for a monoclonal myeloid or lymphoid population. Clinicopathologic features associated with positive FCA results included a history of hematologic malignancy, peripheral blood lymphocytes of ≥20%, the presence of a monomorphic lymphoid population, large atypical cells, and mitoses. This study identifies features that are associated with positive FCA in PE cytology specimens. Using these features by cytopathologists to order FCA on PE specimens as a reflex test would significantly reduce unnecessary testing and improve FCA utilization.


'Nonspecific' rather than 'nonassociative' pathways to phobias: a commentary on Poulton and Menzies.
This commentary attempts to clarify the nature of contemporary associative accounts of phobias, and to describe how they might contribute to the explanation of the diversity of phobic aetiologies. It is argued that conditioning-equivalent associations underpin all phobic conditions, and that the role of experimental psychopathology research is to determine how these associations are acquired. The commentary then proceeds to discuss some of the theoretical problems with the nonassociative account of phobias as it is currently described by Poulton and Menzies, and to suggest that some interpretations of their retrospective and prospective data may not be incompatible with contemporary associative accounts. The outcome of this is that it may be more suitable to describe the fourth pathway to phobia acquisition described by Poulton and Menzies as a 'nonspecific' rather than a 'nonassociative' pathway.


Municipal waste incinerators: air and biological monitoring of workers for exposure to particles, metals, and organic compounds.
To evaluate occupational exposure to toxic pollutants at municipal waste incinerators (MWIs). Twenty nine male subjects working near the furnaces in two MWIs, and 17 subjects not occupationally exposed to combustion generated pollutants were studied. Individual air samples were taken throughout the shift; urine samples were collected before and after. Stationary air samples were taken near potential sources of emission. Occupational exposure did not result in the infringement of any occupational threshold limit value. Atmospheric exposure levels to particles and metals were 10-100 times higher in MWIs than at the control site. The main sources were cleaning operations for particles, and residue transfer and disposal operations for metals. MWI workers were not exposed to higher levels of polycyclic aromatic hydrocarbons than workers who are routinely in contact with vehicle exhaust. The air concentrations of volatile organic compounds and aldehydes were low and did not appear to pose any significant threat to human health. Only the measurement of chlorinated hydrocarbon levels would seem to be a reliable marker for the combustion of plastics. Urine metal levels were significantly higher at plant 1 than at plant 2 because of high levels of pollutants emanating from one old furnace. While biological monitoring is an easy way of acquiring data on long term personal exposure, air monitoring remains the only method that makes it possible to identify the primary sources of pollutant emission which need to be controlled if occupational exposure and environmental pollution are to be reduced.


Microarray analysis of Haemophilus parasuis gene expression under in vitro growth conditions mimicking the in vivo environment.
Haemophilus parasuis is the causative agent of polyserositis in pigs, a mostly fatal disease on the rise especially in early-weaned pigs and in pig herds with a high-health status. The mechanisms by which H. parasuis propagates through the body and colonizes the serous membranes are unknown. We have used an H. parasuis microarray to identify virulence genes involved in host adaptation. H. parasuis gene expression was analysed under in vitro growth conditions mimicking the environmental conditions encountered during an infection. These included iron-limitation, acidic and temperature stress and growth under microaerobic conditions. A kinetic impression of the gene regulation was obtained by analysing the transcription 10, 30 and 60 min after induction of the altered growth conditions. A total of 75 regulated H. parasuis genes were identified, most of which coded for transporters of iron and sugar metabolites, metabolic enzymes, DNA metabolism and hypothetical proteins with unknown functions. Furthermore, H. parasuis genes were identified that have homology to known virulence factors in other pathogenic bacteria. Homologues of some of the identified H. parasuis genes are known to be expressed during natural and experimental infections in pathogens of the Pasteurellaceae family.


Quality of care in U.S. hospitals as reflected by standardized measures, 2002-2004.
In July 2002, the Joint Commission on Accreditation of Healthcare Organizations implemented standardized performance measures that were designed to track the performance of accredited hospitals and encourage improvement in the quality of health care. We examined hospitals' performance on 18 standardized indicators of the quality of care for acute myocardial infarction, heart failure, and pneumonia. One measure assessed a clinical outcome (death in the hospital after acute myocardial infarction), and the other 17 measures assessed processes of care. Data were collected over a two-year period in more than 3000 accredited hospitals. All participating hospitals received quarterly feedback in the form of comparative reports throughout the study. Descriptive analysis revealed a significant improvement (P<0.01) in the performance of U.S. hospitals on 15 of 18 measures, and no measure showed a significant deterioration. The magnitude of improvement ranged from 3 percent to 33 percent during the eight quarters studied. For 16 of the 17 process-of-care measures, hospitals with a low level of performance at baseline had greater improvements over the subsequent two years than hospitals with a high level of performance at baseline. Over a two-year period, we observed consistent improvement in measures reflecting the process of care for acute myocardial infarction, heart failure, and pneumonia. Both quantitative and qualitative research are needed to explore the reasons for these improvements.


Septic encephalopathy.
Every year, more cases of sepsis appear in intensive care units. The most frequent complication of sepsis is septic encephalopathy (SE), which is also the essential determinant of mortality. Despite many years of research, it still is not known at which stage of sepsis the first signs of SE appear; however, it is considered the most frequent form of encephalopathy. Patients have dysfunction of cognitive abilities and consciousness, and sometimes even epileptic seizures. Despite intensive treatment, the effects of SE remain for many years and constitute an important social problem. Numerous studies indicate that changes in the brain involve free radicals, nitric oxide, increased synthesis of inflammatory factors, disturbances in cerebral circulation, microthromboses, and ischemia, which cause considerable neuronal destruction in different areas of the brain. To determine at what point during sepsis the first signs of SE appear, different experimental models are needed to detect the aforementioned changes and to select the proper therapy for this syndrome.


Structural and functional characterization of two human V-ATPase subunit gene promoters.
The vacuolar-ATPase (V-ATPase) is a multi-subunit enzyme that couples ATP hydrolysis to proton pumping across membranes. V-ATPase genes are considered to be housekeeping genes and are expressed in human neoplastic tissue and in cell lines. We have isolated and characterized several genomic clones containing the 5'-end of the human V-ATPase genes. DNA sequence analysis of the promoters of two V-ATPase subunit genes, encoding C (ATP6C) and c (ATP6F), reveals GC-rich regions in the region of the first exon. Neither TATA- nor CCAAT-boxes were found in these promoters, but both GC-boxes and E-boxes were identified. Transient transfection analysis, using a series of 5' nested deletions of promoter-luciferase constructs in human cancer cells, demonstrated that a positive cis-acting regulatory region was present in these TATA-less promoters. The regions between -79 and -40 of the ATP6C promoter and between -245 and -99 of the ATP6F promoter were identified as being likely to be extremely important for basal promoter activity. Electrophoretic mobility shift assays (EMSA) of these cis-regulatory regions revealed the basal promoter to be highly complex, with cooperative binding of several transcription factors, including Sp family members. These data identify the critical regulatory regions for both the ATP6C and ATP6F basal promoters and stress the functional importance of multiple protein complexes, involving the Sp family of transcription factors, in regulating gene expression.


Repurposing the repurposed: thalidomide analogs as immune stimulants to overcome T cell exhaustion.
In this issue of Cell Chemical Biology, Geng and colleagues employ a novel mouse model of humanized cereblon (Crbn) to provide insights into the immunomodulatory effects of lenalidomide and provide rationale for potential therapeutic combinations including anti-PD1 immunotherapy.


Strain- and model-dependent effects of chlordiazepoxide, L-838,417 and zolpidem on anxiety-like behaviours in laboratory mice.
The promise of subtype-selective GABA(A) receptor drugs with anxiolytic properties but with a much reduced side-effect burden (compared to benzodiazepines) is an attainable goal. However, its achievement necessitates the availability of in vivo preclinical assays capable of demonstrating differences as well as similarities between subtype-selective agents and non-selective benzodiazepines. In this study, we have compared three mouse strains (NMRI, C57BL/6J and DBA/2) in four models of anxiety-like behaviour (plus-maze, zero-maze, light-dark, and Vogel conflict). Furthermore, in each model, we have contrasted in detail the behavioural responses of each strain to the non-selective benzodiazepine chlordiazepoxide (CDP; 5-20 mg/kg), and the subtype-selective agents L-838,417 (GABA(A)-alpha(2/3/5); 3-30 mg/kg) and zolpidem (GABA(A)-alpha1; 0.3-3.0 mg/kg). The data show a complex mouse strainxmodelxpharmacological agent interaction. Most importantly, not all mouse strainxmodel test systems showed a positive response to CDP or predicted the response to L-838,417. This dissociation between CDP and L-838,417 opens up opportunities for preclinical test systems that differentiate subtype-selective and non-selective GABA(A) receptor agents, an attribute that might well be important in providing the necessary confidence for further drug development. Present findings suggest the need for a much greater focus on defining test systems appropriate for screening novel chemical entities, rather than self-selection of models or genotypes based on responses to known pharmacological agents. For example, if current data with L-838,417 are confirmed with compounds showing similar selectivity profiles, such agents may in future be best identified and characterised using test systems comprising NMRI mice in the zero-maze and/or C57 mice in the Vogel conflict and/or light-dark tests.


Tailored HIV Pre-exposure Prophylaxis (PrEP) Intervention Needs from a Latent Class Analysis Among U.S. Healthcare Providers.
Interventions are needed to expand HIV pre-exposure prophylaxis (PrEP) prescribing practices among healthcare providers, but research classifying providers to determine tailored intervention needs is lacking. Providers reported demographics, factors related to HIV treatment and prevention experience, and PrEP-related factors such as knowledge and community protection beliefs via online survey. Latent class analysis grouped providers with similar patterns of HIV prevention- and treatment-related care and tested for associations with demographics and PrEP-related factors. Three distinct classes of providers emerged: (1) PrEP naïve, (2) PrEP aware, and (3) PrEP prescribers. Providers with lower community protection beliefs and staff capacity were more likely to be classified as PrEP naïve compared to aware (ps < 0.05). Providers with concerns about PrEP-related tasks and staff capacity were more likely to be classified as PrEP aware compared to prescribers (ps < 0.05). PrEP-naïve providers could benefit from continuing education, whereas PrEP-aware providers might benefit from capacity building and prescribing optimization interventions.


Chiral synthesis and enzymatic resolution of (S)-(-)piperazine-2-carboxylic acid using enzyme alcalase.
Enantiomerically pure (S)-piperazine-2-carboxylic acid was synthesized by kinetic resolution of methyl-4-(tert-butyroxycarbonyl)-piperazine-2-carboxylate using a low cost enzyme alcalase.


Photosensitive erythema multiforme and erythema multiforme-like polymorphous light eruption.
Photosensitive erythema multiforme (EM) is a rare disorder. It usually occurs only if a herpes virus infection or ingestion of drugs precedes exposure to sunlight in selected patients. We report a 37-year-old man who had recurrent EM eruptions following sun exposures over a period of 20 years. Lesions were prevalently located on exposed skin, but unexposed skin and mucosa of the oropharynx were also affected. The patient had poor tolerance to sunlight and denied having herpes simplex infection or using drugs. Provocative phototest induced clinically and histologically similar lesions at low dose thresholds of UVA (10 J/cm2) and UVB (100 mJ/cm2). On the basis of clinical and histological findings and results of phototesting, a diagnosis of photosensitive EM was made. The EM-like variant of polymorphous light eruption is discussed in the differential diagnosis.


Elevated levels of interleukin-8 and transforming growth factor-beta in bronchoalveolar lavage fluid from patients with bronchiolitis obliterans syndrome: proinflammatory role of bronchial epithelial cells. Munich Lung Transplant Group.
Obliterative bronchiolitis (OB), the most important long-term complication after lung transplantation, is thought to be a manifestation of chronic rejection within the airways, with the hallmarks inflammation and fibroproliferation. To characterize the inflammatory process in the context of OB we quantified tumor necrosis factor-alpha, interleukin (IL)-8, IL-10, and transforming growth factor (TGF)-beta on the protein and mRNA level in bronchoalveolar lavage fluid samples obtained from patients with bronchiolitis obliterans syndrome (BOS) and without BOS. In addition, bronchial cells sampled by bronchial brushing were analyzed for mRNA expression. In respiratory epithelial lining fluid (ELF) from BOS patients the protein levels of IL-8 (52.4+/-22.2 vs. 4.4+/-0.9 pg/ml ELF, P<0.005) and TGF-beta (5.6+/-1.9 vs. 0.9+/-0.2 ng/ml ELF, P<0.005) were significantly elevated. In addition, bronchoalveolar lavage fluid cells of BOS patients showed increased expression of TGF-beta (1.13+/-0.44 vs. 0.45+/-0.16, optical density [O.D.]/O.D. glyceraldehyde-3-phosphate dehydrogenase [GAPDH], P=0.11) and IL-8 (0.25+/-0.13 vs. 0.09+/-0.03 O.D/O.D. GAPDH, P=0.53) without the differences reaching statistical significance. In contrast, IL-8 mRNA expression of bronchial cells was significantly higher in the BOS group (0.85+/-0.40 vs. 0.22+/-0.10 O.D./O.D. GAPDH, P<0.05). We assume that IL-8 and TGF-beta may act as key mediators for airway inflammation and fibroproliferation in the pathogenesis of OB, with bronchial epithelial cells serving as a relevant source of IL-8.


Method for the purification of polybrominated diphenyl ethers in sediment for compound-specific isotope analysis.
A purification method for lower polybrominated diphenyl ethers (PBDEs, from tri- to hexa-BDE) in sediment for compound-specific isotope analysis (CSIA) was developed in this study. The compounds were extracted using a Soxhlet apparatus with addition of activated alumina and Florisil in the paper tube during the Soxhlet extraction provided for less complex extracts. Then, the extract was isolated from polar compounds using a multi-layer silica gel column, separated into different fractions using alumina/silica (Al/Si) gel columns and finally purified using a Florisil column. The mean recoveries of the major PBDE congeners in the spiked samples ranged from 76.2% to 82.4%. The purity of the samples was verified by GC-MS in full scan mode. The stable isotopic integrity of the spiked samples after the purification was tested by comparing the stable carbon isotope ratios (δ(13)C) of the processed and the unprocessed standard materials. The differences in the δ(13)C values for each compound between the processed and unprocessed standards were less than 0.5‰, with the exception of BDE100 (0.54‰). Finally, the purification and isotope analysis method was successfully applied to measure the δ(13)C of PBDEs in sediments. This application of the method indicated that CSIA seems to be a promising method for providing intrinsic characteristics for further environmental fate studies of PBDEs.


Recombinant adiponectin does not lower plasma glucose in animal models of type 2 diabetes.
Several studies have shown that adiponectin can lower blood glucose in diabetic mice. The aim of this study was to establish an effective adiponectin production process and to evaluate the anti-diabetic potential of the different adiponectin forms in diabetic mice and sand rats. Human high molecular weight, mouse low molecular weight and mouse plus human globular adiponectin forms were expressed and purified from mammalian cells or yeast. The purified protein was administered at 10-30 mg/kg i.p. b.i.d. to diabetic db/db mice for 2 weeks. Furthermore, high molecular weight human and globular mouse adiponectin batches were administered at 5-15 mg/kg i.p. b.i.d. to diabetic sand rats for 12 days. Surprisingly, none of our batches had any effect on blood glucose, HbA1c, plasma lipids or body weight in diabetic db/db mice or sand rats. In vitro biological, biochemical and biophysical data suggest that the protein was correctly folded and biologically active. Recombinant adiponectin is ineffective at lowering blood glucose in diabetic db/db mice or sand rats.


Mucopolysaccharidoses and other lysosomal storage diseases.
Mucopolysaccharidosis and other lysosomal storage diseases are rare, chronic, and progressive inherited diseases caused by a deficit of lysosomal enzymes. Patients are affected by a wide variety of symptoms. For some lysosomal storage diseases, effective treatments to arrest disease progression, or slow the pathologic process, and increase patient life expectancy are available or being developed. Timely diagnosis is crucial. Rheumatologists, orthopedics, and neurologists are commonly consulted due to unspecific musculoskeletal signs and symptoms. Pain, stiffness, contractures of joints in absence of clinical signs of inflammation, bone pain or abnormalities, osteopenia, osteonecrosis, secondary osteoarthritis or hip dysplasia are the alerting symptoms that should induce suspicion of a lysosomal storage disease.


Successful management of three patients with autoimmune thrombotic thrombocytopenic purpura with paradigm-changing therapy: Caplacizumab, steroids, plasma exchange, rituximab, and intravenous immunoglobulins (CASPERI).
Autoimmune thrombotic thrombocytopenic purpura (aTTP) is a severe disease caused by the production of autoantibodies against von Willebrand factor (vWF)-cleaving ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin-1 motifs; 13th member of the family). In 2018, caplacizumab was approved for the treatment of patients with acute aTTP in conjunction with plasma exchange (PE) and immunosuppressive therapy. Immunosuppressive standard of care includes mainly steroids whereas rituximab is usually reserved for refractory cases. We report three patients with a first acute episode of aTTP who were successfully treated with a paradigm-changing scheme including standard of care (caplacizumab, steroids and PE) plus upfront therapy with rituximab and intravenous immunoglobulins (CASPERI). Rituximab was added 1-4 days after diagnosis, when ADAMTS13 autoantibodies were detected and intravenous immunoglobulins were administered after performing PE using albumin as replacement solution. Successful outcome was observed in all three patients: platelet recovery (>150 × 109/L) was observed after 3, 4, and 5 days from diagnosis; ADAMTS13 activity >5% and ADAMTS13 autoantibodies were negative after 14, 15, and 21 days from diagnosis. In conclusion, caplacizumab, steroids, PE (using fresh frozen plasma or albumin as replacement solution and adding intravenous immunoglobulins) plus upfront rituximab therapy was a safe and efficient combination to induce remission in case of acute aTTP.


Healing of localized gingival recessions treated with a coronally advanced flap alone or combined with an enamel matrix derivative and a porcine acellular dermal matrix: a preclinical study.
This study aimed to evaluate the effects of a porcine acellular dermal matrix (PADM) with or without an enamel matrix derivative (EMD) on gingival recession defects treated with a coronally advanced flap (CAF) in dogs. Miller class II gingival recession defects (5 mm wide and 7 mm deep) were surgically created on the labial side of bilateral maxillary canines in 12 dogs. After 8 weeks of plaque accumulation, the 24 chronic defects were randomly assigned to one of the following 4 treatments: CAF, CAF with PADM (CAF/PADM), CAF with EMD (CAF/EMD), and CAF with EMD and PADM (CAF/EMD/PADM). The animals were sacrificed 10 weeks after surgery for histologic evaluation. In all groups, root coverage was obtained to a varying degree. PADM was well incorporated in gingival connective tissue in the CAF/PADM and in the CAF/EMD/PADM groups. The height of newly formed bone was significantly greater in the CAF/EMD/PADM group than in the CAF and CAF/PADM groups. New cementum with periodontal ligament-like tissue was predominantly found in the CAF/EMD and CAF/EMD/PADM groups. The CAF/EMD/PADM group showed the greatest amount of new cementum among the groups examined, although the difference was not statistically significant. Within the limitations of the present study, it can be concluded that CAF/EMD/PADM treatment may promote periodontal regeneration in gingival recession defects. The present results suggest that the combination of EMD and PADM in conjunction with CAF may represent a promising approach for treating single Miller class II gingival recessions.


1-Year Prospective Evaluation of Clinical Outcomes and Shocks: The Subcutaneous ICD Post Approval Study.
This study evaluated spontaneous arrhythmias and clinical outcomes in the S-ICD System PAS (Subcutaneous Implantable Cardioverter-Defibrillator Post Approval Study) cohort. The U.S. S-ICD PAS trial patient population more closely resembles transvenous ICD cohorts than earlier studies, which included many patients with little structural heart disease and few comorbidities. Early outcomes and low peri-operative complication rates were demonstrated in the S-ICD PAS cohort, but there are no data detailing spontaneous arrhythmias and clinical outcomes. The S-ICD PAS prospective registry included 1,637 de novo patients from 86 U.S. centers. Descriptive statistics, Kaplan-Meier time to event, and multivariate logistic regression were performed using data out to 365 days. Patients (68.5% men; mean ejection fraction of 32.0%; 42.9% ischemic; 13.4% on dialysis) underwent implantation for primary (76.6%) or secondary prevention indication. The complication-free rate was 92.5%. The appropriate shock (AS) rate was 5.3%. A total of 395 ventricular tachycardia (VT) or fibrillation (VF) episodes were appropriately sensed, with 131 (33.2%) self-terminating. First and final shock efficacy (up to 5 shocks) for the 127 discrete AS episodes were 91.3% and 100.0%, respectively. Discrete AS episodes included 67 monomorphic VT (MVT) and 60 polymorphic VT (PVT)/VF, with first shock efficacy of 95.2% and 86.7%, respectively. There were 19 storm events in 18 subjects, with 84.2% conversion success. Storm episodes were more likely PVT/VF (98 of 137). In the first year after implantation, a predominantly primary prevention population with low ejection fraction demonstrated a high complication-free rate and spontaneous event shock efficacy for MVT and PVT/VF arrhythmias at rapid ventricular rates. (Subcutaneous Implantable Cardioverter-Defibrillator System Post Approval Study [S-ICD PAS; NCT01736618).


De-constructing depersonalization: further evidence for symptom clusters.
Depersonalization disorder is defined in the DSM-IV-TR using a single symptom criterion, which does not do justice to the phenomenological complexity of the disorder. In 394 affected adults, the Cambridge Depersonalization Scale yielded five factors (numbing, unreality of self, perceptual alterations, unreality of surroundings, and temporal disintegration), put forth as symptom criteria for a better diagnosis of depersonalization disorder.


Safety of factor VIII inhibitor bypass activity (FEIBA): 10-year compilation of thrombotic adverse events.
Published and unpublished spontaneously reported thrombotic adverse events (AEs) in factor VIII inhibitor bypass activity (FEIBA(R)) recipients were compiled for the most recent 10-year period during which FEIBA(R) units equivalent to 3.95 x 105 typical infusions were distributed worldwide. A total of 16 thrombotic AEs were documented over the 10-year period, corresponding to an incidence of 4.05 per 105 infusions (95% CI, 2.32-6.58 per 105 infusions). Disseminated intravascular coagulation (n=7) and myocardial infarction (n=5) were the most frequent thrombotic AEs. One fatality occurred in an 87-year-old metastatic cancer patient. In 13/16 (81%) patients known risk factors were present, most commonly FEIBA(R) overdose in 8/16 (50%), obesity in 3/16 (19%) and serum lipid abnormalities in 2/16 (12%). These findings indicate that thrombotic AEs in FEIBA(R) recipients are very rare. Recognition of risk factors and avoidance of FEIBA(R) overdosage may avert thrombotic AEs.


Social evolution and the individual-as-maximising-agent analogy.
Does natural selection tend to maximise something? Does it produce individuals who act as if they maximised something? These questions have long occupied evolutionary theorists, and have proven especially tricky in the case of social evolution, which is known for leading to apparently suboptimal states. This paper investigates recent results about maximising analogies - especially regarding whether individuals should be considered as if they maximised their inclusive fitness - and compares the fruitfulness of global and local approaches. I assess Okasha & Martens's recent local approach to the individual-as-maximising-agent analogy and its robustness with respect to interactive situations. I then defend the relative merits of a comparable global approach, arguing that it is conceptually on a par and heuristically advantageous.


Kinetics and models of the Drosophila heat-shock system.
The puffing of Drosophila heat-shock genes after (1) a step-wise temperature increase ("heat-shock"); (2) recovery from anaerobiosis; and (3) incubation with uncoupling reagents was expressed as percent of the maximal size and normalized to the time scale. Data were taken from the literature and new measurements. In addition, puffing was measured after a 30-min temperature pulse and after two 30-min pulses. The latter experiment revealed a second, smaller increase in puff-size. Data on RNA and protein synthesis in Drosophila cells were collected from the literature and also normalized. From the available data, a feed-back control system is derived that consists of a controlled variable x, possibly a metabolic function of the mitochondria, interacting with an activator molecule which exists in an active (A+) and an inactive (A-) configuration. A+ activates the heat-shock genes which in turn produce their mRNA (y) and proteins (z) which then change the controlled variable x into a new steady state. A modified version of this model assumes a feed-back control of the heat-shock proteins on the activator molecule. A mathematical model of this system (Goodwin, 1965) was simulated by computer and compared with the experimental results.


Effect of 5-aminolevulinic acid on the expression of carcinogenesis-related proteins in cultured primary hepatocytes.
Acute intermittent porphyria (AIP) is a heme pathway disorder caused by a decrease in the activity and synthesis of porphobilinogen deaminase. Thus, the first heme precursor 5-aminolevulinic acid (ALA) accumulates in the liver. Reactive oxygen species (ROS) resulting from ALA oxidation may be correlated to a higher incidence of hepatocellular carcinoma (HCC) in AIP patients. However, the molecular mechanisms of this relationship have not been thoroughly elucidated to date. In this study, we investigated the effect of increasing levels of ALA on the expression of proteins related to DNA repair, oxidative stress, apoptosis, proliferation and lipid metabolism. Primary rat hepatocytes were isolated by the collagenase perfusion method, lipoperoxidation was evaluated by a TBA fluorimetric assay and Western blotting was used to assess protein abundance. The data showed that ALA treatment promoted a dose-dependent increase of p53 expression, downregulation of Bcl-2, HMG-CoA reductase and OGG1 and an increase in lipoperoxidation. There was no alteration in the expression of the transcription factor NF-κB, catalase and superoxide dismutase. ALA oxidation products induced protein regulation patterns, suggesting the interconnection of cellular processes, such as the intrinsic pathway of apoptosis, redox homeostasis, cell proliferation, lipid metabolism and DNA repair. This study helps to elucidate the molecular mechanisms of hepatotoxicity mediated by ALA pro-oxidant effects and supports the hypothesis that ALA accumulation correlates with a higher incidence of hepatic carcinogenic events.


Validation of an objective device for assessing circumductive wrist motion.
Circumduction of the wrist consists of a circular motion combining flexion, extension, and radioulnar deviation without simultaneous supination or pronation of the forearm. This pattern of flexion-extension and radial-ulnar deviation coupling is vital in common tasks; however, its evaluation in hand clinics is limited by the availability and ease of current tools. We present the construct, criterion, test-retest, and inter-rater validity of a new circumduction measurement device. Splint volunteers (n = 42) and hand clinic patients (n = 51) were studied to assess different aspects of validity and reliability for the circumduction jig. Known-group validation was used to assess construct validity and demonstrate the ability of the device to differentiate between patients with lesser or greater circumduction values. Criterion validity was demonstrated by comparing the circumduction measures of the device to flexion, extension, ulnar deviation, and radial deviation. Test-retest reliability was established by comparing the results of repeated circumduction measures for the hand clinic patients by 2 blinded, independent researchers, and inter-rater reliability was determined by evaluating the correlation in circumduction measures taken on the same patient by different blinded, independent researchers. Circumduction measurements significantly decreased (test for trend, p < .01) across the 3 different treatments that represented progressively reduced range of motion, establishing construct validity of the device. Flexion, extension, and radioulnar deviation all correlated significantly with circumduction; the correlation values ranged from 0.46 to 0.82 (p < .01) among all subjects (93 subjects, 228 measurements). Intra-rater reliability was 0.98 (p < .01) for both evaluators, and inter-rater reliability was 0.94 (p < .01). The present validation study demonstrated criterion, construct, test-retest, and inter-rater reliability for a newly designed circumduction measurement device.


Zinc, copper, and selenium tissue levels and their relation to subcutaneous abscess, minor surgery, and wound healing in humans.
Trace element involvement in wounds left to heal by secondary intention needs clarification. We have previously reported faster healing of wounds following acute surgery compared with elective excision of pilonidal sinus disease. The effect of topical zinc on the closure of the excisional wounds was mediocre compared with placebo. In contrast, parenteral zinc, copper, and selenium combined appear effective for wound healing in humans. We have investigated zinc, copper, and selenium with respect to (a) impact of acute versus chronic pilonidal sinus and (b) regional concentrations within granulating wounds treated topically with placebo or zinc in 42 (33 males) pilonidal disease patients. Baseline serum and skin concentrations of copper correlated (r S = 0.351, p = 0.033, n = 37), but not of zinc or selenium. Patients with abscesses had elevated serum C-reactive protein (CRP) and copper levels (+29 %; p < 0.001) compared with the elective patients consistent with the strong correlation between serum copper and CRP (r S = 0.715, p < 0.0005, n = 41). Seven days after elective surgery, serum CRP and copper levels were elevated (p = 0.010) versus preoperative values. The copper concentration in wound edges was higher than in periwound skin (p < 0.0005) and wound base (p = 0.010). Selenium levels were increased in wound edge compared to wound base (p = 0.003). Topical zinc oxide treatment doubled (p < 0.050) zinc concentrations in the three tissue localizations without concomitant significant changes of copper or selenium levels. In conclusion, copper and selenium are mobilized to injured sites possibly to enhance host defense and early wound healing mechanisms that are complementary to the necessity of zinc for matrix metalloproteinase activity.


Physicochemical Parameters of Raw Pet Food and Dehydrated Pet Treats Developed from Beef Processing Co-Products.
Pet humanization and premiumization of pet foods have led to significant changes in the co-product market, as pet food companies are looking for more profitable protein sources for their products. Co-products such as beef liver (BL) and beef heart (BH) can be combined to generate restructured pet foods rich in vitamins and nutrients. Sodium alginate and encapsulated calcium lactate (ALGIN) can improve the acceptability of meat pieces by transforming them into a singular shape. The objective of this experiment was to assess the physiochemical parameters of co-products for utilization in raw pet foods and restructured pet treats generated from BL and BH by using ALGIN as a structure-forming agent. Results demonstrated increased cooking loss as ALGIN inclusion decreased, but cooking loss decreased as BL proportions increased (p = 0.0056). Expressible moisture of raw pet food decreased as ALGIN inclusion increased, but more moisture was released from treats when BL proportions increased (p < 0.0001). Increasing ALGIN and BH led to increased water activity of cooked treats (p < 0.0001). Thus, we suggest that BL and BH combinations with ALGIN inclusion produces a viable platform for higher inclusions of co-products in pet treats. Additionally, these ingredients improved the finished product quality characteristics of raw pet foods.


A novel diazonium-sulfhydryl reaction in the inactivation of yeast alcohol dehydrogenase by diazotized 3-aminopyridine adenine dinucleotide.
Diazotized 3-aminopyridine adenine dinucleotide has been found to modify four sulfhydryl groups per molecule of enzyme during the complete inactivation of yeast alcohol dehydrogenase. The reaction of sulfhydryl groups was indicated by titration studies with 5,5-dithiobis(2-nitrobenzoic acid) as well as isolation and quantitation of the cysteinyl derivative released by acid hydrolysis of the modified enzyme. The cysteinyl derivative was identified as S-(3-pyridyl)cysteine. Authentic S-(3-pyridyl)cystein was synthesized and structurally characterized for these studies. Diazonium-sulfhydryl reactions were demonstrated for a number of diazonium derivatives with cysteine, homocysteine, glutathione, and mercaptoethanol at 0-4 degrees and neutral pH. Second order rate constants were determined in reactions of these sulfhydryl compounds with diazotized 1-methyl-3-aminopyridinium chloride, diazotized 3-aminopyridine adenine dinucleotide, and diazotized 3-aminopyridine adenine dinucleotide phosphate.


Adaptation of crops to environment.
Adaptability is defined as the ability of a crop (or variety) to respond positively to changes in agricultural conditions. The trait is genetically controlled and provides an ability to exploit environmental attributes, both natural and agronomic. Values of relative adaptability can be determined by the regression of the yield of the tested crop over the average yield of compared crops from several environments. We evaluated relative adaptability of 12 staple crops in 12 European countries and compared the yield data over a 43-year period from 1961 to 2003. An additional set of average yield data was also available for the 15 European Union (EU15) member countries. A wider range of 26 crop species was investigated that allowed comparisons between Europe and the USA between 1961 and 2003. Adaptability was closely related to the annual yield increases of the crops studied (r2 = 0.999 both in the EU15 and the USA). However, the adaptability of certain crops differed between the two regions. Pulse, maize, millet, wheat and sorghum showed the highest adaptability in the EU15 region, whereas strawberry, pear, tomato, walnut and maize were highest in the USA. The lowest adaptability was found for walnut, pear, apple, cauliflower and hop in the EU15 and for mustard, hop, sugar beet, millet and oat in the USA. In European countries, crops with similar biology, environment and agronomical practices (like the amount of fertilizers and pesticides applied) tended to have similar adaptability values. The data indicate that high adaptability is an important prerequisite for continued yield gains in the best environments.


A Web-based communication aid for patients with cancer: the CONNECT Study.
Cancer patients and their oncologists often report differing perceptions of consultation discussions and discordant expectations regarding treatment outcomes. CONNECT, a computer-based communication aid, was developed to improve communication between patients and oncologists. CONNECT includes assessment of patient values, goals, and communication preferences; patient communication skills training; and a preconsultation physician summary report. CONNECT was tested in a 3-arm, prospective, randomized clinical trial. Prior to the initial medical oncology consultation, adult patients with advanced cancer were randomized to the following arms: 1) control; 2) CONNECT with physician summary; or 3) CONNECT without physician summary. Outcomes were assessed with postconsultation surveys. Of 743 patients randomized, 629 completed postconsultation surveys. Patients in the intervention arms (versus control) felt that the CONNECT program made treatment decisions easier to reach (P = .003) and helped them to be more satisfied with these decisions (P < .001). In addition, patients in the intervention arms reported higher levels of satisfaction with physician communication format (P = .026) and discussion regarding support services (P = .029) and quality of life concerns (P = .042). The physician summary did not impact outcomes. Patients with higher levels of education and poorer physical functioning experienced greater benefit from CONNECT. This prospective randomized clinical trial demonstrates that computer-based communication skills training can positively affect patient satisfaction with communication and decision-making. Measurable patient characteristics may be used to identify subgroups most likely to benefit from an intervention such as CONNECT.


Microdiffraction studies of bone tissues using synchrotron radiation.
This is the first report on a series of studies of the crystallinity of bone tissues. The measurements were done at the microfocused diffraction beamline at ERSF (European Synchrotron Radiation Facility) as a feasibility test on various aspects on microdiffraction analysis. Beside the crystal structure, crystallite size distribution and preferential orientation were also studied, with a spatial resolution of 7 microm. The experiments were performed at the microfocus beam line 1 at European Synchrotron Radiation Facility (ESRF). The samples were longitudinal and transversal cuts from human femoral shafts. Over 65 diffraction lines from apatite structure could be identified. The results show that the bone crystallites seem to be oriented in two orthogonal directions, one parallel with the Haversian system and the other perpendicular following the lamella's curvature. Peak width analysis shows that the crystallites are about 25-40 nm along the c-axis with a width of about 10 nm. The result also shows that the peak width is somewhat larger close to the haversian canal compared with the outer region of the osteon.


Alternations in the activity of some digestive enzymes of Channa punctatus, exposed to lead nitrate.
The effect of exposure of Channa punctatus to a sub-lethal concentration of lead nitrate on the activities of alkaline phosphatase, acid phosphatase amylase, maltase, lactase, trypsin and pepsin has been investigated. A decrease in the activity of alkaline phosphatase has been recorded after 15 days of exposure but there was no significant change after 30 days. Acid phosphatase showed an elevation in activity of both stages. All the three carbohydrases shows elevation after 15 days, followed by an inhibition after 30 days of treatment. The activity of pepsin and trypsin remained above the normal level throughout the tensure of the experiment reveal that the pattern of alteration in enzyme activities is different in liver and digestive system.


Preparation of PVDF/CdS/Bi2WO6/ZnO hybrid membrane with enhanced visible-light photocatalytic activity for degrading nitrite in water.
In this work, a visible light-driven ternary heterojunction photocatalyst, CdS/Bi2WO6/ZnO, was synthesized using hydrothermal, ultrasonic dispersion, and deposition precipitation methods. The results show that photocatalysts with flower-like heterostructures were obtained, which could efficiently separate electron-hole pairs, and the photocatalytic activity was thereby significantly enhanced. Furthermore, CdS/Bi2WO6/ZnO and polyvinylidene fluoride (PVDF) were used to fabricate hybrid membranes via a phase-conversion method. The samples were characterized using SEM, TEM, EDX, XRD, DRS, XPS, PL, and N2 adsorption-desorption isotherms, and the transient photocurrent response. The photocatalytic activity of the hybrid membrane was evaluated, and 92.58% of the nitrite was converted into non-toxic substances within 4 h under simulated sunlight irradiation. This result indicated that the photocatalyst exhibited a good photocatalytic activity after immobilization. The possible mechanism was elucidated by studying the product during the photocatalytic degradation, and the effects of different pH values, electron scavengers, and hole scavengers on the photocatalytic performance were further investigated.


Three-dimensional echocardiography in the diagnosis of pacemaker lead perforation.
Recently, due to increases in the number of cardiac device implantations, especially implantable cardioverter-defibrillators and cardiac resynchronization therapy, device complications have been experienced more frequently. Myocardial perforation of an implanted lead is one of the most severe complications. We report a case of ventricular lead perforation clearly visualized by 3-dimensional echocardiography, which was not identified by 2-dimensional echocardiography.


Subpacket structure in strong VLF chorus rising tones: characteristics and consequences for relativistic electron acceleration.
Van Allen Probes in situ observations are used to examine detailed subpacket structure observed in strong VLF (very low frequency) rising-tone chorus elements observed at the time of a rapid MeV electron energization in the inner magnetosphere. Analysis of the frequency gap between lower and upper chorus-band waves identifies f ceEQ, the electron gyrofrequency in the equatorial wave generation region. Initial subpackets in these strong chorus rising-tone elements begin at a frequency near 1/4 f ceEQ and exhibit smooth gradual frequency increase across their > 10 ms temporal duration. A second much stronger subpacket is seen at frequencies around the local value of 1/4 f ce with small wave normal angle (< 10°) and steeply rising df/dt. Smooth frequency and phase variation across and between the initial subpackets support continuous phase trapping of resonant electrons and increased potential for MeV electron acceleration. The total energy gain for individual seed electrons with energies between 100 keV and 3 MeV ranges between 2 and 15%, in their nonlinear interaction with a single chorus element.


The association between depressive symptoms and self-rated health among university students: a cross-sectional study in France and Japan.
Depressive disorders in University students have risen dramatically in the past few decades to the extent that students' mental health has become a current global public health priority. Obtaining information from University students about their mental health is challenging because of potential embarrassment of disclosing one's concerns and fear of stigmatization. Self-rated health might be a good solution to evaluate mental health state by a simple and neutral indicator. The aim of the study is to investigate the association between depressive symptoms and self-rated health by sex among University students in France and Japan. A cross-sectional study was conducted by using two large cohorts of students aged ≥18 years (n = 5655 in Bordeaux, France and n = 17,148 in Kyoto, Japan). Depressive symptoms (PHQ-2 scale), Likert scale of self-rated health, socio-demographic characteristics and health habits were collected through self-administered questionnaires. Multivariate logistic regression models were performed to describe the association between depressive symptoms and other variables including self-rated health, stratified by sex. A high score of PHQ-2 (high depressive symptoms) was associated with poor self-rated health in both cohorts independently of all other variables (OR 2.82, 95%CI 1.99-4.01 in France, OR 7.10, 95%CI 5.76-8.74 in Japan). Although the prevalence of depressive symptoms between sexes was different in French students (males 15.4%, females 25.0%, p < 0.001), it was similar in Japanese students (males 3.5%, females 3.3%, p = 0.466), who reported less depressive symptoms than French students. The association between depressive symptoms and poor self-rated health was greater in Japanese females (OR 12.40, 95%CI 7.74-20.00) than in males (OR 6.30, 95%CI 4.99-7.95), whereas the strength of the association was almost similar in French students (OR 2.17, 95%CI 0.86-5.47 in males, OR 2.98, 95%CI 2.03-4.38 in females). Depressive symptoms were associated with self-rated health among University students in both countries with slightly differences in sex. Self-rated health would be a simple, reliable and universal indicator for healthcare professionals and University staff to identify students at risk of depression.


[Suture Aneurysms - Aetiopathogenesis, Symptomatology, Diagnostic Testing, Treatment, Outcome and Influencing Factors after Open Vascular Surgical and Image-guided Interventional Reconstruction].
To illustrate incidence, aetiopathogenesis, symptomatology, diagnostic testing, peri-interventional/-surgical management and outcome of SA based on selective references from the scientific medical literature and our own clinical experiences in diagnostic and therapeutic care. Narrative overview RESULTS: CONCLUSION: SA as relevant quantity of care has become a substantial part of basic vascular surgical or image-guided radiology treatment. The vascular surgeon or radiologist (for image-guided interventions) needs to be adequately focused on the demanding diagnostic and therapeutic management, demanding her/his complete competence and expertise.


Computed tomography in the diagnosis and differential diagnosis of glioblastomas. A qualitative study of 295 cases.
The CT patterns of 295 glioblastomas examined with pre- and postcontrast scans using an EMI scanner Mark I (Matrix 160/160) have been reviewed and compared with the CT appearances of other brain tumors, metastases and abscesses. There is a great variety of CT patterns with glioblastomas. However, a garland-shaped CT appearance, representing a subgroup of ring-shaped lesions, seems to be most typical for glioblastomas since it was observed in 19% of ring-shaped glioblastomas but in only one out of 172 metastases and in no case of an astrocytoma grade II or an abscess in our series. The initial CT diagnosis, based on the CT finding, the patient's history and the clinical data, was correct in 69.8% of the glioblastomas, 41 recurrent glioblastomas included. In 12% of the cases the presence of a glioblastoma was within differential diagnosis. These results lead to the conclusion that in many cases additional diagnostic methods, such as serial scintigraphy and/or cerebral angiography, are required for a reliable differential diagnosis.


Amelioration of normothermic canine liver ischemia with prostacyclin.
A model of hepatic ischemia was developed in dogs using a pump-driven splanchnic-to-jugular vein bypass during crossclamping of the portal triad. An LD50 was established with three hours of ischemia. PGI2 given for one hour before the ischemic insult ameliorated the ischemic injury and increased survival.


Delta oscillations are a robust biomarker of dopamine depletion severity and motor dysfunction in awake mice.
Delta oscillations (0.5-4 Hz) are a robust feature of basal ganglia pathophysiology in patients with Parkinson's disease (PD) in relationship to tremor, but their relationship to other parkinsonian symptoms has not been investigated. While delta oscillations have been observed in mouse models of PD, they have only been investigated in anesthetized animals, suggesting that the oscillations may be an anesthesia artifact and limiting the ability to relate them to motor symptoms. Here, we establish a novel approach to detect spike oscillations embedded in noise to provide the first study of delta oscillations in awake, dopamine-depleted mice. We find that approximately half of neurons in the substantia nigra pars reticulata (SNr) exhibit delta oscillations in dopamine depletion and that these oscillations are a strong indicator of dopamine loss and akinesia, outperforming measures such as changes in firing rate, irregularity, bursting, and synchrony. These oscillations are typically weakened, but not ablated, during movement. We further establish that these oscillations are caused by the loss of D2-receptor activation and do not originate from motor cortex, contrary to previous findings in anesthetized animals. Instead, SNr oscillations precede those in M1 at a 100- to 300-ms lag, and these neurons' relationship to M1 oscillations can be used as the basis for a novel classification of SNr into two subpopulations. These results give insight into how dopamine loss leads to motor dysfunction and suggest a reappraisal of delta oscillations as a marker of akinetic symptoms in PD.NEW & NOTEWORTHY This work introduces a novel method to detect spike oscillations amidst neural noise. Using this method, we demonstrate that delta oscillations in the basal ganglia are a defining feature of awake, dopamine-depleted mice and are strongly correlated with dopamine loss and parkinsonian motor symptoms. These oscillations arise from a loss of D2-receptor activation and do not require motor cortex. Similar oscillations in human patients may be an underappreciated marker and target for Parkinson's disease (PD) treatment.


Retention of urine in the neonate possibly due to anticonvulsant drugs.
Three cases of neonatal acute retention were associated with convulsions and heavy sedation. Inhibition of micturition may be due to diazepam-induced depression of the nervous system, in association with other anticonvulsants drugs.


Left ventricular ejection fraction and prevalence of new left ventricular wall motion abnormality at long-term follow-up in patients with automatic implantable cardioverter-defibrillators treated with dual-chamber rate-responsive pacing at a rate of 70/minute versus backup ventricular pacing at a rate of 40/minute.
Baseline and long-term follow-up 2-dimensional echocardiograms were obtained in 160 patients with automatic implantable cardioverter-defibrillators without indications for antibradycardia pacing, who had backup ventricular pacing at a rate of 40/minute (VVI-40) or dual-chamber rate-responsive pacing at a rate of 70/minute (DDDR-70). At 37 months of follow-up for 80 patients treated with VVI-40 and 23 months of follow-up for 80 patients treated with DDDR-70, the mean left ventricular ejection fraction was 36 +/- 8% at baseline and 36 +/- 8% at follow-up and 36 +/- 7% at baseline and 30 +/- 7% at follow-up (p <0.01), respectively. At follow-up, the left ventricular ejection fraction was decreased >7% in 25 of 80 patients (31%)treated with DDDR-70 and in 9 of 80 patients (11%) treated with VVI-40 (p <0.01). A new left ventricular wall motion abnormality developed in 23 of 80 patients (29%) treated with DDDR-70 and in 11 of 80 patients (14%) treated with VVI-40 (p <0.025).


5-HT 2A receptor activation of the external urethral sphincter and 5-HT 2C receptor inhibition of micturition: a study based on pharmacokinetics in the anaesthetized female rat.
Central and peripheral 5-hydroxytryptamine (5-HT) receptors play a critical role in the regulation of micturition. Bolus doses of 5-HT(2A/2C) receptor agonists have been shown to activate the external urethral sphincter (EUS) and to inhibit micturition. This study was designed to determine the contribution of these two 5-HT receptor subtypes to activation of the EUS and inhibition of micturition utilising pharmacokinetic knowledge to better control drug exposure. Recordings of urethral and bladder pressure, EUS-Electromyogram (EMG), the micturition reflex induced by bladder filling, blood pressure and heart rate were made in anaesthetized female rats. The effects of intravenous (i.v.) infusions of the 5-HT(2) receptor agonist (2S)-1-(6-chloro-5-fluoroindol-1-yl)propan-2-amine fumarate (Ro 60-0175) in the absence or presence of the selective 5-HT(2C) receptor antagonist 6-chloro-5-methyl-N-[6-(2-methylpyridin-3-yl)oxypyridin-3-yl]-2,3-dihydroindole-1-carboxamide dihydrochloride (SB 242084) or 5-HT(2A) receptor antagonist (R)-(2,3-dimethoxyphenyl)-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]methanol (MDL-100,907) were studied on these variables. Continuous infusion of increasing concentrations of Ro 60-0175 only evoked EUS-EMG activity at the highest concentration, which was blocked by co-infusion of MDL-100,907 but not SB 242084. Urethral pressure was unaffected by any drug infusion. Ro 60-0175 at the lowest concentration inhibited the micturition reflex but as the concentration increased this was reversed to facilitation. SB 242084 blocked the inhibition while MDL-100,907 blocked the excitation. Activation of 5-HT(2A) not 5-HT(2C) receptors evoked EUS-EMG activity. In conclusion, 5-HT(2A) receptor activation facilitated the micturition reflex and evoked EUS-EMG while 5-HT(2C) receptor activation only inhibited the micturition reflex.


Hot-stop PCR: a simple and general assay for linear quantitation of allele ratios.
We have developed a simple, quantitative assay for measurement of allele ratios that circumvents the problem of heteroduplex formation skewing the results of restriction endonuclease digestion of PCR products. This assay, 'hot-stop PCR', involves addition of a radiolabelled PCR primer at the final cycle. We applied the assay to analysis of loss of imprinting (LOI) of the insulin-like growth factor II gene (IGF2) in tumours.


Flood inundation mapping and monitoring using SAR data and its impact on Ramganga River in Ganga basin.
Remote sensing-based flood inundation mapping and monitoring is very crucial input before, during, and after floods. Ganga-Ramganga doab is one of the prolonged flood-affected area in middle Ganga plain due to seasonal monsoon which leads to rise in water levels of Ganga and Ramganga rivers. The focus of the present study is to map severe flood condition captured through synthetic aperture radar (SAR) data during August-September 2018, and to explain the impact on Ramganga river morphology. SAR data is preferred for flood mapping and real-time monitoring in all weather conditions. In this study, dual-polarized (VV and VH) Sentinel-1 SAR images coupled with hydrological data (river water level) were used to produce flood inundation maps. Thresholding technique has been applied to determine the flood mapping through Sentinel-1 data. VH and VV polarisation methods have been applied for a comparison of their respective accuracies in delineating surface water. Results have been validated against a Sentinel-2 optical image, and both polarisations produced a total accuracy of more than 93%. VV polarisation has high accuracies than VH polarisation as similar results are observed in previous studies as well. The finding reveals that severe bank erosion took place in the Ramganga channel which significantly affected the channel morphology, mainly the massive mobilisation of channel sediments. The results show that the average channel width increased from 46 to 336 m. The proposed approach demonstrates that the microwave remote sensing data along with GIS can be used efficiently for flood inundation mapping, monitoring, and analysing its effect on channel morphology. Therefore, the results of this study will help to take the initiative to reduce the flood hazard impact in the doab area and increase the flexibility in the process of flood management.


Fiberoptic upper intestinal endoscopy in infants and children.
Fiberoptic upper intestinal endoscopy has been shown in the last decade to be the most sensitive technique to diagnose upper gastrointestinal disease. Diagnostic endoscopy has been shown to be safe, with a low complication rate of less than 2 per cent, and most of those reported have been minor. Furthermore, therapeutic endoscopy has been used to treat bleeding varices by sclerotherapy, avoiding the need for shunting procedures, which often fall in young children. Dilation of strictures with wire-guided dilators, endoscopic incision of antral mucosal diaphragms, and percutaneous placement of gastrostomy tubes are other ways endoscopy is being used as a means of treatment. Electrocoagulation and photocoagulation of bleeding upper gastrointestinal lesions have not been used.


Ultrafast high-harmonic nanoscopy of magnetization dynamics.
Light-induced magnetization changes, such as all-optical switching, skyrmion nucleation, and intersite spin transfer, unfold on temporal and spatial scales down to femtoseconds and nanometers, respectively. Pump-probe spectroscopy and diffraction studies indicate that spatio-temporal dynamics may drastically affect the non-equilibrium magnetic evolution. Yet, direct real-space magnetic imaging on the relevant timescales has remained challenging. Here, we demonstrate ultrafast high-harmonic nanoscopy employing circularly polarized high-harmonic radiation for real-space imaging of femtosecond magnetization dynamics. We map quenched magnetic domains and localized spin structures in Co/Pd multilayers with a sub-wavelength spatial resolution down to 16 nm, and strobosocopically trace the local magnetization dynamics with 40 fs temporal resolution. Our compact experimental setup demonstrates the highest spatio-temporal resolution of magneto-optical imaging to date. Facilitating ultrafast imaging with high sensitivity to chiral and linear dichroism, we envisage a wide range of applications spanning magnetism, phase transitions, and carrier dynamics.


Chloride intracellular channel 4 is dysregulated in endometrium of women with infertility and alters receptivity.
The endometrium remodels in each menstrual cycle to become receptive in preparation for embryo implantation which occurs in the mid-secretory phase of the cycle. Failure of blastocyst adhesion and implantation cause infertility. We compared chloride intracellular channel 4 (CLIC4) expression in human endometrium from women with normal fertility and primary unexplained infertility in the mid-secretory/receptive phase of the menstrual cycle. CLIC4 localised to both the epithelial and stromal regions of the endometrium of fertile tissues across the cycle. CLIC4 expression was significantly reduced in the luminal and glandular epithelium and remained unchanged in the stromal region of mid-secretory infertile endometrium compared to fertile endometrium. siRNA knockdown of CLIC4 significantly compromised adhesive capacity of Ishikawa cells (endometrial epithelial cell line). This reduced adhesion and CLIC4 expression was associated with elevated SGK1, p53, SIRT1, BCL2 and MCL1 gene expression in the Ishikawa cells. CLIC4 expression was increased in primary human endometrial stromal cells during decidualization, however, siRNA knockdown of CLIC4 did not affect decidualization. Our data provide evidence that CLIC4 may regulate receptivity and facilitate blastocyst attachment initiating implantation. Reduced CLIC4 levels may be causative of implantation failure in women.


Eversion Endarterectomy - An Alternative Approach to Occlusive External Iliac Artery disease.
While endovascular intervention is the recommended first option for management of common iliac artery (CIA) lesions, it lacks durable patency for Trans-Atlantic Inter-Society Consensus (TASC)-II C and D lesions involving the external iliac artery (EIA). Aorto-femoral bypass is a durable option but is unsuitable in patients with significant co-morbidities. Eversion endarterectomy provides an alternative to both endovascular and extensive open aortoiliac reconstruction for occlusive EIA disease. A single-center, retrospective review (2000-2020) of all patients undergoing eversion endarterectomy for EIA disease was undertaken. Demographic, clinical, operative and follow-up data were recorded. Fifty eversion endarterectomies were performed in 47 patients. The median age was 65.0 years (range 46-82) and 66.6% were male. Sixty-eight percent (n = 34) were ASA grade 3. Indications for intervention were disabling claudication (44%) and critical limb ischaemia (56%). Angiography demonstrated 22 TASC C and 28 TASC D lesions. The median follow-up was 18.5 months (range 0-149). The technical success rate was 100%, and 84% (n = 42) experienced an immediate symptomatic improvement. Primary and primary-assisted patency at one, three and five years was 86%, 82% and 74%, and 100%, 96% and 92%, respectively. The five-year limb salvage rate was 96%. Eight limbs required reintervention to maintain patency, either by open (n = 2), endovascular (n = 3) or hybrid approach (n = 3). Thirty-day mortality was 2% (n = 1) with 10% (n = 5) experiencing a procedure-related morbidity. All-cause mortality was 38% (n = 19) during the follow-up period. Eversion endarterectomy is a safe, effective alternative treatment for occlusive EIA disease. This study reports durable patency at five years and low perioperative morbidity and mortality.


Comparison of four in situ hybridization methods, based on digoxigenin- and biotin-labelled probes, in detecting HPV DNA in male condylomata acuminata.
We have compared the efficacy of digoxigenin- and biotin-labelled probes in detecting HPV DNA by in situ hybridization on paraffin-embedded tissue sections of 57 male condyloma-suspect genital lesions. Each biopsy was hybridized with at least three of the following four methods: digoxigenin-labelled HPV DNA probes (Dig-HPV), biotinylated HPV-DNA probes (Bio-HPV), and two commercial methods (ViraType in situ and PathoGene), both based on biotinylated DNA probes. The hybridization products were visualized with colourigenic enzyme substrates. In most biopsies, the 4 methods gave equal results although cross-hybridization was most often found with the low-stringency ViraType method. Dig-HPV 6/11 probes gave positive results about twice as often as either of the commercial methods. No such difference, however, was found for HPV 16/18 probes. DNA of any type of HPV 6/11, 16/18 or 31/33/35 or 51 was detected in 28/43 (65%) of lesions showing condyloma acuminatum histology but in none of the 14 biopsies with no histological signs of HPV infection. In HPV-positive condylomata with no cellular atypia. HPV 6/11 was detected in 87% (13/15), and HPV 16/18 in 27% (4/15). In biopsies with cellular atypia, HPV types 6/11 were detected in 62% (8/13), HPV types 16/18 in 46% (6/13), and HPV types 31/33/35 or 51 in 50% (6/12). In about 50% of the biopsies where at least one hybridization method gave a positive result, either one of the commercial methods gave a negative result.(ABSTRACT TRUNCATED AT 250 WORDS)


An assessment of various potentially toxic elements and associated health risks in agricultural soil along the middle Gangetic basin, India.
The present study analysed the levels of potentially toxic elements along with physico-chemical properties of agricultural soil samples (n = 59) collected from fields situated along the path of river Ganga in the middle Gangetic floodplain in two districts, Ballia and Ghazipur. Arsenic (As), chromium (Cr), copper (Cu), nickel (Ni), zinc (Zn), lead (Pb), iron (Fe) and manganese (Mn) levels were analysed by Wavelength Dispersive-X-Ray Fluorescence Spectroscopy (WD-XRF) and the associated health risks along with diverse indices were calculated. The mean concentrations of As, Cu, Cr, Pb, Zn and Ni were found to be 15, 42, 85, 18, 87 and 47 mg kg-1, respectively in Ballia and 13, 31, 73, 22, 77 and 34 mg kg-1, respectively in Ghazipur. Physico-chemical properties like pH, ORP and organic matter were found to be 7.91, 209 and 1.20, respectively in Ballia and 8.51, 155 and 1.25, respectively in Ghazipur. The calculated health quotient (HQ) for all the elements was observed to be within the threshold value of one, however with few exemptions. Therefore, the present study showcases the contamination of potentially toxic elements in agricultural fields and possible health hazards for people.


Liver transarterial chemoembolization and sunitinib for unresectable hepatocellular carcinoma: Results of the PRODIGE 16 study.
Trans-arterial chemoembolization (TACE) is one first-line option therapy for patients with hepatocellular carcinoma (HCC) not suitable for surgical resection. We evaluated the effects of sunitinib plus doxorubicin-TACE on bleeding or liver failure. Seventy-eight patients with HCC were included in this randomized, double-blind study. They received one to three TACE plus either sunitinib or placebo four weeks out of six for one year. The occurrence of severe bleeding or liver failure was assessed during the week after the TACE. The safety and survival outcomes were evaluated. No bleeding complication was reported. One and two liver failures were respectively observed in sunitinib and placebo patients. Compliance to sunitinib treatment was acceptable. Sunitinib dose reduction occurred in 37% of patients due to acute toxicity. Main grade 3-4 toxicities were: thrombocytopenia, neutropenia, increased bilirubin, increased ALT and asthenia. In the sunitinib group, the median PFS and OS were 9.05 [5.81;11.63] and 25.0 [13.5;36.8] months, respectively. In the placebo group, the median PFS and OS were 5.51 [4.14;7.79] and 20.5 [15.1;30.6] months, respectively. TACE plus sunitinib in the first-line therapy for patients with HCC not suitable for surgical resection was feasible. CLINICALTRIALS. NCT01164202.


Two hundred and forty-one consecutive liver resections: an experience from India.
Although liver resection has become an established procedure in western countries and South-east Asia it is still not performed frequently in most centres in India. In the last 10 years newly created specialized units have been performing more liver resections but no major series have been reported. We analysed the results of 241 hepatic resections in the Gyan Burman Liver Unit, Sir Ganga Ram Hospital to compare our results with those published from established centres and to identify the factors relating to morbidity and mortality. To examine the effect of a greater experience with the procedure we compared the outcome of our operations from 1996-2000 (first period) and those from 2001-2005 (second period). The overall mortality and morbidity rates were 6.6% and 44.8%, respectively, which are comparable with those of most recently published Western series. Life-threatening complications occurred in 12.4% patients. Multivariate analysis showed that the presence of comorbid conditions, intraoperative blood transfusions of >3 units, hepatocellular carcinoma with underlying cirrhosis and gall bladder carcinoma with jaundice were the independent risk factors for morbidity, whereas the presence of comorbid illness and underlying liver cirrhosis were the risk factors for mortality. During the second period there was an increase in the number of operations performed (66 vs 175; first vs second period), but the mortality rates remained essentially unchanged (6.1% vs 6.8%). Hepatic resections can be performed safely in India with results comparable to those achieved in the West. Increasing experience did not reduce overall mortality. Perhaps more careful patient selection and better perioperative management of comorbid illnesses may reduce the morbidity and mortality further.


Culture media and methods for the isolation of Listeria monocytogenes.
The recovery of low numbers of Listeria monocytogenes from foods and environmental samples requires the use of enrichment cultures followed by selective plating and, where injured organisms are likely to be present, a pre-enrichment step. The development of selective and enrichment media for L. monocytogenes is traced and currently used media are discussed. Comparisons of media and methods for the culture of L. monocytogenes are reported but no single method can be recommended for all situations. Guidance is given on the choice of media and methods which is governed by the type of sample, number and nature of competing flora and cost.


Airway inflammation and hyperresponsiveness in subjects with respiratory symptoms and normal spirometry.
Subjects without a previous history of asthma, presenting with unexplained respiratory symptoms and normal spirometry, may exhibit airway hyperresponsiveness (AHR) in association with underlying eosinophilic (type 2 (T2)) inflammation, consistent with undiagnosed asthma. However, the prevalence of undiagnosed asthma in these subjects is unknown. In this observational study, inhaled corticosteroid-naïve adults without previously diagnosed lung disease reporting current respiratory symptoms and showing normal pre- and post-bronchodilator spirometry underwent fractional exhaled nitric oxide (F ENO) measurement, methacholine challenge testing and induced sputum analysis. AHR was defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20) <16 mg·mL-1 and T2 inflammation was defined as sputum eosinophils >2% and/or F ENO >25 ppb. Out of 132 subjects (mean±sd age 57.6±14.2 years, 52% female), 47 (36% (95% CI 28-44%)) showed AHR: 20/132 (15% (95% CI 9-21%)) with PC20 <4 mg·mL-1 and 27/132 (21% (95% CI 14-28%)) with PC20 4-15.9 mg·mL-1. Of 130 participants for whom sputum eosinophils, F ENO or both results were obtained, 45 (35% (95% CI 27-43%)) had T2 inflammation. 14 participants (11% (95% CI 6-16%)) had sputum eosinophils >2% and PC20 ≥16 mg·mL-1, suggesting eosinophilic bronchitis. The prevalence of T2 inflammation was significantly higher in subjects with PC20 <4 mg·mL-1 (12/20 (60%)) than in those with PC20 4-15.9 mg·mL-1 (8/27 (30%)) or ≥16 mg·mL-1 (25/85 (29%)) (p=0.01). Asthma, underlying T2 airway inflammation and eosinophilic bronchitis may remain undiagnosed in a high proportion of symptomatic subjects in the community who have normal pre- and post-bronchodilator spirometry.


Longitudinal evaluation of the complexed-to-total prostate specific antigen ratio in men with prostate disease. Effect of treatment.
The longitudinal changes in the complexed-to-total prostate specific antigen (PSA) ratio were evaluated in 90 men with benign prostatic hyperplasia (BPH) and 50 men with prostate cancer. The influence of treatment on this ratio was studied in 45 BPH patients and 50 patients with prostate cancer. Using a cut-off of 0.80 for the complexed-to-total PSA ratio, the large majority of prostate cancer patients had a ratio above the cut-off before treatment in serial determinations, whereas most BPH patients had a ratio consistently below that value. However, the few prostate cancer patients who had a ratio < or = 0.80 showed this low ratio in serial determinations, as did BPH patients who had a ratio > or = 0.80. During treatment, the ratio significantly decreased in 43 of the 50 patients with prostate cancer in parallel with the decrease in total PSA, and 34 of the 41 patients that had a pretreatment ratio > 0.80 showed a ratio < or = 0.80 during hormonal therapy. Our results show that neither the physiological changes in total and complexed PSA nor the treatment of BPH patients change the diagnostic efficacy of the complexed-to-total PSA ratio, whereas in prostate cancer patients under hormonal therapy, the ratio decreased in parallel with the decrease in total PSA. This suggests that, apart from improving the diagnostic efficacy of total PSA, the complexed-to-total PSA ratio could also be used to monitor BPH patients for newly developed tumours or to monitor therapy in patients with prostate cancer.


Tissue Regeneration of Human Mesenchymal Stem Cells on Porous Gelatin Micro-Carriers by Long-Term Dynamic In Vitro Culture.
Tissue engineering is a multidisciplinary field which attracted much attention in recent years. One of the most important issue in tissue engineering is how to obtain high cell numbers and tissue regeneration while maintaining appropriate cellular characteristics in vitro for restoring damaged or dysfunctional body tissues and organs. These demands can be achieved by the use of three dimensional (3D) dynamic cultures of cells combined with cell-adhesive micro-carriers. In this study, human mesenchymal stem cells (hMSCs) were cultured in a wave-bioreactor system for up to 100 days, after seeding on Cultisphere-S porous gelatin micro-carriers. Cell counting was performed at the time points of 7, 12, 17, 31 days and compared to those of hMSCs cultured under static condition. Higher growth and proliferation rates was achieved in wave-type dynamic culture, when cell culture continued to day 31. A scanning electron microscope (SEM) photographs, both live and dead and MTT assays were taken to confirm the survival and distribution of cells on porous gelatin micro-carrier surfaces. The results of histological stains such as hematoxylin and eosin, Masson's trichrome, Alcian blue and Alizarin red S also showed improved proliferation and tissue regeneration of hMSCs on porous gelatin micro-carriers. The experimental results demonstrated the effect and importance of both micro-carriers and bioreactor in hMSC expansion on cell proliferation and migration as well as extracellular matrix formation on the superficial and pore surfaces of the porous gelatin micro-carriers, and then their inter-connections, leading to tissue regeneration.


Prenatal stress alters brain catecholaminergic activity and potentiates stress-induced behavior in adult rats.
Previous studies demonstrated that throughout the preweaning period prenatally stressed rats have an overactive hypothalamic-pituitary-adrenal (HPA) system. This increased HPA activity was accompanied by an increase in defensive behavior. This study examined whether these alterations in HPA activity and defensive behavior continued into adulthood. Brain catecholamines in the cerebral cortex and locus coeruleus were also measured in prenatally stressed and control rats. Shock-induced levels of defensive freezing were significantly higher in prenatally stressed rats than in controls. However, plasma ACTH and corticosterone concentrations did not differ between groups either in the basal state or after exposure to foot shock. Concentrations of norepinephrine (NE) in the cerebral cortex and locus coeruleus region were significantly reduced in prenatally stressed rats. In addition, concentrations of NE metabolites were significantly elevated in prenatally stressed rats, suggesting an increased turnover of brain NE. Prenatally stressed rats also had, in the locus coeruleus region, significantly reduced dopamine (DA) levels but elevated concentration of DA metabolites. Results indicate that prenatal stress produces an increased behavioral responsiveness to stress that is evident in early life and continues into adulthood. The early hyperactivity of the HPA system in prenatally stressed rats, however, appears to normalize in adulthood. The increased turnover in brain catecholamines measure in the cerebral cortex and locus coeruleus region of prenatally stressed rats may be associated with the heightened expression of stress-induced behavior.


The First Compound Heterozygous Mutations of DMP1 Causing Rare Autosomal Recessive Hypophosphatemic Rickets Type 1.
Hereditary hypophosphatemic rickets (HR) consists of a group of inherited hypophosphatemia due to mutations of different genes, which need genetic analysis to make a differential diagnosis. Among them, autosomal recessive hypophosphatemic rickets type 1 (ARHR1), caused by a homozygous mutation of dentin matrix protein 1 (DMP1), is extremely rare, with only 30 reported patients. To date, there has been no case with compound heterozygous DMP1 mutations. To report the first compound heterozygous mutations of DMP1 causing ARHR1 and confirm the effect of the mutation on DMP1 protein. We report the clinical features of a Chinese patient with HR. Whole-exome sequencing (WES) was performed on the proband. Then, Cytoscan HD array, Sanger sequencing, and genomic quantitative PCR (qPCR) were used to confirm the mutations. A cell experiment was conducted to explore the effect of the mutation. The proband is a 4-year-old boy, who developed genu varum when he was able to walk at age 1 year and tooth loss after a mild hit at age 3.5 years. Physical examination, biochemical measurement, and imaging finding indicated HR. Family history was negative. WES performed on the proband revealed a novel start codon mutation (c.1A > T, p.Met1Leu) in DMP1 and a large deletion involving most of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family gene, including DSPP, DMP1, IBSP, and MEPE. The novel paternally inherited start codon mutation, which resulted in decreased expression of DMP1 protein with smaller molecular weight and cleavage defect, was confirmed by Sanger sequencing. The maternally inherited deletion was validated by Cytoscan and qPCR, and the breakpoint was finally identified by long-range PCR and Sanger sequencing. Manifestation of dentin dysplasia (DD) or dentinogenesis imperfecta (DGI) caused by DSPP mutations was absent in the patient and his mother, confirming that haploinsufficiency could not lead to DD or DGI. We report for the first time compound heterozygous DMP1 mutations consisting of a large deletion and a novel start codon mutation (c.1A > T, p.Met1Leu) in a Chinese patient with ARHR1.


Synthesis of new 1,2,3-triazole derivatives of uracil and thymine with potential inhibitory activity against acidic corrosion of steels.
Ten 1,4-disubstituted 1,2,3-triazoles were synthesized from one of 1-(azido-methyl)benzene, 1-(azidomethyl)-4-fluorobenzene, 1-(azidomethyl)-4-chlorobenzene, 1-(azidomethyl)-4-bromobenzene or 1-(azidomethyl)-4-iodobenzene, generated in situ from sodium azide and the corresponding benzyl halide, and dipropargyl uracil or dipropargyl thymine. Optimal experimental conditions were established for the conventional click chemistry. The corrosion inhibiting properties of some of these compounds, which were determined by means of an electrochemical technique, are also presented.


Protein expression from synthetic genes: selection of clones using GFP.
Construction of synthetic genes is today the most elegant way to optimize the heterologous expression of a recombinant protein. However, the selection of positive clones that incorporate the correct synthetic DNA fragments is a bottleneck as current methods of gene synthesis introduce 3.5 nucleotide deletions per kb. Furthermore, even when all predictable optimizations for protein production have been introduced into the synthetic gene, production of the protein is often disappointing: protein is produced in too low amounts or end up in inclusion bodies. We propose a strategy to overcome these two problems simultaneously by cloning the synthetic gene upstream of a reporter gene. This permits the selection of clones devoid of frame-shift mutations. In addition, beside nucleotide deletion, an average of three non-neutral mutations per kb are introduced during gene synthesis. Using a reporter protein downstream of the synthetic gene, allows the selection of clones with random mutations improving the expression or the folding of the protein of interest. The problem of errors found in synthetic genes is then turned into an advantage since it provides polymorphism useful for molecular evolution. The use of synthetic genes appears as an alternative to the error-prone PCR strategy to generate the variations necessary in protein engineering experiments.


Diagnostic Value of Magnetic Resonance Spectroscopy in Radiation Encephalopathy Induced by Radiotherapy for Patients with Nasopharyngeal Carcinoma: A Meta-Analysis.
In this study, articles in English and Chinese were selected from available electronic databases prior to September 2014. The metabolic concentrations and patterns of N-acetylaspartic acid (NAA), Choline (Cho), Creatine (Cr), NAA/Cr, NAA/Cho, and Cho/Cr ratios in radiotherapy-induced radiation encephalopathy by proton magnetic resonance spectroscopy were extracted. A meta-analysis was performed to quantitatively synthesize findings of these studies. Weighted mean difference (WMD) and 95% confidence intervals (95%CIs) were calculated using random or fixed effective models. Heterogeneity between studies was assessed using the Cochrane Q test and I (2) statistics. The results indicated that a total of 4 researches involving 214 patients met inclusion criteria. Depending on methodologies of selected studies, control groups were referred to as healthy subjects. The combined analysis revealed that there was no significant difference in value of Cr between radiotherapy group and healthy control group (WMD = -1.483, 95% CI: -67.185-64.219, p = 0.965). However, there were significant difference in values of NAA (WMD = -18.227, 95%CI: -36.317--0.137, p = 0.048), Cho (WMD = 38.003, 95%CI: 5.155-70.851, p = 0.023), NAA/Cr (WMD = -1.175, 95%CI: -1.563--0.787, p = 0.000), NAA/Cho (WMD = -1.108, 95%CI: -2.003-0.213, p = 0.015), and Cho/Cr (WMD = -0.773, 95%CI: 0.239-1.307, p = 0.005). In conclusion, MRS can be regarded as an effective and feasible imaging test for radiotherapy-induced radiation encephalopathy in NPC patients.


An enzyme-release assay for natural cytotoxicity.
A sensitive enzyme-release assay for natural cytotoxicity is described. The kinetic determination of the amount of the enzyme lactate dehydrogenase (LDH) released from lysed target cells was determined to provide a sensitive and precise measure of natural cytotoxicity when used in conjunction with appropriate controls and calculational methods. Values for the percentage of cytotoxicity or kinetic parameters determined by this method were identical, within experimental error, to values determined in parallel 51Cr release assays. Moreover, it was found that the spontaneous release of LDH from the target cells tested was considerably lower than the spontaneous release of 51Cr. This enzyme-release cytotoxicity assay is convenient, inexpensive, and precise, and should be applicable to the study of other cytotoxicity reactions, including antibody-dependent and T-cell mediated reactions.


Direct anterior versus posteriorlateral approachs for clinical outcomes after total hip arthroplasty in the treatment of severe DDH.
The total hip arthroplasty (THA) has gained popularity in in the treatment of severe developmental dysplasia of the hip (DDH). the posterior lateral approach (PLA) has good clinical efficacy and has been confirmed by the majority clinicians. Nevertheless, controversy exists regarding longer-term benefits of the direct anterior approach (DAA). The objective of this study was to investigate the clinical efficacy and placement of S-ROM prosthesis in the treatment of severe DDH by The total hip arthroplasty (THA) with different surgical approaches. A retrospective analysis was performed on 42 patients with severe DDH admitted to our hospital from August 2015 to February 2022, who were treated with S-ROM prosthesis for total hip arthroplasty and subtrochanteric osteotomy of the femur. They were divided into DAA group and PLA group according to different surgical approaches. Perioperative indicators and imaging data were collected. The surgery time, intraoperative blood loss, and creatine kinase difference in DAA group and PLA group was without a statistically significant difference (P > 0.05). The postoperative length of hospitalization was shorter in the DAA group than in the PLA group (6.50 ± 3.15 vs 9.18 ± 4.93, P = 0.045). The acetabular abduction angles、the acetabular anteversion angles, the safe area ratio, The difference of femoral eccentricity, and the vertical difference of rotation center in DAA group and PLA group, there was no statistical significance (P > 0.05). Statistically significant differences were detected the horizontal difference of rotation center (P = 0.044). Total hip arthroplasty with S-ROM prosthesis is a feasible procedure for severe dysplastic DDH. The clinical efficacy and prosthesis placement parameters of DAA approach are advantage to those of PLA approach.


A moving target for drug discovery: Structure activity relationship and many genome (de)stabilizing functions of the RAD52 protein.
BRCA-ness phenotype, a signature of many breast and ovarian cancers, manifests as deficiency in homologous recombination, and as defects in protection and repair of damaged DNA replication forks. A dependence of such cancers on DNA repair factors less important for survival of BRCA-proficient cells, offers opportunities for development of novel chemotherapeutic interventions. The first drugs targeting BRCA-deficient cancers, poly-ADP-ribose polymerase (PARP) inhibitors have been approved for the treatment of advanced, chemotherapy resistant cancers in patients with BRCA1/2 germline mutations. Nine additional proteins that can be targeted to selectively kill BRCA-deficient cancer cells have been identified. Among them, a DNA repair protein RAD52 is an especially attractive target due to general tolerance of the RAD52 loss of function, and protective role of an inactivating mutation. Yet, the effective pharmacological inhibitors of RAD52 have not been forthcoming. In this review, we discuss advances in the state of our knowledge of the RAD52 structure, activities and cellular functions, with a specific focus on the features that make RAD52 an attractive, but difficult drug target.


Detection and purification of a recombinant human B lymphotropic virus (HHV-6) in the baculovirus expression system by limiting dilution and DNA dot-blot hybridization.
A recombinant virus Ac373-HB was detected and purified from the transfection mixture of wild type and recombinant virus in the baculovirus expression system using a combination of limiting dilution and DNA dot-blot hybridization. This method allows for a quick and convenient way of detection and purification of recombinant virus without the need to use a plaque purification step. It is generally applicable to other expression systems besides the baculovirus system described here.


Exposure to repeated, intermittent d-amphetamine induces sensitization of HPA axis to a subsequent stressor.
Previous studies have demonstrated that exposure to psychostimulant drugs can produce a lasting cross-sensitization to the behavioral effects of stress. The main purpose the present study was, therefore, to determine the effects of psychostimulant cross-sensitization on the stress-induced release of adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Rats were given a series of injections of d-amphetamine or vehicle in a regimen that has been shown previously to induce cross-sensitization to a stressor. After two weeks, half the animals in the drug and vehicle-treated conditions were subjected to 30 min restraint stress; the remaining animals served as non-stressed controls. Animals were then sacrificed and trunk blood was assayed for CORT and ACTH. Prior d-amphetamine had no effect upon levels of CORT and ACTH in the non-stressed animals. Following 30 min restraint stress, however, levels of both hormones were significantly higher in drug-treated animals compared to controls. A second experiment confirmed behavioral sensitization to the current schedule of d-amphetamine injections, and demonstrated neuroendocrine sensitization of ACTH and CORT to a subsequent drug challenge. The augmented release of CORT and ACTH observed in d-amphetamine-treated rats might have important implications for human disorders in which processes resembling neurochemical sensitization have been hypothesized to play an etiological role.


Monitoring the effect of chemotherapy in a mixed glioma by C-11-methionine PET.
The effect of chemotherapy with procarbazine, CCNU, and vincristine in an anaplastic oligoastrocytoma was monitored by repeated positron emission tomography (PET) with C-11-methionine (C-11-MET). Chemotherapy caused a continuous decline of active tumor volume at a rate of approximately 2.4% per day, resulting in complete remission that persisted until the end of follow-up at 3 years. Thus, the authors conclude that C-11-MET PET may be useful for monitoring chemotherapy in gliomas and deserves further study.


Jflow: a workflow management system for web applications.
Biologists produce large data sets and are in demand of rich and simple web portals in which they can upload and analyze their files. Providing such tools requires to mask the complexity induced by the needed High Performance Computing (HPC) environment. The connection between interface and computing infrastructure is usually specific to each portal. With Jflow, we introduce a Workflow Management System (WMS), composed of jQuery plug-ins which can easily be embedded in any web application and a Python library providing all requested features to setup, run and monitor workflows. Jflow is available under the GNU General Public License (GPL) at http://bioinfo.genotoul.fr/jflow. The package is coming with full documentation, quick start and a running test portal. firstname.lastname@example.com.


Modulating role of NO in haloperidol-induced catalepsy.
Injection of haloperidol during catalepsy modeling decreased the content of NO in rat cerebral cortex. NO precursor L-arginine arrested catalepsy and prevented the decrease in NO content.