Association between the MTHFR (rs1801133) gene variation and serum trace elements levels (Copper and Zinc) in individuals diagnosed with neural tube defects.

BACKGROUND AND AIMS: Neural tube defects (NTDs) occur when the neural tube fails to close within 28 days of human embryonic development. This results in central nervous system disorders like anencephaly, spina bifida, and encephalocele. Early diagnosis and treatment are crucial to minimize their impact on an individual's health and well-being. The present study aims to define the association between prenatal exposure to trace elements (Cu and Zn) and the single nucleotide polymorphism (SNP) of the MTHFR gene involved in folate metabolism pathways in neural tube defects in children and their mothers. MATERIAL AND METHODS: A cross-sectional study involving 331 participants (90 NTD cases, 88 healthy mothers, 85 NTD children, and 68 healthy children) from antenatal check-ups in Obstetrics and Gynaecology and Pediatric Surgery for Neural Tube Defects in the Outpatient Department (OPD) and Inpatient Department (IPD). Assessed Cu and Zn concentrations and their associations. Genomic DNA was extracted, and real-time PCR was used to determine genotypes. Atomic absorption spectrophotometry measured trace elements. Statistical analyses included Chi-Square tests, odds ratios, and Mann-Whitney U tests. RESULTS: Significant associations were found between MTHFR C677T genotypes and NTD risk in mothers (p = 0.0491) and children (p = 0.0297). Allelic frequency analysis indicated a T allele association with NTD risk in children (p = 0.0107). Recessive models showed significant associations in mothers (p = 0.0169) and children (p = 0.1678). Cu levels differed significantly between NTD cases and controls (p < 0.0001), with MTHFR genotypes influencing Cu levels. Zinc levels also varied significantly (p < 0.0001). CONCLUSION: This study reveals complex associations between MTHFR C677T genotypes, trace element concentrations, and NTD risk in mothers and children. This targeted approach allows healthcare providers to identify at-risk pregnancies early, enabling personalised interventions like folic acid supplementation and counselling to moderate neural tube defect (NTD) risk in a future pregnancy.

Polymorphism of growth hormone (GH) gene and its association with performance and body conformation of Harnali sheep.

The present study was carried out to study the polymorphism in the GH gene and its association with various performance and body conformation traits, viz., birth weight (B-WT), weaning weight (W-WT), six-month body weight (6 M-WT), one-year body weight (Y-WT), annual greasy fleece weight (AGFW), body length (BL), body height (BH), heart girth (HG) and paunch girth (PG) in 138 Harnali sheep. PCR-RFLP was performed to identify polymorphism in the targeted region of the GH gene. The PCR product of 422 bp size of the GH gene was amplified encompassing partial exon 2 and inton 3 in Harnali sheep. The PCR product was digested with HaeIII restriction enzyme for the detection of Single nucleotide polymorphism (SNP). The digested products revealed the presence of two genotypes, i.e. AA and AB in the studied population. A > G mutation (A781G) was observed in our resource population. The AA genotype was found to be the predominant genotype (0.62). Chi square value revealed that resource population was not under Hardy-Weinberg equilibrium with respect to target locus. Period of birth was found to have significant effect on W-WT, Y-WT, BL, BH and PG. Sex of animal was found to have significant (P < 0.05) effect on W-WT and highly significant (P < 0.01) effect on 6 M-WT, Y-WT and AGFW in Harnali sheep. The effect of genotype was found to be significant (P < 0.05) on annual greasy fleece weight. AB genotype was found to be associated with higher annual greasy fleece weight and can be used as a potential candidate marker in selection criteria for improving greasy fleece weight in Harnali sheep.

Estimation of the seminal parameters of rooster and its association with fertility traits in synthetic dam line.

The objective of the present study was to assess the seminal parameters of rooster and its association with fertility traits (%), viz., hatchability of the fertile egg set (HFES), hatchability of the total egg set (HTES), and fertility (FERT). The data records pertained to traits of interest were obtained from various registers maintained at Poultry farm, of the Department of Animal Genetics and Breeding, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar (India). The relationship between seminal and fertility characteristics was investigated using regression analysis and correlation. Moreover, the efficacy of seminal characteristics to distinguish between roosters with low and high fertility traits was evaluated using linear discriminant analysis (LDA). The findings showed that reproductive traits and seminal characteristics were significantly (P < 0.05) correlated. The LDA showed that the seminal parameters can effectively separate the roosters into those with high and poor reproductive features. It was revealed from LDA that seminal features showed higher classification accuracy for FERT (80.77%). Hatchability is dependent on eggs that have been artificially incubated; hence, these crucial traits are comparatively weaker for HTES (65.38%) and HFES (67.31%). Cross-validation of the seminal parameter LDA corroborated the aforementioned and related conclusions. It is suggested that the studied LDA function may be utilised to choose genotypes with improved reproductive traits based on seminal variables.

Correction: SARS-CoV-2 Mutations Responsible for Immune Evasion Leading to Breakthrough Infection.

[This corrects the article DOI: 10.7759/cureus.29544.].

Candidate K232A mutation of DGAT1 gene associated with production and reproduction traits in Indian Dairy cattle.

The present study was conducted on Hardhenu and Sahiwal cows to evaluate the genetic diversity and the effect of candidate K232A mutation of diacylglycerol O-acyltransferase (DGAT1) gene on performance traits. PCR product of 413 bp size targeting K232A mutation of DGAT 1 gene was genotyped by Eae1 restriction enzyme and further confirmed by sequencing. The PCR-RFLP analysis for K232A showed that the frequencies of alleles K and A were 0.80 and 0.20 in Hardhenu and 0.98 and 0.02 in Sahiwal cattle, respectively. The frequencies of genotypes for KK and KA genotype were estimated as 0.60 and 0.40 in Hardhenu and 0.96 and 0.04 in Sahiwal cattle, respectively. Chi-square test showed that K232A SNP did not meet with the Hardy-Weinberg equilibrium (p < .01) in Hardhenu cattle. Association analysis revealed that KA genotype was significantly associated with total milk yield (p < .01) and 305 days milk yield (p < .01)in Hardhenu cattle. Hardhenu cows having KA genotype comparatively revealed favorable mean values for AFS (880.31 ± 26.65), AFC (1166.36 ± 19.94), SP (157.46 ± 22.80), CI (441.41 ± 44.28) and AI/Conception (1.80 ± 0.17), indicating that KA genotype can be used as a candidate marker for simultaneous improvement of both production and reproduction traits.

SARS-CoV-2 Mutations Responsible for Immune Evasion Leading to Breakthrough Infection.

BACKGROUND AND OBJECTIVES: India had faced a devastating second outbreak of COVID-19 infection, in which a majority of the viral sequences were found to be of the B.1.617.2 lineage (Delta-variant). While India and the world focused on vaccination, reports of vaccine-immunity evasion by the virus, termed "breakthrough cases", emerged worldwide. Our study was focused on the primary objective to identify the mutations associated with breakthrough infections SARS-CoV-2. METHODS: In our study, we extracted the SARS-CoV-2 RNA (ribonucleic acid) from reverse transcription-polymerase chain reaction (RT-PCR) positive COVID-19 patients, and 150 random samples were sent for sequencing to the Centre for Cellular & Molecular Biology, Hyderabad. Whole genome sequences of 150 SARS-CoV-2 viral samples were analyzed thoroughly. We mostly found B.1.617 and its sub-lineages in the genomic sequencing results. RESULTS AND INTERPRETATION: On further analysis of patient data, it was seen that nine patients had been vaccinated against the SARS-CoV-2 previously. These nine patients had B.1.617/B.1 or A strains, and all of them had similar genomic variations in spike proteins as well as non-structural proteins (NSPs). The mutations seen in these sequences in the Spike (S), NSPs, and open reading frame (ORF) regions would have produced amino acid changes known to improve viral replication, confer drug resistance, influence host-cell interaction, and lead to antigenic drift. CONCLUSIONS: Increased virulence culminating in vaccine immunity evasion may be inferred from these specific mutations. Our study adds to the growing body of evidence linking rapidly emerging mutations in the S (Spike) and ORF genes of the SARS-CoV-2 genome to immune evasion.

Reliability and Validity of the Adapted Nepali Version of the AO Spine Patient Reported Outcome Spine Trauma.

BACKGROUND: The AO Spine Patient Reported Outcome Spine Trauma has been validated in English and Dutch language, however, there is an absence of a translated and validated version in Nepali language. The purpose of this study was to translate the AO Spine Patient Reported Outcome Spine Trauma into Nepali and adapt cross-culturally as outlined by established guidelines, as well as test its psychometric properties among Nepali speaking spine trauma patients. METHODS: Patients were recruited from two Nepali centers as a cross-sectional multicenter validation study. The English version of AO Spine Patient Reported Outcome Spine Trauma was translated and cross-culturally adapted into Nepali language following international guidelines. Next to AO Spine Patient Reported Outcome Spine Trauma also the EQ-5D-3L was filled out by the patients for concurrent validity. Descriptive statistics were used to analyze the patient characteristics. Assessment of measurement properties included content validity (floor and ceiling effects), internal consistency (Cronbach's ? and item total-correlation coefficients) and test-retest reliability by the Bland-Altman plot and Intraclass Correlation Coefficients. Spearman correlation tests were performed within the items and in correlation to EQ-5D-3L. RESULTS: Sixty two spine trauma patients completed the instrument with a mean time of 6.8 minutes. The translated version showed good content validity with no floor and ceiling effects. The internal consistency was excellent with a Cronbach's ? of 0.95. The Spearman correlations within the AO Spine Patient Reported Outcome Spine Trauma items were 0.07 - 0.65 and the test-retest analysis showed excellent results with an Intraclass Correlation Coefficients value of 0.95 (CI 0.93 - 0.97). Inverse correlation was observed between Nepali AO Spine PROST with EQ-5D-3L components. CONCLUSIONS: The Nepali version of AO Spine Patient Reported Outcome Spine Trauma demonstrated excellent validity and reliability results for measuring patient-reported outcomes of spine trauma patients.

Mathematical modeling for egg production and egg weight curves in a synthetic white leghorn.

This study was conducted to evaluate 8 mathematical models, namely, Logistic (LM), Morgqan Mercer Flodin (MMF), Polynomial Fit (PF), Rational Function (RF), Sinusoidal Fit (SF), Quadratic fit (QF), Gompertz function (GF), and Modification Compartmental Model (MCM) fitted to weekly egg production and egg weight of synthetic White Leghorn (SWL) population 21 to 40 wk of age of 5 generations (2015-16 to 2019-20). The relevant data for the present investigation were collected from SWL population, maintained in the department of Animal Genetics and Breeding, LUVAS, Hisar (India). The efficiency or reliability of the models were obtained by various criteria of goodness of fit such as coefficients of determination (R2), Root Mean Square Error (RMSE), Akaike's Information Criterion (AIC), Bayesian Information Criterion (BIC), graphical analysis, and Chi-square test. The results indicated that RF, MCM, SF, and PF were best models for fitting weekly egg production curve due to higher values of R2 and low values of RMSE, AIC, and BIC as compare to remaining models. In case of weekly egg weight, the best values of goodness of fit criteria were showed by MMF model followed by MCM and LM model. The results indicated that these models could be conveniently used for fitting for weekly egg production and egg weight in synthetic white leghorn, respectively.

Impact of mother genetic and resource environment on her offspring's growth features in Munjal sheep.

The present study evaluated maternal and additive influences that contribute to phenotypic variation in various growth traits in Munjal sheep. The targeted traits that pertained to 2278 records of 706 lambs were birth weight (BWT), weaning weight (WT3), 6-month body weight (WT6), 12-month body weight (WT12), average daily gain (ADG1: 0-3 months; ADG2: 3-6 months, ADG3: 6-12 months of age) and their corresponding Kleiber ratios designated as KR1, KR2 and KR3. The direct heritability estimates for BWT, WT3, WT6, WT12, ADG1, ADG2, ADG3, KR1, KR2 and KR3 under animal models were 0.20 ± 0.08, 0.28 ± 0.08, 0.17 ± 0.07, 0.47 ± 0.09, 0.33 ± 0.08, 0.09 ± 0.06, 0.36 ± 0.10, 0.33 ± 0.08, 0.09 ± 0.06 and 0.32 ± 0.10, respectively. The estimates of maternal genetic effects contributed significantly and were 8% and 7% for BWT and WT3 traits, respectively, which highlighted the considerable role of maternal effects on early growth traits. Genetic and phenotypic correlations ranged from moderate to high between weaning and post-weaning traits. It was concluded that early selection that considered additive as well as maternal effects at weaning age may be delivered to the desired genetic progress in Munjal sheep.

To Determine the Genotyping of Fc-gamma Receptor FCGR2A Polymorphism as Genetic Susceptibility to Neonatal Sepsis: A Study from a Tertiary Center of North India.

Background: Neonatal sepsis term is an infection of newborns <28 days of age. It is a common cause of death in developing countries. The receptor-gamma receptor FCGR2A has been shown to be associated with neonatal sepsis. It is an activating receptor found in many cell types such as monocytes, neutrophils, macrophages, platelets, and others. The receptor has a polymorphism (single-nucleotide polymorphism rs1801274) in its gene (FCGR2A) that encodes either a histidine (H) or arginine (R) at amino acid position 131. There are many studies showing the impact of these FCGR2A polymorphisms on sepsis. Our study aims to determine the prevalence of Fc-gamma receptor FCGR2A (rs1801274) polymorphism in neonatal sepsis and control in Eastern UP populations. Patients and Methods: We conducted a cross-sectional descriptive study of 590 patients (310 healthy individuals and 280 sepsis patients) to determine polymorphisms in the CD32A coding region in neonates. All individuals were genotyped for a variant at position 131 of the FcγRIIA gene. Discussion: In our study, the prevalence of FcγRIIa polymorphism is more in neonates with sepsis than in noninfected neonates. It was observed that the heterozygous allele (AG) were significantly increased in septic neonates when compared to the normal. Conclusion: Our data indicate that FcγRIIA genotyping can be used as a marker of genetic susceptibility to sepsis.

Estimates of covariance components and genetic parameters for growth, average daily gain and Kleiber ratio in Harnali sheep.

The aim of the present study was to estimate the (co)variance components and genetic parameters for various growth traits (weight at birth (BWT) and 3 (WT3), 6 (WT6), 9 (WT9), and 12 (WT12) months of age), average daily gain (ADG1, 0-3; ADG2, 3-6; and ADG3, 6-12 months of age), and Kleiber's ratio (KR1:ADG1/WT30.75 and KR2:ADG2/WT60.75) by using records of 526 lambs of 41 sires and 186 dams in Harnali Sheep maintained at Department of Animal Genetics and Breeding, Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar (Haryana), India for the period of year 2014-2019. Restricted maximum likelihood procedure (REML) was employed for estimation of covariance components and genetic parameters by considering direct effects with or without maternal effects. The estimates of direct heritability for BWT, WT3, WT6, WT9, WT12, ADG1, ADG2, ADG3, KR1, and KR2 were 0.10, 0.45, 0.32, 0.36, 0.23, 0.43, 0.02, 0.001, 0.38, and 0.02, respectively. It was observed that maternal effects had significant influence on BWT trait only, and corresponding estimate of maternal heritability was 0.16. This indicated the importance of maternal ability in Harnali sheep for initial growth performance. Moderate estimate of direct additive heritability of weaning weight (WT3) and moderate genetic correlations of it with other traits indicated that the current practice of selection at 6 months may be replaced by early selection at WT3 in order to improve the growth performance in Harnali sheep.

Antiapoptotic effects of vitamins C and E against cypermethrin-induced oxidative stress and spermatogonial germ cell apoptosis.

Toxicological studies have demonstrated the relation between use of agrochemicals and fertility issues within males. Thus, the present study aimed to elucidate the propensity of cypermethrin (CYP) in bringing testicular germ cell apoptosis and effective attenuation by vitamins C and E in caprines. Reproductive toxicity of CYP was evaluated using histomorphological, cytological, and biochemical changes in the testicular germ cells in dose-dependent (1, 5, 10 µg/mL) and time-dependent (4, 6, 8 h) manner. Histological and ethidium bromide/acridine orange fluorescence staining exhibited that vitamins C and E (0.5 and 1.0 mM) successfully diminished the CYP-induced testicular germ cells apoptosis. CYP exposure along with vitamins C and E supplementation also resulted in significantly increased ferric reducing antioxidant power activity along with the antioxidant enzymes, namely catalase, superoxide dismutase, and glutathione-s-transferase, and decreased lipid peroxidation in testicular germ cells. Thus, vitamins C and E ameliorated CYP-induced testicular germ cell apoptosis, thereby preventing spermatogonial cells degeneration and male infertility.

Evaluation of Systemic Antioxidant Level and Oxidative Stress in Relation to Lifestyle and Disease Progression in Asthmatic Patients.

BACKGROUND: Asthma is a chronic disorder of the airways. Oxidative stress is an important part of asthma pathogenesis. It plays a crucial role in exacerbating the disease, as well as an important consequence of airways inflammation. AIM: The present study was undertaken to investigate the lipid peroxidation and catalase activity in serum and antioxidant level in plasma of asthmatic patients and their association with lifestyle and severity of the disease. METHODS: A total of 210 subjects, 120 asthmatics and 90 healthy controls matched in respect to age, sex, lifestyle and socioeconomic status, were chosen randomly for the present study. The samples were analyzed for MDA concentration and catalase activity in serum and ferric reducing ability of plasma (FRAP). Statistical analysis was done using unpaired Student's t-test, ANOVA with Duncan post hoc test and Pearson coefficient of correlation. RESULTS: The serum MDA was found to be significantly higher in the asthmatics as compared to healthy individuals (p<0.01) while catalase activity in serum and antioxidant level of the plasma were markedly lower in the asthmatics as compared to healthy individuals (p<0.01). A significant difference was observed in serum MDA, catalase activity and plasma antioxidant level among the patients in relation to the severity of disease. There was a marked increase in the serum MDA in the patients with longer duration of the disease (p<0.05). CONCLUSIONS: The oxidant-antioxidant imbalance occurs in asthma leading to oxidative stress and is an important part of the asthma pathogenesis.

The HUman MicroNucleus project on eXfoLiated buccal cells (HUMN(XL)): the role of life-style, host factors, occupational exposures, health status, and assay protocol.

The human buccal micronucleus cytome assay (BMCyt) is one of the most widely used techniques to measure genetic damage in human population studies. Reducing protocol variability, assessing the role of confounders, and estimating a range of reference values are research priorities that will be addressed by the HUMN(XL) collaborative study. The HUMN(XL) project evaluates the impact of host factors, occupation, life-style, disease status, and protocol features on the occurrence of MN in exfoliated buccal cells. In addition, the study will provide a range of reference values for all cytome endpoints. A database of 5424 subjects with buccal MN values obtained from 30 laboratories worldwide was compiled and analyzed to investigate the influence of several conditions affecting MN frequency. Random effects models were mostly used to investigate MN predictors. The estimated spontaneous MN frequency was 0.74‰ (95% CI 0.52-1.05). Only staining among technical features influenced MN frequency, with an abnormal increase for non-DNA-specific stains. No effect of gender was evident, while the trend for age was highly significant (p<0.001). Most occupational exposures and a diagnosis of cancer significantly increased MN and other endpoints frequencies. MN frequency increased in heavy smoking (≥40cig/day, FR=1.37; 95% CI 1.03-.82) and decreased with daily fruit consumption (FR=0.68; 95% CI 0.50-0.91). The results of the HUMN(XL) project identified priorities for validation studies, increased the basic knowledge of the assay, and contributed to the creation of a laboratory network which in perspective may allow the evaluation of disease risk associated with MN frequency.

Genomic diversities and affinities among eight endogamous groups of Haryana (India): a study on insertion/deletion polymorphisms.

BACKGROUND: The present study examines genomic variation among eight endogamous groups (Bania, Kamboh, Lobana, Saini, Bishnoi, Sansi, Balmiki and Ramdasia) of Haryana, north-west India. AIM: The present study examines the eight indel polymorphic loci in the population of Haryana. These loci were further used to compare the genomic diversity of the population in relation to other population groups of India. SUBJECTS AND METHODS: DNA samples from 580 unrelated individuals belonging to eight endogamous groups were analysed at eight human-specific insertion/deletion polymorphic loci following standard protocols. RESULTS: All loci, except Alu CD4 and Alu APO, were found to be highly polymorphic. High average heterozygosity values (0.3886 among Kamboh to 0.4276 among Bishnoi) were observed. The overall coefficient of gene differentiation (0.0270) was found to be remarkably close to the Wahlund's variance (0.0258). Comparison with other Indian populations showed that populations of the same geographic region tend to cluster together, irrespective of their social status. CONCLUSION: In various endogamous groups of Haryana, the time of divergence seems to be too small to reflect the genetic differences between them. It may be possible that gene flow occurred prior to the sub-division into the present endogamous groups or the present populations might have the same sources of genes resulting in a low level of genetic differentiation. Populations of Haryana were found to be more similar with populations of the neighbouring states of Punjab and Uttar Pradesh.

Increased frequency of micronucleated exfoliated cells among humans exposed in vivo to mobile telephone radiations.

The health concerns have been raised following the enormous increase in the use of wireless mobile telephones throughout the world. This investigation had been taken, with the motive to find out whether mobile phone radiations cause any in vivo effects on the frequency of micronucleated exfoliated cells in the exposed subjects. A total of 109 subjects including 85 regular mobile phone users (exposed) and 24 non-users (controls) had participated in this study. Exfoliated cells were obtained by swabbing the buccal-mucosa from exposed as well as sex-age-matched controls. One thousand exfoliated cells were screened from each individual for nuclear anomalies including micronuclei (MN), karyolysis (KL), karyorrhexis (KH), broken egg (BE) and binucleated (BN) cells. The average daily duration of exposure to mobile phone radiations is 61.26 min with an overall average duration of exposure in term of years is 2.35 years in exposed subjects along with the 9.84+/-0.745 micronucleated cells (MNCs) and 10.72+/-0.889 total micronuclei (TMN) as compared to zero duration of exposure along with average 3.75+/-0.774 MNC and 4.00+/-0.808 TMN in controls. The means are significantly different in case of MNC and TMN at 0.01% level of significance. The mean of KL in controls is 13.17+/-2.750 and in exposed subjects is 13.06+/-1.793. The value of means of KH in exposed subjects (1.84+/-0.432) is slightly higher than in controls (1.42+/-0.737). Mean frequency of broken egg is found to be more in exposed subjects (0.65+/-0.276) as compared to controls (0.50+/-0.217). Frequency of presence of more than one nucleus in a cell (binucleated) is also higher in exposed (2.72+/-0.374) in comparison to controls (0.67+/-0.231). Although there is a slight increase in mean frequency of KH, BE and BN in exposed subjects but the difference is not found statistically significant. Correlation between 0-1, 1-2, 2-3 and 3-4 years of exposure and the frequency of MNC and TMN has been calculated and found to be positively correlated.