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Adam Saleh,1,2 Usman Ansari,2 Shaadi Abughazaleh,2 Kerri Glassner,2 Bincy P Abraham2 1Engineering Medicine, Texas A&M University, Houston, TX, USA; 2Department of Medicine – Division of Gastroenterology, Houston Methodist, Houston, TX, USACorrespondence: Bincy P Abraham, Department of Medicine – Division of Gastroenterology, Houston Methodist, 6550 Fannin St. Suite 1201, Houston, TX, 77030, USA, Tel +1-713-441-5042, Fax +1-713-797-0622, Email bpabraham@houstonmethodist.orgAbstract: Several biologic therapies have been approved for enteric diseases. We evaluate each biologic’s role based on their mechanism of action in treating these conditions. This review examines data on efficacy and safety, as well as considerations for using these therapies in clinical practice in inflammatory bowel diseases, enteric infections—specifically Clostridioides difficile colitis—and potentially in the increasingly prevalent disorder of eosinophilic esophagitis. When choosing an appropriate therapy, it is important to assess patient severity, as most biologics are approved for those with moderate to severe disease activity. With many years of data from clinical trials and real-world experience, these therapies have been shown to improve outcomes overall in enteric diseases, contributing to more options for our patients.Keywords: biologics, Crohn’s disease, ulcerative colitis, Clostridioides difficile colitis, microscopic colitis, enteric disease

Byline: R. Negi, A. Srivastava, A. Srivastava, Abhishek. Pandeya, P. Vatsa, U. Ansari, A. Pant BACKGROUND AND OBJECTIVES: Induced pluripotent stem cells (iPSCs) derived three-dimensional (3D) model for rare neurodegenerative [...]

Summary: Supraglottic airway devices are commonly used to manage the airway during general anaesthesia. There are sporadic case reports of temporomandibular joint dysfunction and dislocation following supraglottic airway device use. We conducted a prospective observational study of adult patients undergoing elective surgery where a supraglottic airway device was used as the primary airway device. Pre‐operatively, all participants were asked to complete a questionnaire involving 12 points adapted from the Temporomandibular Joint Scale and the Liverpool Oral Rehabilitation Questionnaire. Objective measurements included inter‐incisor distance as well as forward and lateral jaw movements. The primary outcome was the inter‐incisor distance, an accepted measure of temporomandibular joint mobility. Both the questionnaire and measurements were repeated in the postoperative period and we analysed data from 130 participants. Mean (SD) inter‐incisor distance in the pre‐ and postoperative period was 46.5 (7.2) mm and 46.3 (7.5) mm, respectively (p = 0.521) with a difference (95%CI) of 0.2 (−0.5 to 0.9) mm. Mean (SD) forward jaw movement in the pre‐ and postoperative period was 3.6 (2.4) mm and 3.9 (2.4) mm, respectively (p = 0.018). Mean (SD) lateral jaw movement to the right in the pre‐ and postoperative period was 8.9 (4.1) mm and 9.1 (4.0) mm, respectively (p = 0.314). Mean (SD) lateral jaw movement to the left in the pre‐ and postoperative period was 8.8 (4.0) mm and 9.3 (3.6) mm, respectively (p = 0.008). The number of patients who reported jaw clicks or pops before opening their mouth as wide as possible was 28 (21.5%) vs. 12 (9.2%) in the pre‐ and postoperative period, respectively (p < 0.001) with a difference (95%CI) of 12.3% (6.7–17.9%). There was no significant difference in the responses to the other 11 questions or in the number of patients who reported pain in the temporomandibular joint area postoperatively. No clinically significant dysfunction of the temporomandibular joint following the use of supraglottic airway devices in the postoperative period was identified by either patient questionnaires or objective measurements. [ABSTRACT FROM AUTHOR]

Background: Interventional left atrial appendage occlusion (LAAO) mitigates the risk of thromboembolic events in nonvalvular atrial fibrillation (AF) patients with contraindication for long-term oral anticoagulation (OAC). Patients with prior stroke have a relevantly increased risk of recurrent stroke, so the effectiveness of LAAO could be reduced in this specific very high-risk patient group., Aim: This sub-study of the LAARGE registry investigates the effectiveness and safety of LAAO for secondary prevention in nonvalvular AF patients with a history of stroke., Methods: LAARGE is a prospective, non-randomised registry on the clinical reality of LAAO. The current sub-study employs data from index procedure and 1-year follow-up. Effectiveness and safety were assessed by documentation of all-cause mortality, non-fatal thromboembolism, procedure-related complications, and bleeding events., Results: A total of 638 patients were consecutively included from 38 hospitals in Germany and divided into two groups: 137 patients with a history of stroke (21.5%) and 501 patients without. Successful implantation was consistent between both groups (98.5% vs. 97.4%, p = NS), while peri-procedural MACCE and other complications were rare (0% vs. 0.6% and 4.4% vs. 4.0%, respectively; each p = NS). Kaplan-Meier estimate showed no significant difference in primary effectiveness outcome measure (freedom from all-cause death or non-fatal stroke) between both groups at follow-up (87.8% vs. 87.7%, p = NS). The incidence of transient ischemic attack or systemic embolism at follow-up was low (0% vs. 0.5% and 0.9% vs. 0%, respectively; each p = NS). Severe bleeding events after hospital discharge were rare (0% vs. 0.7%, p = NS)., Conclusions: Patients with prior stroke demonstrated similar effectiveness and safety profile for LAAO as compared to patients without prior stroke. LAAO could serve as a feasible alternative to OAC for secondary stroke prevention in this selected group of nonvalvular AF patients., Gov Identifier: NCT02230748., (© 2024. The Author(s).)

Objective: Selective androgen receptor modulators (SARMs) are potential treatments for ameliorating age-related physical dysfunctions caused by sarcopenia, cachexia and chronic illnesses such as cancer. The purpose of this systematic review is to analyse the effect of SARMs on physical performance and body and evaluate their safety profile., Methods: A systematic review search criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed in three databases for studies reporting physical parameter outcomes after SARM intervention. Study variables included title, author, publication date, study year, number of patients, dosage, mean age, mean follow-up time, pre and post-intervention outcomes and rates of complications., Results: Nine studies, including 970 patients with a mean age of 57.1 years (35.3-75.9) and a mean follow-up of 80 days (14-180), were included. Six SARMs were analysed: LGD-4033, PF-06260414, GSK2881078, GTx-024, MK-0773 and OPK-88004. Mean pre-intervention stair climbing power (five studies), one repetition maximum leg press (four studies) and short physical performance battery (SPPB) score (two studies), lean body mass (seven studies) and fat mass (five studies) were 352.24 W (69.79-678.7), 1822.77 N (1176.8-2407.3), 9.15 (7.95-9.9), 49.46 kg (30.94-63.9) and 21.99 kg (13.3-33), respectively. Mean post-intervention values were 315.16 W (89.46-525.73 W), 2191.27 N (1375.87-2462.9 N), 9.79 (8.88-10.4), 50.86 kg (31.02-67.29) and 21.85 kg (12.54-32.16), respectively., Conclusion: SARMs have a positive effect on physical performance and body composition and are associated with moderate rates of mild to moderate adverse effects (AEs) and a low rate of severe AEs., (© 2024 John Wiley & Sons Ltd.)

Background: Gender inequities remain critical determinants influencing maternal health. Harmful gender norms and gender-based violence adversely affect maternal health. Gendered division of labour, lack of access to and control of resources, and limited women's decision-making autonomy impede women's access to maternal healthcare services. We undertook a cluster randomized controlled trial of universal home visits to pregnant women and their spouses in one local government area in Bauchi State, North-Eastern Nigeria. The trial demonstrated a significant improvement in maternal and child health outcomes and male knowledge, attitudes and behaviours. This paper qualitatively evaluates gender equity in the home visits programme., Methods: The research team explored participants' views about gender equity in the home visits programme. We conducted nine key informant interviews with policymakers and 14 gender and age-stratified focus group discussions with men and women from visited households, with women and men home visitors and supervisors, and with men and women community leaders. Analysis used an adapted conceptual framework exploring gender equity in mainstream health. A deductive thematic analysis of interviews and focus group reports looked for patterns and meanings., Results: All respondents considered the home visits programme to have a positive impact on gender equity, as they perceived gender equity. Visited women and men and home visitors reported increased male support for household chores, with men doing heavy work traditionally pre-assigned to women. Men increased their support for women's maternal health by paying for healthcare and providing nutritious food. Households and community members confirmed that women no longer needed their spouses' permission to use health services for their own healthcare. Households and home visitors reported an improvement in spousal communication. They perceived a significant reduction in domestic violence, which they attributed to the changing attitudes of both women and men due to the home visits. All stakeholder groups stressed the importance of engaging male spouses in the home visits programme., Conclusion: The home visits programme, as implemented, contributed to gender equity., (© 2024. The Author(s).)

Nicotinamide adenine dinucleotide (NAD+) is essential in the proper function of many essential cellular processes in the human body. The purpose of this review is to investigate the effect of nicotinamide mononucleotide (NMN), a NAD+ precursor, on physical performance and evaluate the safety profile of supplementation. A systematic review search criteria following the guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed in four databases for randomized controlled trials on NMN supplementation. Study variables included title, author, publication date, study year, number of patients, dosage, mean age, mean follow-up time, pre- and post-intervention reported outcomes, and rates of complications. Ten studies, including 437 patients, with a mean age of 58.0 years (35.1 to 81.1 years) and a mean follow-up time of 9.6 weeks (4 to 12 weeks) were included in this study. NMN dosages ranged from 150 to 1200 mg/day. Mean pre-intervention grip strength (two studies) and skeletal mass index (two studies) were 29.9 kilograms (kg) (range: 21.4-40.1 kg) and 7.4 kg/m 2 (range: 6.9-7.65 kg/m 2 ), respectively. Mean post-intervention grip strength and skeletal mass index were 30.5 kg (range: 21.7-41.9 kg) and 7.4 kg/m 2 (6.8-7.64 kg/m 2 ), respectively. There were no serious adverse effects observed. Moreover, of the reported side effects, they were determined to be independent of NMN supplementation. Therefore, patients taking NMN supplementation demonstrated non-significantly improved physical performance parameters. NMN is well tolerated with no serious adverse effects observed., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Wen et al.)

An increasing number of reports suggest an association between a newly recognized disease cluster and significant and often disabling gastrointestinal (GI) symptoms. This cluster is composed of diagnoses of hypermobility spectrum disorders (HSDs) such as joint hypermobility and hypermobile variant Ehlers-Danlos syndrome (hEDS), postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS). The diagnosis of these entities remains a challenge, as the pathophysiology of each has not been completely elucidated and the diagnostic criteria continue to evolve. This article describes a cohort of young adult females who shared similar GI symptoms, with intractable nausea and vomiting being most prominent and gastroesophageal reflux disease and constipation also occurring. Most strikingly, these females also exhibited or reported a history of HSD, hEDS, POTS, and/or MCAS. The clinical course of their GI symptoms was remarkable for considerable challenges in management, and artificial nutritional support proved necessary for some. This article describes the clinical features and outcomes of their GI manifestations, examines how these manifestations might be linked to their systemic syndromes, and discusses whether a shared pathophysiology exists. Pending the definition of a common thread between these conditions, this article seeks to raise awareness of their clinical definitions and foster research that will hopefully improve outcomes for these patients., (Copyright © 2024, Gastro-Hep Communications, Inc.)

Schizophrenia is a severe, chronic psychiatric disorder characterized by delusions, hallucinations, cognitive impairments, and emotional dysregulation. This psychiatric illness is often resistant to treatment. This literature review aims to analyze the relationship between this complex psychological disorder and the gut microbiota found within the human body. The brain and gut are interconnected, and emerging research suggests a link between gut dysbiosis and schizophrenia. Gut dysbiosis refers to an imbalance or disruption in the composition and function of the gut microbiome. The studies comparing the gut microbiota of patients with schizophrenia to those without highlight significant differences at the phylum and genus levels, providing evidence of gut microbiome alteration. The lack of diversity of microbiota in schizophrenia patients can be altered and improved to a healthier microbiome by way of dietary intervention. Interventions that target the gut-brain axis, such as dietary probiotics or prebiotics, may help alleviate certain symptoms of schizophrenia and help improve patients' well-being. Understanding the complex interplay between gut microbiome health and schizophrenia may allow for the development of targeted interventions that alter the gut microbiome of patients with schizophrenia and, in turn, mitigate their symptoms and improve their quality of life., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Ansari et al.)

Abstract: Physical Medicine and Rehabilitation (PM&R) has rapidly been garnering interest as healthcare increases the emphasis on rehabilitation and management for acute and chronic diseases. This study analyzes recent geographical trends of PM&R residents via PM&R residents from 2019 to 2023 which were identified from publicly available data. The relative distribution from medical school to residency, medical school to preliminary program, and preliminary program to residency were analyzed. These locations were categorized as within 100 miles, same state, same region, or different region. Odds ratio (OR) were calculated for the aforementioned relative locations with respect to the presence of a home residency program. A total of 1836 residents were included. The majority of residents (51%) stayed within the same region as their medical school. Residents from medical schools with a home program were more likely to stay within 100 miles (OR: 3.64), the same state (OR: 3.19), and same region (OR: 2.56). Overall, PM&R residents are likely to stay within the same region as their medical school and preliminary year. Additionally, the presence of a home program significantly increases the odds of matching within 100 miles, same state, and same region., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The crystalization of the components of bile within the gallbladder can lead to the formation of gallstones (cholelithiasis), which may often require surgical removal of the gallbladder, a procedure known as cholecystectomy, in symptomatic cases. Robotic single-site cholecystectomy (RSSC) is a recently introduced groundbreaking minimally invasive procedure for gallbladder removal. RSSC utilizes robotic technology, offering enhanced dexterity through a single-incision approach, promising improved outcomes such as reduced postoperative pain and superior cosmesis. However, certain limitations, such as restricted instrument movement and heightened hernia risk, necessitate a critical evaluation of this modality. Furthermore, as the widespread adoption of RSSC remains undecided due to concerns over its costs, efficiency, and overall superiority over prior models, this paper assesses future possibilities for RSSC's evolution. In vivo robotics, improved digital imaging, and re-engineering of the surgical instruments themselves are all potential avenues to augment the current RSSC design, although it is currently unclear as to what extent they could impact the procedure's viability. This review critically examines the available literature on the effectiveness and potency of RSSC compared to its predecessors in the modern healthcare setting and proposes future directions through which innovation could more firmly establish the procedure as the standard of care for cholecystectomy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ansari et al.)

Introduction: Infants are at a higher risk of severe illness with COVID-19 infection compared to older children. While COVID-19 vaccination is not recommended for young infants, they can acquire maternally-derived anti-SARS-CoV-2 antibodies passively through the placenta and breastmilk. We described the persistence of infection-induced maternal antibodies in infant circulation at 9-12 months of age., Methodology: This was a cross-sectional study nested within the INTERCOVID multinational cohort study. For each COVID positive pregnant woman, two unmatched consecutive COVID negative pregnant women were enrolled between April and September 2020. Women with a positive PCR test, radiographic signs consistent with COVID-19, or at least 2 predefined symptoms of COVID-19 were considered as COVID positive. For this nested cross-sectional study, all COVID positive and either one of the COVID negative participants recruited from the Aga Khan University, Pakistan were approached 9-12 months after delivery, and maternal and infant sera were collected for antibody detection., Results: Altogether, 83 mothers provided consent, of whom 32 (38.6 %) were COVID positive and 51 (61.4 %) were COVID negative during pregnancy. Anti-SARS-CoV-2 antibodies were present in 13 (41 %) infants born to COVID positive and 19 (39 %) infants born to COVID negative mothers (p = 0.87). The presence of reactive antibodies in infants at follow-up was associated with maternal antibodies at follow-up (OR:9.50, 95 % CI:2.03-44.42; p = 0.004). COVID infection occurred in 3 (6 %) infants born to COVID negative mothers while no infant born to a COVID positive mother had a history of infection (p = 0.27)., Conclusion: The presence of reactive anti-SARS-CoV-2 antibodies in infants at 9-12 months of age is associated with maternal seropositivity 9-12 months after delivery rather than maternal infection during pregnancy. Further studies are required to validate these findings and assess whether passive immunity in infants is protective against COVID-19 infection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a fatal and intricate neurodegenerative disease that impacts upper and lower motor neurons within the central nervous system, leading to their progressive destruction. Despite extensive research, the pathogenesis of this multifaceted disease remains elusive. The United States Food and Drug Administration (FDA) has granted approval for seven medications designed to address ALS and mitigate its associated symptoms. These FDA-sanctioned treatments are Qalsody, Relyvrio, Radicava, Rilutek, Tiglutik, Exservan, and Nuedexta. In this review, the effects of these seven drugs on ALS based on their mechanism of action, dosing, and clinical presentations are comprehensively summarized. Each medication offers a distinct approach to manage ALS, aiming to alleviate the burdensome symptoms and slow the disease's progression, thereby improving the quality of life for individuals affected by this neurological condition. However, despite these advancements in pharmaceutical interventions, finding a definitive cure for ALS remains a significant challenge. Continuous investigation into ALS pathophysiology and therapeutic avenues remains imperative, necessitating further research collaborations and innovative approaches to unravel the complex mechanisms underlying this debilitating condition., Competing Interests: Conflict of interest: The authors declare no conflicts of interest., (© 2024 the Author(s), licensee AIMS Press.)

Background: Socio-economically disadvantaged women have poor maternal health outcomes. Maternal health interventions often fail to reach those who need them most and may exacerbate inequalities. In Bauchi State, Nigeria, a recent cluster randomised controlled trial (CRCT) showed an impressive impact on maternal health outcomes of universal home visits to pregnant women and their spouses. The home visitors shared evidence about local risk factors actionable by households themselves and the program included specific efforts to ensure all households in the intervention areas received visits., Purpose: To examine equity of the intervention implementation and its pro-equity impact., Research Design and Study Sample: The overall study was a CRCT in a stepped wedge design, examining outcomes among 15,912 pregnant women., Analysis: We examined coverage of the home visits (three or more visits) and their impact on maternal health outcomes according to equity factors at community, household, and individual levels., Results: Disadvantaged pregnant women (living in rural communities, from the poorest households, and without education) were as likely as those less disadvantaged to receive three or more visits. Improvements in maternal knowledge of danger signs and spousal communication, and reductions in heavy work, pregnancy complications, and post-natal sepsis were significantly greater among disadvantaged women according to the same equity factors., Conclusions: The universal home visits had equitable coverage, reaching all pregnant women, including those who do not access facility-based services, and had an important pro-equity impact on maternal health., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Huntington's disease (HD), a rare autosomal dominant neurodegenerative disease, causes the gradual deterioration of neurons in the basal ganglia, specifically in the striatum. HD displays a wide range of symptoms, from motor disturbances such as chorea, dystonia, and bradykinesia to more debilitating symptoms such as cognitive decline, behavioral abnormalities, and psychiatric disturbances. Current research suggests the potential use of dietary interventions as viable strategies for slowing the progression of HD. Most notably, the Mediterranean, vegan, carnivore, paleo, and ketogenic diets have gained attention due to their hypothesized impact on neuroprotection and symptomatic modulation in various neurodegenerative disorders. Despite substantial nutritional differences among these diets, they share a fundamental premise-that dietary factors have an influential impact in modifying pertinent biological pathways linked to neurodegeneration. Understanding the intricate interactions between these dietary regimens and HD pathogenesis could open avenues for personalized interventions tailored to the individual's specific needs and genetic background. Ultimately, elucidating the multifaceted effects of these diets on HD offers a promising framework for developing comprehensive therapeutic approaches that integrate dietary strategies with conventional treatments., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© 2024 the Author(s), licensee AIMS Press.)

Objective: A trial of evidence-based health promotion home visits to pregnant women and their spouses in northern Nigeria found significant improvements in maternal and child health outcomes. This study tested the added value for these outcomes of including video edutainment in the visits., Methods: In total, 19,718 households in three randomly allocated intervention wards (administrative areas) received home visits including short videos on android handsets to spark discussion about local risk factors for maternal and child health; 16,751 households in three control wards received visits with only verbal discussion about risk factors. We compared outcomes between wards with and without videos in the visits, calculating the odds ratio (OR) and 95% confidence interval (95%CI) of differences, in bivariate and then multivariate analysis adjusting for socio-economic differences between the video and non-video wards., Results: Pregnant women from video wards were more likely than those from non-video wards to have discussed pregnancy and childbirth often with their husbands (OR 2.22, 95%CI 1.07-4.59). Male spouses in video wards were more likely to know to give more fluids and continued feeding to a child with diarrhoea (OR 1.61, 95%CI 1.21-2.13). For most outcomes there was no significant difference between video and non-video wards. The home visitors who shared videos considered they helped pregnant women and their spouses to appreciate the information about risk factors., Conclusion: The lack of added value of the videos in the context of a research study may reflect the intensive training of home visitors and the effective evidence-based discussions included in all the visits. Further research could rollout routine home visits with and without videos and test the impact of video edutainment added to home visits carried out in a routine service context., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The current polio epidemiology in Pakistan poses a unique challenge for global eradication as the country is affected by ongoing endemic poliovirus transmission. Across the country, 40 union councils (UCs) which serve as core reservoirs for poliovirus with continuous incidences of polio cases are categorized as super-high-risk union councils (SHRUCs)., Methodology: A cross-sectional survey was conducted in 39 SHRUCs using a two-stage stratified cluster sampling technique. 6,976 children aged 12-23 months were covered. A structured questionnaire was used for data collection. Data were analyzed using STATA version 17., Results: Based on both vaccination records and recall, 48.3% of children were fully-, 35.4 % were partially-, and 16.3% were non-vaccinated in the SHRUC districts. A child is considered fully vaccinated when h/she completed vaccination for BCG, OPV0, OPV 1-3, Penta 1-3, PCV 1-3, IPV, and MCV1. Vaccination cards were seen for over half of the children in the SHRUC districts of Khyber Pakhtunkhwa (KP) and the majority of the SHRUC districts in Sindh, except for the SHRUC district of Malir the districts of Balochistan. Results for polio vacancies show that 60.9% of children from the SHRUC districts were vaccinated with at least three doses of OPV and one dose of IPV, while 20.4% were vaccinated with any OPV doses or IPV and 18.7% of children did not receive any polio vaccines. The dropout rate between vaccine visits was higher than the WHO-recommended cutoff point of 10% for all vaccine doses in the SHRUC districts. The likelihood of being fully vaccinated was higher among the children of educated parents. Full vaccination was found significant among the children of any SHRUC districts compared to district Killa Abdullah., Conclusion: Context-specific strategies with more focus on community engagement and targeted mobilization, along with robust monitoring mechanisms, would help address the underlying challenges of under-immunization in the SHRUCs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In Bauchi State, northern Nigeria, communities recognise short birth interval ( kunika in the Hausa language) as harmful, but family planning is a sensitive topic. This paper describes the development of a culturally safe way to communicate about kunika in a conservative Muslim setting. The objective was to co-design culturally safe communication material, based on local knowledge about short birth interval, to share with women and men in households.Six community co-design groups of women and six of men (total 96 participants) reviewed summaries of their previously created maps of perceived local causes of kunika, categorised as frequent sex, family dynamics and non-use of contraception. They advised how these causes could be discussed effectively and acceptably with women and their husbands in households and suggested storylines for three short video docudramas about the prevention of kunika. The research team created the docudramas with a local producer and fieldworkers piloted their use in households.The design groups advised that communication materials should focus on child spacing rather than on limitation of family size. Even sensitive issues could be covered. People would not change their sexual behaviour but could be advised to use contraceptives to prevent kunika . The groups approved the final videos and six focus groups of visited women and men reported they were acceptable and helpful. Community co-design of communication about kunika was feasible and led to videos about a sensitive topic that were acceptable to ordinary men and women in communities in Bauchi., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This literature review explores the pivotal roles of the Uncoordinated-13 (UNC13) protein family, encompassing UNC13A, UNC13B, UNC13C, and UNC13D, in the pathogenesis of various human diseases. These proteins, which are evolutionarily conserved and crucial for synaptic vesicle priming and exocytosis, have been implicated in a range of disorders, spanning from neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) to immune-related conditions such as familial hemophagocytic lymphohistiocytosis (FHL). The involvement of UNC13A in neurotransmitter release and synaptic plasticity is linked to ALS and FTD, with genetic variations affecting disease progression. UNC13B, which is closely related to UNC13A, plays a role in autism spectrum disorders (ASD), epilepsy, and schizophrenia. UNC13C is implicated in oral squamous cell carcinoma (OSCC) and hepatocellular carcinoma (HCC), and has a neuroprotective role in Alzheimer's disease (AD). UNC13D has an essential role in immune cell function, making it a key player in FHL. This review highlights the distinct molecular functions of each UNC13 family member and their implications in disease contexts, shedding light on potential therapeutic strategies and avenues for future research. Understanding these proteins' roles offers new insights into the management and treatment of neurological and immunological disorders., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© 2023 the Author(s), licensee AIMS Press.)

Amyotrophic lateral sclerosis (ALS) is a fatal and complex neurodegenerative disease of upper and lower motor neurons of the central nervous system. The pathogenesis of this multifaceted disease is unknown. However, diet has emerged as a modifiable risk factor that has neuroprotective effects towards other neurological disorders such as Alzheimer's, Parkinson's and dementia. Thus, this review aims to explore how diet can potentially influence ALS onset and/or progression. In this review, five popular diets (Mediterranean, Vegan, Carnivore, Paleolithic and Ketogenic) and their distinct macromolecule composition, nutritional profile, biochemical pathways and their potential therapeutic effects for ALS are thoroughly examined. However, the composition of these diets varies, and the data is controversial, with conflicting studies on the effectiveness of nutrient intake of several of these diets. Although these five diets show that a higher intake of foods containing anti-inflammatory and antioxidant compounds have a positive correlation towards reducing the oxidative stress of ALS, further research is needed to directly compare the effects of these diets and the mechanisms leading to ALS and its progression., Competing Interests: Conflict of interest: The authors declare no conflicts of interest., (© 2023 the Author(s), licensee AIMS Press.)

Background: This study evaluated the prognostic impact of age on patients presenting with ventricular tachyarrhythmias (VTA) and aborted cardiac arrest., Material and Methods: The present registry-based, monocentric cohort study included all consecutive patients presenting at the University Medical Center Mannheim (UMM) between 2002 and 2016 with ventricular tachycardia (VT), ventricular fibrillation (VF) and aborted cardiac arrest. Middle-aged (40-60 years old) were compared to older patients (> 60 years old). Furthermore, age was analyzed as a continuous variable. The primary endpoint was all-cause mortality at 2.5 years. The secondary endpoints were cardiac death at 24 h, all-cause mortality at index hospitalization, all-cause mortality after index hospitalization and the composite endpoint at 2.5 years of cardiac death at 24 h, recurrent VTA, and appropriate implantable cardioverter defibrillator (ICD) treatment., Results: A total of 2259 consecutive patients were included (28% middle-aged, 72% older). Older patients were more often associated with all-cause mortality at 2.5 years (27% vs. 50%; hazard ratio, HR = 2.137; 95% confidence interval, CI 1.809-2.523, p = 0.001) and the secondary endpoints. Even patient age as a continuous variable was independently associated with mortality at 2.5 years in all types of VTA. Adverse prognosis in older patients was demonstrated by multivariate Cox regression analyses and propensity score matching. Chronic kidney disease (CKD), systolic left ventricular dysfunction (LVEF) < 35%, cardiopulmonary resuscitation (CPR) and cardiogenic shock worsened the prognosis for both age groups, whereas acute myocardial infarction (STEMI/NSTEMI) and the presence of an ICD improved prognosis., Conclusion: The results of this study suggest that increasing age is associated with increased mortality in VTA patients. Compared to the middle-aged, older patients were associated with higher all-cause mortality at 2.5 years and the secondary endpoints., (© 2022. The Author(s).)

Pectus excavatum (PE) is a congenital malformation with a funnel-shaped depression of the sternum that can lead to cardiac symptoms. However, there are patients with thoracic constriction (defined as elevated Haller-Index > 3.25 determined by cardiac magnetic resonance imaging (CMR)) without visible evidence of PE, leading to similar complaints. Between January 2004 till June 2020, patients who underwent CMR for further evaluation of the heart, due to cardiac symptoms were enrolled and compared to controls. Biventricular global strain analysis was assessed using feature tracking (CMR-FT). ECG and/or Holter recordings were performed to detect rhythm events. Cardiac symptoms were evaluated in detail using a questionnaire. Finally, 88 patients (male 35, female 53) with elevated Haller-Index (3.9 ± 0.8) were included and compared to CMR data from 25 individuals with confirmed PE and 25 healthy controls (HC). Mean age at time of CMR was 35 ± 16 years. The most common symptoms at presentation were palpitations (41%), followed by dyspnea (24%) and atypical chest pain (14%). Three patients (3%) had atrial fibrillation or atrial flutter. Concomitant phenomena were pericardial effusion in 39% and mitral valve prolapse (MVP) in 27% of the study cohort. While there were no differences in left ventricular function or volumes, right ventricular function (RVEF) was significantly lower in patients with internal PE compared to HC (RVEF (%) 50 ± 5 vs 59 ± 4, p < 0.01). Strain analysis revealed only discrete changes in RV strain, implying a purely mechanical problem in the absence of structural changes. RV dimensions were negatively correlated with the size of thoracic indices (r = 0.41), reflecting the extent of thoracic constriction. MVP was more prevalent in patients with greater thoracic indices (r = 0.24). The described cohort, referred to as internal PE because of the absence of external changes, showed similar CMR morphologic findings as patients with real PE (especially altered dimensions of the right heart and a lower RVEF). In addition, there was a high incidence of rhythm disturbances, such as extrasystoles or arrhythmias. In one-third of the study cohort additional abnormalities such as pericardial effusion or MVP were present, with MVP being found more frequently in patients with larger thoracic indices, suggesting a possible common pathogenesis.Trial registration: ISRCTN registry, ISRCTN15355937, retrospectively registered 03.06.2022, https://www.isrctn.com/ISRCTN15355937?q=15355937&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10 ., (© 2023. The Author(s).)

Background: There is limited evidence between contraceptive use, availability of commodities and distance to the facility in developing countries. Distance to the facility is an essential determinant of contraceptive use. Still, women may not seek family planning services from the nearest facility and may be prepared to travel the farthest distance to receive quality family planning services., Methods: We analyzed women's survey data linked to health facility data and applied an alternate specific conditional logit model to examine the distance a woman is prepared to travel and the quality of services offered by facilities in urban areas in Karachi, Pakistan., Results: This study analyzed data from 336 women and 28 facilities and identified that the mean distance to the nearest facility was 0.44 km; the chosen facility was, on average, 5 km away. Women preferred facilities that offered a range of contraceptive methods and additional services provided by female healthcare providers only. Furthermore, on average, women are willing to travel a further 1.7 km for a facility that offers more family planning methods, 1.4 km for a facility that offers additional health services and 11 km for a facility that offers services delivered by female healthcare providers., Conclusions: The findings highlight the quality measures women prioritize over distance and consider essential when choosing a family planning facility., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Sirtuins (SIRT) are a class of histone deacetylases that regulate important metabolic pathways and play a role in several disease processes. Of the seven mammalian homologs currently identified, sirtuin 1 (SIRT1) is the best understood and most studied. It has been associated with several neurodegenerative diseases and cancers. As such, it has been further investigated as a therapeutic target in the treatment of disorders such as Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD). SIRT1 deacetylates histones such as H1 lysine 26, H3 lysine 9, H3 lysine 56, and H4 lysine 16 to regulate chromatin remodeling and gene transcription. The homolog has also been observed to express contradictory responses to tumor suppression and tumor promotion. Studies have shown that SIRT1 may have anti-inflammatory properties by inhibiting the effects of NF-κB, as well as stimulating upregulation of autophagy. The SIRT1 activators resveratrol and cilostazol have been shown to improve Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores in AD patients. In this review, we aim to explore the various roles of SIRT1 with regard to neuroprotection and neurodegeneration., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Razick et al.)

Hip dysplasia is a condition affecting both infants and adults, characterized by a shallow acetabulum that does not sufficiently cover the head of the femur. This leads to instability of the hip and elevated levels of mechanical stress around the acetabular rim. A popular procedure for the correction of hip dysplasia is the periacetabular osteotomy (PAO), in which fluoroscopically guided osteotomies around the pelvis are made to allow for repositioning of the acetabulum to fit properly on the femoral head. This systematic review aims to analyze patient factors that impact outcomes, as well as patient-reported outcomes such as the Harris Hip Score (HHS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC). The patients in this review did not undergo any prior intervention for acetabular hip dysplasia, allowing for an unbiased reporting of outcomes from all included studies. Of studies reporting HHS, the mean preoperative HHS was 68.92 and the mean postoperative HHS was 89.1. Of the study that reported mHHS, the mean preoperative mHHS was 70, and the mean postoperative mHHS was 91. Of the studies reporting WOMAC, the mean preoperative WOMAC was 66, and the mean postoperative WOMAC was 63. Key findings of this review are that of the seven included studies, six achieved a minimally important clinical difference (MCID) based on patient-reported outcomes, and factors impacting outcome are preoperative Tönnis osteoarthritis (OA) grade, pre and postoperative lateral-center edge angle (LCEA), preoperative hip joint congruency, postoperative Tönnis angle, and age. In patients with no prior intervention for hip dysplasia, the PAO is a successful procedure with significant improvement in postoperative patient-reported outcomes. Despite the reported success of the PAO, proper patient selection is vital to avoid early conversions to total hip arthroplasty (THA) and prolonged pain. However, further investigation is prompted regarding the long-term survivorship of the PAO in patients with no prior intervention for hip dysplasia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Akhtar et al.)

Background: Immunization is one of the most successful public health interventions available, saving millions of lives from death and disability each year. Therefore, improving immunization coverage is a high priority for the Government of Pakistan and essential to progress toward universal health coverage. This survey reports the national and provincial/regional coverage and determinants of fully, partially, and not-vaccinated children 12-23 months of age, antigen-wise coverage, percentage of home-based vaccination records (HBR) retention, and reasons for nonretention; dropout, timeliness, and prevalence of missed opportunities for simultaneous vaccination (MOSV)., Methods: The survey was a descriptive cross-sectional national household survey carried out across Pakistan. The survey included 110,790 children 12-23 months old and their caregivers. A World Health Organization (WHO)-Expanded Program on Immunization (EPI) Survey questionnaire was adapted to collect information. Data were analyzed using the WHO Vaccination Coverage Quality Indicators (VCQI) software and Stata version 17., Results: Nationally excluding Azad Jammu and Kashmir (AJK) and Gilgit Baltistan (GB), the coverage of fully vaccinated children was 76.5%. The likelihood of being fully vaccinated was higher among children of educated parents who belonged to higher wealth quintiles and resided in any province/region other than Balochistan. The main reasons for unimmunization were no faith in immunization, rumors about vaccines, and distance to the facility. About two-thirds (66.2%) of the children had their HBR available, and the main reasons for not having a card were never visiting a health facility and having no awareness about the importance of a card. Dropout was discernible for later doses of vaccines compared with earlier ones. Higher proportions of children received the last doses late by more than two months. Of the 218,002 vaccination visits documented on HBR in the provinces, MOSVs occurred in 17.6% of the visits., Conclusion: The immunization coverage rates provide a direction to strategize the progress to improve the vaccination rates in Pakistan. The country needs to outline the immediate and long-term actions to combat vaccine-preventable diseases, such as escalating integrated immunization campaigns and outreach activities, provision of mobility support, and deploying behavioral interventions as a cross-cutting strategy to improve awareness and reduce misconceptions., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Pectus excavatum is a congenital chest wall deformity, commonly identified in early childhood, creating a "sunken chest" appearance. Over time, the deformity can worsen, thus impacting cardiopulmonary function and creating significant body image disturbance in patients. The Nuss procedure is a minimally invasive technique in which a curved steel bar is introduced underneath the sternum through small bilateral thoracic incisions to correct the deformity. Most studies regarding the procedure to date focus on outcomes and complications in pediatric patients, however, few studies discuss these results in adult patients. This systematic review aims to analyze common complications and outcomes in patients over the age of 18 who have not undergone any prior intervention for pectus excavatum. The most common complications experienced in adult patients were displacement of the implanted steel bar, infection of the surgical site, pneumothorax, pleural effusion, and chronic postoperative pain. Reoperation was common in patients with a displacement of the bar, chronic pain, and bleeding. Additionally, adult patients routinely required a higher number of steel bars to be placed to correct the deformity. Despite evidence that the rate of complications increases with age, the majority of adult patients in our included studies were satisfied with the outcome of the procedure with indications of improved self-image and reduced preoperative symptoms such as dyspnea on exertion, palpitations, chest pain, and depression., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Akhtar et al.)

Background: We investigated the feasibility of evaluating coronary arteries with a contrast-enhanced (CE) self-navigated sparse isotropic 3D whole heart T1-weighted magnetic resonance imaging (MRI) study sequence., Methods: A total of 22 consecutive patients underwent coronary angiography and/or cardiac computed tomography (CT) including cardiac MRI. The image quality was evaluated on a 3-point Likert scale. Inter-reader variability for image quality was analyzed with Cohen's kappa for the main coronary segments (left circumflex [LCX], left anterior descending [LAD], right coronary artery [RCA]) and the left main trunk (LMT)., Results: Inter-reader agreement for image quality of the coronary tree ranged from substantial to perfect, with a Cohen's kappa of 0.722 (RCA mid ) to 1 (LCX prox ). The LMT had the best image quality. Image quality of the proximal vessel segments differed significantly from the mid- and distal segments (RCA prox vs. RCA dist , p < 0.05). The LCX segments showed no significant difference in image quality along the vessel length (LCX prox vs. LCX dist , p = n.s.). The mean acquisition time for the study sequence was 553 s (±46 s)., Conclusion: Coronary imaging with a sparse 3D whole-heart sequence is feasible in a reasonable amount of time producing good-quality imaging. Image quality was poorer in distal coronary segments and along the entire course of the LCX., (© 2022. The Author(s).)

Wettability is the fundamental parameter that influences the productivity of hydrocarbon reservoirs. The knowledge of this regarding shale formation is yet inadequate; thus, detailed analysis is essential for successful development of such reservoirs. The Early Cretaceous Sembar formations in the Lower Indus Basin, Pakistan, is considered as the key target for energy exploration; however, it exhibits large uncertainties due to the lack of data availability. Sembar shales hold significant hydrocarbon volumes rich in organic content; however, prior to this, no comprehensive research has been conducted to quantify the wetting behavior of these shales. Thus, precise information about the wetting behavior of Sembar shale formations is essential, as it is influenced by many factors. Therefore, in this study, we examined the wettability of Sembar shale samples by performing a suit of contact angle (CA) measurements. The CA measurements on shale samples were performed using different salt types (NaCl, KCl, MgCl 2 , and Reef Salt) and concentrations of 0.1 M and 0.5 M under ambient pressures and varying temperatures (25-50 °C). The CA was measured via air-brine and air-oil under prevailing pressure and temperature conditions. Subsequently, the sample morphology and surface topography were examined via field emission scanning electron microscopy and atomic force microscopy, respectively. The mineral compositions were obtained via X-ray diffraction studies. The results clearly show that the Sembar shale possesses a mixed wetting behavior. Under dry surfaces, they have large affinity to oil and deionized water in which the droplet spreads quickly on the sample surfaces. Conversely, the samples aged with n -decane and NaCl brines exhibited higher CAs than the untreated samples. Additionally, the CA measured by changing temperatures led to an increase for all brine droplets; the CA further increased as the concentrations of salts increased from 0.1 to 0.5 M. We then discussed the possible reasons for the discrepancy in CA values due to temperature changes and brine concentrations. Moreover, the CA was measured corresponding to the surface roughness from which it appears that it merely affects the wettability of these shale samples. However, the present study results lead to an improved understanding of the wettability of Sembar shale of the Lower Indus Basin in Pakistan., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

We hypothesized that myocardial septal scarring, assessed by cardiac magnetic resonance (CMR) using late gadolinium enhancement (LGE), at the site of cardiac contractility modulation (CCM) lead placement may predict treatment response. Eligible heart failure (HF) patients underwent LGE CMR imaging before CCM device implantation. The response to CCM therapy at follow-up was determined by a change in NYHA class and echocardiographic left ventricular ejection fraction (LVEF) assessment. Patients were classified as responders, if they showed an improvement in either NYHA class or improvement of LVEF by ≥ 5%. 58 patients were included. 67% of patients were classified as responders according to improved NYHA; 55% according to LVEF improvement. 74% of patients were responders if either NYHA class or LVEF improvement was observed. 90% of responders (according to NYHA class) showed septal LGE < 25% at septal position of the leads, while 44% of non-responders showed septal LGE > 25% (p < 0.01). In patients treated with CCM, an improvement of NYHA class was observed when leads were placed at myocardial segments with a CMR- LGE burden less than 25%., (© 2022. The Author(s).)

Subsurface sequestration of CO 2 produced by industrial production is an effective way to control the excessive emission of greenhouse gases and alleviate the potential global warming. However, CO 2 leakage is likely to occur in its long-term sub-seabed sequestration, posing a great threat to the marine environment and the marine ecology. Previous investigations mainly focused on the implementation of CO 2 sequestration project, ignoring the subsequent potential environmental hazards such as CO 2 leakage, let alone the post-treatment of these accidents. In the present work, secondary sequestration mechanism of hydrate-bearing sediment for leaked CO 2 was explored, and the effect of two important factors (hydrate saturation and sediment thickness) on it was then analyzed. It is expected to provide reference for exploring engineering measures to secondary sequestrate the leaked CO 2 and avoid the catastrophic environmental accidents. The experimental results demonstrate that the role of hydrate in secondary sequestration for leaked CO 2 is mainly due to its filling and occupation of the migration channels in sediment. In addition, due to the secondary sequestration of CO 2 hydrate, change in seawater pH value caused by dissolution of leaked CO 2 in water can be significantly weakened. Besides, with the increasing hydrate saturation and sediment thickness, CO 2 hydrate plays a progressively obvious role in secondary sequestration of CO 2 and avoiding great change in the marine environment. In this way, the leaked CO 2 can be secondary sequestrated by designing/optimizing the characteristics of hydrate-bearing sediment. The investigation demonstrates that most of the leaked CO 2 can be secondary sequestrated only when the hydrate saturation exceeds 0.30 and/or thickness of hydrate-bearing sediment exceeds 3.0 cm. The experimental investigation herein can provide technical support for avoiding environmental disasters caused by the leakage of long-term sequestrated CO 2 ., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: With the rapid influx of COVID-19 admissions during the first wave of the pandemic, there was an obvious need for an efficient and streamlined risk stratification tool to aid in triaging. To this date, no clinical prediction tool exists for patients presenting to the hospital with COVID-19 infection., Methods: This is a retrospective cohort study of patients admitted in one of 13 Northwell Health Hospitals, located in the wider New York Metropolitan area between 1 March 2020 and 27 April 2020. Inclusion criteria were a positive SARS-CoV-2 nasal swab, a 12-lead ECG within 48 hours, and a complete basic metabolic panel within 96 hours of presentation., Results: All-cause, in-hospital mortality was 27.1% among 7098 patients. Independent predictors of mortality included demographic characteristics (male gender, race and increased age), presenting vitals (oxygen saturation <92% and heart rate >120 bpm), metabolic panel values (serum lactate >2.0 mmol/L, sodium >145, mmol/L, blood urea nitrogen >40 mmol/L, aspartate aminotransferase >40 U/L, Creatinine >1.3 mg/dL and glycose >100 mg/L) and comorbidities (congestive heart failure, chronic obstructive pulmonary disease and coronary artery disease). In addition to those, our analysis showed that delayed cardiac repolarisation (QT corrected for heart rate (QTc) >500 ms) was independently associated with mortality (OR 1.41, 95% CI 1.05 to 1.90). Previously mentioned parameters were incorporated into a risk score that accurately predicted in-hospital mortality (AUC 0.78)., Conclusion: In the largest cohort of COVID-19 patients with complete ECG data on presentation, we found that in addition to demographics, presenting vitals, clinical history and basic metabolic panel values, QTc >500 ms is an independent risk factor for in-hospital mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Persistent sinus tachycardia (ST) is frequently encountered during pregnancy and peripartum period and its etiology often remains elusive. We sought to examine the possible association between unexplained persistent ST and obstetric outcomes., Methods: A case control study was conducted using chart review of women admitted in labor to one of 7 hospitals of Northwell Health between January 2015 to June 2021. After excluding women with structurally abnormal hearts, we identified patients with persistent ST during the peripartum period, defined as a heart rate of more than 100 bpm for more than 48 h. A control group was created by randomly subsampling those who did not meet the inclusion criteria for sinus tachycardia. Obstetric outcomes were measured as mother's length of stay (LOS), pre-term labor (PTL), admission to the neonatal ICU (NICU), and whether she received cesarean-section (CS)., Results: Seventy-eight patients with persistent ST were identified, out of 141,769 women admitted for labor throughout the Northwell Health system. 23 patients with ST attributable to infection or hypovolemia from anemia requiring transfusion and 55 with unclear etiology were identified. After adjusting for age and parity, pregnant mothers with ST were 2.35 times more likely to have a CS than those without (95% CI: 1.46-3.81, p = 0.0005) and had 1.38 times the LOS (1.21- 1.56, p < 0.0001). Among mothers with ST, those with unexplained ST were 2.14 times more likely to have a CS (1.22-3.75, p = 0.008)., Conclusion: Among pregnant patients, patients with ST have higher rates of CS.This association is unclear, however potential mechanisms include catecholamine surge, indolent infection, hormonal fluctuations, and medications. More studies are needed to explore the mechanism of ST in pregnant woman to determine the clinical significance and appropriate management., (© 2022. The Author(s).)

Objectives: Examine the association between arrhythmias and adverse maternal outcomes in women with structurally normal hearts., Methods: This was a case-control study of women admitted in labour to one of eight hospitals of Northwell Health from January 2015 to June 2021. After excluding women with structurally abnormal hearts, we identified women with an arrhythmic event and randomly subsampled the rest of the cohort to create a control group of 1025 patients. Multivariate analysis was performed to examine the association between arrhythmias and the incidence of caesarean section (CS), preterm labour (PTL), admission to the neonatal intensive care unit and longer length of stay (LOS)., Results: Of 1 41 769 women admitted in labour with a structurally normal heart, 137 had at least one arrhythmic event (0.097%). Supraventricular tachycardia (SVT), atrial fibrillation/flutter (AF) and frequent premature ventricular complexes or non-sustained ventricular tachycardia (VA) were present in 65 (0.046%), 22 (0.016%) and 46 (0.032%) women, respectively. Arrhythmia was previously diagnosed in 58.0% SVT cases but only in 9.7% AF and 8.1% VA cases. After adjusting for age, parity and comorbidities, the presence of any arrhythmia was an independent predictor of CS (OR 1.7 95% CI 1.2 to 2.5), PTL (OR 1.8, CI 1.1 to 3.0) and LOS (mean ratio 1.6, CI 1.4 to 1.8). This association was driven by presence of SVT and AF, whereas VAs were not associated with adverse outcomes., Conclusions: Arrhythmias, specifically SVT and AF, during labour in women with structurally normal heart are independently associated with adverse obstetrical outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. Recently, the ninth allele of the mobile colistin resistance ( mcr ) gene family, designated mcr-9, was reported. However, its clinical and public health significance remains unclear. We queried genomes of carbapenem-resistant Enterobacterales (CRE) for mcr-9 from a convenience sample of clinical isolates collected between 2012 and 2017 through the Georgia Emerging Infections Program, a population- and laboratory-based surveillance program. Isolates underwent phenotypic characterization and whole-genome sequencing. Phenotypic characteristics, genomic features, and clinical outcomes of mcr-9 -positive and -negative CRE cases were then compared. Among 235 sequenced CRE genomes, 13 (6%) were found to harbor mcr-9 , all of which were Enterobacter cloacae complex. The median MIC and rates of heteroresistance and inducible resistance to colistin were similar between mcr-9 -positive and -negative isolates. However, rates of resistance were higher among mcr-9 -positive isolates across most antibiotic classes. All cases had significant health care exposures. The 90-day mortality was similarly high in both mcr-9 -positive (31%) and -negative (7%) CRE cases. Nucleotide identity and phylogenetic analysis did not reveal geotemporal clustering. mcr-9 -positive isolates had a significantly higher number of median [range] antimicrobial resistance (AMR) genes (16 [4 to 22] versus 6 [2 to 15]; P < 0.001) than did mcr-9 -negative isolates. Pangenome tests confirmed a significant association of mcr-9 detection with mobile genetic element and heavy metal resistance genes. Overall, the presence of mcr-9 was not associated with significant changes in colistin resistance or clinical outcomes, but continued genomic surveillance to monitor for emergence of AMR genes is warranted. IMPORTANCE Colistin is a last-resort antibiotic for multidrug-resistant Gram-negative infections. A recently described allele of the mobile colistin resistance ( mcr ) gene family, designated mcr-9, has been widely reported among Enterobacterales species. However, its clinical and public health significance remains unclear. We compared characteristics and outcomes of mcr-9 -positive and -negative CRE cases. All cases were acquired in the health care setting and associated with a high rate of mortality. The presence of mcr-9 was not associated with significant changes in colistin resistance, heteroresistance, or inducible resistance but was associated with resistance to other antimicrobials and antimicrobial resistance (AMR), virulence, and heavy metal resistance (HMR) genes. Overall, the presence of mcr-9 was not associated with significant phenotypic changes or clinical outcomes. However, given the increase in AMR and HMR gene content and potential clinical impact, continued genomic surveillance of multidrug-resistant organisms to monitor for emergence of AMR genes is warranted.

Background: he distribution and prognostic impact of coronary artery disease (CAD) in ES are still under debate., Methods: Consecutive ES patients with implantable cardioverter-defibrillator (ICD) were included retrospectively from 2002 to 2016. Three analyses were applied to characterize ES patients: (a) ES patients without CAD (non-CAD), (b) ES patients with CAD (CAD), and (c) diagnostic findings assessed by coronary angiography (CA) at the time of ES (immediate CA). CAD was compared with non-CAD ES patients, and progressive CAD was compared with stable CAD ES patients. The primary endpoint was all-cause mortality at 2.5 years. Secondary endpoints were the composite endpoint of first recurrent ventricular tachyarrhythmias and appropriate ICD therapies, and recurrence of ES (ES-R) at 2.5 years., Results: Within a total of 87 consecutive ES patients. CAD was present in more than two-thirds (67%). However, only 52% patients underwent immediate CA at the time of ES. Here, 84% had CAD, of which 39% revealed progressive CAD with the need of target vessel revascularization (TVR) or cardiac transplantation ( n = 1). At long-term follow-up, neither the presence (or absence) of CAD (41% vs. 34%; log rank P = 0.708) nor of progressive CAD (33% vs. 26%; log rank P = 0.372) was associated with all-cause mortality at 2.5 years, and further secondary endpoints including the composite of recurrent ventricular tachyarrhythmias plus appropriate ICD therapies, or ES-R., Conclusion: In ES patients, CAD was more common than non-CAD-related cardiac diseases, accompanied by an underinvestigated rate of CA despite increasing rates of progressive CAD. CAD had no prognostic impact in ES., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Point-of-care ultrasound (POCUS) is a valuable tool to determine endotracheal tube (ETT) placement; however, few studies have compared it with standard confirmation methods. We evaluated the diagnostic accuracy of POCUS and time-to-interpretation for correct identification of tracheal versus esophageal intubations compared to a composite of standard-of-care methods in neonates., Methods: A cross-sectional study was conducted in the Neonatal Intensive Care Unit (NICU) at Aga Khan University Hospital Karachi, Pakistan. All required intubations were performed as per NICU guidelines. The clinical team simultaneously determined the ETT placement using standard-of-care methods (auscultation, colorimetric capnography, and chest X-ray) by POCUS. In addition, the clinical team was blinded to the POCUS images. Timings were recorded for each method by independent study staff., Results: A total of 348 neonates were enrolled in the study. More than half (58%) of intubations were in an emergency scenario. POCUS user interpretation showed 100% sensitivity and 94% specificity using an expert as the reference standard. We found a 99.4% agreement (Kappa: 0.96; p < 0.001). Diagnostic accuracy of POCUS compared with at least two standard-of-care methods demonstrated 99.7% sensitivity, 91% specificity, and 98.9% agreement (Kappa:0.93; p < 0.001). The median time required for POCUS interpretation was 3.0 (interquartile range [IQR] 3.0-4.0) seconds for tracheal intubation. The time recorded for auscultation and capnography was 6.0 (IQR 5.0-7.0) and 3.0 (IQR 3.0-4.0), respectively., Conclusion: POCUS is a rapid and reliable method of identifying ETT placement in neonates. Early and correct identification of airway management is critical to save lives and prevent mortality and morbidity., (© 2022 Wiley Periodicals LLC.)

Background: Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally. Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5-10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored., Methods: Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020. Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher's exact, Pearson's chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05., Results: Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5-48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42-5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers., Conclusions: In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase., (© 2022. The Author(s).)

Background: Interventional left atrial appendage occlusion (LAAO) is routinely performed in patients with nonvalvular atrial fibrillation and contraindications to standard anticoagulation., Aims: We investigated its role in patients at low stroke risk, and compared the effectiveness and safety in patients with low versus high risk., Methods: LAARGE is a prospective registry depicting the clinical reality of LAAO. LAAO was conducted with different standard commercial devices, and follow-up period was 1 year. Patients with started procedure and documented CHA 2 DS 2 -VASc score were selected from the whole database., Results: A total of 638 patients from 38 centers were divided into CHA 2 DS 2 -VASc score ≤2, i.e., low-risk group (10.2%), and >2, i.e., high-risk group (89.8%). The latter had a pronounced cardiovascular risk profile and preceding strokes (0% vs. 23.9%; p < 0.001). Implantation success was consistently high (97.6%), frequencies of intrahospital major adverse cardiac and cerebrovascular events (0% vs. 0.5%) and other major complications (4.6% vs. 4.0%) were low (each p = not significant [NS]). Numerous moderate complications were also observed in the low-risk patients (12.3% vs. 9.4%; p = NS). Frequencies of nonfatal strokes (0% vs. 0.7%) and severe bleedings (0% vs. 0.7%) were low (each p = NS). In a specific analysis, patients at very high risk of stroke (i.e., CHA 2 DS 2 -VASc score >4) did not have increased rates of complications or nonfatal strokes in the first year after the procedure., Conclusions: Low-risk patients had no nonfatal strokes and major bleedings within 1 year after hospital discharge but had unexpectedly high rates of moderate procedural complications. The indication in these patients should be strictly defined based on an individual benefit-risk assessment., (© 2022 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Limited data regarding the prognostic impact of ventricular tachyarrhythmias related to out-of-hospital (OHCA) compared to in-hospital cardiac arrest (IHCA) is available. A large retrospective single-center observational registry with all patients admitted due to ventricular tachyarrhythmias was used including all consecutive patients with ventricular tachycardia (VT) and fibrillation (VF) on admission from 2002 to 2016. Survivors discharged after OHCA were compared to those after IHCA using multivariable Cox regression models and propensity-score matching for evaluation of the primary endpoint of long-term all-cause mortality at 2.5 years. Secondary endpoints were all-cause mortality at 6 months and cardiac rehospitalization at 2.5 years. From 2.422 consecutive patients with ventricular tachyarrhythmias, a total of 524 patients survived cardiac arrest and were discharged from hospital (OHCA 62%; IHCA 38%). In about 50% of all cases, acute myocardial infarction was the underlying disease leading to ventricular tachyarrhythmias with consecutive aborted cardiac arrest. Survivors of IHCA were associated with increased long-term all-cause mortality compared to OHCA even after multivariable adjustment (28% vs. 16%; log rank p = 0.001; HR 1.623; 95% CI 1.002-2.629; p = 0.049) and after propensity-score matching (28% vs. 19%; log rank p = 0.045). Rates of cardiac rehospitalization rates at 2.5 years were equally distributed between OHCA and IHCA survivors. In patients presenting with ventricular tachyarrhythmias, survivors of IHCA were associated with increased risk for all-cause mortality at 2.5 years compared to OHCA survivors., (© 2021. The Author(s).)

As we all know, development and utilization of clean energy is the only way for society to achieve its sustainable development. Although natural gas hydrates is a new type of clean energy, uncontrollable hydrate dissociation and accompanying methane leakage in drilling operation threaten drilling safety, as well as marine environment. However, the dissociation range of natural gas hydrates around wellbore cannot be reasonably determined in previous investigations, which may lead to the inaccurate estimation of borehole collapse and methane leakage. Then, the marine environment will be greatly damaged or affected. The purpose of the present work is to experimentally explore the dissociation characteristics of gas hydrates around wellbore in drilling operation and analyze the influence law and mechanism of various factors (such as hydrate saturation) on hydrate dissociation. It is expected to provide reference for exploring effective engineering measures to avoid the uncontrolled hydrate dissociation, borehole collapse and accompanying methane leakage. The experimental results demonstrate that acoustic velocity of hydrate-bearing sediment can be accurately expressed as quadratic polynomial of hydrate saturation, which is the theoretical basis for determination of hydrate saturation in subsequent experiments. Owing to the fact that hydrate dissociation is an endothermic reaction, hydrate dissociation gradually slows down in experiment. Throughout the experiment, the maximum dissociation rate at the beginning of the experiment is 8.69 times that at the end of the experiment. In addition, sensitivity analysis found that the increase in the stabilizer concentration in drilling fluid can inhibit hydrate dissociation more effectively than the increase in the hydrate saturation. Hydrate dissociation was completely inhibited when the concentration of soybean lecithin exceeds 0.60wt%, but hydrate dissociation definitely occurs in the near-wellbore region no matter what hydrate saturation is. In this way, based on the requirements of drilling safety and/or environment protection, hydrate dissociation and accompanying methane leakage can be controlled by designing and adjusting the stabilizer concentration in drilling fluid., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)