Effectiveness of facilitated tucking on reducing pain during heel stick in neonates: a randomized controlled experimental study.

Background: Pain in neonates is associated with adverse neurodevelopmental outcomes in the later days of life. Facilitated tucking is a nonpharmacological method of pain relief. The study aims to compare the effect of facilitated tucking in pain reduction in neonates. Materials and methods: This was a randomized controlled experimental study conducted in the neonatal ward of a tertiary care center. There were 25 neonates randomized each in the experimental and control groups (total of 50), based on computer-generated random tables. The experimental group was placed in a facilitated tucking position during heel stick, while the control group was kept in the usual position, as done routinely. A self-structured questionnaire and Neonatal Infant Pain Scale were used. The main outcome measures were the mean Neonatal Infant Pain Scale score, and change in preprocedure and postprocedure heart rate and oxygen saturation in the two groups. Ethical clearance and informed written consent were sought. Results: Neonates in the experimental group had significantly lesser pain (less Neonatal Infant Pain Scale score) than the neonates in the control group (P<0.001). There was also a significant increment in the mean heart rate and a decrease in the oxygen saturation after the procedure in the control group, indicating significantly more pain perception (P<0.001) in the control group. Conclusions: Facilitated tucking was found to be effective in reducing the pain during heel stick procedures in neonates.

Simple and convenient mapping of molecular dynamics mechanical property predictions of bisphenol-F epoxy for strain rate, temperature, and degree of cure.

It is well-known that all-atom molecular dynamics (MD) predictions of mechanical properties of thermoset resins suffer from multiple accuracy issues associated with their viscoelastic nature. The nanosecond simulation times of MD simulations do not allow for the direct simulation of the molecular conformational relaxations that occur under laboratory time scales. This adversely affects the prediction of mechanical properties at realistic strain rates, intermediate degrees of cure, and elevated temperatures. While some recent studies have utilized a time-temperature superposition approach to relate MD predictions to expected laboratory observations, such an approach becomes prohibitively difficult when simulating thermosets with a combination of strain rates, intermediate degrees of cure, and temperatures. In this study, a phenomenological approach is developed to map the predictions of Young's modulus and Poisson's ratio for a DGEBF/DETDA epoxy system to the corresponding laboratory-based properties for intermediate degrees of cure and temperatures above and below the glass transition temperature. The approach uses characterization data from dynamical mechanical analysis temperature sweep experiments. The mathematical formulation and experimental characterization of the mapping is described, and the resulting mapping of computationally-predicted to experimentally-observed elastic properties for various degrees of cure and temperatures are demonstrated and validated. This mapping is particularly important to mitigate the strain-rate effect associated with MD predictions, as well as to accurately predict mechanical properties at elevated temperatures and intermediate degrees of cure to facilitate accurate and efficient composite material process modeling.

Molecular mechanism of synovial joint site specification and induction in developing vertebrate limbs.

The vertebrate appendage comprises three primary segments, the stylopod, zeugopod and autopod, each separated by joints. The molecular mechanisms governing the specification of joint sites, which define segment lengths and thereby limb architecture, remain largely unknown. Existing literature suggests that reciprocal gradients of retinoic acid (RA) and fibroblast growth factor (FGF) signaling define the expression domains of the putative segment markers Meis1, Hoxa11 and Hoxa13. Barx1 is expressed in the presumptive joint sites. Our data demonstrate that RA-FGF signaling gradients define the expression domain of Barx1 in the first presumptive joint site. When misexpressed, Barx1 induces ectopic interzone-like structures, and its loss of function partially blocks interzone development. Simultaneous perturbations of RA-FGF signaling gradients result in predictable shifts of Barx1 expression domains along the proximo-distal axis and, consequently, in the formation of repositioned joints. Our data suggest that during early limb bud development in chick, Meis1 and Hoxa11 expression domains are overlapping, whereas the Barx1 expression domain resides within the Hoxa11 expression domain. However, once the interzone is formed, the expression domains are refined and the Barx1 expression domain becomes congruent with the border of these two putative segment markers.

Depression, Anxiety and Stress among Nurses Providing Care to the COVID-19 Patients: A Descriptive Cross-sectional Study.

INTRODUCTION: Addressing adequately the mental health during and after COVID-19, as well as preparation for possible future outbreaks, requires an understanding of the nature and extent of mental health impacts, factors related to negative mental health outcomes and symptoms of mental illness. The aim of this study was to find the prevalence of depression, anxiety and stress among nurses providing care to the COVID-19 patients. METHODS: A descriptive cross-sectional study was conducted from 10th April 2021 to 30th June 2021 among 301 nurses from three COVID-19 dedicated hospitals using self-administered questionnaires. Whole sampling technique was used. Ethical approval was obtained from the Ethical Review Board of Nepal Health Research Council (Registration number: 106/2021P). The data was analyzed using the Statistical Package for the Social Sciences version 16. Descriptive statistics like frequency, percentage, mean and standard deviation were calculated. RESULTS: Out of 301 nurses, the prevalence of depression, anxiety and stress was 258 (85.72%), 189 (62.80%) and 151 (49.84%) respectively. CONCLUSIONS: The study has shown a higher prevalence of depression, anxiety and stress among nurses in comparison to other studies in the similar settings. A quick assessment of the mental health status and mental health requirements of nurses would be helpful in responding to and reducing psychological distress in the crisis situation. The mental health status of nurses should thus be closely monitored by the employing health institutions including managing their workload, providing emotional support and responding to their personal needs.

FokI polymorphism of the vitamin D receptor (VDR) gene and susceptibility to tuberculosis: Evidence through a meta-analysis.

BACKGROUND: Tuberculosis is one of the top ten causes of deaths worldwide. The deficiency of vitamin D was reported to be associated with the increased susceptibility of tuberculosis. Various previous reports were published to check the association of FokI polymorphism of the vitamin D receptor gene with tuberculosis risk. But their results were inconsistent so, we performed a meta-analysis to know the exact relation of the two. METHODS: Different databases were screened up to November 2020 with the keywords "Vitamin D receptor", "VDR", and "FokI", along with "Tuberculosis" and "TB" to find the suitable articles. All the statistical analyses were performed by the Open Meta-Analyst program and all p-values were two-tailed with a significance level of 0.05. RESULTS: No statistically significant association was observed in the allele contrast model (ORfvs.F = 1.11, 95%CI = 0.99-1.24, p = 0.05, I2 = 73.46%), in the dominant model (ORff+Ffvs.FF = 1.11, 95%CI = 0.96-1.28, p = 0.14, I2 = 71.39%), and in the co-dominant model (ORFfvs.FF = 1.05, 95%CI = 0.92-1.21, p = 0.41, I2 = 65.97%). However, a significant association was found in the homozygote model (ORffvs.FF = 1.32, 95%CI = 1.03-1.69, p = 0.02, I2 = 67.02%) and in the recessive model (ORFF+Ff vs.ff = 1.26, 95%CI = 1.03-1.54, p = 0.02, I2 = 58.01%). Further analysis was performed on the bases of the ethnicity. In Asian population a significant association was found in the homozygote model (ORffvs.FF = 1.57, 95%CI = 1.12-2.21, p = 0.008, I2 = 70.37%) and in the recessive model (ORFF+Ff vs.ff = 1.43, 95%CI = 1.08-1.89, p = 0.01, I2 = 63.13%). CONCLUSION: In conclusion, a significant association of FokI with tuberculosis susceptibility was found in the overall analysis and in the Asian population.

Distribution of Methionine Synthase Reductase (MTRR) Gene A66G Polymorphism in Indian Population.

Methionine synthase reductase (MTRR) is an important enzyme of the folate/homocysteine pathway. It is responsible for regulation of methionine enzyme by reductive methylation. A common variant A66G is reported in the FMN-binding domain of the MTRR gene, which leads to substitution of isoleucine by methionine (I22M) in MTRR enzyme with reduced activity. Reduced catalytic activity of enzyme leads to high homocysteine concentration in blood and increases risk for numerous diseases. The frequency of A66G polymorphism varies in different ethnic groups. The present study has been designed to evaluate the frequency of MTRR A66G gene polymorphism in the Eastern UP population by PCR-RFLP method. Along with this we also performed a meta-analysis to evaluate the global prevalence of this polymorphism. Databases were screened to identified the eligible studies. The prevalence of the G allele and GG genotype was determined by the use of prevalence proportion with 95% CI. Open meta-analyst software was used for the meta-analysis. Total 1000 blood samples were analyzed, the frequencies of A and G alleles were 0.35 and 0.65 respectively. Meta-analysis results revealed that the prevalence of G allele and GG genotype were 49.4% (95% CI 40.6-58.1, p ≤ 0.001) and 24.3% (95% CI 17.8-30.9, p ≤ 0.001) respectively. In sub-group meta-analysis, the lowest frequency of G allele was found in South America (32.7%; 95% CI 14.1-51.3, p ≤ 0.001), and highest in Asia (56.4%; 95% CI 39.5-73.3, p ≤ 0.001). The results of the meta-analysis showed that the Asian population has the highest frequency of G allele and highest frequency of the GG genotype was found in the European population.

Maternal biomarkers for early prediction of the neural tube defects pregnancies.

BACKGROUND: Neural tube defects (NTD) are one of the most common congenital birth defects. The reason for the NTD cause is still not completely known, but it is believed that some genetic and environmental factors might play a role in its etiology. Among the genetic factors the polymorphism in the folate gene pathway is crucial. Numerous studies have suggested the possible role of maternal higher plasma concentration of homocysteine and low concentration of folate and cobalamin in the development of NTD but some negative studies are also published. AIM: Aim of the present was to find out the exact relation between NTD and maternal biomarkers like folate, cobalamin and homocysteine by conducting a meta-analysis. METHOD: Different electronic databases were searched for the eligible studies. Standardized mean difference (SMD) with 95% confidence interval (CI) was used to determine association between maternal markers as risk for NTD pregnancy. The p value <0.05 was considered statistically significant in all tests. All the statistical analyses were done in the Open Meta-Analyst program. RESULTS: The homocysteine is significantly associated with the increased risk of NTD (SMD = 0.57; 95% CI: 0.35-0.80, p = <0.001; I2 = 93.01%), s-folate showed protective role in NTD (SMD = -0.48; 95% CI: -0.77 to -0.19, p = 0.001; I2 = 95.73%), similarly cobalamin is also having protective role (SMD = -0.28; 95% CI: -0.43 to -0.13, p = <0.001; I2 = 80.40%). CONCLUSION: In conclusion this study suggest that different maternal biomarkers may be used for the early prediction of the NTDs.

Simultaneous differentiation of articular and transient cartilage: WNT-BMP interplay and its therapeutic implication.

Limb skeleton forms through the process of endochondral ossification. This process of osteogenesis proceeds through an intermediate cartilage template and involves several stages of chondrocyte maturation and eventual bone formation. During the process of endochondral ossification, interplay between BMP and WNT signaling regulate simultaneous differentiation of articular and transient cartilage. In this review, we focus on the recent literature which explores the simultaneous differentiation of these two different types of cartilage. We discuss a new paradigm of developmental biology-inspired tissue engineering of bone and cartilage grafts and provide novel insight into treatment of osteoporosis.

Newborn Care Practices at Home among Mothers of Neonates Admitted with Sepsis.

BACKGROUND: Child rearing practices and family environment determine the health of newborn. Harmful newborn care practices are the risk factors for late onset neonatal sepsis. The objective was to identify newborn practices related to breast feeding, cord care, hygiene of newborn and thermal care practice at home of admitted neonates with diagnosis Late Onset Neonatal Sepsis in pediatric unit of B.P. Koirala Institute of Health Sciences tertiary center in eastern Nepal. METHODS: Descriptive cross sectional study was carried out from December 2014 to January 2015 using consecutive sampling. Semi structured, pretested questionnaire was used to interview 40 mothers. Data were analyzed using SPSS 20, descriptive and inferential statistics were used. RESULTS: Initiation of breastfeeding within one hour of delivery was practiced by only 40% of mother. Among neonates, 65% were given colostrum, 25% were given pre lacteal feed, and 45% were given formula milk and animal milk. Mustard oil was used to care umbilical cord by 72.5 %. Hand washing was practiced by 62.5 % before touching the baby. Application of kajal (52.5%) in eyes and use of mustard oil (95%) for massaging newborn was common. For thermal care, burning charcoal (75%) was mostly used. The study revealed association between newborn care and mother education, per capita income of family and family type (p =0.012, p= 0.012, p=0.039) respectively. CONCLUSIONS: Majority of practices in breast feeding and thermal care were good however in cord care and newborn hygiene practices was poor which stresses the need for the promotion of health education program to mothers by health care facilities.

Three-year clinical application practice report of lung ultrasound in our NICU / 中国小儿急救医学

Objective To retrospectively analyze the application of lung ultrasound in neonatal de-partment of our hospital in the past three years,and summed up the clinical diagnosis and treatment changes brought by it. Methods The clinical data of infants accepted the bedside lung ultrasound examination from May to December 2016(early carry out stage),from January to December 2017(adaptation stage),from Jan-uary to August 2018(normal conduct stage) in our NICU of Jingzhou Central Hospital were collected. The clinical data of 878 infants with different stages of application were compared and analyzed. Results In 878 children,1 225 of lung ultrasound were performed,64. 1% of patients had pulmonary disease,and 35. 9% had no lung disease. There were 67 cases of neonatal respiratory distress syndrome,278 cases of wet lung,259 ca-ses of pneumonia,64 cases of meconium aspiration syndrome,72 cases of acute respiratory distress syn-drome,63 cases of atelectasis and 14 cases of pleural effusion. A total of 1 122 times of lung X-ray examina-tion were performed in 878 children. The number of X-ray examinations per capita decreased from 2. 48 times in 2016 to 1. 40 times in 2017 and 0. 84 times in 2018. A total of 32 times of pulmonary CT examination were performed. The number of lung CT inspection decreased from 0. 060 times in 2016 to 0. 038 times in 2017 and 0. 029 times in 2018. Lung ultrasound was convenient for dynamic observation,and could be used to de-termine the improvement,aggravation or new pulmonary lesions. Conclusion Lung ultrasound is accurate in the diagnosis of lung disease in NICU,especially for children with long hospital stay,repeated illness and dif-ficult to withdraw. It is easy to carry out in clinic,at the bedside,which can reduce the times of chest X-ray and CT per capita examination. Lung ultrasound is an effective and feasible method for NICU to diagnose lung diseases and it is worth promoting.

"NQO1 Gene C609T Polymorphism (dbSNP: rs1800566) and Digestive Tract Cancer Risk: A Meta-Analysis."

Several studies reported that polymorphism C609T (rs1800566) in (NAD(P)H): quinoneoxidoreductase 1 (NQO1) gene is associated with risk to digestive tract (DT) cancers, like esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC). Authors conducted a meta-analysis to investigate association between C609T polymorphism and DT cancer risk. Eligible studies were extracted from the databases of PubMed, Google Scholar, Science Direct, and Springer Link. All retrieved articles were evaluated. All statistical analyses were performed using Open Meta-Analyst and MIX1.7 programs. A total of 34 studies including 12,043 DT cancer cases and 15,209 healthy controls were included in the present meta- analysis. Results of meta-analysis revealed a significant association between NQO1 C609T polymorphism and DT cancer risk adopting all 5 genetic models (T vs. C: OR = 1.21, 95% CI = 1.11-1.31, p < 0.001; TT vs. CC: OR = 1.48, 95% CI = 1.22-1.79, p < 0.001; TT + CT vs. CC: OR = 1.23, 95% CI = 1.12-1.35, p < 0.001; TT vs. CT + CC: OR = 1.36, 95% CI = 1.15-1.60, p < 0.001; CT vs. CC: OR = 1.16, 95% CI = 1.07-1.27, p < 0.001). In the stratified analysis based on cancer types, significant associations were observed between NQO1 C609T polymorphism and GC (OR = 1.38, 95% CI = 1.11-1.72, p = 0.003) and CRC (OR = 1.18, 95% CI = 1.06-1.30, p = 0.001), but not with EC (OR = 1.16, 95% CI = 0.99-1.35, p = 0.06). Furthermore, stratified analysis based on ethnicity indicated that there was a significant association between NQO1 C609T polymorphism and DT cancer risk in the Asian (TT vs. CC: OR = 1.55, 95% CI = 1.21-2.00, p ≤ 0.001) as well as in Caucasian populations (TT vs. CC: OR = 1.34, 95% CI = 1.04-1.73, p = 0.02). In conclusion, the results of meta-analysis suggested that the NQO1 C609T polymorphism is a risk factor for DT cancers, including GC and CRC.

NFIA and GATA3 are crucial regulators of embryonic articular cartilage differentiation.

During appendicular skeletal development, the bi-potential cartilage anlagen gives rise to transient cartilage, which is eventually replaced by bone, and to articular cartilage that caps the ends of individual skeletal elements. While the molecular mechanism that regulates transient cartilage differentiation is relatively well understood, the mechanism of articular cartilage differentiation has only begun to be unraveled. Furthermore, the molecules that coordinate the articular and transient cartilage differentiation processes are poorly understood. Here, we have characterized in chick the regulatory roles of two transcription factors, NFIA and GATA3, in articular cartilage differentiation, maintenance and the coordinated differentiation of articular and transient cartilage. Both NFIA and GATA3 block hypertrophic differentiation. Our results suggest that NFIA is not sufficient but necessary for articular cartilage differentiation. Ectopic activation of GATA3 promotes articular cartilage differentiation, whereas inhibition of GATA3 activity promotes transient cartilage differentiation at the expense of articular cartilage. We propose a novel transcriptional circuitry involved in embryonic articular cartilage differentiation, maintenance and its crosstalk with the transient cartilage differentiation program.

Distribution of MTHFR C677T Gene Polymorphism in Healthy North Indian Population and an Updated Meta-analysis.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate pathway. Several polymorphisms were reported in MTHFR gene but C677T polymorphism is most studied and it has been reported to be risk factor for several diseases/disorders. The present study was designed to explore the frequency of MTHFR C677T polymorphism in North Indian healthy population. In addition to this a meta-analysis of published articles was also performed to estimate the global prevalence of MTHFR C677T polymorphism. A total of 1000 unrelated healthy subjects were selected for MTHFR C677T polymorphism analysis. Different databases were searched for eligible articles. Prevalence proportion with 95 % CI was used to determine global prevalence of T allele and TT genotype. Meta-analysis was performed by Open meta-analyst. In 1000 blood samples analyzed, the frequency of T allele and TT genotype was 11 and 1 % respectively. Results of the meta-analysis showed that the global prevalence of T allele and TT genotype were 24.0 % (95 % CI 21.7-26.5) and 7.7 % (95 % CI 6.5-8.9) respectively. In sub-group meta-analysis, the lowest frequency of T allele was found in Africans (10.3 %; 95 % CI 3.8-16.8), and highest in Europeans (34.1 %; 95 % CI 31.9-36.3). The frequency of T allele in the North India is 11 %. The results of the meta-analysis showed that the frequency of the T allele and the TT genotype of C677T is highest in the Caucasian population.

Methylenetetrahydrofolate reductase A1298C genetic variant& risk of schizophrenia: A meta-analysis.

BACKGROUND & OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme of folate metabolism, whose role in schizophrenia is debatable. Numerous case-control studies have investigated the association of MTHFR A1298C polymorphism with schizophrenia, but results are controversial. The aim of the present study was to find the association between MTHFR A1298C gene polymorphism and schizophrenia. METHODS: PubMed, Google Scholar, Science Direct and Springer link databases were searched for case-control association studies in which MTHFR A1298C polymorphism was investigated as a risk factor for schizophrenia. In all, 19 studies with 4049 cases and 5488 controls were included in this meta-analysis. Odds ratios (ORs) with 95 per cent confidence intervals (CIs) were used as an association measure. RESULTS: The results of meta-analysis reported a significant association between A1298C polymorphism and schizophrenia risk in overall comparisons in all genetic models (C vs. A: OR=1.13, 95% CI=1.01-1.27, P=0.02; CC vs. AA: OR=1.20, 95% CI=1.03-1.39, P=0.02; AC vs. AA: OR=1.13, 95% CI=1.03-1.23, P=0.009; AC+CC vs. AA: OR=1.14, 95% CI=1.02-1.24, P=0.002; CC vs. AA+AC: OR=1.17, 95% CI=1.01-1.35, P=0.04). INTERPRETATION & CONCLUSIONS: MTHFR A1298C polymorphism was found to be a risk factor for schizophrenia and might have played a significant role in the pathogenesis of schizophrenia.

Impact of Catechol-O-Methyltransferase Val 158Met (rs4680) Polymorphism on Breast Cancer Susceptibility in Asian Population

Background: Catechol-O-methyltransferase (COMT) is an important estrogen-metabolizing enzyme. Numerous case-control studies have evaluated the role COMT Val 158Met (rs4680;472G->A) polymorphism in the risk of breast cancer and provided inconclusive results, hence present meta-analysis was designed to get a more reliable assessment in Asian population. Methods: A total of 26 articles were identified through a search of four electronic databases- PubMed, Google Scholar, Science Direct and Springer link, up to March, 2016. Pooled odds ratios (ORs) with 95% con¬fidence intervals (CIs) were used as association measure to find out relationship between COMT Val158Metpolymorphism and the risk of breast cancer. We also assessed between study heterogeneity and publication bias. All statistical analyses were done by Open Meta-Analyst. Results: Twenty six case-control studies involving 5,971 breast cancer patients and 7,253 controls were included in the present meta-analysis. The results showed that the COMT Val158Met polymorphism was significantly associated with breast cancer risk except heterozygote model(allele contrast odds ratio (ORAvsG)= 1.13, 95%CI=1.02-1.24,p=0.01; heterozygote/co-dominant ORGAvsGG= 1.03, 95%CI=0.96-1.11,p=0.34; homozygote ORAAvsGG= 1.38, 95%CI= 1.08-1.76,p=0.009; dominant model ORAA+GAvsGG= 1.08, 95%CI=1.01-1.16,p=0.02; and recessive model ORAAvsGA+GG= 1.35, 95%CI=1.07-1.71,p=0.01). In addition, we also performed subgroup analysis based on source of controls and menopausal state of patients. Conclusions: In conclusion, the COMT Val158Met polymorphism was related to increased breast cancer susceptibility in the Asian population.

Role of MTHFR C677T gene polymorphism in the susceptibility of schizophrenia: An updated meta-analysis.

Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme of folate/homocysteine metabolic pathway. C677T polymorphism of MTHFR gene was reported as risk factor for congenital defects, metabolic and neuropsychiatric disorders. Numerous case-control studies investigated C677T polymorphism as risk factor for schizophrenia but results of these studies were contradictory. To draw a conclusion, a meta-analysis of all available case-control studies was performed. PubMed, Google Scholar, Springer Link and Elsevier databases were searched for eligible case-control studies. Pooled odds ratio with 95%CI was used as an association measure and all statistical analyses were performed by Open Meta-Analyst and MIX software. Total 38 studies with 10,069 cases and 13,372 controls were included in the present meta-analysis. Results of meta-analysis showed significant associated between C677T polymorphism and risk of schizophrenia (ORTvsC=1.18, 95%CI=1.10-1.27, p=<0.001; ORCTvsCC=1.10, 95%CI=1.04-1.17, p=<0.001; ORTTvsCC=1.40, 95%CI=1.20-1.64, p=<0.001; ORTT+CTvsCC=1.19, 95%CI=1.09-1.30, p=<0.001). We also performed subgroup and sensitivity analyses. Subgroup analysis was done according to ethnicity and significant association was found between C677T polymorphism and risk of schizophrenia in all three ethnic populations-African (OR=2.51; 95%CI=1.86-3.40; p=<0.001), Asian (OR=1.21; 95%CI=1.10-1.33; p=<0.001) and Caucasian (OR=1.07; 95%CI=1.01-1.14; p=0.01). In conclusion the results of the present meta-analysis suggested that the MTHFR C677T polymorphism is a risk factor for schizophrenia.

Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility.

There are several evidences supporting the role of 5-10 methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in breast cancer (BC). Case control association studies on breast cancer have been repeatedly performed over the last two decades, but results are inconsistent. We performed a meta-analysis to confirm the association between MTHFR C677T polymorphism and BC risk. The articles were retrieved by searching the PubMed, Google Scholar, and Springer Link databases. Crude odds ratios (OR) with 95% confidence intervals (CIs) was used to assess the strength of association between C677T polymorphism and BC. Publication bias was assessed by Egger's and Begg-Mazumdar tests. Meta-analysis was performed with Open Meta Analyst. Total 75 studies with 31,315 cases and 35, 608 controls were found suitable for the inclusion in the present meta-analysis. The results of meta-analysis suggested that there were moderate significant association between C677T polymorphism and BC risk using overall comparisons in five genetic models (T vs. C: OR = 1.08, 95% CI = 1.03-1.13, p = < 0.001; TT + CT vs. CC: OR = 1.06, 95% CI = 1.02-1.09, p = < 0.001; TT vs. CC: OR = 1.17, 95% CI = 1.06-1.28, p = 0.001; CT vs. CC OR = 1.05, 95% CI = 1.01-1.08, p = 0.005; TT vs. CT + CC: OR = 1.12, 95% CI = 1.03-1.22, p = 0.005). In conclusion, results of present meta-analysis showed modest association between MTHFR C677T polymorphism with breast cancer in total studies. However, sub-group analysis results based on ethnicity showed strong significant association between TT genotype and breast cancer (TT vs. CC; OR°=°1.26; 95% CI: 1.06-1.51; p = 0.009) in Asian population but in Caucasian population such association was not observed (TT vs. CC; OR°=°1.08; 95% CI: 0.99-1.14; p = 0.05).

"Polymorphisms in folate metabolism genes as maternal risk factor for neural tube defects: an updated meta-analysis".

Epidemiological studies have evaluated the association between maternal methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms and risk of neural tube defects (NTDs) in offspring. However, the results from the published studies on the association between these three polymorphisms and NTD risk are conflicting. To derive a clearer picture of association between these three maternal polymorphisms and risk of NTD, we performed meta-analysis. A comprehensive search was conducted to identify all case-control studies of maternal MTHFR and MTRR polymorphisms and NTD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that maternal MTHFR C677T polymorphism (OR(TvsC) =1.20; 95% CI = 1.13-1.28) and MTRR A66G polymorphism (OR(GvsA) = 1.21; 95% CI = 0.98-1.49) were risk factors for producing offspring with NTD but maternal MTHFR A1298C polymorphism (OR(CvsA) = 0.91; 95% CI = 0.78-1.07) was not associated with NTD risk. However, in stratified analysis by geographical regions, we found that the maternal C677T polymorphism was significantly associated with the risk of NTD in Asian (OR(TvsC) = 1.43; 95% CI: 1.05-1.94), European (OR(TvsC) = 1.13; 95% CI: 1.04-1.24) and American (OR(TvsC) = 1.26; 95% CI: 1.13-1.41) populations. In conclusion, present meta-analysis supports that the maternal MTHFR C677T and MTRR A66G are polymorphisms contributory to risk for NTD.

Methylenetetrahydrofolate reductase polymorphism is not risk factor for Down syndrome in North India.

BACKGROUND: Down syndrome (DS) is the most common cause of mental retardation of genetic etiology with the prevalence rate of 1/700 to 1/1000 live births worldwide. Several polymorphisms in folate/homocysteine metabolism pathways genes have been reported as a risk factor in women for bearing DS child, but very few studies investigated these polymorphisms in DS cases whether there are a risk factor for being DS or not. OBJECTIVE: We have investigated the association of methylenetetrahydrofolate reductase (MTHFR) with the occurrence of DS in Indian population. MTHFR is one of the key regulatory enzymes involved in the metabolic pathway of homocysteine responsible for the reduction of methyltetrahydrofolate. A total of 32 DS cases and 64 age, sex matched controls were genotyped for MTHFR C677T polymorphism by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The observed genotype frequencies were CC = 0.81; CT = 0.17 and TT = 0.02 in controls and CC = 0.81 and CT = 0.19 in DS cases. Frequency of T allele in DS and controls were 0.09 and 0.1, respectively. Significant difference in the distribution of mutant 677T allele was not observed between DS cases and controls (odds ratio = 0.915; 95% confidence intervals: 0.331-2.53; P = 0.864). CONCLUSION: Results of this study indicate that MTHFR C677T polymorphism is not risk factor for DS.

Maternal methylenetetrahydrofolate reductase C677T polymorphism and down syndrome risk: a meta-analysis from 34 studies.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of folate metabolic pathway which catalyzes the irreversible conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. 5-methyltetrahydrofolate donates methyl group for the methylation of homocysteine to methionine. Several studies have investigated maternal MTHFR C677T polymorphism as a risk factor for DS, but the results were controversial and inconclusive. To come into a conclusive estimate, authors performed a meta-analysis. AIM: A meta-analysis of published case control studies was performed to investigate the association between maternal MTHFR C677T polymorphism and Down syndrome. METHODS: PubMed, Google Scholar, Elsevier, Springer Link databases were searched to select the eligible case control studies using appropriate keywords. The pooled odds ratio (OR) with 95%confidence interval were calculated for risk assessment. RESULTS: Thirty four studies with 3,098 DS case mothers and 4,852 control mothers were included in the present meta-analysis. The pooled OR was estimated under five genetic models and significant association was found between maternal MTHFR 677C>T polymorphism and Down syndrome under four genetic models except recessive model (for T vs. C, OR = 1.26, 95% CI = 1.09-1.46, p = 0.001; for TT vs. CC, OR = 1.49, 95% CI = 1.13-1.97, p = 0.008; for CT vs. CC, OR = 1.29, 95% CI = 1.10-1.51, p = 0.001; for TT+CT vs. CC, OR = 1.35, 95% CI = 1.13-1.60, p = 0.0008; for TT vs. CT+CC, OR = 0.76, 95% CI = 0.60-0.94, p = 0.01). CONCLUSION: The results of the present meta-analysis support that maternal MTHFR C677T polymorphism is a risk factor for DS- affected pregnancy.