Amplicon-Based Nanopore Sequencing of Patients Infected by the SARS-CoV-2 Omicron (B.1.1.529) Variant in India.

We report the sequencing of SARS-CoV-2 Omicron variants from 75 patients, using nanopore long-read sequencing chemistry. These data show a range of mutations in spike glycoprotein that are both unique and common to other populations.

Aminoacid Profiling of Children with Severe Acute Malnutrition Pre and Post Nutritional Rehabilitation.

Malnutrition is a significant comorbidity in nearly one-third of the 8 million deaths in children under five years of age worldwide. Children with severe acute malnutrition have severely disturbed physiology and metabolism. Considering the vital importance of amino acids and the likely changes with the therapeutic diet, we aimed at evaluating these changes in children with SAM at baseline and after rehabilitation with a therapeutic diet at 14 days. Severe acute malnutrition defined as per WHO, for children between 6 months and 5 years with weight for height/length < -3SD of WHO charts, bilateral pitting edema, and mid-upper arm circumference (MUAC) < 1.5 cm. A total of 38 children were enrolled as cases, whereas the control group comprised of 37 children. Anthropometric measurement and estimation of amino acids in the blood were done at the baseline and after dietary rehabilitation. The individual levels of the essential and non-essential amino acids were significantly lower in the cases as compared to the controls, except for Aspartate and Threonine. The levels of amino acids increased significantly after dietary rehabilitation except for arginine, however not to the levels of those in controls. Most of the metabolites were reflective of maladaptation in SAM. Though nutritional rehabilitation of children with SAM improved the levels of amino acids, these levels were still low when compared to the controls, stipulating that complete metabolic recovery may take a longer duration of time. This necessitates the continuation of nutritional rehabilitation for a longer time and regular follow up of these children to ensure better compliance.

Evaluation of the Utility of Amino Acid Citrulline as a Surrogate Metabolomic Biomarker for the Diagnosis of Celiac Disease.

INTRODUCTION: Citrulline is regarded as a biomarker for celiac disease (CD). Its utility for assessment and evaluation of additive predictive value for latent, potential CD and first degree relatives (FDRs) needs exploration. METHOD: Consecutive 558 index cases diagnosed as per European Society for Pediatric Gastroenterology and Nutrition (ESPGHAN) 2012 guidelines and their 1565 FDRs were evaluated over five and half year period. Serology negative FDRs at initial visit and follow ups were served as controls. HLA typing for DQ2 and DQ8 genotypes, along with plasma and dried blood spot (DBS) filter paper citrulline were evaluated. RESULTS: Median plasma citrulline values were 20.1 and 37.33 µMol/l in cases and controls (P < .001). Cut off values for Marsh grade 3a, 3b, and 3c were 35.0, 32.8, 25.26 µMol/l in CD patients and 36.51, 30.10, 25.26 µMol/l in biopsy proven FDR. Increasing trends of plasma citrulline levels with decreasing tTG-IgA levels were observed on follow up. Low plasma citrulline levels were observed with HLA DQ 2.5 genotype (P < .05). Agreement between DBS and plasma citrulline was 94.8%. CONCLUSION: Citrulline is a good surrogate biomarker for identification of histopathological grade of damage, extent of mucosal recovery and has negative correlation with tTG-IgA. It identifies the silent and latent phase of CD. DBS citrulline provides adequate information and can be used for monitoring CD patients at remote locations.

Mapping of the benzoate metabolism by human gut microbiome indicates food-derived metagenome evolution.

Sodium benzoate is one of the widely used food preservatives and its metabolism in the human body has been studied only with the host perspective. Despite the human gut microbiome being considered as a virtual human organ, its role in benzoate metabolism is yet to be elucidated. The current study uses a multi-omic approach to rationalize the role of human gut microbes in benzoate metabolism. Microbial diversity analysis with multiple features synchronously indicates the dominance of Bacteroidetes followed by Firmicutes, Actinobacteria, and Proteobacteria. Metagenomic exploration highlights the presence of benzoate catabolic protein features. These features were mapped on to the aerobic and anaerobic pathways of benzoate catabolism. Benzoate catabolism assays identified statistically significant metabolites (P < 0.05) associated with the protocatechuate branch of the beta-ketoadipate pathway of the benzoate metabolism. Analysis of the 201 human gut metagenomic datasets across diverse populations indicates the omnipresence of these features. Enrichment of the benzoate catabolic protein features in human gut microbes rationalizes their role in benzoate catabolism, as well as indicates food-derived microbiome evolution.

Coeliac disease presenting atypically: A much wider spectrum.

Atypical coeliac disease in young children is frequently missed when it presents atypically as non-gastrointestinal presentations to different specialties. There was a greater delay (54 months) in establishing the diagnosis in those with atypical coeliac disease (p < 0.001). No difference was observed in the mode of delivery or duration of breast feeding, but significant difference was observed between gestational age at birth (p < 0.001). Most cases showed stunted growth and underweight. Irritability, anaemia, rickets, dermatitis herpetiformis, alopecia and intussusception were other common predictors of atypical coeliac disease. Because of a myriad spectrum of non-gastrointestinal symptoms, at any age with diverse presentation, a high index of suspicion is therefore required.

A prospective study of catch-up growth among Indian children with celiac disease.

OBJECTIVES: The study was done to investigate the response of the gluten-free diet (GFD) on growth and other biochemical parameters in newly diagnosed children with celiac disease (CD). We also determined the association of Marsh biopsy classification and the response in haematological parameters among the children with GFD over the follow-up time. METHODS: A prospective observational study was conducted for 1.5 years where children aged 1-10 years with newly confirmed CD (as per Marsh classification) without pre-existing chronic disease were enrolled. Individual anthropometry, biochemical and haematological parameters were recorded on enrolment and compared with 1, 3 and 6 months (follow-up) after initiating GFD (as per World Health Organization growth charts). STATISTICAL ANALYSIS: The data were entered in MS Excel spreadsheet and analysis was done using Statistical Package for Social Sciences version 21.0. A P value of < 0.05 was considered significant. RESULTS: A total of 51 (out of 55) children with CD completed 6-month follow-up. A significant improvement in the growth and biochemical parameters was seen at 6-month follow-up with the GFD (P < 0.05). There was a significantly decreasing Hb (at enrolment and at 3 months) with increasing Marsh biopsy grade-it was significantly less with Marsh 3C and more with Marsh 3A. A significantly better %Hb improvement was seen in children with Marsh biopsy 3C as compared to 3A and 3B (P < 0.05). We found no significant association of Marsh biopsy with Malabsorption, type of anaemia and Serum ferritin levels (P > 0.05). CONCLUSIONS: GFD showed significant improvement in the growth and development of the child with a significant reduction in anaemia at 6 months. With increasing grade of Marsh biopsy, the severity of anaemia increases but after the initiation of GFD, such children show significantly better improvement in %Hb over time.

Reliability of coeliac serology in monitoring dietary adherence in children with coeliac disease on a gluten-free diet.

This study aimed to determine the utility of coeliac serology for monitoring dietary adherence in coeliac disease. Serum anti-tTg IgA and anti-DGP IgG levels of 42 newly diagnosed patients were measured at diagnosis and at intervals of three, six and 12 months after starting a gluten-free diet. Both anti-tTg and anti-DGP antibodies decreased in all patients. The decline in the former was significantly greater at 3-12 months throughout, while in the latter the decline was seen only at three months but not subsequently. Serial measurement of coeliac serology may help in monitoring adherence to a gluten-free diet.

Evaluation of the impact of celiac disease and its dietary manipulation on children and their caregivers.

BACKGROUND: Lifelong dietary abstinence of gluten is the only treatment available for celiac disease. This is not only challenging but also leads to several psychosocial morbidities and affects the quality of life of children and their parents. METHODS: An observational study was conducted on 50 children (5-18 years) diagnosed with celiac disease on gluten-free diet for at least 6 months and their parents to evaluate of the impact of celiac disease and its dietary manipulation on them. The quality of life was assessed by applying celiac disease-specific questionnaire. Dietary compliant and noncompliant groups were compared to assess the factors leading to poor compliance. Anthropometric parameters were utilized to ascertain clinical response. RESULTS: Fifty children with a mean age of 9.06 years were enrolled. Seventy-four percent of the children were compliant. In the compliant group, height and weight correlated with dietary compliance (p = 0.0087 and p = 0.023). Dietary compliance was found to be better in adolescent males and single child and those living in nuclear families. Quality of life was found to be higher among parents of noncompliant children (quality of life score: 63) as compared to the compliant children (quality of life score: 59). The acceptance of celiac disease was better among children whose parents had a higher level of education. The scale diet proved to be a useful indicator for evaluating compliance among children (p = 0.0036). CONCLUSIONS: Noncompliance to gluten-free diet was noted in 24 % of children with celiac disease.

Clinical, Biochemical and Outcome Profile of Biotinidase Deficient Patients from Tertiary Centre in Northern India.

INTRODUCTION: Biotinidase deficiency is an inherited metabolic disorder with estimated birth incidence of 1 in 61,000 for profound and partial deficiency. Estimated incidence of profound and partial biotinidase deficiency is 1 in 1, 37,000 and 1 in 1, 10,000 respectively. The carrier frequency in general population is 1 in 120. We attempt to study clinical, biochemical and outcome from 10 Biotinidase deficient patients. MATERIALS AND METHODS: A retrospective case record study was conducted to record Clinical, biochemical and outcome profile from genetic records. Biotinidase level was measured using spectrophotometric method. RESULTS: Study group comprised of 8 males and 2 females with median age of presentation 6 (2-45.75) months. Median (interquartile range) Biotinidase level in study group 0.3 (0.08-1.5) nmol/ml/min. Study group was further divided in to early onset group (< 12 months, n-6) and late onset group (> 12 months, n-4). Seizure, alopecia and hearing loss were predominant phenotypes in study group. The other rare presentations were: hypotonia, ataxia, skin rash, seborrhoea. The most common seizure type was focal seizure. Control of seizure activity was important immediate outcome measured in study group. Median duration (interquartile range) of seizure control in early onset group was 3 (2-4)days against 13.5 (12.25-14.75) days in late onset group. CONCLUSION: This study highlights the need of early diagnosis for favourable outcome for a potentially treatable inherited metabolic disorder.

Clinical and histopathological correlation of duodenal biopsy with IgA anti-tissue transglutaminase titers in children with celiac disease.

BACKGROUND: Data correlating anti-tissue transglutaminase (tTG) antibody titers with severity of duodenal involvement is limited. OBJECTIVE: The aim of this study was to correlate IgA anti-tTG antibody titers with symptoms, anthropometric parameters, and duodenal histopathology. METHODS: Consecutively diagnosed patients of celiac disease as per modified ESPGHAN criteria presenting over a year were enrolled. Demographic data, symptoms, weight-for-age z score (WAZ), height-for-age z score (HAZ), IgA anti-tTG titer, and duodenal histopathology graded as per modified Marsh criteria were recorded. Spearman rank correlation test was used for association between TTG age, WAZ, and HAZ. Receiver operating curve (ROC), sensitivity, specificity, negative predictive value, and positive predictive value were used to obtain anti-tTG cutoff value predictive of Marsh grade 3. RESULTS: One hundred and forty-two patients with celiac disease were evaluated. tTG showed significant correlation with WAZ (r = 0.822, p = <0.001) and HAZ (r = 0.722, p = <0.001) but not with age (r = 0.202, p = 0.066). The median anti-tTG titers rose progressively with higher Marsh grade on histopathology (p = 0.001). The median anti-tTG titer was also significantly higher in patients with classic celiac disease as compared to non-diarrheal celiac disease (144 u/mL vs. 27, p = 0.02). Anti-tTG titer of 62.5 u/mL was strongly predictive of duodenal histology of Marsh grade 3a and higher with sensitivity, specificity, positive predictive value, and negative predictive value of 95.4 %, 98 %, 93.8 %, and 88.3 % respectively. CONCLUSIONS: There is a significant correlation between IgA anti-tTG titers and anthropometric parameters and severity of duodenal histopathology. With further validation, strongly positive titers may be sufficient to predict severity of this disease.