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Introduction: Erectile dysfunction (ED) is a well-studied entity in diabetes mellitus (DM). As with DM, prediabetes also appears to be associated with changes in microvascular-related comorbidities. These include retinopathy, neuropathy, nephropathy, and ED. ED is a condition characterized by an inability to maintain penile erection for adequate sexual activity, either consistently or recurrently. Endothelial damage due to any cause corresponding to hyperglycemia signifies the relationship between prediabetes and ED. While the evaluation of ED in diabetics has been extensively studied worldwide, there is a paucity of knowledge about ED among prediabetics., Materials and Methods: The study type was observational and was conducted at a tertiary center in India. Adult males aged 18-50 years with prediabetes were included in the study over a duration of 18 months. Evaluation for ED was performed using the International Index of Erectile Function 5 (IIEF-5)., Results: A total of 139 participants were enrolled in the present study. The severity of ED was categorized as follows: 32.4% of participants had mild ED, 11.5% had mild-to-moderate ED, and 6.5% had moderate ED. A positive association was found between prediabetes-related parameters and ED., Conclusion: There is a significant prevalence of ED in prediabetic males compared to the general population, as found in our study. Overall, 50.3% of participants were found to have ED. We recommend exploring this subject with more structured and larger studies., (© Journal of the Association of Physicians of India 2024.)

Background: The cancer registry provides reliable data from the population. In this article, we provide cancer burden and its patterns from the Varanasi district., Methods: The method adopted by the Varanasi cancer registry is community interaction along with regular visits to more than 60 sources to collect data on cancer patients. The cancer registry was established by the Tata Memorial Centre, Mumbai, in 2017 covering 4 million population (57% rural and 43% urban population)., Results: The registry has recorded 1,907 incidence cases (1,058 male and 849 female). The age-adjusted incidence rate per 100,000 population in male and female of Varanasi district is 59.2 and 52.1, respectively. One in 15 male and one in 17 female are at risk of developing the disease. Mouth and tongue cancers are the predominant cancers in male, whereas breast, cervix uteri, and gallbladder are the leading cancer sites among the female. In female, cervix uteri cancer is significantly higher (double) in rural areas when compared with urban areas (rate ratio [RR] 0.5, 95% confidence interval [CI; 0.36, 0.72]), whereas in male, mouth cancer is higher in urban areas when compared with rural areas (RR 1.4, 95% CI [1.11, 1.72]). More than 50% of cancer cases in male are due to tobacco consumption. There may be underreporting of the cases., Conclusion: The results of the registry warrant policies and activities related to early detection services for the mouth, cervix uteri, and breast cancers. The Varanasi cancer registry is the foundation for cancer control and will play an important role in the evaluation of the interventions., (Copyright © 2024 Copyright: © 2024 Indian Journal of Cancer.)

Cyanobacteria and evolutionarily related chloroplasts of algae and plants possess unique RNA polymerases (RNAPs) with characteristics that distinguish them from canonical bacterial RNAPs. The largest subunit of cyanobacterial RNAP (cyRNAP) is divided into two polypeptides, β'1 and β'2, and contains the largest known lineage-specific insertion domain, Si3, located in the middle of the trigger loop and spanning approximately half of the β'2 subunit. In this study, we present the X-ray crystal structure of Si3 and the cryo-EM structures of the cyRNAP transcription elongation complex plus the NusG factor with and without incoming nucleoside triphosphate (iNTP) bound at the active site. Si3 has a well-ordered and elongated shape that exceeds the length of the main body of cyRNAP, fits into cavities of cyRNAP in the absence of iNTP bound at the active site and shields the binding site of secondary channel-binding proteins such as Gre and DksA. A small transition from the trigger loop to the trigger helix upon iNTP binding results in a large swing motion of Si3; however, this transition does not affect the catalytic activity of cyRNAP due to its minimal contact with cyRNAP, NusG, or DNA. This study provides a structural framework for understanding the evolutionary significance of these features unique to cyRNAP and chloroplast RNAP and may provide insights into the molecular mechanism of transcription in specific environment of photosynthetic organisms and organelle., Competing Interests: Competing interests statement:The authors declare no competing interest.

An easy access to functionalized alkenes has been developed by the C-H functionalization of anilides with Morita-Baylis-Hillman (MBH) bromides in the presence of copper chloride, TBHP and acetic acid. Unsubstituted as well as ortho / meta -substituted anilides exclusively give rise to the para -allylated products, whereas para -substitution brings about the formation of ortho -allylated anilides.

NusG is a transcription elongation factor that stimulates transcription pausing in Gram+ bacteria including B. subtilis by sequence-specific interaction with a conserved pause-inducing - 11 TTNTTT -6 motif found in the non-template DNA (ntDNA) strand within the transcription bubble. To reveal the structural basis of NusG-dependent pausing, we determined a cryo-EM structure of a paused transcription complex (PTC) containing RNA polymerase (RNAP), NusG, and the TTNTTT motif in the ntDNA strand. The interaction of NusG with the ntDNA strand rearranges the transcription bubble by positioning three consecutive T residues in a cleft between NusG and the β-lobe domain of RNAP. We revealed that the RNAP swivel module rotation (swiveling), which widens (swiveled state) and narrows (non-swiveled state) a cleft between NusG and the β-lobe, is an intrinsic motion of RNAP and is directly linked to trigger loop (TL) folding, an essential conformational change of all cellular RNAPs for the RNA synthesis reaction. We also determined cryo-EM structures of RNAP escaping from the paused transcription state. These structures revealed the NusG-dependent pausing mechanism by which NusG-ntDNA interaction inhibits the transition from swiveled to non-swiveled states, thereby preventing TL folding and RNA synthesis allosterically. This motion is also reduced by the formation of an RNA hairpin within the RNA exit channel. Thus, the pause half-life can be modulated by the strength of the NusG-ntDNA interaction and/or the stability of the RNA hairpin. NusG residues that interact with the TTNTTT motif are widely conserved in bacteria, suggesting that NusG-dependent pausing is widespread.

This prospective quasi-experimental study from the NASAM (National Approach to Standardize and Improve Mechanical Ventilation) collaborative assessed the impact of evidence-based practices including subglottic suctioning, daily assessment for spontaneous awakening trial (SAT), spontaneous breathing trial (SBT), head of bed elevation, and avoidance of neuromuscular blockers unless otherwise indicated. The study outcomes included VAE (primary) and intensive care unit (ICU) mortality. Changes in daily care process measures and outcomes were evaluated using repeated measures mixed modeling. The results were reported as incident rate ratio (IRR) for each additional month with 95% confidence interval (CI). A comprehensive program that included education on evidence-based practices for optimal care of mechanically ventilated patients with real-time benchmarking of daily care process measures to drive improvement in forty-two ICUs from 26 hospitals in Saudi Arabia (>27,000 days of observation). Compliance with subglottic suctioning, SAT and SBT increased monthly during the project by 3.5%, 2.1% and 1.9%, respectively (IRR 1.035, 95%CI 1.007-1.064, p = 0.0148; 1.021, 95% CI 1.010-1.032, p = 0.0003; and 1.019, 95%CI 1.009-1.029, p = 0.0001, respectively). The use of neuromuscular blockers decreased monthly by 2.5% (IRR 0.975, 95%CI 0.953-0.998, p = 0.0341). The compliance with head of bed elevation was high at baseline and did not change over time. Based on data for 83153 ventilator days, VAE rate was 15.2/1000 ventilator day (95%CI 12.6-18.1) at baseline and did not change during the project (IRR 1.019, 95%CI 0.985-1.053, p = 0.2812). Based on data for 8523 patients; the mortality was 30.4% (95%CI 27.4-33.6) at baseline, and decreased monthly during the project by 1.6% (IRR 0.984, 95%CI 0.973-0.996, p = 0.0067). A national quality improvement collaborative was associated with improvements in daily care processes. These changes were associated with a reduction in mortality but not VAEs. Registration The study is registered in clinicaltrials.gov (NCT03790150)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Arabi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Self-assembly of macromolecules into higher-order symmetric structures is fundamental for the regulation of biological processes. Higher-order symmetric structure self-assembly by the gene expression machinery, such as bacterial DNA-dependent RNA polymerase (RNAP), has never been reported before. Here, we show that the stress-response σ B factor from the human pathogen, Mycobacterium tuberculosis, induces the RNAP holoenzyme oligomerization into a supramolecular complex composed of eight RNAP units. Cryo-electron microscopy revealed a pseudo-symmetric structure of the RNAP octamer in which RNAP protomers are captured in an auto-inhibited state and display an open-clamp conformation. The structure shows that σ B is sequestered by the RNAP flap and clamp domains. The transcriptional activator RbpA prevented octamer formation by promoting the initiation-competent RNAP conformation. Our results reveal that a non-conserved region of σ is an allosteric controller of transcription initiation and demonstrate how basal transcription factors can regulate gene expression by modulating the RNAP holoenzyme assembly and hibernation., (© 2023. The Author(s).)

Abstract: The prevalent manual destalking of dried red chillies is a labour-intensive, tedious, and unhealthy practice that can cause severe health ailments to the labourers. This study focuses on the design and fabrication of a mechanized system for removing stalks from dried chillies to reduce the drudgery involved in manual operation. The machine's primary components including hopper, rotating cylinder, triangular bridges, cutting blades, destalked chilli outlet, and stalk outlet were fabricated based on the design considerations and ease of operation. The machine was evaluated considering the independent parameters viz. feed rate, cylinder speed, and cylinder inclination for optimization of its performance using one-factor-at-a-time statistical design. Physical properties of chillies, destalking efficiency of the machine, and the effect of destalking on powder characteristics were determined. Optimal performance of the machine was achieved with the chillies having 8-10% (moisture), 6.5 kg/h (feed rate), 20 rpm (cylinder's speed), and 3° (cylinder's inclination) with destalking efficiency of 85-87%. The evaluation of powder characteristics also revealed the prominence of destalking with enhanced colour attributes. The developed machine is compact, efficient, economical, requires less labour and thereby it may encourage its adoption at the farmer's level and strengthening of the value chain of dried chillies., Competing Interests: Conflict of interestThe authors declare that they don’t have any conflict of interest., (© Association of Food Scientists & Technologists (India) 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The transcriptome-wide contributions of Rho-dependent and intrinsic (Rho-independent) transcription termination mechanisms in bacteria are unclear. By sequencing released transcripts in a wild-type strain and strains containing deficiencies in NusA, NusG and/or Rho (10 strains), we produced an atlas of terminators for the model Gram-positive bacterium Bacillus subtilis. We found that NusA and NusG stimulate 77% and 19% of all intrinsic terminators, respectively, and that both proteins participate in Rho-dependent termination. We also show that Rho stimulates termination at 10% of the intrinsic terminators in vivo. We recapitulated Rho-stimulated intrinsic termination at 5 terminators in vitro and found that Rho requires the KOW domain of NusG to stimulate this process at one of these terminators. Computational analyses of our atlas using RNAstructure, MEME suite and DiffLogo, combined with in vitro transcription experiments, revealed that Rho stimulates intrinsic terminators with weak hairpins and/or U-rich tracts by remodelling the RNA upstream of the intrinsic terminator to prevent the formation of RNA structures that could otherwise compete with the terminator hairpin. We also identified 56 putative examples of 'hybrid Rho-dependent termination', wherein classical Rho-dependent termination occurs after readthrough of a Rho-stimulated intrinsic terminator., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To examine the accuracy of our national Life-Saving Protocol (LSP). To the best of our knowledge, this is the first study addressing this issue in Saudi Arabia., Background: LSP was created to facilitate triaging patients with LIFE or LIMB threatening conditions in peripheral hospitals with limited services to large regional hospitals to receive definitive care., Method: This is a retrospective single-center observational study over 12 months studying the patients who arrived via LSP to our Emergency room (ED), at the only regional pediatric hospital. For the subgroup of patients who were admitted to PICU through LSP, we further assessed their outcomes like mortality and length of stay (LOS) through a matched case-control study of 1:1 with similar patients who were admitted to our PICU via other routes rather than LSP. The primary outcome is to assess the accuracy of the LSP in triaging pediatric patients with LIFE of LIMB conditions. Secondary outcomes include assessing the association between LSP and (mortality, LOS) for those who were admitted to the regional PICU via LSP compared to patients admitted to PICU via other sources of admission., Results: During the study period, 118 patients arrived at our ED via LSP. Only 43 patients (36 %) were admitted to the PICU with LIFE or LIMB conditions. A total of 64 patients (54%) of the patients were admitted directly to the general pediatric ward from ED level due to absence of LIFE of LIMB threatening condition and 8% (n=9) were discharged immediately home from the ED level due to lack of any significant illness. One patient died at ED level, and one was referred to another hospital with a minor orthopedic injury. For those who were admitted to the PICU via LSP, the mortality rate was (13.9%) (6/43), and the control group was (4.6%) (2/43) with a p-value of 0.08., Conclusion: LSP is an excellent initiative and essential tool in our healthcare system; however, our study showed huge variation in the ability of the system to recognize true pediatric patients with LIFE or LIMB conditions. Our study might form a stepping-stone in future studies assessing the LSP at the national level.

Background: It is unclear whether screening for sepsis using an electronic alert in hospitalized ward patients improves outcomes. The objective of the Stepped-wedge Cluster Randomized Trial of Electronic Early Notification of Sepsis in Hospitalized Ward Patients (SCREEN) trial is to evaluate whether an electronic screening for sepsis compared to no screening among hospitalized ward patients reduces all-cause 90-day in-hospital mortality., Methods and Design: This study is designed as a stepped-wedge cluster randomized trial in which the unit of randomization or cluster is the hospital ward. An electronic alert for sepsis was developed in the electronic medical record (EMR), with the feature of being active (visible to treating team) or masked (inactive in EMR frontend for the treating team but active in the backend of the EMR). Forty-five clusters in 5 hospitals are randomized into 9 sequences of 5 clusters each to receive the intervention (active alert) over 10 periods, 2 months each, the first being the baseline period. Data are extracted from EMR and are compared between the intervention (active alert) and control group (masked alert). During the study period, some of the hospital wards were allocated to manage patients with COVID-19. The primary outcome of all-cause hospital mortality by day 90 will be compared using a generalized linear mixed model with a binary distribution and a log-link function to estimate the relative risk as a measure of effect. We will include two levels of random effects to account for nested clustering within wards and periods and two levels of fixed effects: hospitals and COVID-19 ward status in addition to the intervention. Results will be expressed as relative risk with a 95% confidence interval., Conclusion: The SCREEN trial provides an opportunity for a novel trial design and analysis of routinely collected and entered data to evaluate the effectiveness of an intervention (alert) for a common medical problem (sepsis in ward patients). In this statistical analysis plan, we outline details of the planned analyses in advance of trial completion. Prior specification of the statistical methods and outcome analysis will facilitate unbiased analyses of these important clinical data., Trial Registration: ClinicalTrials.gov NCT04078594 . Registered on September 6, 2019., (© 2021. The Author(s).)

Graphene oxide-strontium (GO-Sr) composites prepared under different ambient conditions were characterized using morphological and spectroscopic techniques to optimize the uptake of Sr from aqueous solutions. These studies indicated that interactions among GO and Sr 2+ ions are highly sensitive to size and aging of GO sheets, as well as pH of the ambience. Further, the extent of Sr uptake on GO sheets was found to be largely influenced by relative fractions of the associated -COOH, -OH, C-O-C functional groups and sp 2 -C domains. Membranes prepared using various forms of GO were evaluated for their Sr separation ability and, a window of parameters for optimum separation of Sr has been proposed. Among the variety of membranes studied, those made up of fresh and large GO sheets were found to exhibit superior Sr adsorption capacity (~296 mg/g) at limited GO mass. Further, adsorption efficiency of these GO membranes was observed to deteriorate with aging of GO sheets and rise of GO mass on membrane. The membrane based filtration procedure introduced in present work facilitates to provide a lamellar structure of GO sheets with abundant surface area, diverse and accessible sites for Sr 2+ ion uptake and offer high Sr adsorption efficiencies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)