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The Hirschsprung disease (HSCR) is an inherited disease that is controlled by multiple genes and has a complicated genetic mechanism. HSCR patients suffer from various extents of constipation due to dysplasia of the enteric nervous system (ENS), which can be so severe as to cause complete intestinal obstruction. Many genes have been identified as playing causative roles in ENS dysplasia and HSCR, among them the endothelin receptor type B gene (Ednrb) has been identified to play an important role. Mutation of Ednrb causes a series of symptoms that include deafness, pigmentary abnormalities, and aganglionosis. In our previous studies of three rat models carrying the same spotting lethal (sl) mutation on Ednrb, the haplotype of a region on chromosome (Chr) 2 was found to be responsible for the differing severities of the HSCR-like symptoms. To confirm that the haplotype of the responsible region on Chr 2 modifies the severity of aganglionosis caused by Ednrb mutation and to recreate a rat model with severe symptoms, we selected the GK inbred strain, whose haplotype in the responsible region on Chr 2 resembles that of the rat strain in which severe symptoms accompany the Ednrbsl mutation. An Ednrb mutation was introduced into the GK rat by crossing with F344-Ednrbsl and by genome editing. The null mutation of Ednrb was found to cause embryonic death in F2 progeny possessing the GK haplotype in the responsible region on Chr 2. The results of this study are unexpected, and they provide new clues and animal models that promise to contribute to studies on the genetic regulatory network in the development of ENS and on embryogenesis.

IntroductionNo statutory mental health services exist for justice-involved individuals in Pakistan. The lack of expertise in forensic psychiatry serves to deny individuals with mental illness the critical support needed for mental healthcare and adequate court dispositions with serious unintended consequences including capital punishment for those who could otherwise be deemed treatment and not punishment worthy. A landmark judgement by the Supreme Court of Pakistan in February 2021 criticized the lack of forensic psychiatry expertise in Pakistan and directing the development of forensic mental health services and forensic psychiatry training in Pakistan.ObjectivesThe key objectives are: 1. Understanding the timeline of how justice invloved individuals are manged by psychiatric services 2. The importance of the Supreme Court of Pakistan Judgement in affecting change 3. Highlights on how Queen’s University will enhance forensic psychiatry in PakistanMethodsA literature review and personal networking facilitated the collection of important data in how justice invloved individuals are supported in Pakistan. The author has published and presented to Pakistani psychiatrists and the Pakistani judiciary on this topic. Queen’s University is aiming to implement a 3-year plan to develop an online curriculum and certificate course to help train the trainers.ResultsIn the Pakistan’s most populous province, Punjab, prevalence rates for psychotic illnesses (3.7%), major depression (10%), and personality disorders (65%) among men with higher rates for psychotic disorders (4.0%) and major depression (12%) among women.ConclusionsIn conclusion there is a dire need to develop forensic psychiatry in Pakistan and other low/middle income countries.DisclosureNo significant relationships.

Atherosclerosis, the main contributor to coronary heart disease, is characterised by an accumulation of lipids such as cholesterol in the arterial wall. Reverse cholesterol transport (RCT) reduces cholesterol via its conversion into bile acids (BAs). During RCT in non-hepatic peripheral tissues, cholesterol is transferred to high-density lipoprotein (HDL) particles and returned to the liver for conversion into BAs predominantly via the rate-limiting enzyme, cholesterol 7 α-hydroxylase (CYP7A1). Numerous reports have described that polyphenol induced increases in BA excretion and corresponding reductions in total and LDL cholesterol in animal and in-vitro studies, but the process whereby this occurs has not been extensively reviewed. There are three main mechanisms by which BA excretion can be augmented: (1) increased expression of CYP7A1; (2) reduced expression of intestinal BA transporters; and (3) changes in the gut microbiota. Here we summarise the BA metabolic pathways focusing on CYP7A1, how its gene is regulated via transcription factors, diurnal rhythms, and microRNAs. Importantly, we will address the following questions: (1) Can polyphenols enhance BA secretion by modulating the CYP7A1 biosynthetic pathway? (2) Can polyphenols alter the BA pool via changes in the gut microbiota? (3) Which polyphenols are the most promising candidates for future research? We conclude that while in rodents some polyphenols induce CYP7A1 expression predominantly by the LXRα pathway, in human cells, this may occur through FXR, NF-KB, and ERK signalling. Additionally, gut microbiota is important for the de-conjugation and excretion of BAs. Puerarin, resveratrol, and quercetin are promising candidates for further research in this area.

Herpes simplex virus (HSV) is a prevalent and persistent human pathogen belonging to the family Herpesviridae and classified as an alpha-herpesvirus. It comprises two distinct types, HSV-1 and HSV-2, which together infect a significant portion of the global population and pose substantial public health challenges. HSV-1 is typically associated with oral herpes, while HSV-2 primarily causes genital herpes; both are characterized by recurrent lesions, latent infection, and mucocutaneous discomfort. Conventional antiviral drugs such as acyclovir and its derivatives are limited by drug resistance, potential toxicity, and their inability to eradicate latent viral reservoirs. These limitations have prompted increasing interest in alternative therapeutic strategies. Phenolic acids and tannins, plant-derived polyphenolic compounds, have attracted considerable attention due to their potent antiviral properties against various viruses, including HSV. This review summarizes current research on phenolic acids and tannins as promising natural antivirals against HSV, with a focus on their mechanisms of action and efficacy in disrupting multiple stages of the HSV life cycle.

The Epstein–Barr virus (EBV), a member of the human gamma-herpesviruses, is intricately linked to various human malignancies. Current treatment options for EBV infection involve the use of acyclovir and its derivatives, which exhibit limited efficacy and are associated with drug resistance issues. Therefore, there is a critical need for new medications with more effective therapeutic actions and less susceptibility to resistance. This review explores the therapeutic promise of flavones and flavonols, naturally occurring molecules, against EBV and its correlated cancers. It thoroughly delves into the molecular mechanisms underlying the therapeutic efficacy of these compounds and scrutinizes their complex interplay in EBV-linked processes and cancer transformation by targeting key genes and proteins pivotal to both the viral life cycle and tumor development. Additionally, the review covers current research, highlights key findings, and discusses promising avenues for future investigations in the pursuit of targeted therapies against EBV and its related tumors.

Abstract The study aimed to evaluate the suitability of Hassawi dried lemon powder (HDLP), a cheap rich source of fibre, as a pectin substitute in jam. Pectin was replaced with HDLP at 25%–100%. Increasing HDLP level decreased water activity (0.813–0.759) and pH value (3.17–2.80), while increased % acidity (0.79%–0.87%) (p ≤ .05). Total soluble solids (TSS) and moisture content remained unchanged. Increasing HDLP level significantly increased the hardness from 56.3 to 63.0 g, while decreased the cohesiveness value (p ≤ .05). Colour parameters were unchanged except for b* and hue values both increased from 0.10 to 0.23 and 4.1 to 8.8, respectively (p ≤ .05). Replacing pectin at 75%–100% slightly affected mouthfeel and spreadability, while other sensory attributes remained stable. Microstructure analysis showed minor changes, while maintaining uniformity and distribution. Low replacement levels (25% and 50%) achieved optimal sensory and quality balance, emphasising its potential as cheap and successful pectin substitute. Graphical Abstract Graphical Abstract

The herpes simplex virus (HSV) is a double-stranded DNA human virus that causes persistent infections with recurrent outbreaks. HSV exists in two forms: HSV-1, responsible for oral herpes, and HSV-2, primarily causing genital herpes. Both types can lead to significant complications, including neurological issues. Conventional treatment, involving acyclovir and its derivatives, faces challenges due to drug resistance. This underscores the imperative for continual research and development of new drugs, with a particular emphasis on exploring the potential of natural antivirals. Flavonoids have demonstrated promise in combating various viruses, including those within the herpesvirus family. This review, delving into recent studies, reveals the intricate mechanisms by which flavonoids decode their antiviral capabilities against HSV. By disrupting key stages of the viral life cycle, such as attachment to host cells, entry, DNA replication, latency, and reactivation, flavonoids emerge as formidable contenders in the ongoing battle against HSV infections.

Accurate annotation of genes and transposable elements (TEs) is vital for understanding genomes, but current annotation pipelines often misannotate TEs as genes. This study reveals how the general transcription factor II-I repeat domain-containing protein 2 (GTF2IRD2) erroneously annotated DNA transposons in non-mammalian species, as it contains a 3′ fused hAT transposase domain. We also demonstrate the generality of this problem by identifying misannotated TEs as genes in other vertebrate genomes. Such misannotations can lead to errors in phylogenetic analyses and wasted time for investigators. The study proposes adding a final TE-check to gene annotation pipelines to mitigate this problem.

PurposeThis study uses the Conservation of Resource theory to examine the influence of abusive supervision on organizational citizenship behavior (OCB) via emotional exhaustion, using a moderated mediation framework.Design/methodology/approachA questionnaire was adapted to collect data from 212 full-time employees in 22 private health centers in Nineveh governorate in Iraq in two waves. Hypotheses were tested using hierarchical regression and bootstrapping analyses.FindingsThis study suggests that workplace friendship reduces the positive relationship between abusive supervision and emotional exhaustion of employees and reduces the negative indirect effect of abusive supervision on OCB.Originality/valueFirst, this study provides academicians with a better understanding of the moderating effect of workplace friendship on the relationship between abusive supervision and emotional exhaustion and then its impact on OCB. Second, the paper is one of the few studies that dealt with the abusive supervision in the health sector using data from the Middle East in Iraq, while most leadership research is conducted in the western part of the world.

Adolescence is the last opportunity to reverse any growth faltering accumulated from fetal life through childhood and it is considered a crucial period to optimize human development. In Bangladesh, a growing double burden of underweight and obesity in adolescents is recognized, yet limited data exists on how, when, and where to intervene. This study assesses the dynamics of growth among adolescent girls in Bangladesh, providing insight about critical junctures where faltering occurs and where immediate interventions are warranted. We pooled data from Bangladesh's Food Security and Nutrition Surveillance Project collected between 2011 and 2014 to document the age dynamics of weight and linear growth. 20,572 adolescent girls were measured for height and 19,345 for weight. We constructed growth curves for height, weight, stunting, and underweight. We also stratified growth dynamics by wealth quintile to assess socioeconomic inequities in adolescent trajectories. Height-for-age z-score (HAZ) in Bangladeshi girls deteriorates throughout adolescence and especially during the early years. Mean HAZ decreases by 0.20 standard deviations (sd) per year in early adolescence (10-14 years) vs 0.06 sd/year during late adolescence (15-19 years), while stunting increases by 16 percentage points (pp) vs 6.7 pp, respectively. Conversely, BMI-for-age z-score (BAZ) increases by 0.13 sd/year in early adolescence vs 0.02 sd/year in late adolescence, and underweight decreases by 12.8 pp vs 3.2 pp. Adolescent girls in all socioeconomic groups show a similar pattern of HAZ and BAZ dynamics, but the curve for the richest quintile stays above that of the poorest across all ages. Trends and levels of stunting and underweight among adolescent girls in Bangladesh are worrisome, suggesting substantial linear growth faltering in early adolescence, with improving weight-for-age occurring only as linear growth slows and stops. Given the rising burden of non-communicable diseases (NCDs) in Bangladesh and emerging evidence of the link between stunting and later chronic diseases, greater attention to adolescent growth and development is needed. Our findings suggest that, to address stunting, interventions in early adolescence would have the greatest benefits. School-based interventions could be a way to target this population.