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Gender disparities are prevalent in the neurosurgical field, particularly for female trainees, despite the growing demand for neurosurgeons. The situation is bleaker in low-and middle-income countries, where gender disparities among neurosurgical trainees have not been evaluated. We aimed to gauge the gender differences in opportunities and perceptions of neurosurgery training in Pakistan by comparing responses between males and females. A nationwide web-based survey was conducted in Pakistan, covering 22 College of Physicians and Surgeons of Pakistan (CPSP) accredited neurosurgery training programs. Convenience sampling was used with a pilot-tested questionnaire. Data analysis was performed using SPSS version 26. A total of 120 trainees participated in our survey. The mean age of the participants was 30.4 ± 4.1 years, with 29.2% females and 70.8% males. Concerns about gender equity were more among females (34.3%) than males (27.1%). Poor work-life balance was reported by more females (34.3%) than males (30.6%). Burnout due to working hours was strongly agreed by more females (54.3%) than males (35.3%). More females (40%) acknowledged sufficient mentorship opportunities versus males (25%). Female respondents (65.7%) worked 50–100 hours per week, less than males (69.4%). Satisfaction with surgical exposure was lower among females (2.9%) compared to males (18.8%). More females reported access to teaching courses (82.9% vs. 77.6% males) and neurosurgical conferences (85.7% vs. 80.0% males), cadaver workshops (17.1% vs. 12.9% males), morbidity and mortality meetings (88.6% vs. 82.4% males), case-based sessions (82.9% vs. 75.3% males), and radiology discussions (82.9% vs. 74.1% males). Our study highlights substantial gender gaps in neurosurgical training, concerns over working hours, burnout, mentorship, work-life balance, and gender equity. These findings underscore the necessity for interventions to rectify these disparities and foster gender equity in neurosurgical training.

The management of high-grade gliomas is challenging considering their infiltrative nature, involvement of the eloquent cortex, and high recurrence rate. Photodynamic therapy (PDT) is an emerging modality that selectively destroys tumour cells while preserving normal brain tissue. Its safety, and the concurrent use with surgery, radiation, and chemotherapy, is some of its appealing tenets. Here, we present a review of the literature regarding the mechanism, safety, and efficacy of PDT. Keywords: brain tumour, glioma, adjuvant treatment

With advances in molecular genetics, exploring targetable mutations for treating glioblastoma (GBM) patients, has become a centre of interest in modern day neuropathology. BRAF mutation has been extensively reported in several brain tumours. Recent studies report identification of BRAF mutation in GBM patients, especially isocitrate dehydrogenase wildtype glioblastomas (IDH-WT GBM), and its potential role in patient outcomes. Here we discuss the existing literature on the prognostic value of BRAF mutation in GBM. Keywords: Glioblastoma, BRAF mutation, prognosis

Next-generation sequencing technology has revolutionised pathogen surveillance over the last two decades. However, the benefits are not equitably distributed, with developing countries lagging far behind in acquiring the required technology and analytical capacity. Recent declines in the cost associated with sequencing—equipment and running consumables have created an opportunity for broader adoption. During the COVID-19 pandemic, rapid diagnostics development and DNA sequencing revolutionised the ability to diagnose and sequence SARS-CoV-2 rapidly. Socioeconomic inequalities substantially impact the ability to sequence SARS-CoV-2 strains and undermine a developing country’s pandemic preparedness. Low- and middle-income countries face additional challenges in establishing, maintaining and expanding genomic surveillance. We present our experience of establishing a genomic surveillance system at the Aga Khan University, Karachi, Pakistan. Despite being at a leading health sciences research institute in the country, we encountered significant challenges. These were related to collecting standardised contextual data for SARS-CoV-2 samples, procuring sequencing reagents and consumables, and challenges with library preparation, sequencing and submission of high-quality SARS-CoV-2 genomes. Several technical roadblocks ensued during the implementation of the genomic surveillance framework, which were resolved in collaboration with our partners. High-quality genome sequences were then deposited on open-access platforms per the best practices. Subsequently, these efforts culminated in deploying Pakistan’s first SARS-CoV-2 phyllo surveillance map as a Nextstrain build. Our experience offers lessons for the successful development of Genomic Surveillance Infrastructure in resource-limited settings struck by a pandemic.

Raman Spectroscopy (RS) is one of several techniques being used to identify tumour tissue during brain surgery. It is emerging as a novel investigative and diagnostic tool. The application of RS in cancer treatment has displayed promising results. This review centers around its clinical implication in brain tumours. Keywords: Raman spectroscopy, brain tumour, neurosurgery

Schwannomas are benign tumours of the peripheral nerve sheath. When they occur in spine, they are most commonly found in intradural-extramedullary location. Surgery is the mainstay of treatment. Radiation has a limited role in the management of residual or recurrent lesions not suitable for surgery. Here we discuss the existing literature on the outcomes of spinal schwannoma after surgery. Continue...

Spinal subependymoma (SSE) is a rare intramedullary, benign tumour. Surgical excision is the preferred approach. However, the interwoven pattern of neural tissue within the tumour dictates the extent of resection. Where gross total resection is linked with possible neurological deficits, subtotal resection or close observation may support better functional outcomes. The evidence for the management of SSE is based mostly on case reports. Herein, we review the existing literature regarding treatment options and clinical outcomes of spinal subependymoma.

ABSTRACT Science literacy has many personal and societal benefits that allows for better informed decision-making. Although the importance of science literacy is recognized globally, there are many challenges associated with its promotion. Scientists are more frequently engaging with nonscientific audiences through public outreach activities and with increasing support from institutions and professional societies. This is especially true regarding microbiologists and other related professionals since the start of the global 2019 coronavirus disease pandemic heightened the need to convey novel and rapidly evolving scientific information to lay audiences. The means by which professionals engage with these audiences affect the efficacy of the relay of scientific information. One method of engagement is the “ambassador approach,” which aims to establish dialogue among different groups of people and scientists. In this perspective article, we discuss this approach, highlighting activities for the promotion of science literacy organized by the American Society for Microbiology Ambassador Program and similar programs of other scientific societies. We discuss the benefits and challenges of implementing an ambassador approach, propose potential improvements that could be made to existing programs promoting science literacy, and ultimately advocate for increased implementation of science ambassador programs.

The current study was designed to evaluate the effects of metformin in some physiological and histological parameters of reproductive system in the diabetic male rats experimentally. Forty rats were randomly divided into four groups. The (control) first group was treated with normal saline; the second was infected group which included rats diabetic experimentally treated by alloxan; the third and fourth groups were induced diabetic experimentally and received metformin suspension (150 mg kg-1 daily) at one and two doses respectively. Twelve hours was time between these two doses. Reproductive ability was measured by determination of some physiological parameters as count sperm, malformations, motility, dead sperm, weights of sex organs (testes, epididymis, prostate glands and seminal vesicles) and the damaged testicular structure. The present results indicated that the administrated metformin at high doses led to significant decrease (p < 0.05) in total count of sperm, motility and in weights of all sex organs such as testes, epididymis, prostate glands and seminal vesicle, while significant increase (p < 0.05) in sperm abnormalities and dead sperm. Also, the results showed that the diabetes and exposure to metformin caused many malformations of sperm such as shattered sperm, the lacking, hooked and quirky tail, while the abnormalities of head included the lacking, Globozoospermia and elliptical head. The histological damages in testicular structure were observed including the destroyed and raised thickness of connective tissue among seminiferous tubules, necrosis and reduction numbers of spermatocytes along with the congestion of blood vessels. Many histological alterations occurred clearly due to treated with high dose of metformin after diabetic experimentally including the most affected structural troubles as large fracture of seminiferous tubules, expansion of bloody congestion and raise of necrosis in testicular structure.

IntroductionEnvironmental enteropathy is an important contributor to childhood malnutrition in the developing world. Chronic exposure to fecal pathogens leads to alteration in intestinal structure and function, resulting in impaired gut immune function, malabsorption, and growth faltering leading to environmental enteropathy.MethodsA community-based intervention study was carried out on children till 24 months of age in Matiari district, Pakistan. Blood and fecal specimens were collected from the enrolled children aged 3–6 and 9 months. A real-time PCR-based TaqMan array card (TAC) was used to detect enteropathogens.ResultsGiardia, Campylobacter spp., enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia coli (EPEC), Enterotoxigenic Escherichia coli (ETEC), and Cryptosporidium spp. were the most prevailing enteropathogens in terms of overall positivity at both time points. Detection of protozoa at enrollment and 9 months was negatively correlated with rate of change in height-for-age Z (ΔHAZ) scores during the first and second years of life. A positive association was found between Giardia, fecal lipocalin (LCN), and alpha 1-Acid Glycoprotein (AGP), while Campylobacter spp. showed positive associations with neopterin (NEO) and myeloperoxidase (MPO).ConclusionProtozoal colonization is associated with a decline in linear growth velocity during the first 2 years of life in children living in Environmental enteric dysfunction (EED) endemic settings. Mechanistic studies exploring the role of cumulative microbial colonization, their adaptations to undernutrition, and their influence on gut homeostasis are required to understand symptomatic enteropathogen-induced growth faltering.

Objective: To compare the effectiveness of intradermal platelet-rich plasma with 30% Trichloroacetic acid in treating atrophic acne scars. Study Design: Quasi-experimental study. Place and Duration of Study: Tertiary Care Hospital of Multan Pakistan, from Aug 2019 to Sep 2020. Methodology: A total of 76 patients (38 in each group), were enrolled in the study. Platelet-rich plasma treatment was given to Group-A, and 30% Trichloroacetic acid treatment was given to Group-B patients. Platelet-rich plasma was injected in the dermis with an insulin syringe while 30%Trichloracetic acid was applied with a cotton tip applicator. The effectiveness of treatment was measured by Goodman and Baron quantitative acne scar scale. Results: A total of 76 patients with atrophic acne scars were included in the study. The mean age of patients in Plate rich plasma Group was 29.63±5.08 years and 29.92±5.85 years in the 30% Trichloroacetic acid Group. Platelet Rich Plasma was an effective treatment of atrophic acne scar (p= 0.030) with post-procedure improvement in the Goodman and Baron quantitative acne scar scale. Conclusion: Atrophic acne scar treatment with intradermal Plate-rich plasma is more effective than 30% Trichloroacetic acid.

IntroductionThe COVID-19 pandemic has resulted in enormous increases in laboratory activities to keep pace with diagnostic testing and research efforts. However, traditional training, technical assistance, and capacity-building approaches were disrupted by the travel and movement restrictions put in place to control the spread of the disease. To address the needs of laboratorians and managers to conduct laboratory activities safely and securely during the pandemic, a highly interactive virtual training (IVT) workshop on biorisk management during COVID-19 was conducted through active learning strategies that connected speakers with participants. The objective of the training was to increase the basic knowledge and standards of biosafety and biosecurity practices, risk assessment, and control measures with reference specifically to the context of the COVID-19 pandemic and apply a rigorous evaluation methodology to assess the effectiveness of the IVT. The training covered a broad range of topics and encompassed national to international guidelines.MethodsParticipants were selected through official channels at the national level, focusing on institutions within Pakistan. The sessions included lectures from international experts in biorisk management concepts, and incorporated poll questions as well as pre- and post-tests and feedback on the speakers' knowledge and presentation skills, to increase interactivity. The pre- and post-test comprised similar multiple-choice questions and provided to every participant to ascertain the impact of the training on awareness and knowledge of biorisk management topics and concepts, and results were compared using paired t-tests. For feedback on the speakers, participants were asked to submit their ratings measured on a five-point Likert scale. The reliability of the Likert scale was estimated using Cronbach's alpha. Analyses were performed using Microsoft Excel and SPSS version 23.ResultsIn total, 52 individuals from different laboratories across Pakistan and Pakistani students from abroad (China) as well participated in at least one session of the IVT. The participants' pre- and post-test scores showed a significant increase in knowledge and awareness (p < 0.001). The obtained Cronbach's alpha score was >0.8, indicating high reliability of the generated feedback on the IVT approach and speakers.ConclusionThe IVT on biosafety and biosecurity in the context of the COVID-19 pandemic proved beneficial for laboratory professionals and could be a useful model to continue in the future for raising awareness and knowledge.

Integrated, data-driven criteria are necessary to evaluate delivery outcomes in pregnancies affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the ongoing COVID-19 pandemic. This study analyzed maternal demographics, clinical characteristics, treatments, and delivery outcomes of 85 ethnically diverse, adult pregnant women who tested positive for SARS-CoV-2 at the time of delivery. Median maternal and gestational ages were 27 years (interquartile range [IQR]: 23–31) and 39 weeks (IQR: 37.3–40.0), respectively. Of the 85 SARS-CoV-2–positive participants, 67 (79%) had no COVID-19 symptoms at the time of routine COVID-19 admission testing, 14 (16%) reported mild COVID-19 symptoms, and 4 (5%) presented severe COVID-19 symptoms that required hospitalization. Patients in the severe COVID-19 group had significantly longer hospitalizations than those with nonsevere COVID-19 (7 [IQR: 4.5–9.5] vs 2 [IQR: 2–3] days; P < 0.01). Neonatal outcomes included 100% live births with a median 1-minute Apgar score of 8 and 15% preterm births. No neonatal deaths or vertical transmissions were reported, and all neonatal intensive care unit admissions were related to prematurity. Overall, maternal symptom prevalence and peripartum complication rates were low, suggesting a generally good prognosis for pregnant women with SARS-CoV-2 infections at the time of delivery.

Background & Aims: Acute-on-chronic liver failure (ACLF) is a recently (re)defined syndrome of acute decompensation of cirrhosis that presents with extrahepatic organ failure(s) and poor outcome. Given the prominent role of inflammation and activation of coagulation in ACLF, we hypothesized that ACLF might be characterized by the generation of neutrophil extracellular traps (NETs), that could drive both activation of coagulation and progression of organ failure. Methods: We measured markers of circulating DNA, activation of coagulation, inflammation, and oxidative stress in 52 patients with acute decompensation (AD) of cirrhosis and 57 patients with ACLF on admission, and compared levels with 40 healthy controls. Results: All analytes were higher in patients compared to controls. Plasma levels of cell-free DNA, but not of the specific NET marker myeloperoxidase-DNA complexes were higher in patients with ACLF compared to AD cirrhosis. In addition, TAT complexes (coagulation), IL-6 (inflammation), and TBARS (oxidative stress) were higher in ACLF compared to AD. Markers for activation of coagulation were not associated with circulating DNA, IL-6, or TBARS. In contrast, levels of circulating DNA, IL-6, and TBARS were higher in patients with more severe disease, higher in patients with organ failure, and higher in patients that died within 30 days of admission. Importantly, myeloperoxidase-DNA levels did not differ between patients with complications and poor outcome. Conclusions: Collectively, we show that cell-free DNA, inflammation, and oxidative stress are associated with outcomes in AD and ACLF, but not with activation of coagulation. Our data argue against a role of NETs in activation of coagulation and in progression of organ failure in patients with AD and ACLF. Lay summary: Acute-on-chronic liver failure is a devastating syndrome that can follow acute decompensation of chronic liver disease. Herein, we demonstrate that these patients accumulate DNA released from dying cells in their blood, and that the quantity of this DNA is related to the outcome of disease. We also show that outcome of disease is not related to recently described neutrophil extracellular traps, which have been shown in animal models to play vital roles in the progression of liver diseases. Keywords: cirrhosis, liver, acute-on-chronic liver disease, neutrophil extracellular trap, coagulation, sepsis, mortality, inflammation, oxidative stress

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 (25th, 75th 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.

Directional clinical evaluation and management of coronavirus disease (Covid-19) was initially presumptive based on the Wuhan data set as reported by World Health Organization (WHO). The current recommendations emanate primarily from the Chinese experience and subsequent Centers for Disease Control and Prevention (CDC) guidelines. Here we report a case with an “atypical” patient risk profile and variant longitudinal disease progression contrasting from existing recommendations. Our case report suggests that a universal 14-day quarantine timeline may not be sufficient; that correlation is needed between viral presence as determined by RT-PCR and a patient’s humoral response tested by serologic immunoassay of IgM & IgG. Hence, a clinical decision-making algorithm that can help clinicians clear a patient from “active infection” status would require testing that is sufficiently reliable, and should include serological testing for immunity.

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (

Tungsten oxide (WO3), MXene, and an WO3/MXene nanocomposite were synthesized to study their photocatalytic and biological applications. Tungsten oxide was synthesized by an easy and cost-effective hydrothermal method, and its composite with MXene was prepared through the sonication method. The synthesized tungsten oxide, MXene, and its composite were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), Fourier transform infrared (FTIR), energy-dispersive X-ray analysis (EDX), and Brunauer–Emmett–Teller (BET) for their structural, morphological, spectral, elemental and surface area analysis, respectively. The crystallite size of WO3 calculated from XRD was ~10 nm, the particle size of WO3 was 130 nm, and the average thickness of MXene layers was 175 nm, which was calculated from FESEM. The photocatalytic activity of as-synthesized samples was carried out for the degradation of methylene blue under solar radiation, MXene, the WO3/MXene composite, and WO3 exhibited 54%, 89%, and 99% photocatalytic degradation, respectively. WO3 showed maximal degradation ability; by adding WO3 to MXene, the degradation ability of MXene was enhanced. Studies on antibacterial activity demonstrated that these samples are good antibacterial agents against positive strains, and their antibacterial activity against negative strains depends upon their concentration. Against positive strains, the WO3/MXene composite’s inhibition zone was at 7 mm, while it became 9 mm upon increasing the concentration. This study proves that WO3, MXene, and the WO3/MXene nanocomposite could be used in biological and environmental applications.

Background: Viral flu is the predominant cause of hospitalization in young children, which invariably leads to enhanced morbidity and mortality in children in developing countries. Initial treatment of viral flu is based on presumptive diagnosis. Bedside testing is not common in clinical settings because of variable sensitivity and specificity of rapid tests in different settings. Methods: To address this issue, we evaluated the performance of Binax influenza A/B rapid testing kit against two robust molecular platforms (quantitative real-time polymerase chain reaction [qRT-PCR] and TaqMan array card [TAC]) in 24 nasopharyngeal (NP) swabs, collected from children under 5 years of age. Results: Binax was found to be less sensitive (56%), but 100% specific compared to qRT-PCR (100%) and TAC (>100%). Using TAC cards, 75% of samples were found to be coinfected with other bacterial and viral targets. Conclusion: Binax flu is suitable for bedside testing in clinical and community settings. The negative results of Binax should be interpreted with caution and confirmed by rapid molecular tests.

This study aimed to identify differentially expressed non-coding RNAs (ncRNAs) associated with preterm birth (PTB) and determine biological pathways being influenced in the context of PTB. We processed cell-free RNA sequencing data and identified seventeen differentially expressed (DE) ncRNAs that could be involved in the onset of PTB. Per the validation via customized RT-qPCR, the recorded variations in expressions of eleven ncRNAs were concordant with the in-silico analyses. The results of this study provide insights into the role of DE ncRNAs and their impact on pregnancy-related biological pathways that could lead to PTB. Further studies are required to elucidate the precise mechanisms by which these DE ncRNAs contribute to adverse pregnancy outcomes (APOs) and their potential as diagnostic biomarkers.

Objective: To determine the frequency of symptomatic osteoarthritis in general population of Karachi presenting with joint pain. Introduction: People easily get tired due to heavy duty occupations to keep pace with the society. Arthralgia commonly called as “Joint pain” is one of the most frequently observed complain, especially in individuals aged 50 above. Methods: A cross-sectional study was conducted at Jinnah Postgraduate Medical Centre (JPMC) from 1st November 2013 to 25th November 2013. The data was collected from 316 patients presenting to the department of rheumatology and orthopedics with joint pain. A structured questionnaire was designed based on the clinical symptomatology of osteoarthritis. It was administered to the participants aged above 18 yrs. old. 17.7% of males and 82.3% of females participated in the study. Result: Out of 316 patients with joint pain, 71.2% (n=225) were diagnosed osteoarthritis on the basis of symptoms present with a high prevalence in females than males. The most common joints to be involved in osteoarthritis were found to be knee joint (90.2%) and hip joint (55.7%). The majority of the patients (n=109) had an X-ray of their joint and n=125 was getting analgesics as an effective therapy for osteoarthritis. Conclusion: The frequency of osteoarthritis is increasing in Karachi with globalization due to high level occupational stress along with recreational activity stress and other contributive factors. Female predominance as compare to that of man is quite alarming that needs to be controlled for maintaining future quality of life and providing ease for daily activities.

Summary: Background: Optimum management of childhood diarrhoea in low-resource settings has been hampered by insufficient data on aetiology, burden, and associated clinical characteristics. We used quantitative diagnostic methods to reassess and refine estimates of diarrhoea aetiology from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study. Methods: We re-analysed stool specimens from the multisite MAL-ED cohort study of children aged 0–2 years done at eight locations (Dhaka, Bangladesh; Vellore, India; Bhaktapur, Nepal; Naushero Feroze, Pakistan; Venda, South Africa; Haydom, Tanzania; Fortaleza, Brazil; and Loreto, Peru), which included active surveillance for diarrhoea and routine non-diarrhoeal stool collection. We used quantitative PCR to test for 29 enteropathogens, calculated population-level pathogen-specific attributable burdens, derived stringent quantitative cutoffs to identify aetiology for individual episodes, and created aetiology prediction scores using clinical characteristics. Findings: We analysed 6625 diarrhoeal and 30 968 non-diarrhoeal surveillance stools from 1715 children. Overall, 64·9% of diarrhoea episodes (95% CI 62·6–71·2) could be attributed to an aetiology by quantitative PCR compared with 32·8% (30·8–38·7) using the original study microbiology. Viral diarrhoea (36·4% of overall incidence, 95% CI 33·6–39·5) was more common than bacterial (25·0%, 23·4–28·4) and parasitic diarrhoea (3·5%, 3·0–5·2). Ten pathogens accounted for 95·7% of attributable diarrhoea: Shigella (26·1 attributable episodes per 100 child-years, 95% CI 23·8–29·9), sapovirus (22·8, 18·9–27·5), rotavirus (20·7, 18·8–23·0), adenovirus 40/41 (19·0, 16·8–23·0), enterotoxigenic Escherichia coli (18·8, 16·5–23·8), norovirus (15·4, 13·5–20·1), astrovirus (15·0, 12·0–19·5), Campylobacter jejuni or C coli (12·1, 8·5–17·2), Cryptosporidium (5·8, 4·3–8·3), and typical enteropathogenic E coli (5·4, 2·8–9·3). 86·2% of the attributable incidence for Shigella was non-dysenteric. A prediction score for shigellosis was more accurate (sensitivity 50·4% [95% CI 46·7–54·1], specificity 84·0% [83·0–84·9]) than current guidelines, which recommend treatment only of bloody diarrhoea to cover Shigella (sensitivity 14·5% [95% CI 12·1–17·3], specificity 96·5% [96·0–97·0]). Interpretation: Quantitative molecular diagnostics improved estimates of pathogen-specific burdens of childhood diarrhoea in the community setting. Viral causes predominated, including a substantial burden of sapovirus; however, Shigella had the highest overall burden with a high incidence in the second year of life. These data could improve the management of diarrhoea in these low-resource settings. Funding: Bill & Melinda Gates Foundation.

Summary: Background: Enteropathogen infections in early childhood not only cause diarrhoea but contribute to poor growth. We used molecular diagnostics to assess whether particular enteropathogens were associated with linear growth across seven low-resource settings. Methods: We used quantitative PCR to detect 29 enteropathogens in diarrhoeal and non-diarrhoeal stools collected from children in the first 2 years of life obtained during the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite cohort study. Length was measured monthly. We estimated associations between aetiology-specific diarrhoea and subclinical enteropathogen infection and quantity and attained length in 3 month intervals, at age 2 and 5 years, and used a longitudinal model to account for temporality and time-dependent confounding. Findings: Among 1469 children who completed 2 year follow-up, 35 622 stool samples were tested and yielded valid results. Diarrhoeal episodes attributed to bacteria and parasites, but not viruses, were associated with small decreases in length after 3 months and at age 2 years. Substantial decrements in length at 2 years were associated with subclinical, non-diarrhoeal, infection with Shigella (length-for-age Z score [LAZ] reduction −0·14, 95% CI −0·27 to −0·01), enteroaggregative Escherichia coli (−0·21, −0·37 to −0·05), Campylobacter (−0·17, −0·32 to −0·01), and Giardia (−0·17, −0·30 to −0·05). Norovirus, Cryptosporidium, typical enteropathogenic E coli, and Enterocytozoon bieneusi were also associated with small decrements in LAZ. Shigella and E bieneusi were associated with the largest decreases in LAZ per log increase in quantity per g of stool (−0·13 LAZ, 95% CI −0·22 to −0·03 for Shigella; −0·14, −0·26 to −0·02 for E bieneusi). Based on these models, interventions that successfully decrease exposure to Shigella, enteroaggregative E coli, Campylobacter, and Giardia could increase mean length of children by 0·12–0·37 LAZ (0·4–1·2 cm) at the MAL-ED sites. Interpretation: Subclinical infection and quantity of pathogens, particularly Shigella, enteroaggregative E coli, Campylobacter, and Giardia, had a substantial negative association with linear growth, which was sustained during the first 2 years of life, and in some cases, to 5 years. Successfully reducing exposure to certain pathogens might reduce global stunting. Funding: Bill & Melinda Gates Foundation.

Background: Non-anemic iron deficiency precedes iron deficiency anaemia and has an estimated prevalence of 1-2 billion worldwide. Few studies have comprehensively researched the idea of treating non-anemic iron deficiency (NAID) with iron to improve the outcome of the mother and the offspring. Methods and Analysis: FAIR will be a multicenter randomized controlled trial that will be conducted in multiple clinical academic obstetrics units in Lahore (including Services Institute of Medical Sciences, Lahore, Allama Iqbal Medical College, Lahore and Fatima Jinnah Medical University). Pregnant women at gestational age <20 weeks with hemoglobin 11-13 g/L and ferritin below the threshold (<30 ng/ml) will be invited to take part in the study. Randomization will be done by computer based generated random numbers. One group (usual care or oral group) will be offered routine care prophylactic dose of oral iron (30-45 mg/day) and the other group (intervention arm or IV group) will be offered therapeutic dose of IV iron (dose calculated by Ganzoni formula) in addition to usual care. All patients will be followed up till delivery. Primary maternal outcome will be hemoglobin at 36 weeks’ gestation. Secondary outcomes are fetal birthweight or small for gestational age, preterm birth, preeclampsia, multidimensional fatigue inventory, breast feeding initiation, blood transfusion, and fetal cord ferritin and hemoglobin. Discussion: The study will generate evidence as to whether screening serum ferritin in non-anemic pregnant women and replenishing their iron stores will likely reduce the rate of predelivery anemia in pregnant women, improve birthweight and preventing perinatal complications. Roles and responsibilities: Tayyiba Wasim is principal Investigator and other members of data management team are Natasha Bushra, Shamsa Humayoun, Khalid Saeed Khan, Fatima Shehbaz, Saba Rasool, Anam Riaz and Sonia Irshad. Principal investigator will assume the full responsibility of Fair trial including training of research assistants, administration of informed consent and protecting participants confidentiality. Data management team will help in the management, development and execution of trial. Khadija Irfan Khawaja is the operational lead for fair trial´s technology team comprising of Aziz Fatima and Zubia Zafar, responsible for gathering requirements from study teams and supporting the operational implementation of technology to drive the collection of high-quality study data. Protocol contributors are Gynae unit I of Services Institute of Medical Sciences/ Services hospital, Lahore, Gynae Unit II of Allama Iqbal Medical College/ Jinnah hospital, Lahore and Gynae unit 1 of Fatima Jinnah Medical College/ Sir Ganga Ram hospital, Lahore. These coordinating centres will recruit patients (sample size=600) and will discuss their progress in trial management meetings quarterly. Steering committee has an independent chair Prof Samia Malik, one expert member Prof Faiza Bashir and Ms Neelam to represent patients, public and consumers. Trial steering committee with independent chair and member with a patient representative will oversee the study. Chair of steering committee has the authority to stop the trial whenever needed in case of positive or negative results. Steering committee meetings will be held on annual basis. Independent Data monitoring committee comprises of Dr. Shehnoor Azhar as chair and Prof Ejaz Hussain and Dr. Shehla Javed Akram as members. Data monitoring committee will assess the progress, data safety and if needed critical efficacy points of the clinical study and will show their results quarterly in data interim meetings. The committee will focus on integrity of the whole process and compliance of all sites with all aspects of the protocol. It will perform confidential interim analyses quarterly, which may be used to determine if an effect` is observed and if the study should continue to its planned sample size. Data monitoring committee will report to the Chair of the steering committee. [ABSTRACT FROM AUTHOR]