Childlessness among Muthuvan Tribes of Tamil Nadu, India: An Exploratory Study.

INTRODUCTION: Childlessness is a global concern and it has serious demographic, social, and health implications. The declining Muthuvan child population may reduce their population on the whole. OBJECTIVE: The study explored the prevalence of childlessness and its underlying reasons in the Muthuvan tribes of Tamil Nadu. SUBJECTS AND METHODS: The study applied the mixed-method design, and the snowball technique was adopted to identify eight Muthuvan hamlets. Descriptive and thematic analysis was done for the collected quantitative and qualitative information. RESULTS: The study found the prevalence of childlessness among Muthuvan couples as 30.65%. The underlying reasons were their cultural practices of confinement during menstruation and restriction on engaging in productive work and family care, which gave them the idea of regular intake of oral contraceptive pills and lessen their desire to have children. CONCLUSION: The study concludes that the comfort of their daily life has taken over more important than the consequences of objects used for comfort, to their health and future generations.

Mumps Antibody Titer in MMR-Vaccinated and Vaccine Naïve Children at a Public Hospital in Delhi.

OBJECTIVE: To compare the mumps antibody titers in Measles-Mumps-Rubella (MMR)-vaccinated and vaccine naive children. METHODS: This cross-sectional study was conducted at a tertiary-care public hospital in Delhi from November, 2016 to April, 2018 among 78 healthy children (aged 16 month-12 years) attending the pediatric outpatient department. Serum IgG and IgM rubella antibodies were measured by ELISA for confirmation of MMR vaccination status. Qualitative determination of IgG mumps was done followed by quantitative determination in samples positive for IgG mumps antibodies. RESULTS: IgG mumps was present in 69.2% of study population, with seroprotective titers in 32% taking endpoint titer as 1:4. Among MMR vaccinated children, 41.1% were sero-protected and in MMR vaccine naïve children 9.1% were seroprotected for mumps. CONCLUSION: Single dose of MMR vaccine does not provide effective (>90%) sero-conversion required for successful herd immunity to prevent mumps outbreak.

Requirement of a Booster Dose of Hepatitis B Vaccine in Children With Thalassemia After 5 Years of Primary Vaccination: A Prospective Study.

OBJECTIVE: To determine anti-HBs antibody levels in multi-transfused children with beta-thalassemia major who had received primary hepatitis B vaccination ≥5 years ago, and to document their antibody response to a booster dose of hepatitis B vaccine. METHODS: We included 85 children each of beta-thalassemia major and age-matched healthy controls, who had completed primary hepatitis B vaccination ≥5 years ago. Participants were assessed for anti-HBs titres, and those with beta-thalassemia major who were seronegative (titres<10 mIU/mL) were administered a single booster dose of hepatitis B vaccine. CD4 counts, serum levels of IL-2 and IFN-g, and anti-HBs titres were evaluated at baseline and following booster dose of vaccine. RESULTS: Seroprotection rates for hepatitis B after an average (SD) duration of 10.8 (3.8) years of completion of primary immunization were significantly higher among children with beta thalassemia major compared to healthy controls (72.9% vs. 52.9%, P=0.007). All the 23 seronegative children with beta-thalassemia major achieved seroprotection after a single booster dose of hepatitis B vaccine. CONCLUSIONS: A single booster dose of hepatitis B vaccine after 5 years of primary immunization is adequate to provide seroprotection to multi-transfused children with beta-thalassemia major.

Functional impact of allelic variations/haplotypes of TNF-α on reproductive tract infections in Indian women.

The aim of the present study is to investigate the functional role of TNF-α single-nucleotide polymorphisms/haplotypes in an association with reproductive tract infections (RTIs) in symptomatic and asymptomatic women. A total of 850 consecutive subjects consisting of 400 cases and 450 healthy controls, were screened for RTIs, along with their risk factors and associated symptoms. The propensity score matching was performed to reduce the confounding bias arise owing to covariates and to balance the data between two groups. A total of 211 pairs (1:1) have been created. Genotyping of rs1800629 (-308) and rs361525 (-238) SNPs of TNF-α was done by PCR-RFLP followed by sequencing. The functional implication of TNF-α SNPs in an association with RTIs was also checked by using ELISA. The frequency of -238A allele and -308A allele was found to be twofold (P < 0.0001) and threefold (P < 0.0001) higher in the presence of RTIs. AA haplotype emerged as a major player in an association with RTIs and elevated TNF-α expression. The present study revealed the functional role of rs1800629 (-308) and rs361525 (-238) of TNF-α in an association with RTIs. This information may be used to establish biomarkers for an inflammatory response during the persistence of RTIs.

Molecular and Genetic Characterization of Natural Variants of HIV-1 Nef Gene from North India and its Functional Implication in Down-Regulation of MHC-I and CD-4.

BACKGROUND: HIV-1 Nef is an important accessory protein with multiple effector functions. Genetic studies of the HIV-1 Nef gene show extensive genetic diversity and the functional studies have been carried out mostly with Nef derived from regions dominated by subtype B (North America & Europe). OBJECTIVE: This study was carried out to characterize genetic variations of the Nef gene from HIV-1 infected individuals from North India and to find out their functional implications. METHODS: The unique representative variants were sub-cloned in a eukaryotic expression vector and further characterized with respect to their ability to downregulate cell surface expression of CD4 and MHC-1 molecules. RESULTS: The phylogenetic analysis of Nef variants revealed sequence similarity with either consensus subtype B or B/C recombinants. Boot scan analysis of some of our variants showed homology to B/C recombinant and some to wild type Nef B. Extensive variations were observed in most of the variants. The dN/dS ratio revealed 80% purifying selection and 20% diversifying selection implying the importance of mutations in Nef variants. Intracellular stability of Nef variants differed greatly when compared with wild type Nef B and C. There were some variants that possessed mutations in the functional domains of Nef and responsible for its differential CD4 and MHC-1 downregulation activity. CONCLUSION: We observed enhanced biological activities in some of the variants, perhaps arising from amino acid substitutions in their functional domains. The CD4 and MHC-1 down-regulation activity of Nef is likely to confer immense survival advantage allowing the most rare genotype in a population to become the most abundant after a single selection event.

Novel frameshift variant (c.409dupG) in SLC25A38 is a common cause of congenital sideroblastic anaemia in the Indian subcontinent.

AIMS: Congenital sideroblastic anaemias (CSAs) are a group of rare disorders with the presence of ring sideroblasts in the bone marrow. Pathogenic variants are inherited in an autosomal recessive/X-linked fashion. The study was aimed at characterising the spectrum of mutations in SLC25A38 and ALAS2 genes in sideroblastic anaemia patients, exploring the genotype-phenotype correlation and identifying the haplotype associated with any recurrent mutation. PATIENTS AND METHODS: Twenty probable CSA patients were retrospectively analysed for genetic variants in ALAS2 and SLC25A38 genes by direct bidirectional sequencing. Real-time PCR was used to quantify gene expression in a case with promoter region variant in ALAS2. Three single nucleotide polymorphisms were used to establish the haplotype associated with a recurrent variant in the SLC25A38 gene. RESULTS: Six patients had causative variants in ALAS2 (30%) and 11 had variants in SLC25A38 (55%). The ALAS2 mutated cases presented at a significantly later age than the SLC25A38 cases. A frameshift variant in SLC25A38 (c.409dupG) was identified in six unrelated patients and was a common variant in our population exhibiting 'founder effect'. CONCLUSION: This is the largest series of sideroblastic anaemia cases with molecular characterisation from the Indian subcontinent.

High-Throughput RNA Sequencing Analysis of Plasma Samples Reveals Circulating microRNA Signatures with Biomarker Potential in Dengue Disease Progression.

The circulating microRNA (miRNA) profile has been widely used for identifying potential biomarkers against viral infections. However, data on circulating microRNA expression patterns in dengue patients are scanty. Considering the impact of severity caused by dengue infection, circulating miRNA profiles in plasma of dengue patients may prove to be valuable for developing early prognostic markers for the disease severity. Here, we described an in-depth analytical study of small RNA sequencing data obtained from the plasma of 39 dengue patients. Integrating bioinformatics and in vitro studies, we identified differentially expressed miRNAs (DEMs) (log2 fold change ≥1.5, P < 0.05) associated with dengue disease progression. In comparing miRNA expression pattern with the follow-up samples, nine miRNAs were found to exhibit an altered expression that could distinguish between severe dengue and the convalescent patients. To understand the abundance and specificity of the DEMs in the context of dengue infection and disease progression, eight top-hit DEMs were further validated in the dengue virus-infected cell lines as well as in the patient's plasma and peripheral blood mononuclear cells (PBMCs) using the quantitative reverse transcription-PCR (qRT-PCR) method. Importantly, receiver operating curve analysis further confirmed that the plasma expression pattern of hsa-miR-122-5p could differentiate between different stages of dengue infection (area under the concentration-time curve [AUC] = 0.792), and dengue-negative patients with other febrile illnesses (AUC = 0.984). The in silico analysis of DEM target genes suggested an enrichment of the pathways associated with metabolism and inflammation. Our study gives a global view of miRNA expression in the plasma from dengue patients and provides a precious resource of candidate miRNAs involved in dengue infection and disease progression.IMPORTANCE Dengue virus (DENV) infection usually causes dengue fever (DF) with flu-like illness affecting infants, young children, and adults. The DF occasionally evolves into a potentially lethal complication called dengue severe (DS) leading to a rapid fall in platelet count along with plasma leakage, fluid accumulation, respiratory distress, and severe bleeding. The diverse clinical spectrum of dengue disease, as well as its significant similarity to other febrile viral illnesses, makes early identification more challenging in this high-risk group. microRNAs (miRNAs) are small (∼19 to 21 nucleotides [nt] in length), noncoding RNAs, extremely stable and easily detectable in the plasma; thus, they have potential as biomarkers for diagnosing and monitoring human diseases. This study provides a comprehensive analysis of miRNAs circulating in plasma of dengue virus-infected patients and identifies the miRNA signatures that have biomarker potential for dengue infection and disease progression.

Gold Standard Cholera Diagnostics Are Tarnished by Lytic Bacteriophage and Antibiotics.

A fundamental, clinical, and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question, because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophage and the etiologic agent Vibrio cholerae share commonalities across bacterial taxa. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection and exposure to the first-line antibiotic azithromycin, detected in stool samples by mass spectrometry. Among diarrheal samples positive by nanoliter quantitative PCR (qPCR) for V. cholerae (n = 78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (odds ratio [OR], 0.108; 95% confidence interval [CI], 0.002 to 0.872) and 87% (OR, 0.130; 95% CI, 0.022 to 0.649), respectively, when lytic bacteriophage were detected. The odds that an RDT or qPCR was positive was reduced by more than 99% (OR, 0.00; 95% CI, 0.00 to 0.28) and 89% (OR, 0.11; 95% CI, 0.03 to 0.44), respectively, when azithromycin was detected. Analysis of additional samples from South Sudan found similar phage effects on RDTs; antibiotics were not assayed. Cholera burden estimates may improve by accommodating for the negative effects of lytic bacteriophage and antibiotic exposure on diagnostic positivity. One accommodation is using bacteriophage detection as a proxy for pathogen detection. These findings have relevance for other diagnostic settings where bacterial pathogens are vulnerable to lytic bacteriophage predation.

Expression of CD117 and platelet-derived growth factor receptor α in patients with alopecia areata.

BACKGROUND: Alopecia areata is a disease of uncertain, probably autoimmune etiology. The role of growth factors like platelet-derived growth factor and C-kit (CD117) in alopecia areata is unknown. AIMS: To compare the expression of CD117 and platelet-derived growth factor receptor α in tissue samples of alopecia areata and normal controls. METHODS: Thirty biopsy samples of alopecia areata and eighteen normal control samples were included in this cross-sectional study. Immunohistochemistry was done to detect the expression of CD117 and platelet-derived growth factor receptor α in cases and controls. The mean percentage of follicles expressing CD117 and platelet-derived growth factor receptor α was compared among cases and controls. RESULTS: The mean number of follicles expressing CD117 in anagen and catagen hairs differed significantly among cases and controls. The extent and intensity of staining with platelet-derived growth factor receptor α correlated significantly with the severity of alopecia areata based on the severity of alopecia tool score. LIMITATIONS: Confirmation of the expression pattern of molecules observed in immunohistochemistry with western blot or polymerase chain reaction would have strengthened the report. CONCLUSIONS: The expression of CD117 varied in cases and controls. The expression of platelet-derived growth factor receptor α correlated with the severity of the disease. This could explain how platelet-rich plasma works in the treatment of alopecia areata. Further studies are required to explore the role of these molecules in autoimmune pathogenesis.

World War against COVID-19: How strong is our armamentarium?

No abstract provided.

Determinants of periodontitis among a rural Indian population: A case control study.

OBJECTIVES: Identify the determinants of periodontitis in a rural Indian population aged 35-44 years. BASIC RESEARCH DESIGN: Case-control clinical and questionnaire study in a cluster sample of 50 villages. METHODS: A total of 3000 persons were screened for the presence of periodontitis using the CDC case definition in full mouth examination. Equal numbers of cases (604 persons with periodontitis) and controls (604 without periodontitis) were recruited and interviewed with a piloted questionnaire. Univariate and multivariate analysis estimated crude and adjusted odds ratios (aOR) respectively with 95% confidence limits. RESULTS: Six factors were determined by multivariate analysis to predict periodontitis: education less than or equal to twelve years of schooling (aOR=2.51, 95% CI=1.18-5.34), alcohol consumption (aOR= 1.7, 95% CI=1.16-2.49), consuming a non-vegetarian diet (aOR=1.38, 95% CI=1.08-1.76), not drinking milk (aOR=1.7, 95% CI= 1.29-2.24), not using a toothbrush for cleaning of teeth (aOR=2.98, 95% CI =1.71-5.21) and not cleaning teeth at least once a day (aOR=2.13, 95% CI=1.58-2.87). CONCLUSION: Risk factors for periodontitis in a rural Indian population were identified. Further studies should validate these findings and appropriate recommendations should be developed to decrease the prevalence and burden of periodontitis in this population.

Space time analysis of dengue fever diagnosed through a network of laboratories in India from 2014-2017.

BACKGROUND & OBJECTIVES: The Department of Health Research and the Indian Council of Medical Research, Government of India, have established Virus Research and Diagnostic Laboratory Network (VRDLN) to strengthen the laboratory capacity in the country for providing timely diagnosis of disease outbreaks. Fifty-one VRDLs were functional as on December 2017 and had reported about dengue fever across Indian states. The objectives of the study were to detect space time clusters and purely temporal clusters of dengue using Kulldorff's SaTScan statistics using patient level information; and to identify regions at greater risk of developing the disease using Kriging technique aggregating at district level. METHODS: A total of 211,432 patients from 51 VRDLs were investigated for IgM antibodies or NS1 antigen against dengue virus during the period from 1 January 2014 to 31 December 2017 and among them 60,096 (28.4%) were found to be positive. Kulldorff's space time analysis was used to identify significant clusters over space and time. Kriging technique was used to interpolate dengue data for areas not physically sampled using the relationship in the spatial arrangement of the data set. Maps obtained using both the methods were overlaid to identify the regions at greater risk of developing the disease. RESULTS: Kulldorff Space time Scan Statistics using the Bernoulli model with monthly precision revealed eight statistically significant clusters (P <0.001) for the time period, 1 January 2014 to 31 December 2017. Eight significant clusters identified were districts of Nagpur, Jhunjhunu, Gadag, Dakshin Kannada, Kancheepuram, Sivaganga, Ernakulam and Malda. The purely temporal clusters occurred during the last quarter of 2015 and 2016. The Kriging technique identified north eastern part of the country (Arunachal Pradesh, Nagaland and Manipur) and Gujarat. INTERPRETATION & CONCLUSION: Dengue fever has spread in all directions in the country. Hence, it is need of the hour to perform an in-depth investigation.

Constructing calendars in the brain.

By studying an enigmatic condition called, "calendar synesthesia", we explored the elusive boundary between perception, visual imagery, and the manner in which we construct an internal mental calendar by mapping time-sequences onto spatial maps. We use a series of demonstrations to establish that these calendars act more like real objects activating sensory pathways rather than purely abstract symbolic descriptions that bear no resemblance to an actual calendar. We propose that the calendar is enshrined in acircuitry involving the hippocampal place-cells and entorhinal grid-cells, which are connected to the angular gyrus (involved with computing sequences) via the inferior longitudinal fasciculus.

Screening of genetic variants in ELANE mutation negative congenital neutropenia by next generation sequencing.

AIMS: Congenital neutropenia (CN) is a rare inherited disease that results in recurrent, life-threatening bacterial infections due to a deficiency of mature neutrophils. They are usually caused by heterozygous ELANE mutations although mutations in other genes like HAX-1, G6PC3 and GFI1 have also been reported. Identifying the causative mutation aids in the establishment of diagnosis and rules out other secondary causes of neutropenia like autoimmune cytopenia and evolving aplasia. We aimed to identify the molecular defects in CN patients who had no mutations in ELANE gene, by next generation sequencing (NGS) targeting a customised panel of genes. METHODS: DNA samples were sequenced with an Illumina NextSeq sequencer using an in-house customised panel of genes at ≥100× depth. Bioinformatics analysis was carried out and the pathogenic variants were identified using a stepwise filtering and analysis strategy. Specific mutations identified were subsequently validated by Sanger sequencing. RESULTS: The pathogenic variants identified in the study includes previously reported variants in SBDS (compound heterozygous c.258+2T>C and c.1A>T), GATA2 (heterozygous c.1186C>T) and novel variants in WAS (hemizygous c.812T>C), JAGN1 (homozygous c.70G>A) and RTEL1 (heterozygous c.2893G>C) genes. CONCLUSION: This study highlights that the absence of ELANE mutations does not rule out the diagnosis of CN and this NGS based approach with a customised panel will help in diagnostic confirmation in such patients. The early onset of the disease, clinical severity and associated high risk of malignant transformation in CN strongly suggests the need for early diagnosis and therapeutic intervention.

Computed Tomography Score an Excellent Marker: Differentiates Eosinophilic and Non-eosinophilic Variants of Chronic Rhinosinusitis with Nasal Polyp.

Eosinophilic and non-eosinophilic subtypes of chronic rhinosinusitis with nasal polyp (CRSwNP) have different clinical profile and management. Currently the 2 subtypes are differentiated based on tissue eosinophilic infiltration, which is identified after surgery by histopathological examination. Hence this study was conducted to compare utility of computed tomography (CT) scans, serum IgE levels, absolute eosinophil count (AEC) and Sino-nasal Outcome Test (SNOT)-20 score for discriminating the 2 subtypes. In this prospective study of 1 year duration, patients suspected of CRSwNP were recruited. Serum IgE levels and AEC estimation were performed by ELISA and standard numerical formula respectively, along with histopathological examination of nasal polyp biopsies. CT score and ratio of CT score for ethmoid sinus and maxillary sinus (E/M ratio) were calculated. Patients were asked to fill SNOT-20 questionnaire. Receiver-operating characteristic (ROC) curve analysis was performed. Out of 52 patients studied, 38 and 14 were no. of eosinophilic and non-eosinophilic CRSwNP cases respectively on the basis of histopathological examination. E/M ratio and overall CT score were found to be highly accurate with area under ROC curve of 0.990 and 0.964 respectively, while rest 3 parameters had low accuracy. Optimal cut-off of CT score and E/M ratio for eosinophilic CRSwNP were 6 and 2.065 respectively. This study demonstrated E/M ratio and total CT score as the most useful surrogate markers for preoperative differentiation of eosinophilic and non-eosinophilic CRSwNP, and hence can be used to predetermine postoperative management before surgery.

Hepatitis B & C virus infection in HIV seropositive individuals & their association with risk factors: A hospital-based study.

Background & objectives: Hepatitis B and hepatitis C virus (HBV and HCV) cause acute and chronic hepatitis, and infections with HBV and HCV are common in HIV-infected patients. The present study was conducted to determine the co-infection of hepatitis B and C virus in stored serum samples of HIV-positive/negative individuals attending an Integrated Counselling and Testing Centre (ICTC) in north India and their association with certain risk factors. Methods: This study included a total of 840 serum samples, of which 440 were from HIV seropositive individuals and 400 were from control individuals seeking voluntary check-up of HIV status at ICTC. Serum samples were used for the detection of HBV and HCV infection. Results: HBV infection (11%) was found to be less in contrast to HCV (13%) amongst the HIV seropositive. In controls, HBV and HCV infection was two and three per cent, respectively. Co-infection of HBV and HCV was found in 15 of 109, and in controls, it was 2 of 15. Age group between 21 and 40 was significantly associated with HBV and HCV infection. Heterosexual contact was the leading mode of acquiring HBV and HCV infection. Interpretation & conclusions: HBV and HCV co-infection was found to be significantly higher in HIV-positive individuals in comparison to normal population. Hepatitis virus infection leads to rapid progression of liver cirrhosis in HIV-infected patients. Routine check-up of HIV seropositive patients for hepatitis virus may be required to monitor clinical outcome.