Recent Admixture in an Indian Population of African Ancestry

053907Quantum Matter and Optic

Effect of multilevel lower-limb botulinum injections & intensive physical therapy on children with cerebral palsy

Background & objectives: Botulinum toxin is considered as an effective treatment for spasticity in children with cerebral palsy (CP). However, there are only a few long-term studies, and the effects on motor function have been inconclusive. Moreover, due to its high cost and need for intensive post-injection therapy, utility in context of developing nations has not been established. This retrospective study was undertaken to assess the long term effects of botulinum toxin-A with physical therapy in children with CP. Methods: This retrospective study was conducted at a tertiary care centre in India, where a limited supply of botulinum toxin was introduced in the year 2009. It was used in a selective group of patients with CP along with intensive physical therapies. All children who received lower-limb botulinum injections over a 42-month period were analyzed. For evaluation of treatment effect, the measurement at 1st pre-injection assessment and the last measurements, i.e. 12 wk after last injection received by that child were compared. Results: Twenty nine patients (20 males, median age 51 months) received 69 sessions of botulinum toxin injections in the lower limbs over a 42-month period. Thirteen patients were diplegic, 10 were quadriplegic, five were triplegic and one was hemiplegic. There was a significant improvement in pre- and post-injection scores on Observational Gait Scale (right side 7.1±3.6 to 10.7±3.7, left side 6.7±3.5 to 9.9±3.4), Gross Motor Function Measure Scale (47.9±17.7 to 67.6±17.2), Modified Ashworth Scale, passive range of motion and Gross Motor Function Classification System. Most of the patients showed gain in motor milestones as well. Interpretation & conclusions: Our results showed that judicious use of botulinum injections along with intensive physio/occupational therapies could yield good results in children with CP

Intranasal glioma (Nasal heterotopia): A rare cause of nasal polyp in neonates

A 3-month-old boy presented with an intranasal polypoidal mass protruding out of the nostril which was present since birth and growing slowly. The mass was non-pulsatile and soft to firm in consistency. It did not increase in size on coughing, crying, or compression of the jugular vein. Magnetic resonance imaging and contrast-enhanced computed tomography (CT) revealed a lobulated well-circumscribed soft tissue mass in the left nasal cavity with no intracranial communication. Complete surgical excision of the mass was carried out via an intranasal endoscopic approach. Histopathological examination confirmed the diagnosis of intranasal glioma

Sleep Quality and Duration in Children That Consume Caffeine: Impact of Dose and Genetic Variation in <i>ADORA2A</i> and <i>CYP1A</i>

Caffeine is the most consumed drug in the world, and it is commonly used by children. Despite being considered relatively safe, caffeine can have marked effects on sleep. Studies in adults suggest that genetic variants in the adenosine A2A receptor (ADORA2A, rs5751876) and cytochrome P450 1A (CYP1A, rs2472297, rs762551) loci are correlated with caffeine-associated sleep disturbances and caffeine intake (dose), but these associations have not been assessed in children. We examined the independent and interaction effects of daily caffeine dose and candidate variants in ADORA2A and CYP1A on the sleep quality and duration in 6112 children aged 9–10 years who used caffeine and were enrolled in the Adolescent Brain Cognitive Development (ABCD) study. We found that children with higher daily caffeine doses had lower odds of reporting > 9 h of sleep per night (OR = 0.81, 95% CI = 0.74–0.88, and p = 1.2 × 10−6). For every mg/kg/day of caffeine consumed, there was a 19% (95% CI = 12–26%) decrease in the odds of children reporting > 9 h of sleep. However, neither ADORA2A nor CYP1A genetic variants were associated with sleep quality, duration, or caffeine dose. Likewise, genotype by caffeine dose interactions were not detected. Our findings suggest that a daily caffeine dose has a clear negative correlation with sleep duration in children, but this association is not moderated by the ADORA2A or CYP1A genetic variation

Prevalence of early childhood caries in 3- to 5-year-old preschool children in Rohtak City, Haryana

Introduction: Early childhood caries (ECC) is a significant dental public health problem that affects infants and preschool children all over the world, and there is scarcity of epidemiological data regarding ECC in Rohtak city. Aim: This study aims to assess the prevalence of ECC among 3- to 5-year-old preschool children in Rohtak city, Haryana, India. Materials and Methods: A descriptive cross-sectional study was carried out among 489 preschool children aged 3–5 years in Rohtak city, Haryana. Children were randomly selected from preschools of Rohtak. Caries experience was recorded using “deft” index, and questionnaire comprising sociodemographic details and oral hygiene practices was also used. Data were analyzed using Statistical Package for Social Sciences version 20.0. Chi-square tests were used for the comparison of proportions. P < 0.05 was considered as statistically significant. Results: The overall prevalence of ECC was found to be 32% with mean deft 1.08 ± 2.27. No significant association of dental caries was found with sociodemographic factors such as gender, parental education, parental occupation, socioeconomic status, number of children, birth order, type of family, and oral hygiene practices. Conclusion: As burden of dental caries is high, treatment of dental caries would impose a great financial burden; hence, effective preventive strategies should be developed and implemented

Recent Admixture in an Indian Population of African Ancestry

Identification and study of genetic variation in recently admixed populations not only provides insight into historical population events but also is a powerful approach for mapping disease loci. We studied a population (OG-W-IP) that is of African-Indian origin and has resided in the western part of India for 500 years; members of this population are believed to be descendants of the Bantu-speaking population of Africa. We have carried out this study by using a set of 18,534 autosomal markers common between Indian, CEPH-HGDP, and HapMap populations. Principal-components analysis clearly revealed that the African-Indian population derives its ancestry from Bantu-speaking west-African as well as Indo-European-speaking north and northwest Indian population(s). STRUCTURE and ADMIXTURE analyses show that, overall, the OG-W-IPs derive 58.7% of their genomic ancestry from their African past and have very little inter-individual ancestry variation (8.4%). The extent of linkage disequilibrium also reveals that the admixture event has been recent. Functional annotation of genes encompassing the ancestry-informative markers that are closer in allele frequency to the Indian ancestral population revealed significant enrichment of biological processes, such as ion-channel activity, and cadherins. We briefly examine the implications of determining the genetic diversity of this population, which could provide opportunities for studies involving admixture mapping

Extensive copy number variations in admixed Indian population of African ancestry: potential involvement in adaptation

Admixture mapping has been enormously resourceful in identifying genetic variations linked to phenotypes, adaptation, and diseases. In this study through analysis of copy number variable regions (CNVRs), we report extensive restructuring in the genomes of the recently admixed African-Indian population (OG-W-IP) that inhabits a highly saline environment in Western India. The study included subjects from OG-W-IP (OG), five different Indian and three HapMap populations that were genotyped using Affymetrix version 6.0 arrays. Copy number variations (CNVs) detected using Birdsuite were used to define CNVRs. Population structure with respect to CNVRs was delineated using random forest approach. OG genomes have a surprising excess of CNVs in comparison to other studied populations. Individual ancestry proportions computed using STRUCTURE also reveals a unique genetic component in OGs. Population structure analysis with CNV genotypes indicates OG to be distant from both the African and Indian ancestral populations. Interestingly, it shows genetic proximity with respect to CNVs to only one Indian population IE-W-LP4, which also happens to reside in the same geographical region. We also observe a significant enrichment of molecular processes related to ion binding and receptor activity in genes encompassing OG-specific CNVRs. Our results suggest that retention of CNVRs from ancestral natives and de novo acquisition of CNVRs could accelerate the process of adaptation especially in an extreme environment. Additionally, this population would be enormously useful for dissecting genes and delineating the involvement of CNVs in salt adaptation

Whole Exome Sequencing in Healthy Individuals of Extreme Constitution Types Reveals Differential Disease Risk: A Novel Approach towards Predictive Medicine

Precision medicine aims to move from traditional reactive medicine to a system where risk groups can be identified before the disease occurs. However, phenotypic heterogeneity amongst the diseased and healthy poses a major challenge for identification markers for risk stratification and early actionable interventions. In Ayurveda, individuals are phenotypically stratified into seven constitution types based on multisystem phenotypes termed “Prakriti”. It enables the prediction of health and disease trajectories and the selection of health interventions. We hypothesize that exome sequencing in healthy individuals of phenotypically homogeneous Prakriti types might enable the identification of functional variations associated with the constitution types. Exomes of 144 healthy Prakriti stratified individuals and controls from two genetically homogeneous cohorts (north and western India) revealed differential risk for diseases/traits like metabolic disorders, liver diseases, and body and hematological measurements amongst healthy individuals. These SNPs differ significantly from the Indo-European background control as well. Amongst these we highlight novel SNPs rs304447 (IFIT5) and rs941590 (SERPINA10) that could explain differential trajectories for immune response, bleeding or thrombosis. Our method demonstrates the requirement of a relatively smaller sample size for a well powered study. This study highlights the potential of integrating a unique phenotyping approach for the identification of predictive markers and the at-risk population amongst the healthy