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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

Thorsten Gietzen,1,2,* Ibrahim El-Battrawy,1,2,* Siegfried Lang,1,2 Xiao-Bo Zhou,1,2 Michael Behnes,1 Uzair Ansari,1 Martin Borggrefe,1,2 Ibrahim Akin1,2 1First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim (UMM), University of Heidelberg, Mannheim, Germany; 2German Center for Cardiovascular Research (DZHK), Partner Site, Heidelberg-Mannheim, Mannheim, Germany *These authors contributed equally to this work Background: Recent studies have highlighted that Takotsubo syndrome (TTS), mimicking acute coronary syndrome (ACS), is associated with poor clinical outcome. TTS is associated with different repolarization disorders including ST-segment elevation. ST elevation myocardial infarction (STEMI) in ACS is associated with declined prognosis. However, the clinical and prognostic impact of ST-segment elevation on TTS remains lacking. Aim: The aim of this study was to determine the short- and long-term prognostic impact of ST-segment elevation on TTS patients as compared with STEMI patients. Patients and methods: Our institutional database constituted a consecutive cohort of 138 TTS patients and 138 ACS patients matched for age and sex. TTS patients (n=41) with ST-segment elevation were compared with ACS patients with ST-segment elevation (n=64). Results: Chest pain was significantly more documented in STEMI patients as compared with TTS patients (48.8% vs 78.1%; P

KJ Weidner,1,* I El-Battrawy,1,2,* M Behnes,1 K Schramm,1 C Fastner,1,2 J Kuschyk,1 U Hoffmann,1,2 U Ansari,1 M Borggrefe,1,2 I Akin1,2 1First Department of Medicine, University Medical Centre Mannheim, Faculty of Medicine Mannheim, University of Heidelberg, 2DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg, Mannheim, Germany *These authors contributed equally to this work Background: Previous studies revealed that patients with Takotsubo cardiomyopathy (TTC) have a higher mortality rate than the general population. It is still unclear whether sex differences may influence long-term prognosis of TTC patients. The purpose of this study was to determine whether sex differences do influence the short- and long-term outcomes of TTC. Methods and results: A total of 114 patients with TTC were admitted to the University Medical Centre Mannheim from January 2003 to September 2015 and entered into the TTC database of the University Medical Centre Mannheim, and retrospectively analyzed. Patients were diagnosed by the Mayo Clinic criteria. All-cause mortality over mean follow-up of 1,529±1,121 days was revealed. Significantly more male patients died within long-term follow-up compared to female TTC patients (log-rank test; P=0.01). Most males died of noncardiac causes. In multivariate Cox regression analysis, the male sex (P=0.02, hazard ratio [HR] 2.8, 95% CI 1.1–7.2), the ejection fraction ≤35% (P=0.01, HR 3.3, 95% CI 1.2–9.2) and glomerular filtration rate

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 [...]

Aim: Takotsubo syndrome (TTS) patients have a higher mortality rate than the general population. Our study was conducted to determine the short- and long-term outcome of TTS patients associated with a significantly compromised mitral annular plane systolic excursion (MAPSE) on hospital admission. Methods and results: Our institutional database constituted a collective of 53 patients diagnosed with TTS between 2003 and 2016. The patients were classified into two groups based on the MAPSE, with those presenting with an MAPSE<1cmon admission categorized into one group (n=20, 38%) and those presenting with MAPSE-1cm(n=33, 62%) categorized into another group. Preliminary results indicated that patients with an MAPSE<1 cmhad a greater risk of developing thromboembolic events. The long-termmortality was significantly higher in TTS patients with an MAPSE<1 cm. In the multivariate Cox regression analysis, cardiogenic shock (hazard ratio 3.5; 95% confidence interval: 1.2-10.7; P=0.02) and MAPSE<1cm (hazard ratio 5.1; 95% confidence interval: 1.3-19.2; P=0.01) figured as independent predictors of the mortality. Conclusion: Although the short-term mortality rates among TTS patients diagnosed with a reduced MAPSE on admission were as similar as without reduced MAPSE, the long-termmortality rates among TTS patients diagnosed with a reduced MAPSE on admission were significantly higher. There is an urgent need for randomized trials, which could help define uniform clinical management strategies for high-risk TTS patients. [ABSTRACT FROM AUTHOR]

The solid–liquid phase equilibria (SLE) and densities of H2O–NaCl– –MnCl2–Mn(H2PO2)2 quaternary system and H2O–NaCl–MnCl2 and H2O– –MnCl2–Mn(H2PO2)2 ternary systems were investigated at 323.15 K by the isothermal solution saturation method. The analyses of the liquid and solid phases were used to determine the composition of the solid phase using the Schreinemakers graphic method. The ternary systems contain one invariant point, two invariant curves and two crystallization regions. In the quaternary system, there is one invariant point, three invariant curves and three crystallization areas corresponding to NaCl, MnCl2⋅4H2O and Mn(H2PO2)⋅2H2O. The crystallization area of Mn(H2PO2)2⋅H2O, being the largest in comparison with those of other salts, occupied 80.75 % of the total crystallization area.

Abstract Background Nigeria continues to have high rates of maternal morbidity and mortality. This is partly associated with lack of adequate obstetric care, partly with high risks in pregnancy, including heavy work. We examined actionable risk factors and underlying determinants at community level in Bauchi and Cross River States of Nigeria, including several related to male responsibility in pregnancy. Method In 2009, field teams visited a stratified (urban/rural) last stage random sample of 180 enumeration areas drawn from the most recent censuses in each of Bauchi and Cross River states. A structured questionnaire administered in face-to-face interviews with women aged 15-49 years documented education, income, recent birth history, knowledge and attitudes related to safe birth, and deliveries in the last three years. Closed questions covered female genital mutilation, intimate partner violence (IPV) in the last year, IPV during the last pregnancy, work during the last pregnancy, and support during pregnancy. The outcome was complications in pregnancy and delivery (eclampsia, sepsis, bleeding) among survivors of childbirth in the last three years. We adjusted bivariate and multivariate analysis for clustering. Findings The most consistent and prominent of 28 candidate risk factors and underlying determinants for non-fatal maternal morbidity was intimate partner violence (IPV) during pregnancy (ORa 2.15, 95%CIca 1.43-3.24 in Bauchi and ORa 1.5, 95%CI 1.20-2.03 in Cross River). Other spouse-related factors in the multivariate model included not discussing pregnancy with the spouse and, independently, IPV in the last year. Shortage of food in the last week was a factor in both Bauchi (ORa 1.66, 95%CIca 1.22-2.26) and Cross River (ORa 1.32, 95%CIca 1.15-1.53). Female genital mutilation was a factor among less well to do Bauchi women (ORa 2.1, 95%CIca 1.39-3.17) and all Cross River women (ORa 1.23, 95%CIca 1.1-1.5). Interpretation Enhancing clinical protocols and skills can only benefit women in Nigeria and elsewhere. But the violence women experience throughout their lives – genital mutilation, domestic violence, and steep power gradients – is accentuated through pregnancy and childbirth, when women are most vulnerable. IPV especially in pregnancy, women's fear of husbands or partners and not discussing pregnancy are all within men's capacity to change.

Abstract Background The government of Pakistan introduced devolution in 2001. Responsibility for delivery of most health services passed from provincial to district governments. Two national surveys examined public opinions, use, and experience of health services in 2001 and 2004, to assess the impact of devolution on these services from the point of view of the public. Methods A stratified random cluster sample drawn in 2001 and revisited in 2004 included households in all districts. Field teams administered a questionnaire covering views about available health services, use of government and private health services, and experience and satisfaction with the service. Focus groups in each community discussed reasons behind the findings, and district nazims (elected mayors) and administrators commented about implementation of devolution. Multivariate analysis, with an adjustment for clustering, examined changes over time, and associations with use and satisfaction with services in 2004. Results Few of 57,321 households interviewed in 2002 were satisfied with available government health services (23%), with a similar satisfaction (27%) among 53,960 households in 2004. Less households used government health services in 2004 (24%) than in 2002 (29%); the decrease was significant in the most populous province. In 2004, households were more likely to use government services if they were satisfied with the services, poorer, or less educated. The majority of users of government health services were satisfied; the increase from 63% to 67% between 2002 and 2004 was significant in two provinces. Satisfaction in 2004 was higher among users of private services (87%) or private unqualified practitioners (78%). Users of government services who received all medicines from the facility or who were given an explanation of their condition were more likely to be satisfied. Focus groups explained that people avoid government health services particularly because of bad treatment from staff, and unavailable or poor quality medicines. District nazims and administrators cited problems with implementation of devolution, especially with transfer of funds. Conclusions Under devolution, the public did not experience improved government health services, but devolution was not fully implemented as intended. An ongoing social audit process could provide a basis for local and national accountability of health services.

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.)

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.)

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.)

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.)

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.)

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.)

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).)

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: 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).)