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Translational regulation by riboswitches is an important mechanism for the modulation of gene expression in bacteria. Here the authors show that the ligand-induced allosteric switch in the adenine-sensing riboswitch from V. vulnificus is insufficient and leads only to a partial opening of the ribosome binding site and requires interaction with 30S-bound ribosomal protein S1, which acts as an RNA chaperone.

Maham Hayat,1 Hassaan Zia,2 Salman Nusrat2 1Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; 2Section of Digestive Diseases & Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA Abstract: Chronic idiopathic constipation, if inadequately treated, can be bothersome with a detrimental effect on patients’ quality of life (QOL). This may also result in frequent health care visits, increasing the burden of this ailment’s medical cost. Management strategies, focused on lifestyle changes, include increased exercise, a high-fiber diet, and toilet training. Pharmacologic options include fiber supplementation, laxatives, serotonergic agents, and prosecretory agents such as lubiprostone. In this review, we were able to conclude that lubiprostone, when used for chronic idiopathic constipation, has a significantly beneficial effect on both patients’ symptoms and their QOL. In multiple randomized controlled trials, it has been found to have increased the number of spontaneous bowel movements at different time endpoints. Corresponding improvements were also observed for abdominal bloating, discomfort, stool frequency, and straining symptoms among patients. Keywords: functional, gastrointestinal disorders, spontaneous bowel movements, secretory agents, abdominal pain, cost-effectiveness

While children with appendicitis often have excellent clinical outcomes, some develop life-threatening complications including sepsis and organ dysfunction requiring pediatric intensive care unit (PICU) support. Our study applied a metabolomics and inflammatory protein mediator (IPM) profiling approach to determine the bio-profiles of children who developed severe appendicitis compared with those that did not. We performed a prospective case-control study of children aged 0–17 years with a diagnosis of appendicitis. Cases had severe disease resulting in PICU admission. Primary controls had moderate appendicitis (perforation without PICU); secondary controls had mild appendicitis (non-perforated). Serum samples were analyzed using Proton Nuclear Magnetic Resonance (1H NMR) Spectroscopy and Gas Chromatography-Mass Spectrometry (GC-MS); IPM analysis was performed using plasma bead-based multiplex profiling. Comparisons were made using multivariate data statistical analysis. Fifty-three children were included (15 severe, 38 non-severe). Separation between severe and moderate appendicitis demonstrated excellent sensitivity and specificity (100%, 88%; 14 compounds), separation between severe and mild appendicitis also showed excellent sensitivity and specificity (91%, 90%; 16 compounds). Biomarker patterns derived from metabolomics and IPM profiling are capable of distinguishing children with severe appendicitis from those with less severe disease. These findings provide an important first step towards developing non-invasive diagnostic tools for clinicians in early identification of children who are at a high risk of developing severe appendicitis.

Over one billion Muslims worldwide fast during the month of Ramadan. Ramadan fasting brings about some changes in the daily lives of practicing Muslims, especially in their diet and sleep patterns, which are associated with the risk of cardiovascular diseases. Over the years, many original studies have made the effort to identify the possible impact of the Ramadan fast on cardiovascular diseases. This systematic review and meta-analysis is an attempt to present the summary of key findings from those articles and an appraisal of selected literature. A systematic search using keywords of “;Ramadan fasting” and “;cardiovascular diseases” was conducted in primary research article and gray-literature repositories, in combination with hand searching and snow balling. Fifteen studies were finally selected for data extraction on the outcomes of stroke, myocardial infarction, and congestive heart failure. The analysis revealed that the incidence of cardiovascular events during the Ramadan fast was similar to the nonfasting period. Ramadan fast is not associated with any change in incidence of acute cardiovascular disease.

Various limitations hinder the timely and accurate diagnosis of appendicitis in pediatric patients. The present study aims to investigate the potential of metabolomics and cytokine profiling for improving the diagnosis of pediatric appendicitis. Serum and plasma samples were collected from pediatric patients for metabolic and inflammatory mediator analyses respectively. Targeted metabolic profiling was performed using Proton Nuclear Magnetic Resonance Spectroscopy and Flow Injection Analysis Mass Spectrometry/Mass Spectrometry and targeted cytokine/chemokine profiling was completed using a multiplex platform to compare children with and without appendicitis. Twenty-three children with appendicitis and 35 control children without appendicitis from the Alberta Sepsis Network pediatric cohorts were included. Metabolomic profiling revealed clear separation between the two groups with very good sensitivity (80%), specificity (97%), and AUROC (0.93 ± 0.05) values. Inflammatory mediator analysis also distinguished the two groups with high sensitivity (82%), specificity (100%), and AUROC (0.97 ± 0.02) values. A biopattern comprised of 9 metabolites and 7 inflammatory compounds was detected to be significant for the separation between appendicitis and control groups. Integration of these 16 significant compounds resulted in a combined metabolic and cytokine profile that also demonstrated strong separation between the two groups with 81% sensitivity, 100% specificity and AUROC value of 0.96 ± 0.03. The study demonstrated that metabolomics and cytokine mediator profiling is capable of distinguishing children with appendicitis from those without. These results suggest a potential new approach for improving the identification of appendicitis in children.

Abstract Despite the constant development of antimicrobial resistance (AMR), few new antimicrobials are currently becoming available clinically. Alternative approaches, such as different mechanisms to fund their use, are being explored to encourage development of new antimicrobials.

Abstract Background Leadership is a critical competency for medical professionals, yet it is often neglected in medical training. For ObGyn residents, leadership training is particularly crucial as it significantly impacts both maternal and newborn outcomes, as well as the operational efficiency of healthcare teams. The main objective of this study was to assess the perceptions of obstetrics and gynecology residents who served as group leaders in the emergency team at the Department of Gynecology, Ward 3, Dr. Ruth K.M. Pfau Civil Hospital Karachi. Methods A Cross-sectional survey was conducted with purposively sampled 28 year-4 residents who worked as group leaders during last 3 years (from 2018 to 2020) of their residency program at the emergency team in the department of Gynecology Ward 3 Dr Ruth KM Pfau Civil Hospital Karachi. The perceptions on leadership were assessed on 25 items scale sent through a questionnaire on email. Grading of responses was done using a 4-point ordinal scale where 1 meant little importance and 4 was regarded as having great importance. Data was summarized with relevant descriptive statistics and was analyzed on SPSS version 22. Results The mean age of residents was 30.36. The mean leadership scores of the group of residents were calculated to be 77.50 (SD ± 9.57) while 14(50%) residents showed good and 14 (50%) showed excellent leadership skills based on cumulative scores. Of the 25 traits examined in this study, the highest reported trait was humility 3.82 (± 0.39) followed by empowerment 3.68 (± 0.77) and effective communication 3.68 (± 0.77). While responding about learning experiences, 89.3% of participants felt that the experience enhanced their decision-making skills and boosted their confidence in dealing with emergencies. Conclusion Our study highlights the critical importance of leadership development in the training of ObGyn residents, particularly in high-pressure emergency settings. The findings reveal that residents value leadership traits such as humility, empowerment, and effective communication, which are essential for building teamwork and ensuring optimal patient outcomes and patient satisfaction.

Abstract Understanding the evolving nature of coronary hemodynamics is crucial for early disease detection and monitoring progression. We require digital twins that mimic a patient’s circulatory system by integrating continuous physiological data and computing hemodynamic patterns over months. Current models match clinical flow measurements but are limited to single heartbeats. To this end, we introduced the longitudinal hemodynamic mapping framework (LHMF), designed to tackle critical challenges: (1) computational intractability of explicit methods; (2) boundary conditions reflecting varying activity states; and (3) accessible computing resources for clinical translation. We show negligible error (0.0002–0.004%) between LHMF and explicit data of 750 heartbeats. We deployed LHMF across traditional and cloud-based platforms, demonstrating high-throughput simulations on heterogeneous systems. Additionally, we established LHMFC, where hemodynamically similar heartbeats are clustered to avoid redundant simulations, accurately reconstructing longitudinal hemodynamic maps (LHMs). This study captured 3D hemodynamics over 4.5 million heartbeats, paving the way for cardiovascular digital twins.

Abstract Background The advancement of sequencing technologies results in the rapid release of hundreds of new genome assemblies a year providing unprecedented resources for the study of genome evolution. Within this context, the significance of in-depth analyses of repetitive elements, transposable elements (TEs) in particular, is increasingly recognized in understanding genome evolution. Despite the plethora of available bioinformatic tools for identifying and annotating TEs, the phylogenetic distance of the target species from a curated and classified database of repetitive element sequences constrains any automated annotation effort. Moreover, manual curation of raw repeat libraries is deemed essential due to the frequent incompleteness of automatically generated consensus sequences. Results Here, we present an example of a crowd-sourcing effort aimed at curating and annotating TE libraries of two non-model species built around a collaborative, peer-reviewed teaching process. Manual curation and classification are time-consuming processes that offer limited short-term academic rewards and are typically confined to a few research groups where methods are taught through hands-on experience. Crowd-sourcing efforts could therefore offer a significant opportunity to bridge the gap between learning the methods of curation effectively and empowering the scientific community with high-quality, reusable repeat libraries. Conclusions The collaborative manual curation of TEs from two tardigrade species, for which there were no TE libraries available, resulted in the successful characterization of hundreds of new and diverse TEs in a reasonable time frame. Our crowd-sourcing setting can be used as a teaching reference guide for similar projects: A hidden treasure awaits discovery within non-model organisms.

The pomegranate fruit (locally known as Dalim) is a rich source of various bioactive metabolites. The cardioprotective effect was aimed to investigate on polyphenol-rich pomegranate peel extract (PPE) that were administered isoproterenol, a synthetic catecholamine used to induce cardiac stress in rats. Twenty four adult rats were taken to evaluate the effects. The selected rats were divided into four groups, serving as the control (Group I), Isoproterenol (ISO) administered (Group II), PPE with ISO treatment (Group III) and gallic acid (polyphenol) along with ISO administration (Group IV). ISO administration increased inflammatory cell infiltration, fibrosis and lipid peroxidation. However, antioxidant enzyme activities were reduced in heart tissues by using isoproterenol. The findings of the study indicate that the various detrimental effects arose on the rat's heart tissues by ISO administration which seemed to be protected by the administration of the polyphenol-rich PPE. This protection was associated with several positive outcomes, including: reduced inflammatory cell infiltration and fibrosis, reduction in free radicals by improving antioxidant enzymes activities (SOD, catalase), suppression of oxidative stress markers (MDA, NO, APOP), and reduction in inflammatory marker (MPO). Besides, PPE treatment normalized the elevated ALT, AST, ALP, and CK-MB levels. The cardioprotective effects shown by PPE may be due to the presence of polyphenolic compounds, as determined by HPLC analysis. Overall, the outcomes recommend that polyphenol enriched PPE may protect cardiac tissues in ISO-administered rats by suppressing oxidative stress, fibrosis, and myocardial infarction as well as enhancing antioxidant enzyme functions. [ J Adv Biotechnol Exp Ther 2024; 7(1.000): 190-204]

Abstract Biodegradable poly(butylene succinate‐co‐adipate)/Poly(3‐hydroxybutyrate‐co‐3‐hydoxyvalerate) (PBSA/PHBV) filled with lignocellulosic sidestream/fibers from cowpea, a neglected and underutilized African crop are produced by injection molding and extrusion film casting. Differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) suggests that the fibers have more affinity and interfacial interaction with PBSA than PHBV. This is shown by a decrease in dampening of PBSA and an increase in dampening of PHBV with fiber addition. In addition, fiber addition results in more homogeneous crystal morphology of PBSA, while resulting in more heterogeneous crystal morphology of PHBV. The tensile strength of injection molded bio‐composites increases with fiber addition due to good interfacial adhesion between the matrix and fibers revealed by scanning electron microscope. In contrast, the tensile strength of bio‐composite films decreases with fiber addition due to the high‐volume fraction of pores in bio‐composite films that act as stress raisers. The stiffness of both injection molded, and bio‐composite films increase with fiber addition, as revealed by an increase in Young's modulus and storage modulus, while the tensile strain decreases. In conclusion, low‐value cowpea sidestream can be used as a filler to produce injection molded bio‐composites and bio‐composite films for potential application as rigid and flexible packaging.

Liver fibrosis, developed in almost all chronic liver injuries. Epidermal growth factor receptors (EGFR) have been thought to contribute to cirrhosis and liver fibrosis. Therefore, using a rat model of carbon tetrachloride (CCl4)-induced liver fibrogenesis, we investigated the preventive effects of cetuximab, an inhibitor of the EGF receptor (EGFR). Ameliorative effects of cetuximab were examined in rats, brought on by biweekly doses of 50 mg/kg of carbon tetrachloride (CCl4). There were a total of 24 male Long Evans rats split up into four distinct groups such as control, CCl4, control+cetuximab and CCl4+cetuximab. After two weeks of treatment with cetuximab (100 μg/kg), samples of tissue and blood were taken after all the rats had been sacrificed. Plasma samples were examined for the biochemical indicators of inflammation and oxidative stress. Histological staining on liver sections was performed for morphologic pathologies, and related genes expressions analysis were done with RT-PCR in liver tissue. The findings showed that cetuximab could raise the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) and considerably lower the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA), and nitric oxide (NO). Sirius red staining and hematoxylin-eosin (H&E) displayed that cetuximab therapy reduced the inflammatory cells infiltration and enhanced fibrotic lesions. In the meantime, cetuximab therapy also dramatically reduces the expression of genes linked to inflammation in the liver tissue, including NF-кB, iNOS, IL-6, TNF-α, and TGF-β. To sum up, the anti-inflammatory, antifibrotic, and antioxidant properties of cetuximab confer curative efficacy against liver fibrosis.