Residual blood specimens provide a sample repository that could be analyzed to estimate and track changes in seroprevalence with fewer resources than household-based surveys. We conducted parallel facility and community-based cross-sectional serological surveys in two districts in India, Kanpur Nagar District, Uttar Pradesh, and Palghar District, Maharashtra, before and after a measles-rubella supplemental immunization activity (MR-SIA) from 2018 to 2019. Anonymized residual specimens from children 9 months to younger than 15 years of age were collected from public and private diagnostic laboratories and public hospitals and tested for IgG antibodies to measles and rubella viruses. Significant increases in seroprevalence were observed following the MR SIA using the facility-based specimens. Younger children whose specimens were tested at a public facility in Kanpur Nagar District had significantly lower rubella seroprevalence prior to the SIA compared to those attending a private hospital, but this difference was not observed following the SIA. Similar increases in rubella seroprevalence were observed in facility-based and community-based serosurveys following the MR SIA, but trends in measles seroprevalence were inconsistent between the two specimen sources. Despite challenges with representativeness and limited metadata, residual specimens can be useful in estimating seroprevalence and assessing trends through facility-based sentinel surveillance.

The diagnosis of functional constipation (FC) relies on patient-reported outcomes evaluated as criteria based on the clustering of symptoms. Although the ROME IV criteria for FC diagnosis is relevant for a multicultural population(1), how an individual’s lifestyle, environment and culture may influence the pathophysiology of FC remains a gap in our knowledge. Building on insights into mechanisms underpinning disorders of gut-brain interactions (formerly functional gastrointestinal disorders) in the COMFORT Cohort(2), this study aimed to investigate the differences in gastrointestinal (GI) symptom scores among participants with FC in comparison to healthy controls between Chinese and non-Chinese New Zealanders. The Gastrointestinal Understanding of Functional Constipation In an Urban Chinese and Urban non-Chinese New Zealander Cohort (GUTFIT) study was a longitudinal cohort study, which aimed to determine a comprehensive profile of characteristics and biological markers of FC between Chinese and non-Chinese New Zealanders. Chinese (classified according to maternal and paternal ethnicity) or non-Chinese (mixed ethnicities) adults living in Auckland classified as with or without FC based on ROME IV were enrolled. Monthly assessment (for 3 months) of GI symptoms, anthropometry, quality of life, diet, and biological samples were assessed monthly over March to June 2023. Demographics were obtained through a self-reported questionnaires and GI symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS) and Structured Assessment of Gastrointestinal Symptoms Scale (SAGIS). This analysis is a cross-sectional assessment of patient-reported outcomes of GI symptoms. Of 78 enrolled participants, 66 completed the study (male, n = 10; female, n = 56) and were distributed across: Chinese with FC (Ch-FC; n = 11), Chinese control (Ch-CON; n = 19), non-Chinese with FC (NCh-FC; n = 16), non-Chinese control (NCh-CON; n = 20). Mean (SD) age, body mass index, and waist circumference were 40 ± 9 years, 22.7 ± 2.5 kg/m2, and 78.0 ± 7.6 cm, respectively. Ethnicity did not impact SAGIS domain scores for GI symptoms (Ethnicity x FC severity interaction p>0.05). Yet, the constipation symptoms domain of the GSRS was scored differently depending on ethnicity and FC status (Ethnicity x FC interaction p<0.05). In post hoc comparison, NCh-FC tended to have higher GSRS constipation severity scores than Ch-FC (3.4 ± 1.0 versus 3.8 ± 0.8 /8, p<0.1) Although constipation symptom severity tended to be higher in NCh-FC, on the whole, ethnicity did not explain variation in this cohort. FC status was a more important predictor of GI symptoms scores. Future research will assess differences in symptom burden to explore ethnicity-specific characteristics of FC.

Distinct pathophysiology has been identified with disorders of gut-brain interactions (DGBI), including functional constipation (FC)(1,2), yet the causes remain unclear. Identifying how modifiable factors (i.e., diet) differ depending on gastrointestinal health status is important to understand relationships between dietary intake, pathophysiology, and disease burden of FC. Given that dietary choices are culturally influenced, understanding ethnicity-specific diets of individuals with FC is key to informing appropriate symptom management and prevention strategies. Despite distinct genetic and cultural features of Chinese populations with increasing FC incidence(3), DGBI characteristics are primarily described in Caucasian populations(2). We therefore aimed to identify how dietary intake of Chinese individuals with FC differs to non-Chinese individuals with FC, relative to healthy controls. The Gastrointestinal Understanding of Functional Constipation In an Urban Chinese and Urban non-Chinese New Zealander Cohort (GUTFIT) study was a longitudinal case-control study using systems biology to investigate the multi-factorial aetiology of FC. Here we conducted a cross-sectional dietary intake assessment, comparing Chinese individuals with FC (Ch-FC) against three control groups: a) non-Chinese with FC (NCh-FC) b) Chinese without FC (Ch-CON) and c) non-Chinese without FC (NCh-CON). Recruitment from Auckland, New Zealand (NZ) identified Chinese individuals based on self-identification alongside both parents self-identifying as Chinese, and FC using the ROME IV criteria. Dietary intake was captured using 3-day food diaries recorded on consecutive days, including one weekend day. Nutrient analysis was performed by Foodworks 10 and statistical analysis with SPSS using a generalised linear model (ethnicity and FC status as fixed factors). Of 78 enrolled participants, 66 completed the study and 64 (39.4 ± 9.2 years) completed a 3-day food diary at the baseline assessment. More participants were female (84%) than male (16%). FC and ethnicity status allocated participants into 1 of 4 groups: Ch-FC (n = 11), Ch-CON (n = 18), NCh-FC (n = 16), NCh-CON (n = 19). Within NCh, ethnicities included NZ European (30%), non-Chinese Asian (11%), Other European (11%), and Latin American (2%). Fibre intake did not differ between Ch-FC and NCh-FC (ethnicity × FC status interaction p>0.05) but was independently lower overall for FC than CON individuals (21.8 ± 8.7 versus 27.0 ± 9.7 g, p<0.05) and overall for Ch than NCh (22.1 ± 8.0 versus 27.0 ± 10.4 g, p<0.05). Carbohydrate, protein, and fat intakes were not different across groups (p>0.05 each, respectively). In the context of fibre and macronutrient intake, there is no difference between Ch-FC and NCh-FC. Therefore, fibre and macronutrients are unlikely to contribute to potential pathophysiological differences in FC between ethnic groups. A more detailed assessment of dietary intake concerning micronutrients, types of fibre, or food choices may be indicated to ascertain whether other dietary differences exist.

Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.

Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.

Introduction: Individualizing risk for stroke following a transient ischemic attack (TIA) is a topic of intense research, as existing scores are context-dependent or have not been well validated. The Canadian TIA Score stratifies risk of subsequent stroke into low, moderate and high risk. Our objective was to prospectively validate the Canadian TIA Score in a new cohort of emergency department (ED) patients. Methods: We conducted a prospective cohort study in 14 Canadian EDs over 4 years. We enrolled consecutive adult patients with an ED visit for TIA or nondisabling stroke. Treating physicians recorded standardized clinical variables onto data collection forms. Given the ability of prompt emergency carotid endarterectomy (CEA) to prevent stroke (NNT = 3) in high risk patients, our primary outcome was the composite of subsequent stroke or CEA ≤7 days. We conducted telephone follow-up using the validated Questionnaire for Verifying Stroke Free Status at 7 and 90 days. Outcomes were adjudicated by panels of 3 local stroke experts, blinded to the index ED data collection form. Based on prior work, we estimated a sample size of 5,004 patients including 93 subsequent strokes, would yield 95% confidence bands of +/− 10% for sensitivity and likelihood ratio (LR). Our analyses assessed interval LRs (iLR) with 95% CIs. Results: We prospectively enrolled 7,569 patients with mean 68.4 +/−14.7 years and 52.4% female, of whom 107 (1.4%) had a subsequent stroke and 74 (1.0%) CEA ≤7 days (total outcomes = 181). We enrolled 81.2% of eligible patients; missed patients were similar to enrolled. The Canadian TIA Score stratified the stroke/CEA ≤7days risk as: Low (probability <0.2%, iLR 0.20 [95%CI 0.091-0.44]; Moderate (probability 1.3%, iLR 0.79 [0.68-0.92]; High (probability 2.6%, iLR 2.2 [1.9-2.6]. Sensitivity analysis for just stroke ≤7 days yielded similar results: Low iLR 0.17 [95%CI 0.056-0.52], Medium iLR 0.89 [0.75-1.1], High iLR 2.0 [1.6-2.4]. Conclusion: The Canadian TIA Score accurately identifies TIA patients risk for stroke/CEA ≤7 days. Patients classified as low risk can be safely discharged following a careful ED assessment with elective follow-up. Patients at moderate risk can undergo additional testing in the ED, have antithrombotic therapy optimized, and be offered early stroke specialist follow-up. Patients at high risk should in most cases be fully investigated and managed ideally in consultation with a stroke specialist during their index ED visit.

Influenza A(H1N1) viruses of the 2009 pandemic (A(H1N1)pdm09) continue to cause outbreaks in the post-pandemic period. During January to May 2015, an upsurge of influenza was recorded that resulted in high fatality in central India. Genetic lineage, mutations in the hemagglutinin (HA) gene and infection by quasi-species are reported to affect disease severity. The objective of this study is to present the molecular and epidemiological trends during the 2015 influenza outbreak in central India. All the referred samples were subjected to qRT–PCR for diagnosis. HA gene sequencing (23 survivors and 24 non-survivors) and cloning were performed and analyzed using Molecular Evolutionary Genomic Analyzer (MEGA 5·05). Of the 3625 tested samples, 1607 (44·3%) were positive for influenza A(H1N1)pdm09, of which 228 (14·2%) individuals succumbed to death. A significant trend was observed in positivity (P = 0·003) and mortality (P < 0·0001) with increasing age. The circulating A(H1N1)pdm09 virus was characterized as belonging to clade-6B. Clinically significant mutations were detected. Patients infected with the quasi-species of the virus had a greater risk of death (P = 0·009). This study proposes a robust molecular and clinical surveillance program for the detection and characterization of the virus, along with prompt treatment protocols to prevent outbreaks.

The Global Muon Detector Network (GMDN) is composed by four ground cosmic ray detectors distributed around the Earth: Nagoya (Japan), Hobart (Australia), Sao Martinho da Serra (Brazil) and Kuwait city (Kuwait). The network has operated since March 2006. It has been upgraded a few times, increasing its detection area. Each detector is sensitive to muons produced by the interactions of ~50 GeV Galactic Cosmic Rays (GCR) with the Earth′s atmosphere. At these energies, GCR are known to be affected by interplanetary disturbances in the vicinity of the earth. Of special interest are the interplanetary counterparts of coronal mass ejections (ICMEs) and their driven shocks because they are known to be the main origins of geomagnetic storms. It has been observed that these ICMEs produce changes in the cosmic ray gradient, which can be measured by GMDN observations. In terms of applications for space weather, some attempts have been made to use GMDN for forecasting ICME arrival at the earth with lead times of the order of few hours. Scientific space weather studies benefit the most from the GMDN network. As an example, studies have been able to determine ICME orientation at the earth using cosmic ray gradient. Such determinations are of crucial importance for southward interplanetary magnetic field estimates, as well as ICME rotation.

Rotavirus (RV) infection causes acute infantile diarrhoea in humans and animals and remains a major concern for vaccine development. The close proximity of humans to animals may foster cross-species infection resulting in the emergence of novel/unusual strains by genetic reassortment. In this study, we characterized 500 diarrhoeal samples for group A rotaviruses (RVA) from children (n = 290), piglets (n = 95) and calves (n = 115) in Northeast India during 2012–2013. The data showed that 142/500 (28·4%) faecal samples were positive for RVA with the highest level of infection detected in piglets (57/142, 40·1%) followed by children (51/142, 35·9%) and calves (34/142, 23·9%). Sequence-based G- and P-typing showed G1P[8] (25%) and G1P[7] (35%) were the prevailing genotypes in both humans and animals. Single cases of unusual genotypes, i.e. G9P[8], G5P[8] in humans and G1P[13], G1P[23] and G3P[7] in animals were also identified. Cluster analyses of the sequences showed regional strains were genetically closer to their homologous strains. However, human G5P[8] and porcine G1P[8] strains showed homology to heterologous hosts of their prototype strains. The subsequent global spread of unusual RV strains may result in their establishment over time, presenting challenges to future vaccine evaluation programmes. More studies on emerging genotypes are required to elucidate how RVA strains evolve post-vaccination. This study supports the need for continuous surveillance of RVA infections after detecting from diverse hosts in a common setting.

The collapse of South Asia's Gyps vulture populations is attributable to the veterinary use of the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Vultures died after feeding on carcasses of recently-medicated animals. The governments of India, Nepal and Pakistan banned the veterinary use of diclofenac in 2006. We analysed results of 62 necropsies and 48 NSAID assays of liver and/or kidney for vultures of five species found dead in India between 2000 and 2012. Visceral gout and diclofenac were detected in vultures from nine states and three species: Gyps bengalensis, Gyps indicus and Gyps himalayensis. Visceral gout was found in every vulture carcass in which a measurable level of diclofenac was detected. Meloxicam, an NSAID of low toxicity to vultures, was found in two vultures and nimesulide in five vultures. Nimesulide at elevated tissue concentrations was associated with visceral gout in four of these cases, always without diclofenac, suggesting that nimesulide may have similar toxic effects to those of diclofenac. Residues of meloxicam on its own were never associated with visceral gout. The proportion of Gyps vultures found dead in the wild in India with measurable levels of diclofenac in their tissues showed a modest and non-significant decline since the ban on the veterinary use of diclofenac. The prevalence of visceral gout declined less, probably because some cases of visceral gout from 2008 onwards were associated with nimesulide rather than diclofenac. Veterinary use of nimesulide is a potential threat to the recovery of vulture populations.