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The 297 winter rice accessions of Assam, North East India were genotyped by sequencing (GBS). The 50,985 high-quality SNPs were filtered and assigned to 12 rice chromosomes. The population structure analysis revealed three major subgroups SG1, SG2, and SG3 consisting of 30, 8, and 143 accessions respectively. The remaining 116 accessions were grouped as admixture population. Phenotypic data were recorded on13 agronomical traits for genome-wide association studies (GWAS). The 60 significant marker-trait associations (MTAs) were identified for 11 agronomical traits, which explained 0 to 15% of phenotypic variance (PV). A QTL 'hot spot' was detected near the centromeric region on chromosome 6. The identified QTLs may be validated and utilized in 'genomics assisted breeding' for improvement of existing rice cultivars of Assam and North East India.The recent outbreak of coronavirus disease 2019 (COVID-19) by SARS-CoV-2 has led to uptodate 24.3 M cases and 0.8 M deaths. It is thus in urgent need to rationalize potential therapeutic targets against the progression of diseases. An effective, feasible way is to use the pre-existing ΔORF6 mutant of SARS-CoV as a surrogate for SARS-CoV-2, since both lack the moiety responsible for interferon antagonistic effects. By analyzing temporal profiles of upregulated genes in ΔORF6-infected Calu-3 cells, we prioritized 55 genes and 238 ligands to reposition currently available medications for COVID-19 therapy. Eight of them are already in clinical trials, including dexamethasone, ritonavir, baricitinib, tofacitinib, naproxen, budesonide, ciclesonide and formoterol. We also pinpointed 16 drug groups from the Anatomical Therapeutic Chemical classification system, with the potential to mitigate symptoms of SARS-CoV-2 infection and thus to be repositioned for COVID-19 therapy.Cardiovascular diseases are among the leading causes of mortality worldwide. Besides environmental and genetic changes, these disorders can be influenced by processes which do not affect DNA sequence yet still play an important role in gene expression and which can be inherited. These so-called 'epigenetic' changes include DNA methylation, histone modifications, and ATP-dependent chromatin remodeling enzymes, which influence chromatin remodeling and gene expression. Next to these, microRNAs are non-coding RNA molecules that silence genes post-transcriptionally. Both epigenetic factors and microRNAs are known to influence cardiac development and homeostasis, in an individual fashion but also in a complex regulatory network. In this review, we will discuss how epigenetic factors and microRNAs interact with each other and how together they can influence cardiovascular diseases.Although Saccharomyces cerevisiae and S. cerevisiae var. boulardii share more than 95% genome sequence homology, only S. cerevisiae var. boulardii displays probiotic activity. In this study, the transcriptomic differences exhibited by S. cerevisiae and S. cerevisiae var. boulardii in intestinal like medium were evaluated. S. cerevisiae was found to display stress response overexpression, consistent with higher ability of S. cerevisiae var. boulardii to survive within the human host, while S. cerevisiae var. boulardii exhibited transcriptional patterns associated with probiotic activity, suggesting increased acetate biosynthesis. selleck Resorting to the creation of a S. cerevisiae var. boulardii genomic database within Yeastract+, a possible correlation between loss or gain of transcription factor binding sites in S. cerevisiae var. boulardii promoters and the transcriptomic pattern is discussed. This study suggests that S. cerevisiae var. boulardii probiotic activity, when compared to S. cerevisiae, relies, at least partially, on differential expression regulation, based on promoter variability.Acute postoperative pain is frequently evaluated by pain intensity scores. However, interpretation of the results is difficult and thresholds requiring treatment are not well defined. Additional patient-reported outcome measures (PROMs) might be helpful to better understand individual pain experience and quality of pain management after surgery. We used data from the QUIPS pain registry for a cross-sectional study in order to investigate associations between the desire to receive more pain treatment (D2RMPT) with pain intensity ratings and other PROMs. Responses from 79,996 patients were analyzed, of whom 10.7% reported D2RMPT. A generalized estimating equation Poisson model showed that women had a lower risk ratio (RR) to answer this question with "yes" (RR .92, P less then .001). Factors that increased the risk most were "maximal pain intensity ≥ 6/10 on a numerical rating scale" (RR 2.48, P less then .001) and "any pain interference" (RR 2.48, P less then .001). The largest reduction in risk was observed if patients were "allowed to participate in pain treatment decisions" (RR .41, P less then .001) and if they felt that they "received sufficient treatment information" (RR .58, P less then .001). Our results indicate that the (easily assessed) question D2RMPT gives additional information to other PROMs like pain intensity. The small proportion of patients with D2RMPT (even for high pain scores) opens the discussion about clinicians' understanding of over- und under-treatment and questions the exclusive use of pain intensity as quality indicator. Future studies need to investigate whether asking about D2RMPT in clinical routine can improve postoperative pain outcome. PERSPECTIVE This article presents characteristics of the patient-reported outcome measure "Desire to receive more pain treatment." This measure could be used to apply pain treatment in a more individualized way and lead to improved treatment strategies and quality.
Gallbladder perforation is a known morbid sequela of acute cholecystitis, yet evidence for its optimal management remains conflicting. This study compares outcomes in patients with perforated cholecystitis who underwent cholecystectomy at the time of index hospital admission with those in patients who underwent interval cholecystectomy.
A retrospective analysis was conducted of 654 patients from the American College of Surgeons NSQIP database who underwent cholecystectomy for perforated cholecystitis (2006-2018). Primary outcomes were 30-day postoperative major and minor morbidity, 30-day mortality, and need for prolonged hospitalization. Patient and procedure characteristics and outcomes were compared using Mann-Whitney rank sum test for continuous variables and Pearson chi-square tests for categorical variables. A subset analysis was conducted of patients matched on propensity for undergoing interval cholecystectomy.
The 30-day postoperative mortality rate of matched cohort patients undergoing index c with perforated cholecystitis can benefit from operative management on an interval, rather than urgent, basis.Cardiac implantable electronic devices establish proper therapy for the prevention of sudden cardiac death, significantly reducing the morbidity and mortality of patients with arrhythmias and heart failure. It is well-known that the number of electrodes increases the risk of complications. To preserve the benefit of atrial sensing without the need to implant an additional lead, a single-lead ICD system with a floating atrial dipole (DX ICD lead) has been developed. Besides all of the potential benefits, the necessity of a reliable and stable atrial sensing via the floating dipole could be the main concern against the use of this lead type. In the current generation of DX devices, the specially filtered atrial signal seems to be high enough and stable over time, which is crucial in the early detection of atrial arrhythmias, discrimination between different forms of tachycardias in order to prevent inappropriate ICD therapy, and achieving an optimal atrioventricular and interventricular synchrony in patients with a two-lead CRT-DX system. The present review summarizes the benefits and potential drawbacks of the DX ICD systems based on the available literature, furthermore, proposes an evidence-based algorithm of ICD type selection.The article reviews our studies of contextual fear conditioning (CFC) in rats during a period of development---Postnatal Day (PND) 17-33---that represents the late-infant, juvenile, and early-adolescent stages. These studies seek to acquire 'systems level' knowledge of brain and memory development and apply it to a rodent model of Fetal Alcohol Spectrum Disorder (FASD). This rodent model focuses on alcohol exposure from PND4-9, a period of brain development equivalent to the human third trimester, when neocortex, hippocampus, and cerebellum are especially vulnerable to adverse effects of alcohol. Our research emphasizes a variant of CFC, termed the Context Preexposure Facilitation Effect (CPFE, Fanselow, 1990), in which context representations incidentally learned on one occasion are retrieved and associated with immediate shock on a subsequent occasion. These representations can be encoded at the earliest developmental stage but seem not to be retained or retrieved until the juvenile period. This is associated with developmental differences in context-elicited expression, in prefrontal cortex, hippocampus, and amygdala, of immediate early genes (IEGs) that are implicated in long-term memory. Loss-of-function studies establish a functional role for these regions as soon as the CPFE emerges during ontogeny. In our rodent model of FASD, the CPFE is much more sensitive to alcohol dose than other commonly used cognitive tasks. This impairment can be reversed by acute administration during behavioral testing of drugs that enhance cholinergic function. This effect is associated with normalized IEG expression in prefrontal cortex during incidental context learning. In summary, our findings suggest that long-term memory of incidentally-learned context representations depends on prefrontal-hippocampal circuitry that is important both for the normative development of context conditioning and for its disruption by developmental alcohol exposure.These studies investigate the possibility of developing and using choline salicylate (CS) in ophthalmic therapy in the form of eye drops with increased viscosity. A 0.5% addition of hydroxypropyl methylcellulose (HPMC) was used as the viscosity increasing agent. The ability of CS to cross a hydrophilic membrane (regenerated cellulose membrane) was assessed by determining a rate constant consistent with zero order kinetics. In studies on a porcine cornea, the ability of CS to penetrate into the structure of the cornea was confirmed by determining the content of CS in the cornea after 5 minutes and 3 hours exposure to eye drops. The quality parameters of eye drops were assessed pH, viscosity, osmolarity and microbiological purity. Stability tests were also performed on eye drops stored in unit minims packaging and in multi-dose bottle packaging. The following storage conditions were adopted 40°C/75% RH, 25°C/60% RH, 2-8°C. The sensitivity of CS to light was also confirmed. The UV and HPLC-UV methods were used to assess the CS content, while the HPLC-UV and HPLC-MS/MS methods were used to assess the chromatographic purity.
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