Estrogen Receptor 1 Gene Polymorphism and its Association with Idiopathic Short Stature in North Indian Population.

Background: In the hypothalamic-pituitary-gonadotrophin (HPG) axis, estrogen plays a key role in the bone maturation regulation and growth plates closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in the North Indian population. Methods: Four SNPs of the ESR1 gene (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in 52 ISS patients and 68 controls. Linkage disequilibrium (LD) and haplotyping were done by SNPstat and SHESISplus softwares. Extent of LD was determined by calculating D' and r2 values in SNPs paired combinations. Results: A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility as compared to controls. The frequencies of the rs6557177 CC genotype (p=0.030; OR=0.13; 95% CI:0.01-1.10) and rs543650 genotype TT (p =0.043; OR=0.29; 95% CI: 0.09-0.92) were observed to be increased in ISS group as compared with the control group. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 shown strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Conclusion: Our study showed that CC genotype at rs6557177 and TT genotype of rs543650 of ESR1 constitutes risk factor for developing ISS in North Indian children. In the future, these findings may lead to a better understanding of the SNPs associated with ISS susceptibility.

Growth charts for weight and height of Indian children with Down syndrome.

Age and gender specific growth charts for Indian children with Down syndrome (DS) based on longitudinal data have not been published. To establish percentile growth charts for DS children inhabiting northwestern parts of India, body weight and length/height of 1125 (Male: 752, Female: 373) children with DS aged <1 month to 10 years, enrolled from the "Genetics Clinic" were measured at half yearly age intervals in the "Growth Clinic" of the Institute from August 1994 to November 2018. A total of 2089 observations were made on these children using standardized anthropometric techniques and instruments following a prospective mixed-longitudinal growth research design. Using the LMS method, age and sex-specific percentile growth charts (<1 month to 10 years) for weight, and length/ height were generated. Unpaired t-test was used to compare mean growth attainments of study children with those of DS patients representing other population groups as well as their normal Multicentre Growth Reference Study (MGRS and Indian Academy of Pediatrics (IAP) counterparts. The 50th percentile growth curves for both weight and length/height of Indian children with DS demonstrated a regular increase. As compared to their normal MGRS and Indian (IAP) counterparts, the children with DS had lower weight and height attainments. The boys and girls with Down syndrome showed short stature (height < 3rd centile) from the age of 1 year till 10 years and also became underweight beyond 5 years. As compared to their normal counterparts, children with Down syndrome exhibited compromised auxological attainments. The use of growth charts presented herein may be used to compare and monitor growth and nutritional status of Indian children with Down syndrome.

SHOX Variations in Idiopathic Short Stature in North India and a Review of Cases from Asian Countries

Objective: Short stature homeobox (SHOX) haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis. The worldwide prevalence of SHOX variations in ISS varies from 2.5% to 15.0%. The aim of this study was to assess the implication of SHOX variation in ISS in North Indians and compare this with other cases of SHOX variations from Asian population. Methods: SHOX gene analysis was carried out by multiplex ligation-dependent probe amplification followed by Sanger sequencing in 54 patients with variable phenotypes. Comparison with other reports in a meta-analysis comprising the current study and 11 previous studies (n=979) was performed. Results: SHOX analysis resulted in 12.9% positivity (7.4% deletions and 5.5% duplications). SHOX association was seen significantly related to gender, with predominance in females (p=0.047). Short arms and forearms were the only significantly associated trait seen in 51.9% of children. The overall prevalence of SHOX variation was 15.2% in Asians with ISS. No significant difference was found in geographical region-specific analysis. Conclusion: This study summarises findings from the last decade and provides an updated picture of the prevalence of SHOX variations in Asians, emphasizing their potential as therapeutic targets in ISS patients. Further high quality, large investigations including functional validation is warranted to validate this association.

Understanding the Constraints and Optimization of Serum Immunofixation Electrophoresis and Serum Free Light Chains for Detecting Monoclonal Proteins: A Single-Center Experience.

Introduction Serum immunofixation electrophoresis (SIFE) and serum free light chain (SFLC) assay are imperative investigations in diagnosis and follow-up of multiple myeloma (MM). SFLC assays are reported to have higher sensitivity than SIFE. However, discrepancies have been reported between them. The current study was aimed at assessing concordance and discordance between SIFE and SFLC results in MM. Methods A total of 450 observations of both SIFE and SFLC were obtained from treatment-naive and follow-up MM patients. Results One hundred and twenty-nine (28.7%) values were observed as discordant, that is, positive SIFE with normal SFLC ratio or negative SIFE with abnormal SFLC ratio ( p -value < 0.00001). Proportion of discordance was higher in SIFE positive-SFLC normal cases than SIFE negative-SFLC abnormal cases. Discordance was more frequent in follow-up cases. Conclusion Negative SFLC alone may not be reliable for MM follow-up. Algorithm may be based on SFLC measurements on each follow-up till attainment of normal SFLC ratio. Once SFLC normalizes, follow-up may be done with SIFE. If SIFE is positive, further follow-up with SIFE may be initiated.

Estimation of Reference Values for External Genitalia Parameters in North Indian Preterm and Term Female Newborns.

OBJECTIVES: To establish gestation-wise normative data of external genitalia measurements in North Indian term and preterm female newborns. METHODS: In this cross-sectional descriptive study, institutionally-born female neonates between 28-42 wk gestation were consecutively enrolled between 24-72 h of life. Newborns with major congenital malformations, chromosomal anomalies, multifetal gestation and birth injuries were excluded. Data on various genital measurements were collected [Clitoral length (CL), clitoral width (CW), ano-clitoral distance (AGDAC), ano-fourchette distance (AGDAF) and anogenital ratio (AGR)]. RESULTS: One hundred ninety-eight of 508 neonates (39%) were preterm and 310 (61%) were term. Mean (± SD) CL and CW were 4.6 ± 1.8 mm and 3.9 ± 1.6 mm, respectively. Mean (± SD) values for AGDAF, AGDAC and AGR were 9.3 ± 1.8 mm, 30.2 ± 3.9 mm, and 0.31 ± 0.05, respectively. According to these results, term female newborns with CL more than 7 mm and/or CW more than 6 mm (95th centile) warrant evaluation for clitoromegaly. An anogenital ratio greater than 0.45 should be considered as a sign of virilization in a female neonate. Gestation-wise percentile charts for CL, CW, AGDAF, AGDAC and AGR were generated. CONCLUSIONS: The percentile values defined in the study can serve as local normative data for accurate interpretation of genital measurements in North Indian female newborns and enable health care professionals for early identification of genital virilization.

Estimation of Reference Values for External Genitalia Parameters in North Indian Preterm and Term Male Newborns.

OBJECTIVES: To generate gestation-wise normative data of external genitalia measurements in North Indian term and preterm male newborns. METHODS: This was a hospital-based cross-sectional observational study. Male neonates born between 28-42 wk of gestation (at 24-72 h of life) were consecutively recruited in the study. Newborns with major congenital malformations, chromosomal anomalies, multifetal gestation and birth injuries were excluded. Data on various genital measurements were collected [Stretched penile length (SPL), penile width (PW), upper anogenital distance (AGDu), lower anogenital distance (AGDl) and anogenital ratio (AGR)]. RESULTS: Out of 532 newborns, 208 (39.1%) were preterm. Mean (± SD) SPL and PW were 27.9 ± 3.6 mm and 10.6 ± 1.3 mm respectively. The mean values for AGDl, AGDu and AGR were 20.13 ± 4.04 mm, 39.2 ± 5.59 mm, and 0.51 ± 0.07, respectively. SPL less than 21 mm in a term male newborn and 17.5 mm in preterm should be considered micropenis (<2.5 SD) in our population. Gestation-wise percentile charts for SPL, PW, AGDl, AGDu and AGR were generated. CONCLUSIONS: The reference values and percentile charts generated can serve as local normative data for accurate interpretation of genital measurements in North Indian newborns, assessment of ambiguous genitalia and avoiding diagnostic errors.

Growth Pattern and Use of Inter-pupillary Distance in the Detection of Ocular Hypertelorism and Hypotelorism in Indian Down Syndrome Children.

Use of inter-pupillary distance (IPD) for objective evaluation of ocular hypertelorism and hypotelorism is recommended to corroborate diagnosis of syndromic conditions. In view of complete absence of serial data on growth of IPD, this study aims to unfold auxological dynamics of IPD in Down syndrome (DS) children of Indian origin. Inner canthal distance (ICD) and outer canthal distance (OCD) were measured on a total of 1,125 (male: 752, female: 373) DS children, aged 0 to 3 months to 10 years at 6 monthly age intervals using a "Digimatic Sliding Caliper" in the Growth Laboratory/Growth Clinic of the Institute. Using Feingold and Bossert (1974) formula, IPD at each age was calculated from ICD and OCD measured among male and female DS children. IPD, like OCD and ICD increased un-interruptedly among DS children. IPD grew rapidly up to 5 years thereafter, its rapidity became slower. Boys in general, possessed larger IPD than girls, however, gender differences became statistically significant up to first 4 years of life. Our study children possessed significantly smaller IPD as compared with their normal Indian counterparts. None of our DS children depicted ocular hypertelorism while hypotelorism, was noticed amongst 4.9% male and 16.8% female DS patients. Comparison with normative IPD data failed to establish existence of ocular hypertelorism in DS children (<10 years) of north-western Indian origin. Use of age and gender-specific data presented for IPD of DS children may be made for comparative purpose to ascertain inter-population variability.

Percentile Charts for Body Mass Index of Indian Down Syndrome Children.

Growth charts are used to detect growth impairment, overweight, and obesity among Down syndrome (DS) children belonging to different population groups. Due to nonavailability of similar information, age, and gender specific body mass index (BMI) charts for DS children of Indian origin, based on serial data, have been developed. A total of 752 boys and 373 girls diagnosed as cases of DS at <1 month to 10 years of age enrolled from the "genetic clinic" were followed up in the "growth clinic/growth laboratory" of the institute, following a mixed-longitudinal growth research design. BMI was calculated from body weight and length/height measured at 6-month-age intervals by using standardized techniques and instruments. Age and sex-specific percentile growth charts for BMI were generated for age range <1 month to 10 years by using the LMS method. DS children remained wasted (BMI <3rd percentile) up to 6 months of age; thereafter, BMI increased to exhibit close similarity with their normal Multicentre Growth Reference Study (World Health Organization 2006) and Indian Academy of Pediatrics (2015) counterparts up to 5 to 10 years, respectively. The percentage of obese DS girls (8.76%) outnumbered boys with DS (4.1%). The use of age and gender specific BMI growth charts may be made for comparative purpose, to assess nutritional status of Indian children with DS, to initiate suitable need-based intervention to improve their overall health and for timely institution of target interventions to prevent growth faltering in this vulnerable population.

Detection of ocular hypertelorism among Indian children.

Background & objectives: Ocular hypertelorism constitutes an important component of many clinical syndromes. It is typically recommended to use inter-pupillary distance (IPD) for objective evaluation of ocular hypo/hypertelorism. Barring infancy, there is a scarcity of data on this anthropometric parameter relating to the ocular apparatus. This study aims to study auxological dynamics of IPD in children of Indian origin. Methods: A total of 3622 ( 2239 males and, 1383 females) normal, healthy Indian children of North-western origin, aged one month to 14 yr comprised the sample for this study. Inner and outer-canthal distance were measured using standardized anthropometric techniques. None of the children who participated in this study had craniofacial dysmorphism or any body deformity. Mean (standard deviation SD) and percentiles were calculated for IPD in male and female subjects at different age levels. Results: IPD increased from 4.68±0.21 to 6.19±0.36 cm in males and from 4.59±0.26 to 6.08±0.25 cm in females between one month and 14 yr of age. Boys in general, possessed larger IPD than girls, however, the gender differences became significant (P≤0.05) at 10, 11, 16-18 and 22-24 months, respectively, and five and 10 yr of age, respectively. Interpretation & conclusions: The results of this study suggest that the patients having IPD less than the 3rd percentile should be treated as cases of hypotelorism while, those exceeding 97th percentile as cases of hypertelorism. The use of percentile grids presented for IPD may be used to detect ocular hypotelorism and hypertelorism in male and female children to corroborate diagnosis of different syndromes.

Transcriptome analysis identifies TODL as a novel lncRNA associated with proliferation, differentiation, and tumorigenesis in liposarcoma through FOXM1.

Liposarcoma, the most common soft tissue sarcoma, is a group of fat cell mesenchymal tumors with different histological subtypes. The dysregulation of long non-coding RNAs (lncRNAs) has been observed in human cancers including a few studies in sarcoma. However, the global transcriptome analysis and potential role of lncRNAs remain unexplored in liposarcoma. The present investigation uncovers the transcriptomic profile of liposarcoma by RNA sequencing to gain insight into the global transcriptional changes in liposarcoma. Our RNA sequencing analysis has identified that many oncogenic lncRNAs are differentially expressed in different subtypes of liposarcoma including MALAT1, PVT1, SNHG15, LINC00152, and MIR210HG. Importantly, we identified a highly overexpressed, unannotated, and novel lncRNA in dedifferentiated liposarcomas. We have named it TODL, transcript overexpressed in dedifferentiated liposarcoma. TODL lncRNA displayed significantly higher expression in dedifferentiated liposarcoma cell lines and patient samples. Interestingly, functional studies revealed that TODL lncRNA has an oncogenic function in liposarcoma cells by regulating proliferation, cell cycle, apoptosis, differentiation, and tumorigenesis in the murine model. Silencing of TODL lncRNA highlighted the enrichment of several key oncogenic signaling pathways including cell cycle, transcriptional misregulation, FOXM1 network, p53 signaling, PLK1 signaling, FoxO, and signaling Aurora signaling pathways. RNA pull-down assay revealed the binding of TODL lncRNA with FOXM1, an oncogenic transcription factor, and the key regulator of the cell cycle. Silencing of TODL lncRNA also induces adipogenesis in dedifferentiated liposarcomas. Altogether, our finding indicates that TODL could be utilized as a novel, specific diagnostic biomarker, and a pharmacological target for therapeutic development in controlling aggressive and metastatic dedifferentiated liposarcomas.

Comprehensive assessment of cardiovascular disease risk in children with short stature due to isolated growth hormone deficiency: a case-control study.

OBJECTIVES: Growth hormone deficiency (GHD) in adults is associated with an increased risk of cardiovascular morbidity and mortality. Although children with GHD are also believed to have a similar cardiovascular disease (CVD) risk beginning at an early age, the available data in children is scarce. We aimed to determine the various CVD risk parameters in children with isolated GHD (IGHD). METHODS: A cross-sectional case-control study was conducted at a tertiary care centre in North India comparing various auxological, biochemical, and echocardiographic parameters between 20 IGHD children aged 5-15 years and their age and sex-matched healthy controls. RESULTS: The mean age of children with IGHD and controls was similar (10.5 ± 2.6 yr vs. 9.9 ± 2.7 yr, p=0.48). Children with IGHD had significantly higher waist-hip-ratio (p=0.01), total cholesterol (p=0.02), non-high-density lipoprotein-cholesterol (p=0.02), serum homocysteine (p<0.001), C-reactive protein (CRP) (p=0.01) and pro-brain natriuretic peptide (pro-BNP) (p=0.04) levels as compared to healthy controls. Left ventricular mass (LVM) and interventricular septal thickness were significantly lower (p=0.04; p=0.02) in IGHD children. Correlation analysis showed that pro-BNP and CRP levels had negative correlation (p<0.001, r=-0.70; and p=0.04, r=-0.44, respectively) and LVM had a positive correlation (p=0.02, r=0.53) with height SDS among IGHD children. CONCLUSIONS: Children with IGHD showed abnormalities in several biochemical and cardiac parameters that may be associated with an increased CVD risk in later life. More extensive studies, including younger children with IGHD, are needed to determine the lower ages at which the CVD risk is detectable.

Epigenetics in Kawasaki Disease.

Kawasaki disease (KD) is a common febrile multisystemic inflammatory illness in children that preferentially affects coronary arteries. Children with KD who develop coronary artery aneurysms have a life-long risk of premature coronary artery disease. Hypothesis of inherent predisposition to KD is supported by epidemiological evidence that suggests increased risk of development of disease in certain ethnicities and in children with a previous history of KD in siblings or parents. However, occurrence of cases in clusters, seasonal variation, and very low risk of recurrence suggests an acquired trigger (such as infections) for the development of illness. Epigenetic mechanisms that modulate gene expression can plausibly explain the link between genetic and acquired predisposing factors in KD. Analysis of epigenetic factors can also be used to derive biomarkers for diagnosis and prognostication in KD. Moreover, epigenetic mechanisms can also help in pharmacogenomics with the development of targeted therapies. In this review, we analysed the available literature on epigenetic factors such as methylation, micro-RNAs, and long non-coding RNAs in KD and discuss how these mechanisms can help us better understand the disease pathogenesis and advance the development of new biomarkers in KD.

Comparative efficacy of early morning versus bedtime administration of levothyroxine in children with hypothyroidism: a prospective, open label, randomized, case-control study.

INTRODUCTION: Studies in adults with hypothyroidism suggest an equal efficacy of bedtime versus early morning intake of levothyroxine. There is limited data on timing of levothyroxine administration in children. MATERIAL AND METHODS: Children with hypothyroidism on early morning levothyroxine, and clinically and biochemically euthyroid, were assigned to receive levothyroxine at bedtime (group A) or were continued on early morning levothyroxine intake (group B). Clinical, anthropometric and laboratory evaluation (thyroid and lipid profiles, liver enzymes and creatinine) was done at baseline, and at 3 and 6 months. RESULTS: Eighty-four children, 42 in each group, completed the study. The clinical and anthropometric parameters remained similar in the two groups at baseline and at 3- and 6-month follow-up visits. There was no difference in the mean serum concentrations of triiodothyronine, thyroxine and thyrotropin at the 3 time-points in the study. In addition, mean serum aspartate transaminase, alanine transaminase, creatinine and parameters of lipid profiles remained similar in the two groups. The requirement of levothyroxine was similar at baseline (48.6 ±16.9 µg vs. 49.6 ±19.5 µg, p-value 0.80) and at the endpoint (48.3 ±17.2 µg vs. 51.9 ±18.0 µg, p-value 0.46) in both groups. At the study end, 25 (60%) patients in group A and 17 (40%) in group B preferred bedtime dosing of levothyroxine. CONCLUSIONS: We found an equal efficacy of bedtime intake compared to early morning intake of levothyroxine in maintaining an euthyroid state in children with hypothyroidism. Further studies are required to see if bedtime levothyroxine administration improves the quality of life of patients.

Auxological dynamics of children with Juvenile Idiopathic Arthritis: a mixed-longitudinal study from Chandigarh, North India.

Objective: To study growth pattern of weight and length/height in male and female children with Juvenile Idiopathic Arthritis (JIA). Methods: A total of 348 patients (boys: 182, girls: 166) aged 1 to 18 years, diagnosed as cases of JIA and categorized into oligoarthritis, polyarthritis and systemic arthritis were enrolled in this mixed-longitudinal study from Pediatric Rheumatology Clinic of Advanced Pediatrics Centre, PGIMER, Chandigarh, India. Weight and length/height measurements were recorded at approximately 6 monthly intervals in Growth Laboratory/Growth Clinic of the department over a period of 13 years. Mean (SD) for weight and length/height were computed. Unpaired Student's t-test was employed to ascertain gender differences. Analysis of variance and post-hoc Bonferroni tests were applied to evaluate inter-group differences. Results: A regular increase in weight and length/height of all children representing three types of JIA was noticed throughout the study period. Maximum growth impairment was seen in patients with systemic JIA. Children with oligoarthritis were least affected. Boys with oligoarthritis, measured lighter and shorter than girls. Gender differences for children with polyarthritis demonstrated inconsistent trends. Boys with systemic JIA generally measured lighter than girls. Boys with systemic JIA measured taller than girls upto 4 years and thereafter they remained shorter till 14 years. Conclusions: As compared to normal children (2000 CDC), impaired weight and length/height growth attainments were recorded in oligoarthritis, polyarthritis and systemic JIA patients throughout the study span. However, the magnitude of this impairment appears to be related to the subtype of JIA.

Growth pattern of skinfold thicknesses in term symmetric & asymmetric small for gestational age infants.

Background & objectives: A etiologically symmetric and asymmetric small for gestational age (SGA) infants are two distinct entities. In view of absence of longitudinal information on growth pattern of skinfold thicknesses (SFTs) among Indian infants, this study was conducted to assess the auxological dynamics of SFTs (sub-cutaneous fat) of symmetric and asymmetric SGA infants. Methods: Triceps, sub-scapular, biceps, mid-axillary and anterior thigh SFTs among full-term, 100 symmetric SGA, 100 asymmetric SGA and 100 appropriate for gestational age (AGA) infants were measured at one, three, six, nine and 12 months. Ponderal Index (PI) was used to categorize infants into symmetric SGA (PI ≥2.2 g/cm3) and asymmetric SGA (PI <2.2 g/cm3). Intra-group (symmetric vs. asymmetric), inter-group (SGA vs. AGA) and gender differences were quantified. Results: SFTs among symmetric, asymmetric SGA infants increased to attain peak by six months. Maximum fat deposition in SGA infants was noticed for triceps, minimum for mid-axillary SFT. Mean triceps and sub-scapular skinfolds were measured higher in symmetric SGA than in asymmetric infants. SGA infants had significantly (P≤0.05) thinner SFTs than AGA. Growth velocity for SFTs, among symmetric and asymmetric SGA, was measured maximum between one and three months, threreafter it declined and relatively, steepness of fall was maximum for mid-axillary SFT followed by sub-scapular SFT. Interpretation & conclusions: Thinner SFTs obtained for symmetric and asymmetric SGA as compared to AGA infants reveal their compromised adiposity and nutritional status. Comparatively, higher SFTs in symmetric than in asymmetric SGA infants appear to suggest that the former have a tendency to accumulate more fat, than the latter during infancy.

TP63, SOX2, and KLF5 Establish a Core Regulatory Circuitry That Controls Epigenetic and Transcription Patterns in Esophageal Squamous Cell Carcinoma Cell Lines.

BACKGROUND & AIMS: We investigated the transcriptome of esophageal squamous cell carcinoma (ESCC) cells, activity of gene regulatory (enhancer and promoter regions), and the effects of blocking epigenetic regulatory proteins. METHODS: We performed chromatin immunoprecipitation sequencing with antibodies against H3K4me1, H3K4me3, and H3K27ac and an assay for transposase-accessible chromatin to map the enhancer regions and accessible chromatin in 8 ESCC cell lines. We used the CRC_Mapper algorithm to identify core regulatory circuitry transcription factors in ESCC cell lines, and determined genome occupancy profiles for 3 of these factors. In ESCC cell lines, expression of transcription factors was knocked down with small hairpin RNAs, promoter and enhancer regions were disrupted by CRISPR/Cas9 genome editing, or bromodomains and extraterminal (BET) family proteins and histone deacetylases (HDACs) were inhibited with ARV-771 and romidepsin, respectively. ESCC cell lines were then analyzed by whole-transcriptome sequencing, immunoprecipitation, immunoblots, immunohistochemistry, and viability assays. Interactions between distal enhancers and promoters were identified and verified with circular chromosome conformation capture sequencing. NOD-SCID mice were given injections of modified ESCC cells, some mice where given injections of HDAC or BET inhibitors, and growth of xenograft tumors was measured. RESULTS: We identified super-enhancer-regulated circuits and transcription factors TP63, SOX2, and KLF5 as core regulatory factors in ESCC cells. Super-enhancer regulation of ALDH3A1 mediated by core regulatory factors was required for ESCC viability. We observed direct interactions between the promoter region of TP63 and functional enhancers, mediated by the core regulatory circuitry transcription factors. Deletion of enhancer regions from ESCC cells decreased expression of the core regulatory circuitry transcription factors and reduced cell viability; these same results were observed with knockdown of each core regulatory circuitry transcription factor. Incubation of ESCC cells with BET and HDAC disrupted the core regulatory circuitry program and the epigenetic modifications observed in these cells; mice given injections of HDAC or BET inhibitors developed smaller xenograft tumors from the ESCC cell lines. Xenograft tumors grew more slowly in mice given the combination of ARV-771 and romidepsin than mice given either agent alone. CONCLUSIONS: In epigenetic and transcriptional analyses of ESCC cell lines, we found the transcription factors TP63, SOX2, and KLF5 to be part of a core regulatory network that determines chromatin accessibility, epigenetic modifications, and gene expression patterns in these cells. A combination of epigenetic inhibitors slowed growth of xenograft tumors derived from ESCC cells in mice.

Low serum copper and zinc concentrations in North Indian children with overweight and obesity

INTRODUCTION: There are limited data on the alterations of serum copper and zinc, which have been proposed to have associations among children with obesity. MATERIAL AND METHODS: A total of 173 children were enrolled and grouped into overweight/obese (n = 69) and non-obese (n = 104) according to CDC 2000 growth charts. Serum and whole blood zinc and copper concentrations were measured by validated ICP-MS method, and copper/zinc ratios were calculated and correlated to various anthropometric parameters. RESULTS: Mean BMI in obese (24.78 ±3.93) was significantly higher as compared to non-obese (16.44 ±2.34; p < 0.0001, 95% CI: 15.9873-16.8998) children. Mean serum copper levels in obese children (1099.80 ±478.67 µg/l) were significantly lower than for non-obese children (2063.77 ±1006.81 µg/l; p = 0.0001, 95% CI: 1867.9755-2259.5755). Similarly, the mean serum zinc levels in obese children (851.53 ±406.33 µg/l) were also significantly lower as compared to non-obese children (1528.72 ±796.82 µg/l; p = 0.0001, 95% CI: 1373.76-1683.6879). Mean whole blood copper levels were significantly lower in obese (929.56 ±200.15 µg/l) as compared to non-obese (1393.22 ±861.92 µg/l; p = 0.0001, 95% CI: 1225.6023-1560.8481) children. Similarly, the mean whole blood zinc levels in obese (4384.11 ±881.87 µg/l) were also significantly lower as compared to non-obese (5380.14 ±2236.77 µg/l; p = 0.001, 95% CI: 4945.1491-5815.1416) children. CONCLUSIONS: The serum and whole blood concentrations of zinc and copper were found to be significantly lower in children with exogenous obesity as compared to controls. Additional investigations are recommended to see the underlying aspect of these elements in the development of obesity along with their co-morbidities.

Longitudinal growth dynamics of term symmetric and asymmetric small for gestational age infants.

ABSTRACT: Background: Available information on auxological attainments of symmetric and asymmetric SGA (small for gestational age) infants presents conflicting views. The complete absence of longitudinal data on growth patterns of both types of Indian SGA infants prompted us to undertake this study. Aim: To study distance and velocity growth pattern of weight and crown-heel length (CHL) of symmetric and asymmetric SGA infants. Subjects & Methods: Weight and CHL amongst full-term 100 symmetric SGA, 100 asymmetric SGA and 100 AGA infants from upper socio-economic strata were mixed-longitudinally measured at birth, 1, 3, 6, 9 and 12 months in the Department of Pediatrics, PGIMER, Chandigarh, India. Results: The symmetric SGA infants measured significantly lighter and shorter than asymmetric infants. SGA infants of both types and sexes possessed significantly (p ≤ 0.001) lower weight and length values than AGA, normal Indian and western infants. Weight and CHL growth velocities demonstrated inconsistent trends. Peak growth velocity for weight and CHL of symmetric, asymmetric SGA and AGA infants was attained between 1-3 months. Average z-scores for weight and CHL were found to be lesser amongst symmetric SGA as compared to asymmetric infants, revealing compromised catch-up growth. Conclusion: The poorer postnatal auxological attainments of SGA infants as compared to normal infants reveals continuation of effect of intra-uterine nutritional insult during infancy, which measured significantly more in symmetric than asymmetric SGA infants.

Candida species epidemiology 2000-2013: a laboratory-based report.

OBJECTIVE: To describe a prospective laboratory-based surveillance of Candida species that were collected from different anatomical sites of patients admitted to the University of Malaya Medical Centre, Malaysia, from the year 2000 to 2013. METHODS: Conventional (culture, microscopic examination and carbohydrate assimilation test) and molecular (PCR amplification and DNA sequencing) techniques were used to identify Candida species. RESULTS: A total of 16 Candida species isolated from 34 392 clinical samples were from the oral cavity (oral swabs and throat swabs), blood, respiratory tract (sputum, tracheal secretions, nasopharyngeal aspirates, bronchoalveolar lavage), high vaginal swab, pus and urine. C. albicans (66.70%, 22 941/34 392), C. glabrata (11.71%, 4029/34 392), C. parapsilopsis (10.74%, 3692/34 392), C. tropicalis (9.19%, 3162/34 392) and C. krusei (1.15%, 396/34 392) were the five predominant Candida species. C. albicans was the predominant species isolated from the oral cavity, respiratory tract and high vaginal swab; while the Candida species isolated from blood, urine and pus were predominant non-albicans Candida. Uncommon Candida species, such as C. lusitaniae, C. haemulonii, C. humicola, Pichia ohmeri and C. ciferrii, were also isolated in this study. CONCLUSION: Our study expands the current knowledge of the epidemiology of non-invasive and invasive candidiasis in Malaysia. The variability of the Candida species distribution from different anatomical sites highlights the significance of local epidemiology in disease management and selection of antifungal agents.