Unraveling the genetic tapestry of pediatric sarcomeric cardiomyopathies and masquerading phenocopies in Jordan.

Pediatric cardiomyopathies are mostly attributed to variants in sarcomere-related genes. Unfortunately, the genetic architecture of pediatric cardiomyopathies has never been previously studied in Jordan. We sought to uncover the genetic landscape of 14 patients from nine families with several subtypes of pediatric cardiomyopathies in Jordan using Exome sequencing (ES). Our investigation identified pathogenic and likely pathogenic variants in seven out of nine families (77.8%), clustering in sarcomere-related genes. Surprisingly, phenocopies of sarcomere-related hypertrophic cardiomyopathies were evident in probands with glycogen storage disorder and mitochondrial-related disease. Our study underscored the significance of streamlining ES or expanding cardiomyopathy-related gene panels to identify plausible phenocopies of sarcomere-related cardiomyopathies. Our findings also pointed out the need for genetic testing in patients with cardiomyopathy and their at-risk family members. This can potentially lead to better management strategies, enabling early interventions, and ultimately enhancing their prognosis. Finally, our findings provide an initial contribution to the currently absent knowledge about the molecular underpinnings of cardiomyopathies in Jordan.

Epidemiology, microbiological, clinical characteristics, and outcome of Burkholderia cepacia complex infections in non-cystic fibrosis adult patients from Qatar.

Objectives: Burkholderia species infections are associated with diverse and challenging clinical presentations because of distinct virulence and antimicrobial resistance factors. The study aims to evaluate the epidemiology, microbiological, and clinical outcomes of Burkholderia cepacia complex (Bcc) infections in non-cystic fibrosis (CF) patients from Qatar. Methods: A retrospective study was conducted on adult patients across all hospitals at Hamad Medical Corporation between January 2012 and December 2018 to evaluate clinically relevant Bcc in non-CF adult patients. Results: Over 7 years, 72 episodes of Burkholderia species infections were recorded, 64 were secondary to Bcc primarily affecting males (78.12%) with a mean age of 53 years, from the Middle and Southeastern region (92.2%) affected predominantly by diabetes mellitus (34.4%), chronic kidney (23.4%), coronary heart (20.3%), and hypertensive diseases (17.2%) while recent hospitalization and admission to critical care were evident in 45.3% and 93.8% of cases, respectively. Main infection sites were urinary (43.8%) and respiratory (29.7%) with associated bacteremia recorded in 26.6% of cases. Microbiological characteristics demonstrated high-level resistance profiles leading to delayed microbiological clearance in case of bacteremia (61%) and management with multiple therapeutic agents (range 4-6) resulting in disease resolution in 90.6% of cases with observed 30-day mortality of 7.8%. Conclusions: B. cepacia infections are infrequent, recorded mainly in middle-aged males with chronic comorbidities presenting as urinary, respiratory, and bacteremia associated with hospitalization, admission to critical care, and invasive procedures. High-level antimicrobial resistance is observed necessitating multiple therapeutic agents and suboptimal bacteriological clearance.

A comprehensive evaluation of online inhaler use techniques for obstructive airway disease.

BACKGROUND: Pulmonary inhaler therapy is a core treatment modality for >600 million individuals affected by obstructive airways disease globally. Poor inhaler technique is associated with reduced disease control and increased health care utilization; however, many patients rely on the internet as a technical resource. This study assesses the content and quality of online resources describing inhaler techniques. METHODS: A Google search was conducted in April 2023 capturing the top 5 search results for 12 common inhaler devices. Websites were compared to product monographs for preparation/first use, inhalational technique, and post-usage/device care. They were also assessed using accepted quality metrics (GQS, DISCERN, JAMA Benchmark scores) and clinically relevant aspects based on the literature and consensus statements. RESULTS: Websites regularly excluded critical steps important for proper inhaler technique. They performed best on information related directly to inhalation technique (average median score 78%), whereas steps related to preparation/first use (58%) or post-usage/device care (50%) were less frequently addressed. Median GQS, DISCERN, and JAMA Benchmark scores were 3 [IQR 3-4], 3 [IQR 2-4], and 1 [IQR 1-3], respectively. Clinically relevant factors were only addressed in about one-fifth of websites with no websites addressing smoking cessation, environmental considerations, or risk factors for poor technique. CONCLUSIONS: This study highlights gaps in online resources describing inhaler technique, particularly related to preparation/first use and post-usage/device care steps. Clinically relevant factors were rarely addressed across websites. Improvements in these areas could lead to enhanced inhaler technique and clinical outcomes.

Quality of life in Arab children with congenital heart disease.

BACKGROUND AND PURPOSE: Management strategies for children with congenital health diseases (CHDs) should encompass more than just the medical aspect of the disease and consider how heart diseases affect their everyday activities and, subsequently, their quality of life (QoL). Global studies witnessed a greater emphasis on studying the QoL associated with CHD. However, there is still a great lag in such data in the Arab region. The purpose of this study was to evaluate QoL in children with CHD using an Arab sample from Jordan. The specific objectives were twofold: (1) to contrast the assessments of children's QoL reported by their parents with those reported by the children themselves, and (2) to assess the factors that influence the QoL of children with CHD. METHODS: A total of 79 children aged 2-18 with a confirmed diagnosis of CHD were included in the study, along with their mothers. Of them, 38.0% were girls, 67.1% were diagnosed with non-cyanotic CHD, 58.2% had a severe CHD, 92.4% had undergone at least one operation, 81.0% had repaired defects, 13.9% underwent palliated procedures, and 24.1% were admitted to a neonatal intensive care unit after delivery. The Pediatric Quality of Life Inventory was used to assess QoL of children with CHD. Both children's and parents' reports of QoL were analyzed using paired-sample t-tests, ANOVAs, and multiple linear regression. RESULTS: Older children reported significantly lower QoL scores, whereas there were no differences in parents-reported QoL scores across different children age groups. There was a divergence in perceptions of QoL between parents-reported and children-reported scores with parents reporting significantly lower scores. The children-reported QoL in this study seemed to be significantly associated with their gender, age, and the presence of learning difficulties, whereas the parent-reported QoL was only associated with the presence of learning difficulties. CONCLUSIONS: Responses from both children and parents need to be considered to understand the similarities and differences between them and to provide further insight into the optimal way to help children with CHD effectively navigate the transition into adulthood. Future research studies of outcomes for survivors of children with CHD are needed to identify high-risk survivors for worse psychosocial functioning and assess prevention measures and treatment interventions to improve their QoL.

Predictors of non-adherence to antihypertensive medications: A cross-sectional study from a regional hospital in Afghanistan.

BACKGROUND: Non-adherence to antihypertensive medications (AHMs) is a widespread problem. Cardiovascular morbidity and mortality reduction is possible via better adherence rates among hypertensive patients. OBJECTIVES: This study aimed to assess the prevalence of non-adherence to AHMs and its predictors among hypertensive patients who attended Mirwais Regional Hospital in Kandahar, Afghanistan. METHODS: A cross-sectional study using random sampling method was conducted among hypertensive patients, aged ≥18 years in Mirwais Regional Hospital at a 6-month follow-up between October and December 2022. To assess non-adherence to AHMs, we employed the Hill-Bone Medication Adherence scale. A value below or equal to 80% of the total score was used to signify non-adherence. A multivariable binary logistic regression model was used to identify predictors of non-adherence to AHMs. RESULTS: We used data from 669 patients and found that 47.9% (95%CI: 44.1-51.8%) of them were non-adherent to AHMs. The majority (71.2%) of patients had poorly controlled blood pressure (BP). The likelihood of non-adherence to AHMs was significantly higher among patients from low monthly-income households [Adjusted odds ratio (AOR) 1.70 (95%CI: 1.13-2.55)], those with daily intake of multiple AHMs [AOR 2.02 (1.29-3.16)], presence of comorbid medical conditions [AOR 1.68 (1.05-2.67), lack of awareness of hypertension-related complications [AOR 2.40 (1.59-3.63)], and presence of depressive symptoms [AOR 1.65 (1.14-2.38)]. CONCLUSION: Non-adherence to AHMs was high. Non-adherence to AHMs is a potential risk factor for uncontrolled hypertension and subsequent cardiovascular complications. Policymakers and clinicians should implement evidence-based interventions to address factors undermining AHMs adherence in Afghanistan.

The Impact of Non-Adherence to Antihypertensive Drug Therapy.

Medication non-adherence is a major healthcare barrier, especially among diseases that are largely asymptomatic, such as hypertension. The impact of poor medication adherence ranges from patient-specific adverse health outcomes to broader strains on health care system resources. The Centers for Disease Control (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database was used to retrieve Centers for Medicare and Medicaid Services' data pertaining to blood pressure (BP) medication adherence, socio-economic variables, and cardiovascular (CV) outcomes across the United States. Multivariable linear regression models were used to estimate the change in total CV deaths as a function of non-adherence to BP medications. For every percent increase in the non-adherence rate, the total number of CV deaths increased by 7.13 deaths per 100,000 adults (95% CI: 6.34-7.92), even after controlling for the percentage of residents with access to insurance, the percentage of residents who were eligible for Medicaid, the percentage of residents without a college education, median home value, income inequality, and the poverty rate (p < 0.001). There is a significant association between non-adherence to BP medications and total CV deaths. Even a one percent increase in the adherence rate in the United States could result in tens of thousands of preventable CV deaths. Based on recently published CDC data, this could also have a tremendous impact on health care costs. This provides compelling evidence for increased efforts to improve adherence.

Conducting Health Research in the Current Afghan Society: Challenges, Opportunities, and Recommendations.

Research makes a significant contribution to academic excellence and holds the potential to facilitate societal development. Despite the increasing importance of health research in developing new therapies and galvanizing notable progress in public health, the landscape of health research in Afghanistan remains profoundly deficient. This article reveals that health research in Afghanistan requires significant growth to meet the standards set on regional and global grounds.

Prevalence of soil-transmitted helminths and associated risk factors among primary school children in Kandahar, Afghanistan: A cross-sectional analytical study.

BACKGROUND: Soil-transmitted helminth (STH) infections are global health problem, especially in low-income countries. Main objectives of this study were to estimate the prevalence and intensity of STH and its risk factors among school children in Kandahar city of Afghanistan. METHODOLOGY/PRINCIPAL FINDINGS: This was a school-based cross-sectional analytical study, with data collected during eight-month-period (May-December, 2022) from 6- and 12-years old school children in Kandahar city, Afghanistan. All the stool samples were examined by saline wet mount method and Kato-Katz technique. Data were analyzed by using descriptive statistics, Chi square test, and multivariate logistic regression. A total of 1275 children from eight schools of Kandahar city were included in this study. Mean age of these children was 8.3 years with 53.3% boys. The overall prevalence of any intestinal parasitic infection was 68.4%. The overall prevalence of STH infection was 39.1%, with Ascaris lumbricoides (29.4%) as the most prevalent STH species. Mean intensity of overall STH infection was 97.8. Multivariate logistic regression revealed playing barefoot (AOR 1.6, 95% CI 1.1-2.2), not washing hands after defecating and before eating (AOR 1.3, 95% CI 1.0-1.7), having untrimmed nails (AOR 1.4, 95% CI 1.1-1.8), and belonging to poor families (AOR 1.3, 95% CI 1.0-1.7) as the risk factors associated with the predisposition of school children for getting STH in Kandahar city of Afghanistan. CONCLUSIONS/SIGNIFICANCE: There is high prevalence of STH among school children of Kandahar city in Afghanistan. Most of the risk factors are related to poverty, decreased sanitation, and improper hygiene. Improvement of socioeconomic status, sanitation, and health education to promote public awareness about health and hygiene together with periodic mass deworming programs are better strategies for the control of STH infections in Afghanistan.

Afghan medical students' perceptions, and experiences of their medical education and their professional intentions: a cross-sectional study.

BACKGROUND: Numerous challenges have crippled the Afghan healthcare system on individual, organizational, and societal levels. The Afghans have acknowledged that an evidence-based perspective is paramount to enhancing medical training capacities across the country, which may, in turn, best ensure appointing highly competent authorities to address health system problems on such multiple levels. OBJECTIVES: This study assessed current Afghan senior medical students' perceptions, and experiences of their medical education and their future professional intentions. METHODS: We conducted this cross-sectional study at seven public and private Afghan medical institutes from March to April 2022. We invited 665 senior medical students through an anonymous survey using the Google survey online forms via social-media platforms, such as WhatsApp Messenger. Descriptive statistics were employed for the data analyses. RESULTS: The mean age (± SD) of the students was 23.7 (± 2.2) years and males constituted 79.9% (510) of the study sample. About 22.6% of them rated their medical training as excellent, and nearly a third of them (37%) said that it is good. Nearly half (48.7%) of the students would prefer to stay in Afghanistan. The leading motives for moving overseas were to obtain more advanced and quality education (69.9%), and a decent personal life (43.9%). Nearly two-thirds (67.4%) of them asserted that current political and armed conflicts in Afghanistan may have influenced their professional choices. CONCLUSION: This study epitomizes that the quality of medical education in Afghanistan has room for growth and development to meet the standards set on regional and global grounds.

High Prevalence of Uncontrolled Hypertension Among Afghan Hypertensive Patients: A Multicenter Cross-Sectional Study.

Background: Despite striking advances in the management of hypertension, blood pressure (BP) control remains suboptimal worldwide. Sustainable Development Goals (SDGs) call for 80% control rates by 2030, highlighting the urgency for improvements in hypertension control. Objective: We aimed to determine the prevalence of uncontrolled hypertension (≥140/90 mmHg) and assess its associated factors in Afghan hypertensive patients. Methods: We conducted this multicenter cross-sectional study at three Afghan public hospitals in Afghanistan. We recruited hypertensive patients (n=950) on antihypertensive medications (AHMs) from August to December 2022. We analyzed only complete datasets (853). We employed the 14-item Hill-Bone compliance scale to assess compliance with AHMs. We performed multivariable logistic regression analyses to determine factors associated with uncontrolled hypertension. Results: The mean age (±SD) of the patients was 47.5 (± 9.5) years and males constituted 50.5% (431) of the study sample. The prevalence of uncontrolled hypertension in this study was 77.3% (95% CI: 74.2-79.9%). Factors associated with uncontrolled hypertension and their adjusted OR (95% CI) were physical inactivity: 3.45 (1.87-6.35), current smoking: 3.04 (1.50-6.15), high salt intake: 3.57 (1.9-6.7), presence of comorbid medical disease: 2.22 (1.20-4.08), higher BMI: 3.32 (1.12-9.88), poor compliance to AHMs: 8.50 (4.62-15.6), and presence of depressive symptoms: 1.99 (1.2-3.27). Conclusion: The prevalence of uncontrolled hypertension was high in the present study. Factors associated with uncontrolled hypertension may epitomize potential targets for public/individual health interventions in Afghanistan.

Feasibility of a Home-Based Cognitive-Physical Exercise Program in Patients With Chronic Obstructive Pulmonary Disease: Protocol for a Feasibility and Pilot Randomized Controlled Trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive condition associated with physical and cognitive impairments contributing to difficulty in performing activities of daily living (ADLs) that require dual tasking (eg, walking and talking). Despite evidence showing that cognitive decline occurs among patients with COPD and may contribute to functional limitations and decreased health-related quality of life (HRQL), pulmonary rehabilitation continues to focus mainly on physical training (ie, aerobic and strength exercises). An integrated cognitive and physical training program compared to physical training alone may be more effective in increasing dual-tasking ability among people living with COPD, leading to greater improvements in performance of ADLs and HRQL. OBJECTIVE: The aims of this study are to evaluate the feasibility of an 8-week randomized controlled trial of home-based, cognitive-physical training versus physical training for patients with moderate to severe COPD and derive preliminary estimates of cognitive-physical training intervention efficacy on measures of physical and cognitive function, dual task performance, ADLs, and HRQL. METHODS: A total of 24 participants with moderate to severe COPD will be recruited and randomized into cognitive-physical training or physical training. All participants will be prescribed an individualized home physical exercise program comprising 5 days of moderate-intensity aerobic exercise (30-50 minutes/session) and 2 days of whole-body strength training per week. The cognitive-physical training group will also perform cognitive training for approximately 60 minutes, 5 days per week via the BrainHQ platform (Posit Science Corporation). Participants will meet once weekly with an exercise professional (via videoconference) who will provide support by reviewing the progression of their training and addressing any queries. Feasibility will be assessed through the recruitment rate, program adherence, satisfaction, attrition, and safety. The intervention efficacy regarding dual task performance, physical function, ADLs, and HRQL will be evaluated at baseline and at 4 and 8 weeks. Descriptive statistics will be used to summarize intervention feasibility. Paired 2-tailed t tests and 2-tailed t tests will be used to compare the changes in the outcome measures over the 8-week study period within and between the 2 randomized groups, respectively. RESULTS: Enrollment started in January 2022. It is estimated that the enrollment period will be 24 months long, with data collection to be completed by December 2023. CONCLUSIONS: A supervised home-based cognitive-physical training program may be an accessible intervention to improve dual-tasking ability in people living with COPD. Evaluating the feasibility and effect estimates is a critical first step to inform future clinical trials evaluating this approach and its effects on physical and cognitive function, ADL performance, and HRQL. TRIAL REGISTRATION: ClinicalTrials.gov NCT05140226; https://clinicaltrials.gov/ct2/show/NCT05140226. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48666.

Post-traumatic stress disorder (PTSD) probability among parents who live in Kandahar, Afghanistan and lost at least a child to armed conflict.

The last 4 decades of conflict in Afghanistan resulted in incalculable deaths, injuries, and millions of displacements. Although there are routine reports on casualties of the warfare, the information on its long-term psycho-social sequelae is somehow discounted. This study aimed to assess post-traumatic stress disorder (PTSD) probability and its associated factors among parents who live in Kandahar, the southern province of Afghanistan, and lost at least one child to armed conflict. We conducted a health-facility-based cross-sectional study involving 474 bereaved parents in Kandahar province from November/2020 to January/2021. The questionnaire was composed of sections on socio-demographic characteristics and mental and medical histories of the parent, features of the traumatic event and the time elapsed since then, age and gender of the lost child, and PCL-5. We performed multivariable logistic analysis to determine factors associated with PTSD probability in such parents. A staggering number of the parents (430; 90.72%) scored > 33 on PCL-5 denoting presence of probable PTSD. We noticed that several attributes of the bereaved parents (rural residence [AOR = 3.71 (95% CI 1.37-9.97)], older age [AOR = 2.41 (95% CI 1.03-5.57)], experiencing more than one traumatic event [AOR = 2.91 (95% CI 1.05-7.94)], pre-existing medical condition [AOR = 3.5 (95% CI 1.55-8.05)], and losing a < 5-years-old child [AOR = 2.38 (95% CI 1.16-4.70)] were significantly associated with PTSD probability. We assert that a very high number of bereaved parents are susceptible to probable PTSD. This finding signifies the eminent necessity of mental health services in such settings and provides implicit insights to relevant humanitarian assistance providers.

Association of Hydroxychloroquine Dose With Adverse Cardiac Events in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: To determine whether hydroxychloroquine (HCQ) dose is associated with adverse cardiac outcomes in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE taking HCQ and with ≥1 echocardiogram followed at a tertiary care center in the Bronx, New York between 2005 and 2021 were included. The HCQ weight-based dose at the HCQ start date was the main exposure of interest. The outcome was incident all-cause heart failure with reduced ejection fraction (HFrEF), life-threatening arrhythmia, or cardiac death. We used Fine-Gray regression models with death as a competing event to study the association of HCQ dose with the outcome. Due to a significant interaction between smoking and HCQ exposure, models were stratified by smoking status. Propensity score analysis was performed as a secondary analysis. RESULTS: Of 294 patients, 37 (13%) developed the outcome over a median follow-up time of 7.9 years (interquartile range [IQR] 4.2-12.3 years). In nonsmokers (n = 226), multivariable analysis adjusted for age, body mass index, hypertension, chronic kidney disease, diabetes mellitus, and thromboembolism showed that higher HCQ weight-based doses were not associated with an increased risk of the outcome (subdistribution hazard ratio [HR] 0.62 [IQR 0.41-0.92], P = 0.02). Similarly, higher baseline HCQ doses were not associated with a higher risk of the outcome among smokers (n = 68) (subdistribution HR 0.85 [IQR 0.53-1.34] per mg/kg, P = 0.48). Propensity score analysis showed comparable results. CONCLUSION: Higher HCQ doses were not associated with an increased risk of HFrEF, life-threatening arrhythmia, or cardiac death among patients with SLE and may decrease the risk among nonsmokers.

Effect of Non-Woven Polyethylene Terephthalate (PET) Tissue on Fresh and Hardened Properties of Concrete.

This study will investigate the effect of non-woven PET plastic tissue on the fresh, physical, mechanical, acoustic, thermal, and microstructural behaviors of concrete. Including reference specimens, non-woven fabrics were considered in two ways: (a) as a layer with four various configurations of 1-layer, 2-sides, 3-sides, and full wrapping (4-sides) to strengthen specimens, and (b) as (10 × 10) mm cut pieces with three different incorporated percentages of 0.25%, 0.50%, and 0.75%. Based on the experimental results, mechanical properties (compressive, split tensile, and flexural strengths) were remarkably improved by applying non-woven sheets as a layer. For instance, the cylindrical compressive and split tensile strengths were improved by 13.40% and 15.12% for the strengthened specimens compared to the reference specimens, respectively. Moreover, control specimens were damaged to many fragments after mechanical testing, but the samples strengthened by such fabrics or containing cut pieces were maintained and not separated into many small parts. The acoustic behavior and thermal conductivity declined by 9.83% and 19.67% with the attachment of tissue on one side and 2-sides, respectively. Acoustic behaviors decreased by 10.0%, 17.60%, and 26.30% and thermal conductivity decreased by 6.60%, 12.10%, and 15.50%, with the incorporation of 0.25%, 0.50%, and 0.75% of cut pieces, respectively. Finally, it was discovered that non-woven tissue is advised to enhance particular properties of concrete.

Impact of Frailty on Outcomes After Transcatheter Edge-to-Edge Repair With MitraClip (from the National Inpatient Sample Database).

Transcatheter edge-to-edge repair (TEER) with MitraClip (Abbott, Santa Clara, California) is a frequently chosen method for mitral valve repair for patients at high surgical risk. We investigated the impact of frailty on outcomes of patients who underwent TEER. We reviewed the National Inpatient Sample to identify patients that underwent TEER with MitraClip. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. The primary end point was in-hospital mortality. The secondary end points included blood transfusion, respiratory failure, sepsis, length of stay, and total hospitalization cost. Univariate and multivariate logistic regression analyses were performed to determine any association between frailty and primary or secondary outcomes. From January 2016 to December 2017, 10,055 patients underwent TEER in the United States, and 10.6% of them met the criteria for frailty. The frail group showed increased in-hospital mortality (7.04% vs 1.61%, p <0.001) and respiratory failure (3.75% vs 0.95%, p <0.001). Similarly, the frail group had longer lengths of stay (6 vs 2 days, p <0.001) and higher hospitalization costs ($224.8k vs $180.9k, p <0.001). After multivariable logistic regression analysis, frailty was associated with increased in-hospital mortality (odds ratio [OR] 3.70, 95% confidence interval [CI] 1.91 to 7.18, p <0.001), transfusion (OR 1.85, 95% CI 1.07 to 3.19, p = 0.029), respiratory failure (OR 3.56, 95% CI 1.48 to 8.52, p = 0.005), and sepsis (OR 4.17, 95% CI 1.84 to 9.46, p = 0.001). In conclusion, frailty was present in about 10% of patients who underwent TEER from 2016 to 2017. The presence of frailty was associated with worse in-hospital outcomes and greater resource use.

Potential Composite Digenic Contribution of NPC1 and NOD2 Leading to Atypical Lethal Niemann-Pick Type C with Initial Crohn's Disease-like Presentation: Genotype-Phenotype Correlation Study.

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral disease characterized by progressive neurodegeneration with variable involvement of multisystemic abnormalities. Crohn's disease (CD) is an inflammatory bowel disease (IBD) with a multifactorial etiology influenced by variants in NOD2. Here, we investigated a patient with plausible multisystemic overlapping manifestations of both NPC and CD. Her initial hospitalization was due to a prolonged fever and non-bloody diarrhea. A few months later, she presented with recurrent skin tags and anal fissures. Later, her neurological and pulmonary systems progressively deteriorated, leading to her death at the age of three and a half years. Differential diagnosis of her disease encompassed a battery of clinical testing and genetic investigations. The patient's clinical diagnosis was inconclusive. Specifically, the histopathological findings were directed towards an IBD disease. Nevertheless, the diagnosis of IBD was not consistent with the patient's subsequent neurological and pulmonary deterioration. Consequently, we utilized a genetic analysis approach to guide the diagnosis of this vague condition. Our phenotype-genotype association attempts led to the identification of candidate disease-causing variants in both NOD2 and NPC1. In this study, we propose a potential composite digenic impact of these two genes as the underlying molecular etiology. This work lays the foundation for future functional and mechanistic studies to unravel the digenic role of NOD2 and NPC1.

TBX5 variant with the novel phenotype of mixed­type total anomalous pulmonary venous return in Holt­Oram Syndrome and variable intrafamilial heart defects.

Variants in T­box transcription factor 5 (TBX5) can result in a wide phenotypic spectrum, specifically in the heart and the limbs. TBX5 has been implicated in causing non­syndromic cardiac defects and Holt­Oram syndrome (HOS). The present study investigated the underlying molecular etiology of a family with heterogeneous heart defects. The proband had mixed­type total anomalous pulmonary venous return (mixed­type TAPVR), whereas her mother had an atrial septal defect. Genetic testing through trio­based whole­exome sequencing was used to reveal the molecular etiology. A nonsense variant was identified in TBX5 (c.577G>T; p.Gly193*) initially showing co­segregation with a presumably non­syndromic presentation of congenital heart disease. Subsequent genetic investigations and more complete phenotyping led to the correct diagnosis of HOS, documenting the novel association of mixed­type TAPVR with HOS. Finally, protein modeling of the mutant TBX5 protein that harbored this pathogenic nonsense variant (p.Gly193*) revealed a substantial drop in the quantity of non­covalent bonds. The decrease in the number of non­covalent bonds suggested that the resultant mutant dimer was less stable compared with the wild­type protein, consequently affecting the protein's ability to bind DNA. The present findings extended the phenotypic cardiac defects associated with HOS; to the best of our knowledge, this is the first association of mixed­type TAPVR with TBX5. Prior to the current analysis, the molecular association of TAPVR with HOS had never been documented; hence, this is the first genetic investigation to report the association between TAPVR and HOS. Furthermore, it was demonstrated that the null­variants reported in the T­box domain of TBX5 were associated with a wide range of cardiac and/or skeletal anomalies on both the inter­and intrafamilial levels. In conclusion, genetic testing was highlighted as a potentially powerful approach in the prognostication of the proper diagnosis.

Prevalence and associated risk factors of soil-transmitted helminth infections in Kandahar, Afghanistan.

BACKGROUND: Soil-transmitted helminth (STH) infections are still a major health problem, especially in resource-limited countries. The community-based prevalence of STH is unknown in Afghanistan. Main objectives of this study were to estimate the prevalence and associated factors of STH among children in Daman district of Kandahar province in Afghanistan. METHODS: This was a community-based cross-sectional study, with data collected during five months (June-October, 2020) from children living in five villages of Daman district in Kandahar, Afghanistan. All the stool samples were examined by saline wet mount method. Data were analyzed by using descriptive statistics, Chi square test, and multivariate logistic regression. RESULTS: A total of 1426 children were studied, with majority (61.8%) of males and the mean age of 6.3 years. The overall prevalence of any intestinal parasitic infection was 39.8%. The overall prevalence of STH infection was 22.7%, with Ascaris lumbricoides (18.7%) as the most prevalent STH species, followed by hookworm (7.5%) and Trichuris trichiura (1.4%). Single, double, and triple STH infections were present in 14.9%, 7.2%, and 0.6% of the children, respectively. Multivariate logistic regression revealed that not washing hands after defecating/before eating (AOR 7.0, 95% CI 3.4-14.0), living in mud house (AOR 3.5, 95% CI 1.6-7.4), walking barefoot (AOR 2.2, 95% CI 1.6-3.1), living in overcrowded house (AOR 1.6, 95% CI 1.1-2.3), and practicing open defecation (AOR 1.4, 95% CI 1.1-2.0) as the risk factors associated with the predisposition of rural children for getting STH in Daman district of Afghanistan. CONCLUSIONS: Prevalence of STH is high among children of Daman district in Afghanistan. Most of the risk factors are related to poverty, decreased sanitation, and improper hygiene. Improvement of socioeconomic status, sanitation, and health education to promote public awareness about health and hygiene together with periodic mass deworming programs are better strategies for the control of STH infections in Afghanistan. Also, government and international donor agencies in Afghanistan should help in improving socio-economic status of the rural areas through provision of basic facilities such as piped water, electricity, good housing, and proper toilets.