Vitamin D and its association with severity and control of childhood bronchial asthma.

Background: Bronchial asthma is a common disease in childhood. Vitamin D deficiency is a common unidentified nutritional deficiency. In spite of high prevalence, an association between the two has not been well understood. Objectives: Our study aimed to determine serum Vitamin D levels among asthmatic children and its association with clinical severity and level of control. Methods: A hospital-based cross-sectional study was conducted from 2017 to 2019 where 64 recurrent wheezers, classified into 6-15 years and the under 5 wheezers as per Global Initiative for Asthma guidelines, were included. The group of asthmatic children was comparable with respect to their demographic profiles with good adherence and proper inhaler use. Serum Vitamin D levels were estimated using an enzyme-linked immunosorbent assay and classified using the US Endocrine Society classification. Association between Vitamin D status and outcome variables was analyzed using Chi-square test, Fisher's exact test, unpaired t-test, and ANOVA. Results: Among the 64 wheezers, 29 (45.3%) had intermittent symptoms and 35 (54.7%) had persistent symptoms. Mean Vitamin D levels in the entire study population were in deficiency range (18.96 ng/ml ± 2.23). Persistent asthmatics had significantly lower Vitamin D levels (13.75 ng/ml) as compared to intermittent asthmatics (28.52 ng/ml). Those asthmatics who had hypovitaminosis D had higher rates of hospitalization (P = 0.048), increased use of rescue medications (P = 0.008), and poor symptom control (P = 0.001). Conclusions: Asthmatic children had a higher incidence of reduced Vitamin D levels showing a statistically significant association. There is also a significant association between Vitamin D level and poor symptom control, hospitalization for exacerbations, and requirement of rescue medication in asthmatic children.

Vitamin D levels and left ventricular function in beta-thalassemia major with iron overload.

Heart disease is the primary cause of death in patients with beta-thalassemia major. The study aimed to determine the association between vitamin D and left ventricular function in patients with beta-thalassemia major with iron overload. A cross-sectional hospital-based study was conducted, where the vitamin D and ferritin levels of children living with beta-thalassemia major were measured, and left ventricular function was assessed utilizing ejection fraction (EF) and fractional shortening (FS) using 2D echocardiography. The mean serum ferritin was 4622 ± 2289 ng/ml, and the mean serum vitamin D levels were 22 ± 7.7 ng/ml. The mean values of EF were 62.30 ± 6.9%, and FS was 31.21 ± 4.8%. Statistically significant negative correlation (r = -0.447, p < 0.001) was found between vitamin D and serum ferritin values, and a significant positive association was found between vitamin D levels concerning EF and FS with a p-value of 0.034 and 0.014, respectively.Conclusion: It was observed  that increasing ferritin was associated with lower vitamin D levels which in turn influenced fractional shortening /cardiac function in these patients.  What is Known: • Patients with Beta Thalassemia major on long term transfusion are prone to develop heart disease / cardiac failure due to chronic iron overload. What is New: • Patients with beta thalassemia major on long term term transfusions with iron overload who are vitamin D deficient are more prone to the cardiac complications which inturn can be prevented by vitamin D supplementation.

Perceptions of teachers towards COVID appropriate behaviors for school children in coastal South India.

COVID appropriate behavioral measures need to be followed once school reopens. School teachers being in the forefront could substantiate the feasibility of suggested safety measures. This study aimed to assess teachers' perceptions towards COVID appropriate behaviors for children with school reopening and compare their mean scores between public versus private schools and across school boards. We conducted an observational school-based study of teachers over two months. Perceptions were scored using a five-point Likert symmetric agree to disagree scale. Results were expressed as proportions and analyzed using an independent sample t-test. Of the 547 teachers surveyed, most (> 90%) agreed to the suggested social distancing and hygiene measures. There was a significant difference in perception scores between private versus public schools and across boards regarding i) reducing the academic syllabus, ii) adopting a cloud-based system to integrate online-offline learning, and iii) conducting meetings online. In addition, measures such as i) teaching classes on alternate days with a limited number of children, ii) arranging benches/desks to maintain six feet distance between students, iii) dealing with psychological stress by counselors, and iv) arrangement with local hospitals for medical services were significant statistically across school boards. To conclude, most schoolteachers agreed with the need for social distancing and hygiene measures for children. There was a significant difference in perceptions between public versus private schools and across boards regarding academic syllabus, integration of online-offline student learning, number of children per class, the timing of classes, student seating arrangement, and medical/psychological guidance availability.

Clinical and Genetic Spectrum of Inborn Errors of Immunity in a Tertiary Care Center in Southern India.

OBJECTIVES: To study the incidence, clinical manifestations, and genetic spectrum of primary immunodeficiency diseases (PID)/inborn errors of immunity (IEI) in a tertiary care hospital in Southern India. METHODS: A retrospective analysis of all patients with a clinical suspicion of PID/IEI seen at a tertiary care hospital was performed. All patients had at least one or more warning signs of PID. Serum immunoglobulin levels and other targeted investigations were performed as warranted by the clinical presentation. All families with suspected PID were counseled and offered genetic testing. RESULTS: A total of 225 children were evaluated for PID during the study period of 6 y. Fifty-six of them did not meet the European Society of Immunodeficiencies (ESID) criteria (working definition of clinical diagnosis) and were excluded. An IEI was found in 30/49 (61.2%) patients. The most frequent reason for referral was recurrent/unusual or serious infections (28%), or cytopenia (16%). Group IV diseases of immune dysregulation was the most common category (19%), followed by group III predominant antibody deficiencies in 23/163 (14%), as per the International Union of Immunological Societies (IUIS) classification. CONCLUSIONS: This study highlights the heterogeneity of the present cohort, the underuse of genetic tests, and efforts to provide optimal care for children with possible IEI in this center.

Auditory Brainstem Response in Children with Thalassemia Major under Chelating Therapy.

The present study compared the Auditory Brainstem Response (ABR) of children with thalassemia major and typically developing children. A total of 16 children participated in this study. Group I included 8 children with thalassemia major regularly undergoing blood transfusions and chelating therapy. Group II included 8 age and gender-matched typically developing children. All children in both groups had hearing sensitivity within normal limits. The Auditory Brainstem Response (ABR) was recorded monaurally for click stimuli from both ears. Results showed that the mean latencies of peaks of ABR were similar in both groups. The mean peak amplitude of peaks I and V of the ABR were different between groups, but it was not statistically significant. The present study showed no abnormality in the latency and amplitude of peaks of the ABR in children with thalassemia major with hearing sensitivity within normal limits.

Hypovitaminosis D and Parathyroid Hormone Response in Critically Ill Children with Sepsis: A Case-control Study.

Background: Critically ill Indian children have a higher prevalence of vitamin D deficiency. However, there is not much data available on the subgroup with sepsis. It has been reported that there is an impaired response of parathyroid hormone (PTH) to vitamin D deficiency in critically ill children and adults. Hence, we also sought to analyze the PTH response to vitamin D among the subgroup of critically ill children with sepsis. Patients and methods: Vitamin D and PTH levels of 84 critically ill children with sepsis (cases) and 84 controls were compared between November 2018 and February 2020. Hypovitaminosis D was defined as levels <30 ng/mL. Results: The median (IQR) of vitamin D for cases was 26 (21.30-29.95) ng/mL and that for controls 39.3 (33.65-50.2) ng/mL; p <0.001. Cases had a higher prevalence of hypovitaminosis D as compared to controls (79.7 vs 9.5%; p <0.001). Among the cases, mortality was 24.6% in the 65 children with hypovitaminosis D and 10.5% in those with sufficient vitamin D; the differences were not statistically significant (p = 0.339). There were no significant differences in the duration of pediatric intensive care unit (PICU) stay, serum calcium, PTH, and disease severity among the aforementioned groups. Out of the 65 children with hypovitaminosis D, only 9 (13.8%) were PTH responders. There were no statistically significant differences in mortality, the PICU stay, or disease severity at admission between PTH responders and nonresponders. Conclusions: Hypovitaminosis D was more prevalent among critically ill children with sepsis compared to controls. Parathyroid gland response to hypovitaminosis D was impaired in children with sepsis. How to cite this article: Kubsad P, Ravikiran SR, Bhat KG, Kamath N, Kulkarni V, Manjrekar PA, et al. Hypovitaminosis D and Parathyroid Hormone Response in Critically Ill Children with Sepsis: A Case-control Study. Indian J Crit Care Med 2021;25(8):923-927.

A Delphi survey based construction and validation of test for oropharyngeal dysphagia in Indian neonates.

BACKGROUND: SLPs have a crucial need to depend on comprehensive clinical swallowing assessments to determine the presence of dysphagia in neonates. A comprehensive clinical swallowing assessment that is ethnoculturally sensitive may help to identify the presence and severity of swallowing problems in neonates. OBJECTIVE: The study aimed to construct and validate the contents of a test for oropharyngeal dysphagia in Indian neonates (TOD-IN). METHOD: The test for oropharyngeal dysphagia in Indian neonates (TOD-IN) was developed using the Delphi process. Five expert panelists served as participants; two rounds of electronic questionnaire-based survey was carried out to develop and validate the contents of TOD-IN. RESULTS: Round one rendered descriptive data that was analyzed quantitatively and qualitatively. At the end of round one, panelists unequivocally agreed on the need for research to develop a validated assessment tool for dysphagia in Indian neonates. The second round dealt with establishing the face and content validity of the final version of TOD-IN. A unanimous consensus was obtained regarding the format, scoring system, and the construct of the final version of the tool. CONCLUSION: Practicing clinicians in India are met with several challenges such as resource constraints, limited infrastructure, increasing caseload, and a lack of trained workforce. We believe that inexperienced clinicians will benefit from the structured guidance provided by TOD-IN in a restrained resource context where prioritization of patients is the key. Further studies investigating the psychometric properties of TOD-IN are in progress.

Resource limited centres can deliver treatment for children with acute lymphoblastic leukaemia with risk-stratified minimal residual disease based UKALL 2003 protocol with no modification and a good outcome.

OBJECTIVES: Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in children. With improved supportive care and a better understanding of the disease biology, it is now a curable cancer in the developed world. However, in low-income countries, the cure rate remains relatively poor. We report our experience on the survival of children with ALL treated on the MRD-based risk-stratified UKALL 2003 protocol, from a center in South India. METHODS: All consecutive children diagnosed with ALL between years 2013 and 2019 were included in this retrospective study. All received uniform treatment as per the UKALL 2003 protocol based on NCI risk and post-induction MRD status. All the details including the type of leukemia, NCI risk status, date of diagnosis, treatment start date, the regimen, MRD status, cytogenetics, molecular genetics, and complications were captured. Analysis was done using prism GraphPad version 8.0. RESULTS: A total of 107 children were started on treatment during this period. The majority of them were boys (68/107). Fifty-nine of them were NCI standard risk (55%). B-ALL was the most common type (92%).Total of 56/107(52.3%) children received treatment under the government's insurance scheme for low-income bracket. The post-induction MRD was performed in 95/107 children. It was >0.01% in 22% (21/95) of children. Five (4.7%) children relapsed so far with a mean follow up of 27 months from the diagnosis. There were 17 deaths (15.9%). The EFS at 3 years was 85% (95% CI 75% to 92%). CONCLUSION: It is feasible to deliver chemotherapy as per the UKALL2003 protocol without any modifications in resource-limited setting. The survival rates have significantly improved over the years in our center from 5 years EFS of 60% in 2010 and now to 3 year EFS of 85%. It is important to note that there was no treatment abandonment in our cohort.

Modified Sick Neonatal Score (MSNS): A Novel Neonatal Disease Severity Scoring System for Resource-Limited Settings.

Neonatal disease severity scoring systems are needed to make standardized comparison between performances of different units and to give prognostic information to parents of individual babies admitted. Existing scoring systems are unsuitable for resource-limited settings which lack investigations like pH, pO2/FiO2 ratio, and base excess. This study was planned to evaluate Modified Sick Neonatal Score (MSNS), a novel neonatal disease severity score designed for resource-constrained settings. It was a facility-based cross-sectional analytical study, conducted in the "Special Newborn Care Unit" (SNCU) of government district hospital, attached to Kasturba Medical College, Mangalore, India from November 2016 to October 2017. A convenience sample of 585 neonates was included. Disease severity was assessed immediately at admission using MSNS. MSNS had 8 parameters with 0, 1, and 2 scores for each. 41% of study population was preterm (n=240), and 84.1% had birth weight less than 2500 grams (n=492). The mean (SD) of the total MSNS scores for neonates who expired and discharged was, respectively, 8.22 (2.96) and 13.4 (2.14), a difference being statistically significant at P < 0.001. Expired newborns had statistically significant frequency of lower scores across each of the parameters. An optimum cutoff score of ≤10 with 80% sensitivity and 88.8% specificity in predicting mortality was obtained when the ROC curve was generated with the MSNS score as the test variable. Area under the curve was 0.913 (95% CI: 0.879-0.946). In conclusion, MSNS is a practicable disease severity score in resource-restricted settings like district SNCUs. It is for application in both term and preterm neonates. Total score ≤10 has a good sensitivity and specificity in predicting mortality of admitted neonates when used early during the course of hospitalization. MSNS could be used as a tool to compare performance of SNCUs and also enable early referral of individual cases to units with better facilities.

Diagnostic and Prognostic Validity of Proadrenomedullin among Neonates with Sepsis in Tertiary Care Hospitals of Southern India.

INTRODUCTION: To evaluate Proadrenomedullin (Pro-ADM) as the diagnostic and prognostic marker in neonatal sepsis. MATERIALS AND METHODS: In this cross-sectional study, Pro-ADM levels were estimated in 54 neonates with clinical sepsis and positive sepsis screen (cases) and 54 controls without clinical sepsis. Repeat Pro-ADM levels were estimated after 72 hours in cases. Pro-ADM levels were compared with the clinical outcome. RESULTS AND DISCUSSION: Median Pro-ADM levels in cases were 31.8 (IQR: 27.8-39.4) pmol/ml which was significantly higher than controls 5.1 (IQR; 3.1-7.7) pmol/ml. From the constructed ROC curve, a value of 14.5 pmol/ml was taken as the cut-off for sepsis. Pro-ADM had 100% sensitivity, specificity, and positive predictive values (PPV) in detecting sepsis at 14.5 pmol/ml. Among cases, a decrease in Pro-ADM level by 10 pmol/ml was associated with 99% survival. Pro-ADM value of 35 pmol/ml had 100% specificity and PPV in predicting mortality. CONCLUSION: Pro-ADM can be used as a single biomarker for detecting neonatal sepsis, predicting clinical outcome and prognosis.

Impact of care at foster homes on the health-related quality of life of HIV-infected children and adolescents: a cross-sectional study from India.

PURPOSE: To assess the impact of care at foster homes on the health-related quality of life (HRQOL) of children living with HIV (CLHIV), attending a referral ART Centre, and to compare their HRQOL with children living in their own homes. METHODS: A cross-sectional study was conducted in 144 CLHIV between 5 and 18 years of age, attending a referral ART Centre in South India to assess their HRQOL using the standard PedsQL™ 4.0 questionnaire. Data were then analysed to compare the HRQOL of children living in foster homes to those children living in their own homes. The child report and the parent proxy-report on the child's HRQOL were also compared to see for any differences in their perspectives. RESULTS: 56.25% CLHIV were brought up in different foster homes. In the child's self-report, the mean HRQOL was higher for children living in foster homes [physical score (76.54 ± 12.40), psychosocial score (71.41 ± 12.40) and total score (73.20 ± 11.13)] when compared to children living in their own homes [physical score (75.09 ± 14.76), psychosocial score (70.60 ± 13.48) and total score (72.17 ± 12.00)]. There was no statistically significant difference in the HRQOL between these two groups (p > 0.05). In the parent proxy-report also, there was no statistically significant difference in the HRQOL in all the three scores. The child self-report depicted a significantly higher HRQOL in all the domains compared to the parent proxy-report (p < 0.05). CONCLUSIONS: HRQOL of children living in foster homes is at par with the quality of life enjoyed by children living in their own homes. Foster care manages to provide a reasonable HRQOL in CLHIV, and has become an inseparable component of quality health care delivery for these children.

Study of Insulin Resistance in Patients With ß Thalassemia Major and Validity of Triglyceride Glucose (TYG) Index.

Complications like impaired glucose tolerance and diabetes mellitus due to iron overload need early identification in thalassemia. We studied the proportion of insulin resistance in thalassemia major patients on chronic transfusion, identified insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride glucose (TYG) index, compared them and validated TYG index. In total, 73 thalassemia patients on regular transfusion for 3 years with serum ferritin >1500 ng/mL were studied. Serum ferritin, fasting blood glucose, triglycerides, and insulin levels were measured, HOMA-IR, and TYG index calculated and analyzed. Mean fasting glucose, triglyceride, and serum insulin values were 104 mg/dL, 164.18 mg/dL, and 19.6 m IU/mL, respectively. Mean serum ferritin was 5156 ng/mL. Insulin resistance was prevalent in one third of thalassemia patients and showed increase with age and serum ferritin. Insulin resistance by HOMA-IR was 32% as against 16% by TYG index with a cut-off value of 4.3. Using receiver operating charecteristic curve analysis, it was found that, by lowering the value of TYG index to 4.0215, sensitivity improved to 78.3% (from 39.13%) with specificity of 70%. Hence, we recommend a newer lower cut-off value of 4.0215 for TYG index for better sensitivity and specificity in identifying insulin resistance.

Effect of Conventional and LED Phototherapy on the Antioxidant-Oxidant Status in Preterm Neonates with Jaundice.

OBJECTIVE: To compare oxidative stress due to conventional and LED phototherapy among jaundiced preterm neonates. METHODS: Cross-sectional study conducted in NICU on 82 neonates (equal numbers received conventional and LED phototherapy). Total antioxidant capacity (TAC), total oxidant status (TOS) and Oxidative stress index (OSI) were assessed. RESULTS: Post-phototherapy, mean (SD) OSI increased significantly compared to baseline in both conventional [0.26 (0.24) vs. 0.61 (0.41); P<0.001] and LED groups [0.24 (0.20) vs. 0.32 (0.23); P<0.001]. Across groups, mean (SD) TAC was lower [0.28 (0.16) vs. 0.53 (0.27); P<0.001] mmol Trolox equiv/L; mean (SD) TOS higher [15.6 (10.9) vs. 14.6 (10.2); P=0.711] µmol H2O2/L and mean (SD) OSI higher [0.61 (0.42) vs. 0.33 (0.23); P<0.001] in conventional as compared to LED phototherapy. CONCLUSION: Both modes increased oxidative stress index; however, conventional phototherapy resulted in higher oxidative stress.

Acute lymphoblastic leukemia and genetic variations in BHMT gene: Case-control study and computational characterization.

BACKGROUND: Remethylation of homocysteine is catalyzed by B12 dependent methionine synthase (MTR) in all types of cells and by B12 non-dependent betaine homocysteine methyltransferase (BHMT) in liver and kidney cells. Of many etiologies of cancer, an unexplored area is the variations of genes implicated in methylation reaction. OBJECTIVE: The study evaluated the association of BHMT (rs3733890) with acute lymphoblastic leukemia (ALL), followed by in-silico characterization of variations in BHMT gene. METHODS: BHMT [rs3733890; c.742G > A, which substitutes an arginine by a glutamine at codon 239 (R239Q)] was screened by Tetra-primer Amplification Refractory Mutation System PCR (T-ARMS-PCR) and confirmed using DNA sequencing. In-silico analysis was conducted using bioinformatics tools. RESULTS: BHMT (rs3733890) showed an insignificant association with both childhood and adult ALL. Bioinformatics analysis showed that 18 nsSNPs are deleterious, 3 SNPs in 3'-UTR (rs59109725, rs116634518 and rs138578732) alter the miRNA-binding site, and 11 CNVs are present in the BHMT gene. As consequence of BHMT (rs3733890) polymorphism the free energy changes from -101210.1 kJ/mol to -200021.8 kJ/mol. CONCLUSIONS: BHMT (rs3733890) polymorphism showed no association with ALL. Hence this investigation needs further evaluation in larger sample size and effect of other SNPs, CNVs and miRNA's is required to elucidate the role of BHMT gene in ALL development.

Problem-Based Learning as an Effective Learning Tool in Community Medicine: Initiative in a Private Medical College of a Developing Country.

BACKGROUND: Knowledge of community medicine is essential for health care professionals to function as efficient primary health care physicians. Medical students learning Community Medicine as a subject are expected to be competent in critical thinking and generic skills so as to analyze community health problems better. However, current teaching by didactic lectures fails to develop these essential skills. Problem-based learning (PBL) could be an effective strategy in this respect. This study was hence done to compare the academic performance of students who were taught Community Medicine by the PBL method with that of students taught by traditional methods, to assess the generic skills of students taught in a PBL environment and to assess the perception of students toward PBL methodology. MATERIALS AND METHODS: This study was conducted among seventh-semester final-year medical students between June and November 2014. PBL was introduced to a randomly chosen group of students, and their performance in an assessment exam at the end of postings was compared with that of the remaining students. Generic skills and perception toward PBL were also assessed using standardized questionnaires. RESULTS: A total of 77 students took part in the brainstorming session of PBL. The correlation between self-assigned scores of the participants and those assigned by the tutor in the brainstorming session of PBL was significant (r = 0.266, P = 0.05). Out of 54 students who took part in the presentation session, almost all 53 (98.1%) had good perception toward PBL. Demotivational scores were found to be significantly higher among males (P = 0.024). The academic performance of students (P < 0.001) and success rates (P = 0.05) in the examination were higher among students who took part in PBL compared to controls. CONCLUSION: PBL helped improve knowledge of students in comparison to those exposed only to didactic lectures. As PBL enabled students to identify the gaps in their knowledge and enhanced their group functioning and generic skills, we recommend PBL sessions: They would help optimize the training in Community Medicine at medical schools. Good correlation of tutor and self-assessment scores of participants in the brainstorming session suggests that the role of tutors could be restricted to assessment in presentation sessions alone. Demotivation, which hinders group performance in PBL, needs to be corrected by counselling and timely feedback by the tutors.

Recurrent and novel GLB1 mutations in India.

GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme ß-d-galactosidase. In this study, we report molecular findings in 50 Asian Indian families with GM1 gangliosidosis. We sequenced all the exons and flanking intronic sequences of GLB1 gene. We identified 33 different mutations (20 novel and 13 previously reported). The novel mutations include 12 missense (p.M1?, p.E129Q, p.G134R, p.L236P, p.G262E, p.L297F, p.Y331C, p.G414V, p.K493N, p.L514P, p.P597L, p.T600I), four splicing (c.246-2A>G, c.397-2A>G, c.552+1G>T, c.956-2A>G), three indels (p.R22Qfs*8, p.L24Cfs*47, p.I489Qfs*4) and one nonsense mutation (p.Q452*). Most common mutations identified in this study were c.75+2InsT (14%) and p.L337P (10%). Known mutations accounted for 67% of allele frequency in our cohort of patients, suggesting that these mutations in GLB1 are recurrent across different populations. Twenty three mutations were localized in the TIM barrel domain, ß-domain 1 and ß-domain 2. In silico sequence and structure analysis of GLB1 reveal that all the novel mutations affect the function and structure of the protein. We hereby report on the largest series of patients with GM1 gangliosidosis and the first from India.

Nephropathic Cystinosis Presenting as Renal Fanconi Syndrome without Glycosuria.

Renal Fanconi syndrome is diagnosed by its cardinal features of glycosuria without diabetes, aminoaciduria, phosphaturia, and renal tubular acidosis. It is often associated with hypokalaemia, hypophosphatemia and rickets. We report a seven-year-old boy with nephropathic cystinosis who presented with all the cardinal features of renal Fanconi syndrome associated with rickets, pathological fractures, stage IV chronic kidney disease (CKD) and hypothyroidism. Slit-lamp examination of the cornea confirmed the diagnosis. However glycosuria was conspicuously absent. Whenever there are features of rickets with failure to thrive and recurrent vomiting renal rickets should be ruled out. Cystinosis is one such disorder and we report this case due its rarity and interesting clinical presentation.

Significance of 5,10-methylenetetrahydrofolate reductase gene variants in acute lymphoblastic leukemia in Indian population: an experimental, computational and meta-analysis.

Acute lymphoblastic leukemia (ALL) arises due to several genetic alterations in progenitor cells, and methotrexate is frequently used as part of the treatment regimen. Although there is evidence for an effect of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T and A1298C variations on drug response in ALL, its risk association for ALL is still unresolved. In a case-control study of 203 patients with ALL and 246 controls and meta-analysis in the Indian population, we showed an insignificant association of MTHFR C677T and A1298C genotypes with childhood and adult ALL. Comprehensive in silico characterization of non-synonymous single nucleotide polymorphisms (nsSNPs) and SNPs of the 3' untranslated region (UTR) revealed nine nsSNPs as deleterious, and three SNPs in the 3'UTR could possibly alter the binding of miRNAs. The study revealed that several overlooked SNPs may contribute to the risk of ALL susceptibility and further studies of these SNPs with functional characterization in a large sample size are required to understand the significant role of MTHFR in ALL development.

Effect of long-term transfusion therapy on the glycometabolic status and pancreatic Beta cell function in patients with Beta thalassemia major.

BACKGROUND: Diabetes mellitus is a major complication of iron overload in patients with beta thalassemia major. DESIGN: This is a descriptive study conducted in a Tertiary Care Teaching Hospital to analyze beta cell function and insulin resistance, and their relation to iron overload status in beta thalassemia major. Fasting glucose, two-hour post load glucose, fasting insulin, alanine amino transaminase (ALT), and ferritin were used as outcome measures. The homeostatic model assessment (HOMA model) was used to calculate the beta cell function and insulin resistance index. RESULTS: Of the 30 cases, 20% had impaired fasting glucose, 3.3% had impaired glucose tolerance, and none had diabetes. Fasting glucose was not significant between the cases and controls (P = 0.113). Fasting insulin (P = 0.001), ferritin (P = 0.001), and ALT (P = 0.001) levels were significantly high in the cases. Insulin resistance index was significantly higher in the cases (P = 0.001) as also the beta cell function (P = 0.001). With increase in age and the number of units transfused there is a decline in beta cell function, fasting insulin, and insulin resistance after attaining the maximum level. This suggests that initial insulin resistance is followed by insulin depletion due to loss of beta cell function, leading to diabetes mellitus. CONCLUSION: Impaired glucose tolerance (IGT) and insulin resistance precede the onset of insulin-dependent diabetes and adequate chelation therapy is essential for delaying the onset or for prevention of diabetes.