Explore the vast range of titles available.

Introduction Smokeless tobacco (SLT) use is a growing and significant public health issue in low- and middle-income countries. SLT consumption impairs nutrient absorption, particularly iron, leading to poor nutritional status and reduced hemoglobin levels. The study aimed to assess the association between SLT consumption and hemoglobin levels (Hb) among 6 to 12-year-old school-going children in rural Matiari, Pakistan. Methods An analytical cross-sectional study was conducted over 40 days (August-September 2024) in four schools in Matiari, Pakistan. Children aged 6-12 years from classes I-V who provided assent and parental consent were included. Those with hematological diseases, nutritional deficiencies, or a history of intestinal worm infestation were excluded. A systematic sampling strategy was employed to enroll at least 14 students per class and a minimum of 70 children per school. Data on SLT use, dietary habits, and health-related factors were collected using a structured, pre-tested questionnaire via REDCap software. SLT use was defined as consuming any SLT product for at least five minutes per day within the last 30 days. Hemoglobin (Hb) levels (g/dL) were measured using the HemoCue Hb 301 system device, while height (cm) and weight (kg) were recorded using a digital scale. Data were analyzed using Stata version 17.0. Result Among 283 participants, 34 (12.01%) reported SLT use. The median hemoglobin level among SLT users was 10.8 g/dL (IQR: 9.8-11.7) compared to 11.2 g/dL (IQR: 10.1-12.2) among non-users. The difference in hemoglobin levels was not statistically significant (p = 0.17). 151 (53.36%) were boys, and the median age was 8.06 years (IQR: 7-9). In multivariable analysis, SLT use was associated with a - 0.40 g/dL change in hemoglobin (95% CI: - 0.97 to 0.17) (p = 0.28). Most of the children used SLT for 1-3 days in the past 30 days (79.41%). Conclusion SLT users had lower hemoglobin levels, although the results were not statistically significant. Overall, children have lower hemoglobin levels, and most of them used SLT for the first time before age 6 or between ages 7 and 8, which is a major public health concern. Keywords: Smokeless tobacco, Hemoglobin, Children, Public health, Pakistan

Environmental enteric dysfunction (EED) is a subclinical condition of intestinal inflammation, barrier dysfunction and malabsorption associated with growth faltering in children living in poverty. This study explores association of altered duodenal permeability (lactulose, rhamnose and their ratio) with higher burden of enteropathogen in the duodenal aspirate, altered histopathological findings and higher morbidity (diarrhea) that is collectively associated with linear growth faltering in children living in EED endemic setting. In a longitudinal birth cohort, 51 controls (WHZ > 0, HAZ > −1.0) and 63 cases (WHZ< -2.0, refractory to nutritional intervention) were recruited. Anthropometry and morbidity were recorded on monthly bases up to 24 months of age. Dual sugar assay of urine collected after oral administration of lactulose and rhamnose was assessed in 96 children from both the groups. Duodenal histopathology (n = 63) and enteropathogen analysis of aspirate via Taqman array card (n = 60) was assessed in only cases. Giardia was the most frequent pathogen and was associated with raised L:R ratio (p = 0.068). Gastric microscopy was more sensitive than duodenal aspirate in H . pylori detection. Microscopically confirmed H . pylori negatively correlated with HAZ at 24 months (r = −0.313, p = 0.013). Regarding histopathological parameters, goblet cell reduction significantly correlated with decline in dual sugar excretion (p< 0.05). Between cases and controls, there were no significant differences in the median (25 th , 75 th percentile) of urinary concentrations (μg/ml) of lactulose [27.0 (11.50, 59.50) for cases vs. 38.0 (12.0, 61.0) for controls], rhamnose [66.0 (28.0, 178.0) vs. 86.5 (29.5, 190.5)] and L:R ratio [0.47 (0.24, 0.90) vs. 0.51 (0.31, 0.71)] respectively. In multivariable regression model, 31% of variability in HAZ at 24 months of age among cases and controls was explained by final model including dual sugars. In conclusion, enteropathogen burden is associated with altered histopathological features and intestinal permeability. In cases and controls living in settings of endemic enteropathy, intestinal permeability test may predict linear growth. However, for adoption as a screening tool for EED, further validation is required due to its complex intestinal pathophysiology.

Environmental Enteric Dysfunction (EED) is an acquired small intestinal inflammatory condition underlying high rates of stunting in children <5 years of age in low- and middle-income countries. Children with EED are known to have repeated exposures to enteropathogens and environmental toxins that leads to malabsorptive syndrome. We aimed to characterize association of linear growth faltering with enteropathogen burden and subsequent changes in EED biomarkers. In a longitudinal birth cohort (n = 272), monthly anthropometric measurements (Length for Age Z score- LAZ) of asymptomatic children were obtained up to 18 months. Biological samples were collected at 6 and 9 months for the assessment of biomarkers. A customized TaqMan array card was used to target 40 enteropathogens in fecal samples. Linear regression was applied to study the effect of specific enteropathogen infection on change in linear growth (ΔLAZ). Presence of any pathogen in fecal sample correlated with serum flagellin IgA (6 mo, r = 0.19, p = 0.002), fecal Reg 1b (6 mo, r = 0.16, p = 0.01; 9mo, r = 0.16, p = 0.008) and serum Reg 1b (6 mo, r = 0.26, p<0.0001; 9 mo, r = 0.15, p = 0.008). At 6 months, presence of Campylobacter [β (SE) 7751.2 (2608.5), p = 0.003] and ETEC LT [β (SE) 7089.2 (3015.04), p = 0.019] was associated with increase in MPO. Giardia was associated with increase in Reg1b [β (SE) 72.189 (26.394), p = 0.006] and anti-flic IgA[β (SE) 0.054 (0.021), p = 0.0091]. Multiple enteropathogen infections in early life negatively correlated with ΔLAZ, and simultaneous changes in gut inflammatory and permeability markers. A combination vaccine targeting enteropathogens in early life could help in the prevention of future stunting.

Undernutrition among women and children is a pressing global health problem. Environmental enteric dysfunction (EED) is a disease of the small intestine (SI) associated with impaired gut mucosal barrier function and reduced capacity for nutrient absorption. The cause of EED is ill-defined. One emerging hypothesis is that alterations in the SI microbiota contribute to EED. We performed a culture-independent analysis of the SI microbiota of a cohort of Pakistani children with undernutrition who had failed a standard nutritional intervention, underwent upper gastrointestinal tract endoscopy, and had histologic evidence of EED in their duodenal mucosal biopsies. The results revealed a shared group of bacterial taxa in their duodenums whose absolute abundances were correlated with levels of the expression of genes in the duodenal mucosa that are involved in inflammatory responses. A number of these bacterial taxa are more typically found in the oral microbiota, a finding that has potential physiologic and therapeutic implications.

BackgroundReady-to-use supplemental foods (RUSF) are energy-dense meals used to treat moderate and severe acute childhood malnutrition. Weight recovery with RUSF is heterogeneous, therefore we investigated whether environmental enteric dysfunction (EED), systemic inflammation, and gut microbiota predict RUSF response.MethodsWe followed nutritional status and RUSF outcomes in a rural birth cohort of 416 Pakistani infants. Acha Mum, a chickpea-based RUSF, was administered daily for 8 weeks to children who developed wasting (weight-for-length Z-score <-2).ResultsOf 187 treated with RUSF, 112 showed no immediate improvement in weight-for-age. Machine learning identified nine biomarkers that collectively predicted RUSF response with 73% accuracy. Gut microbiome composition before and after supplementation predicted response with 93% and 98% accuracy, respectively. Responders showed microbiome restructuring, with increased growth-associated taxa and reduced Gammaproteobacteria relative to nonresponders. A subset of extreme nonresponders-whose microbiome profiles resembled those of responders-displayed markedly abnormal biomarkers of inflammation, suggesting adverse host factors constrain gut microbiota benefits for RUSF efficacy.ConclusionEED, systemic inflammation, and gut microbiota predict acute nutritional responses to Acha Mum, setting the stage for precision use of RUSF and adjunctive therapies in addressing the global burden of childhood malnutrition in low- and middle-income countries.

Kisspeptin (KP) is a neuropeptide that causes the release of the gonadotropin releasing hormone, which controls hypothalamo pituitary ovarian axis and exerts a number of peripheral effects on reproductive organs. The primary objective of this study was to compare baseline KP levels in females with different types of infertility and identify possible correlations with risk of failure to conceive, preclinical abortion and pregnancy after intracytoplasmic sperm injection (ICSI). A longitudinal cohort study was carried out from August 2014 until May 2015 by recruiting 124 female patients undergoing ICSI, after obtaining ethical approval from the Australian Concept Infertility Medical Center. Cause of infertility due to male, female and unexplained factors was at a frequency of 32 (24%), 33 (31%) and 59 (45%) among the individuals respectively. KP levels were measured by ELISA assay before the initiation of the ICSI treatment protocol. Outcome of ICSI was categorized into three groups of non-pregnant with beta-human chorionic gonadotropin (β-hCG)<5-25 mIU/ml, preclinical abortion with β-hCG>25 mIU/ml and no cardiac activity, and clinical pregnancy declared upon confirmation of cardiac activity. Results based on cause of infertility and outcome groups were analyzed by one-way ANOVA. Females with unexplained infertility had significantly lower levels of KP when compared with those with male factor infertility (176.69 ± 5.03 vs. 397.6 ± 58.2, P=0.001). Clinical pregnancy was observed in 28 (23%) females of which 17 (71%) had a female cause of infertility. In the non-pregnant group of 66 (53%) females, common cause of infertility was unexplained 56(85%). A weak positive correlation of KP levels with fertilized oocytes and endometrial thickness was observed (P=0.04 and 0.01 respectively). Deficiency of KP in females with unexplained infertility was associated with reduced chances of implantation after ICSI.

Background: This study aimed to evaluate the strength of anti-Mullerian hormone (AMH) and follicle stimulating hormone (FSH) in reflecting the antral follicle count (AFC) in infertile females. Materials and Methods: This cross-sectional study was conducted on 160 females, visiting infertility clinic for assisted reproduction. Serum samples collected on the 3rd day of the cycle were assayed for FSH, luteinizing hormone, and AMH while AFC was assessed via transvaginal ultrasound. The study cohort was segregated into three groups based on AFC. Results: Chronological age and FSH was significantly high in females with very low AFC (P < 0.01 and 0.009, respectively), yet they failed to discriminate patients with normal and higher follicle count (P = 0.65 and 0.84). Conversely, AMH reported highly significant difference between very low AFC and with those having either normal AFC (P = 0.002) or higher AFC (P = 0.001). Moreover, a significant difference in AMH was observed between normal and higher AFC group (P = 0.04). Conclusion: Compared to female's age and FSH, AMH is superior in clustering study cohort on the bases of antral follicular pool, especially in setups with nonavailability of technological expertise to assess AFC. Incorporation of AMH along with other biomarkers improves estimation of baseline ovarian reserve, required to standardize dose for optimum response; avoiding the risk of failure to retrieve oocyte or inappropriate stimulation leading to ovarian hyperstimulation syndrome. Further prospective studies are required to ascertain its role in predicting the outcomes of ART in such patients.

Environmental enteric dysfunction (EED) is a subclinical syndrome of intestinal inflammation, malabsorption and barrier disruption that is highly prevalent in low- and middle-income countries in which poverty, food insecurity and frequent exposure to enteric pathogens impair growth, immunity and neurodevelopment in children. In this Review, we discuss advances in our understanding of EED, intestinal adaptation and the gut microbiome over the ‘first 1,000 days’ of life, spanning pregnancy and early childhood. Data on maternal EED are emerging, and they mirror earlier findings of increased risks for preterm birth and fetal growth restriction in mothers with either active inflammatory bowel disease or coeliac disease. The intense metabolic demands of pregnancy and lactation drive gut adaptation, including dramatic changes in the composition, function and mother-to-child transmission of the gut microbiota. We urgently need to elucidate the mechanisms by which EED undermines these critical processes so that we can improve global strategies to prevent and reverse intergenerational cycles of undernutrition.In this Review, Cowardin, Moore and colleagues discuss advances in our understanding of environmental enteric dysfunction in the context of intestinal adaptation and the gut microbiome during pregnancy, lactation and early childhood.

Introduction Smokeless tobacco (SLT) use is a growing and significant public health issue in low- and middle-income countries. SLT consumption impairs nutrient absorption, particularly iron, leading to poor nutritional status and reduced hemoglobin levels. The study aimed to assess the association between SLT consumption and hemoglobin levels (Hb) among 6 to 12-year-old school-going children in rural Matiari, Pakistan. Methods An analytical cross-sectional study was conducted over 40 days (August–September 2024) in four schools in Matiari, Pakistan. Children aged 6–12 years from classes I–V who provided assent and parental consent were included. Those with hematological diseases, nutritional deficiencies, or a history of intestinal worm infestation were excluded. A systematic sampling strategy was employed to enroll at least 14 students per class and a minimum of 70 children per school. Data on SLT use, dietary habits, and health-related factors were collected using a structured, pre-tested questionnaire via REDCap software. SLT use was defined as consuming any SLT product for at least five minutes per day within the last 30 days. Hemoglobin (Hb) levels (g/dL) were measured using the HemoCue Hb 301 system device, while height (cm) and weight (kg) were recorded using a digital scale. Data were analyzed using Stata version 17.0. Result Among 283 participants, 34 (12.01%) reported SLT use. The median hemoglobin level among SLT users was 10.8 g/dL (IQR: 9.8–11.7) compared to 11.2 g/dL (IQR: 10.1–12.2) among non-users. The difference in hemoglobin levels was not statistically significant ( p  = 0.17). 151 (53.36%) were boys, and the median age was 8.06 years (IQR: 7–9). In multivariable analysis, SLT use was associated with a − 0.40 g/dL change in hemoglobin (95% CI: − 0.97 to 0.17) ( p  = 0.28). Most of the children used SLT for 1–3 days in the past 30 days (79.41%). Conclusion SLT users had lower hemoglobin levels, although the results were not statistically significant. Overall, children have lower hemoglobin levels, and most of them used SLT for the first time before age 6 or between ages 7 and 8, which is a major public health concern.

The underperformance of oral vaccines in children of low- and middle-income countries is partly attributable to underlying environmental enteric dysfunction (EED). We conducted a longitudinal, community-based study to evaluate the association of oral rotavirus vaccine (Rotarix®) seroconversion with growth anthropometrics, EED biomarkers and intestinal enteropathogens in Pakistani infants. Children were enrolled between three to six months of their age based on their nutritional status. We measured serum anti-rotavirus immunoglobulin A (IgA) at enrollment and nine months of age with EED biomarkers and intestinal enteropathogens. A total of 391 infants received two doses of rotavirus (RV) vaccine. 331/391 provided paired blood samples. Of these 331 children, 45% seroconverted at 9 months of age, 35% did not seroconvert and 20% were seropositive at baseline. Non-seroconverted children were more likely to be stunted, wasted and underweight at enrollment. In univariate analysis, insulin-like growth factor (IGF) concentration at 6 months were higher in seroconverters, median (25th, 75th percentile): 26.3 (16.5, 43.5) ng/ml vs. 22.5 (13.6, 36.3) ng/ml for non-seroconverters, p-value = 0.024. At nine months, fecal myeloperoxidase (MPO) concentrations were significantly lower in seroconverters, 3050(1250, 7587) ng/ml vs. 4623.3 (2189, 11650) ng/ml in non-seroconverted children, p-value = 0.017. In multivariable logistic regression analysis, alpha-1 acid glycoprotein (AGP) and IGF-1 concentrations were positively associated with seroconversion at six months. The presence of sapovirus and rotavirus in fecal samples at the time of rotavirus administration, was associated with non-seroconversion and seroconversion, respectively. We detected high baseline RV seropositivity and impaired RV vaccine immunogenicity in this high-risk group of children. Healthy growth, serum IGF-1 and AGP, and fecal shedding of rotavirus were positively associated with RV IgA seroconversion following immunization, whereas the presence of sapovirus was more common in non-seroconverters. Trial registration: Clinical Trials ID: NCT03588013.