Association of vitamin D receptor gene polymorphisms with type 2 diabetes mellitus in Taif population: a case-control study / Associação de polimorfismos do gene do receptor de vitamina D com diabetes mellitus tipo 2 na população Taif: um estudo de caso-controle

Abstract Several reasons may underlie the dramatic increase in type2 diabetes mellitus. One of these reasons is the genetic basis and variations. Vitamin D receptor polymorphisms are associated with different diseases such as rheumatoid arthritis and diabetes. The aim of this study is to investigate the possible association of two identified mutations ApaI (rs7975232) and TaqI (rs731236). Eighty-nine healthy individuals and Fifty-six Type 2 Diabetic (T2D) patients were investigated using RFLP technique for genotyping and haplotyping as well. The distribution of Apal genotypes was not statistically significant among the control (P=0.65) as well as for diabetic patients (P=0.58). For Taql allele frequencies of T allele was 0.61 where of G allele was 0.39. The frequency distribution of Taql genotypes was not statistically significant among the control (P=0.26) as well as diabetic patients (P=0.17). Relative risk of the allele T of Apa1 gene is 1.28 and the odds ratio of the same allele is 1.53, while both estimates were < 1.0 of the allele G. Similarly, with the Taq1 gene the relative risk and the odds ratio values for the allele T are 1.09 and 1.27 respectively and both estimates of the allele C were 0.86 for the relative risk and 0.79 for the odds ratio. The pairwise linkage disequilibrium between the two SNPs Taq1/apa1 was statistically significant in control group (D = 0.218, D' = 0.925 and P value < 0.001) and similar data in diabetic groups (D = 0.2, D' = 0.875 and P value < 0.001). These data suggest that the T allele of both genes Apa1 and Taq1 is associated with the increased risk of type 2 diabetes. We think that we need a larger number of volunteers to reach a more accurate conclusion.

Resumo Várias razões podem estar subjacentes ao aumento dramático da diabetes mellitus tipo 2. Um desses motivos é a base genética e variações. Os polimorfismos do receptor da vitamina D estão associados a diferentes doenças, como artrite reumatoide e diabetes. O objetivo deste estudo é investigar a possível associação de duas mutações identificadas ApaI (rs7975232) e TaqI (rs731236). Oitenta e nove indivíduos saudáveis ​​e 56 pacientes com diabetes tipo 2 (T2D) foram investigados usando a técnica RFLP para genotipagem e haplotipagem também. A distribuição dos genótipos Apal não foi estatisticamente significativa entre o controle (P = 0,65), bem como para os pacientes diabéticos (P = 0,58). Para as frequências do alelo Taql, o alelo T foi de 0,61, onde o alelo G foi de 0,39. A distribuição de frequência dos genótipos Taql não foi estatisticamente significativa entre o controle (P = 0,26), bem como os pacientes diabéticos (P = 0,17). O risco relativo do alelo T do gene Apa1 é 1,28 e a razão de chances do mesmo alelo é 1,53, enquanto ambas as estimativas foram < 1,0 do alelo G. Da mesma forma, com o gene Taq1, os valores de risco relativo e razão de chances para o alelo T são 1,09 e 1,27, respectivamente, e ambas as estimativas do alelo C foram de 0,86 para o risco relativo e 0,79 para o odds ratio. O desequilíbrio de ligação par a par entre os dois SNPs Taq1 / apa1 foi estatisticamente significativo no grupo de controle (D = 0,218, D' = 0,925 e valor P < 0,001) e dados semelhantes em grupos diabéticos (D = 0,2, D' = 0,875 e valor P < 0,001). Esses dados sugerem que o alelo T de ambos os genes Apa1 e Taq1 está associado ao aumento do risco de diabetes tipo 2. Achamos que precisamos de um número maior de voluntários para chegar a uma conclusão mais precisa.

Increased yield performance of mutation induced Soybean genotypes at varied agro-ecological conditions / Aumento no desempenho de rendimento de genótipos de soja induzidos por mutação em condições agroecológicas variadas

Abstract In soybean breeding program, continuous selection pressure on traits response to yield created a genetic bottleneck for improvements of soybean through hybridization breeding technique. Therefore an initiative was taken to developed high yielding soybean variety applying mutation breeding techniques at Plant Breeding Division, Bangladesh Institute of Nuclear Agriculture (BINA), Bangladesh. Locally available popular cultivar BARI Soybean-5 was used as a parent material and subjected to five different doses of Gamma ray using Co60. In respect to seed yield and yield attributing characters, twelve true breed mutants were selected from M4 generation. High values of heritability and genetic advance with high genotypic coefficient of variance (GCV) for plant height, branch number and pod number were considered as favorable attributes for soybean improvement that ensure expected yield. The mutant SBM-18 obtained from 250Gy provided stable yield performance at diversified environments. It provided maximum seed yield of 3056 kg ha-1 with highest number of pods plant-1 (56). The National Seed Board of Bangladesh (NSB) eventually approved SBM-18 and registered it as a new soybean variety named 'Binasoybean-5' for large-scale planting because of its superior stability in various agro-ecological zones and consistent yield performance.

Resumo No programa de melhoramento da soja, a pressão pela seleção contínua para a resposta das características de rendimento criou um gargalo genético para melhorias da soja por meio da técnica de melhoramento por hibridação. Portanto, foi desenvolvida uma variedade de soja de alto rendimento, aplicando técnicas de reprodução por mutação, na Divisão de Melhoramento de Plantas, no Instituto de Agricultura Nuclear de Bangladesh (BINA), em Bangladesh. A cultivar popular BARI Soybean-5, disponível localmente, foi usada como material original e submetida a cinco doses diferentes de raios gama usando Co60. Em relação ao rendimento de sementes e às características de atribuição de rendimento, 12 mutantes genuínos foram selecionados a partir da geração M4. Altos valores de herdabilidade e avanço genético com alto coeficiente de variância genotípico (GCV) para altura da planta, número de ramos e número de vagens foram considerados atributos favoráveis ​​ao melhoramento da soja, garantindo, assim, a produtividade esperada. O mutante SBM-18, obtido a partir de 250Gy, proporcionou desempenho de rendimento estável em ambientes diversificados e produtividade máxima de sementes de 3.056 kg ha-1 com o maior número de vagens planta-1 (56). O Conselho Nacional de Sementes de Bangladesh (NSB) finalmente aprovou o SBM-18 e o registrou como uma nova variedade de soja, chamada 'Binasoybean-5', para plantio em larga escala por causa de sua estabilidade superior em várias zonas agroecológicas e desempenho de rendimento consistente.

Characterization of the Bipolaris maydis: symptoms and pathogenicity in popcorn genotypes (Zea mays L. ) / Caracterização de Bipolaris maydis: sintomas e patogenicidade em genótipos de milho-pipoca (Zea mays L. )

Southern corn leaf blight (SCLB) is one of the most important corn leaf diseases. Appropriate management strategies and the use of resistant cultivars allow disease control. Therefore, knowing the aspects related to the pathogen and the response of hosts makes it possible to design efficient strategies for selecting genotypes resistant to this disease. In this sense, the objective was to carry out the Bipolaris maydis isolate characterization, evaluating the pathogenicity in different popcorn lines and the symptoms generated in the host after inoculation. The isolate characterization consisted of the macromorphological evaluation of the colonies and the micromorphological evaluation of the conidia in the PDA medium. An experiment was carried out in a greenhouse to evaluate the pathogenicity of the isolate, using 20 inbred lines of popcorn in a randomized block design with four replicates. Inoculation was carried out by spraying leaves, with a suspension containing 1.0 x 104 conidia.ml-1 of the CF/UENF 501 isolate of B. maydis. An incidence assessment and three assessments of disease symptom severity were performed, with seven days intervals between evaluations. The morphological characterization data of the isolate were analyzed using descriptive statistics, and for disease severity, the linear regression model was applied the first-degree model. The variance analysis was performed for the linear and angular coefficients obtained for each treatment. When a difference was found, the Scott-Knott clustering algorithm at 5% significance was applied. The isolate had gray-green colonies, a cottony appearance, and an irregular shape. The lines L353, L354, and L624 show more resistance at the beginning and throughout the evaluations. The high virulence of the CF/UENF 501 isolate made it possible to differentiate the lines in terms of disease intensity and the pattern of symptoms presented.

Mancha-de-Bipolaris é uma das mais importantes doenças foliares do milho. Estratégias de manejo adequadas e o uso de cultivar resistente permitem o controle da doença, mas para tanto, conhecer os aspectos associados ao patógeno e a resposta do hospedeiro é necessário para traçar estratégias eficientes para seleção de genótipos resistentes a essa doença. Neste sentido, objetivou-se realizar a caracterização do isolado de Bipolaris maydis avaliando a patogenicidade em diferentes linhagens de milho-pipoca e os sintomas gerados no hospedeiro a partir da inoculação. A caracterização do isolado consistiu na avaliação macromorfológica das colônias e micromofológica dos conídios em meio nutritivo BDA. Para avaliação da patogenicidade do isolado foi conduzido um experimento em casa de vegetação utilizando 20 linhagens endogâmicas de milho-pipoca, com delineamento em blocos casualizados, com quatro repetições. A inoculação foi realizada por meio de pulverização em folhas, com uma suspensão contendo 1,0 x 104 conídios.ml-1 do isolado CF/UENF 501 de B. maydis. Foi realizada uma avaliação de incidência e três avaliações de severidade dos sintomas da doença, com o intervalo de sete dias para cada avaliação. Os dados da caracterização morfológica do isolado foram analisados por meio da estatística descritiva e para severidade da doença foi aplicado o modelo de regressão linear de primeiro grau. Realizou-se a análise de variância para o coeficiente linear e angular obtido para cada tratamento e quando constatada diferença aplicou-se o agrupamento de médias de Scott-knott a 5% de significância. O isolado apresentou colônias com coloração cinza esverdeado, aspecto algodonoso e forma irregular. As linhagens L353 e L354 e L624 estão entre as linhagens que apresentaram maior resistência no inicio e ao longo das avaliações. A elevada virulência do isolado CF/UENF 501 possibilitou diferenciar as linhagens quanto a intensidade da doença, bem como o padrão dos sintomas apresentados.

Visual symptoms with Sofosbuvir in hepatitis C treatment - a case report from Pakistan.

Hepatitis C virus infection is one of the main causes of chronic liver disease worldwide. The highly efficacious direct-acting antiviral (DAA) drugs licensed for therapy have revolutionised the treatment and are reported to have few side effects. Sofosbuvir is a pan-genotypic DAA that acts by inhibition of the hepatitis C NS5B polymerase. It has shown high efficacy in combination with several other drugs with low toxicity, a high resistance barrier, and minimal drug interactions with other hepatitis C DAA drugs. We describe a first of its kind case from Pakistan with visual disturbances caused by Sofosbuvir. A temporal relationship was observed between the treatment initiation and the onset of visual disturbances. The aim of this case report is to draw attention to the unanticipated side effects of this relatively new class of drug that have not been reported previously.

Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood?

Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother-child pairs, and 6,222 father-child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this sample, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining individual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale samples of genotyped families with information on childhood psychiatric outcomes.

Accelerating Cervical Cancer Screening With Human Papillomavirus Genotyping.

INTRODUCTION: Selective utilization of human papillomavirus (HPV) genotyping in cervical cancer screening can accelerate clinical management, leading to earlier identification and treatment of precancerous lesions and cancer. Specifically, immediate colposcopy (instead of 1-year return) is recommended in persons with normal cytology and HPV genotypes 16 and/or 18, and expedited treatment (instead of colposcopy) is recommended in persons with high-grade squamous intraepithelial lesion (HSIL) cytology and HPV genotype 16. The effects of implementing HPV testing and genotyping into a screening program are largely unknown. METHODS: Average-risk persons aged 30-65 years screened for cervical cancer in the National Breast and Cervical Cancer Early Detection Program from 2019 to 2020 were included (N=104,991). Percentage HPV genotyping test positivity was estimated within cytology result categories. Analyses were performed in 2022. RESULTS: The most common abnormality was positive high-risk HPV testing with normal cytology, representing 40.1% (7,155/17,832) of all abnormal test result categories; HSIL cytology represented 3.0% (530/17,832) of all abnormal test result categories. In high-risk HPV‒positive persons with normal or high-grade cytology, HPV genotyping could accelerate management (immediate colposcopy and expedited treatment) in 5.4% of all persons with abnormal screening test results; if HPV genotyping had been performed in all high-risk HPV‒positive persons with normal or HSIL cytology, approximately 13.1% could have accelerated management. CONCLUSIONS: HPV genotyping in human papillomavirus‒positive persons with normal or HSIL cytology could accelerate management in a sizable percentage of persons with abnormal test results and may be particularly useful in populations with challenges adhering to longitudinal follow-up.

Overview of the SARS-CoV-2 genotypes circulating in Latin America during 2021.

Latin America is one of the regions in which the COVID-19 pandemic has a stronger impact, with more than 72 million reported infections and 1.6 million deaths until June 2022. Since this region is ecologically diverse and is affected by enormous social inequalities, efforts to identify genomic patterns of the circulating SARS-CoV-2 genotypes are necessary for the suitable management of the pandemic. To contribute to the genomic surveillance of the SARS-CoV-2 in Latin America, we extended the number of SARS-CoV-2 genomes available from the region by sequencing and analyzing the viral genome from COVID-19 patients from seven countries (Argentina, Brazil, Costa Rica, Colombia, Mexico, Bolivia, and Peru). Subsequently, we analyzed the genomes circulating mainly during 2021 including records from GISAID database from Latin America. A total of 1,534 genome sequences were generated from seven countries, demonstrating the laboratory and bioinformatics capabilities for genomic surveillance of pathogens that have been developed locally. For Latin America, patterns regarding several variants associated with multiple re-introductions, a relatively low percentage of sequenced samples, as well as an increment in the mutation frequency since the beginning of the pandemic, are in line with worldwide data. Besides, some variants of concern (VOC) and variants of interest (VOI) such as Gamma, Mu and Lambda, and at least 83 other lineages have predominated locally with a country-specific enrichments. This work has contributed to the understanding of the dynamics of the pandemic in Latin America as part of the local and international efforts to achieve timely genomic surveillance of SARS-CoV-2.

In silico analysis of single nucleotide polymorphism (rs34377097) of TBXA2R gene and pollen induced bronchial asthma susceptibility in West Bengal population, India.

Introduction: Prevalence of asthma is increasing steadily among general population in developing countries over past two decades. One of the causative agents of broncho-constriction in asthma is thromboxane A2 receptor (TBXA2R). However few studies of TBXA2R polymorphism were performed so far. The present study aimed to assess potential association of TBXA2R rs34377097 polymorphism causing missense substitution of Arginine to Leucine (R60L) among 482 patients diagnosed with pollen-induced asthma and 122 control participants from West Bengal, India. Also we performed in-silico analysis of mutated TBXA2R protein (R60L) using homology modeling. Methods: Clinical parameters like Forced expiratory volume in 1 second (FEV1), FEV1/Forced vital capacity (FVC) and Peak expiratory flow rate (PEFR) were assessed using spirometry. Patients' sensitivity was measured by skin prick test (SPT) against 16 pollen allergens. Polymerase chain reaction-based Restriction fragment length polymorphism was done for genotyping. Structural model of wild type and homology model of polymorphic TBXA2R was generated using AlphaFold2 and MODELLER respectively. Electrostatic surface potential was calculated using APBS plugin in PyMol. Results: Genotype frequencies differed significantly between the study groups (P=0.03). There was no significant deviation from Hardy-Weinberg equilibrium in control population (χ2=1.56). Asthmatic patients have significantly higher frequency of rs34377097TT genotype than control subjects (P=0.03). SPT of patients showed maximum sensitivity in A. indica (87.68%) followed by C. nusifera (83.29%) and C. pulcherima (74.94%). Significant difference existed for pollen sensitivity in adolescent and young adult (P=0.01) and between young and old adult (P=0.0003). Significant negative correlation was found between FEV1/FVC ratio and intensity of SPT reactions (P<0.0001). Significant association of FEV1, FEV1/FVC and PEFR was observed with pollen-induced asthma. Furthermore, risk allele T was found to be clinically correlated with lower FEV1/FVC ratio (P=0.015) in patients. Our data showed R60L polymorphism, which was conserved across mammals, significantly reduced positive electrostatic charge of polymorphic protein in cytoplasmic domain thus altered downstream pathway and induced asthma response. Discussion: The present in-silico study is the first one to report association of TBXA2R rs34377097 polymorphism in an Indian population. It may be used as prognostic marker of clinical response to asthma in West Bengal and possible target of therapeutics in future.

Genetic screening of PLA1/PLA2 polymorphous marker of integrin beta 3 (ITGB3) GP IIIA gene in adolescent girls with puberty menorrhagia.

Puberty menorrhagia is one of the urgent problems of modern reproductive medicine. The study aimed to investigate the relationship between polymorphism of the GP IIIa (PLA1/PLA2) gene and improve the diagnosis of puberty menorrhagia in girls with thyroid gland pathology. Ninety-seven girls at puberty age were divided into three groups: group 1 (main) - girls with puberty menorrhagia and thyroid gland pathology (30 individuals), group 2 (comparison) - 40 girls with puberty menorrhagia, group 3 (control) - 27 practically healthy girls. Polymorphism of the GP IIIa (PLA1/PLA2) gene was studied by isolating genomic DNA from peripheral blood leukocytes, followed by amplification with a polymerase chain reaction. Results showed that mutation in the 17th chromosome of q21.32 of the GP IIIa gene occurred in 8.6% of cases among adolescents with menorrhagia, in contrast to the control group, where it was not observed at all. The A1A1-genotype occurred by 11.7% (X2=4.01, p=0.041) more often in adolescents with menorrhagia than in girls with concomitant thyroid gland pathology and by 15.0% (X2=4.54, p=0.033) more often than in the control group. It was also found that the presence of the A1A2-genotype unreliably reduced the chances of uterine bleeding in adolescent girls by 1.45 times (OR=2.12) and was a protective factor in the puberty menorrhagia occurrence (OR=0.47). It may be concluded that the identification of a hereditary factor of the reproductive system diseases of adolescent girls fundamentally changes the point of view on the tactics of disease management and subsequent therapy.

Association between ESR1 rs2234693 single nucleotide polymorphism and uterine fibroids in Taiwanese premenopausal and postmenopausal women.

BACKGROUND: Uterine fibroids (UFs) are uterine smooth muscle neoplasms that affect women, especially during the reproductive stage. Both genetic and lifestyle factors affect the onset of the disease. We examined the association between the estrogen receptor 1 (ESR1) rs2234693 variant (whose genotypes are TT, TC, and CC) and UFs in Taiwanese premenopausal and postmenopausal women. METHODS: We linked individual-level data of 3588 participants from the Taiwan Biobank to the National Health Insurance Research Database at the Health and Welfare Data Science Center. The association of the ESR1 rs2234693 variant and other variables with UFs was determined by multiple logistic regression, and the results were presented as odds ratios and 95% confidence intervals (CIs). RESULTS: The 3588 participants comprised 622 cases and 2966 controls. In all the participants, the ESR1 rs2234693 TC and CC genotypes compared to the reference genotype (TT) were associated with a lower risk of UFs. However, the results were significant only for the CC genotype (OR; 95% CI = 0.70; 0.52-0.93). Noteworthy, the association of TC and CC with UFs was dose-dependent (p-trend = 0.012). Based on menopausal status, both TC and CC were significantly and dose-dependently associated with a lower risk of UFs in premenopausal women (OR; 95% CI = 0.76; 0.59-0.98 for TC and 0.64; 0.43-0.95 for CC: p-trend = 0.010). CONCLUSION: The TC and CC genotypes of the ESR1 rs2234693 variant may reduce susceptibility to UFs, especially in premenopausal women.

Relationship between APOE, PER2, PER3 and OX2R Genetic Variants and Neuropsychiatric Symptoms in Patients with Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the presence of neuropsychiatric or behavioral and psychological symptoms of dementia (BPSD). BPSD have been associated with the APOE_ε4 allele, which is also the major genetic AD risk factor. Although the involvement of some circadian genes and orexin receptors in sleep and behavioral disorders has been studied in some psychiatric pathologies, including AD, there are no studies considering gene-gene interactions. The associations of one variant in PER2, two in PER3, two in OX2R and two in APOE were evaluated in 31 AD patients and 31 cognitively healthy subjects. Genotyping was performed using real-time PCR and capillary electrophoresis from blood samples. The allelic-genotypic frequencies of variants were calculated for the sample study. We explored associations between allelic variants with BPSD in AD patients based on the NPI, PHQ-9 and sleeping disorders questionnaires. Our results showed that the APOE_ε4 allele is an AD risk variant (p = 0.03). The remaining genetic variants did not reveal significant differences between patients and controls. The PER3_rs228697 variant showed a nine-fold increased risk for circadian rhythm sleep-wake disorders in Mexican AD patients, and our gene-gene interaction analysis identified a novel interaction between PERIOD and APOE gene variants. These findings need to be further confirmed in larger samples.

Prevalence of Polymorphism and Post-Training Expression of ACTN3 (R/X) and ACE (I/D) Genes in CrossFit Athletes.

BACKGROUND: CrossFit is known as a functional fitness training high-intensity exercise to improve physical performance. The most studied polymorphisms are the ACTN3 R577X gene, known for speed, power, and strength, and ACE I/D, related to endurance and strength. The present investigation analyzed the effects of training on ACTN3 and ACE gene expression in CrossFit athletes for 12 weeks. METHODS: the studies included 18 athletes from the Rx category, where ACTN3 (RR, RX, XX) and ACE (II, ID, DD) characterization of genotypes and tests of maximum strength (NSCA), power (T-Force), and aerobic endurance (Course Navette) were performed. The technique used was the reverse transcription-quantitative PCR real-time polymerase chain reaction (RT-qPCR) for the relative expression analysis. RESULTS: the relative quantification (RQ) values for the ACTN3 gene increased their levels 2.3 times (p = 0.035), and for ACE, they increased 3.0 times (p = 0.049). CONCLUSIONS: there is an overexpression of the ACTN3 and ACE genes due to the effect of training for 12 weeks. Additionally, the correlation of the expression of the ACTN3 (p = 0.040) and ACE (p = 0.030) genes with power was verified.

Polymorphic Variants of Genes Encoding Angiogenesis-Related Factors in Infertile Women with Recurrent Implantation Failure.

Recurrent implantation failure (RIF) is a global health issue affecting a significant number of infertile women who undergo in vitro fertilization (IVF) cycles. Extensive vasculogenesis and angiogenesis occur in both maternal and fetal placental tissues, and vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) family molecules and their receptors are potent angiogenic mediators in the placenta. Five single nucleotide polymorphisms (SNPs) in the genes encoding angiogenesis-related factors were selected and genotyped in 247 women who had undergone the ART procedure and 120 healthy controls. Genotyping was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A variant of the kinase insertion domain receptor (KDR) gene (rs2071559) was associated with an increased risk of infertility after adjusting for age and BMI (OR = 0.64; 95% CI: 0.45-0.91, p = 0.013 in a log-additive model). Vascular endothelial growth factor A (VEGFA) rs699947 was associated with an increased risk of recurrent implantation failures under a dominant (OR = 2.34; 95% CI: 1.11-4.94, padj. = 0.022) and a log-additive model (OR = 0.65; 95% CI 0.43-0.99, padj. = 0.038). Variants of the KDR gene (rs1870377, rs2071559) in the whole group were in linkage equilibrium (D' = 0.25, r2 = 0.025). Gene-gene interaction analysis showed the strongest interactions between the KDR gene SNPs rs2071559-rs1870377 (p = 0.004) and KDR rs1870377-VEGFA rs699947 (p = 0.030). Our study revealed that the KDR gene rs2071559 variant may be associated with infertility and rs699947 VEGFA with an increased risk of recurrent implantation failures in infertile ART treated Polish women.

Shattering and yield expression of sesame (Sesamum indicum L) genotypes influenced by paclobutrazol concentration under rainfed conditions of Pothwar.

Seed shattering is a critical challenge that significantly reduces sesame production by 50%. These shattering losses can be reduced by selecting shattering resistant genotypes or by incorporating modern agronomic management such as paclobutrazol, which can boost productivity and prevent seed shattering in sesame. Two-years of field trials were conducted to examine the effect of sesame genotypes, environment, and paclobutrazol (PBZ) concentrations. Twelve sesame genotypes were used in a four-way factorial RCBD with three replications and five PBZ concentrations (T0 = Control; T1 = 150; T2 = 300; T3 = 450; and T4 = 600 mg L- 1) under rainfed conditions of Pothwar. The findings revealed significant variations in the major effects of all examined variables (genotypes, locations, years, and PBZ levels). Sesame genotypes PI-154304 and PI-175907 had the highest plant height, number of capsule plant- 1, seed capsule- 1, 1000 seed weight, biological yield, and seed yield, while also having the lowest seed losses and shattering percentage. Regarding environments, NARC-Islamabad generated the highest plant height, number of capsule plant- 1, shattering percentage, and biological yield; however, the URF-Koont produced the highest seed yield with the lowest shattering percentage. Additionally, plant height, capsules plant- 1, and biological yield were higher in 2021, while seed capsule- 1, 1000 seed weight, seed losses, shattering percentage, and seed yield were higher in 2020. PBZ concentration affected all measured parameters; plant height and number of seed capsule- 1 decreased with increasing PBZ concentrations. 450 mg L- 1 PBZ concentration generated the highest biomass, number of capsules plant- 1, and seed yield. At the same time, PBZ concentration 600 mg L- 1 generated the smallest plant, the lowest seed capsules- 1, the greatest thousand seed weight, and the lowest shattering percentage. The study concluded that paclobutrazol could dramatically reduce shattering percentage and shattering losses while increasing economic returns through better productivity. Based on the findings, the genotypes PI-154304 and PI-175907 with paclobutrazol level 450 mgL- 1 may be suggested for cultivation in Pothwar farming community under rainfed conditions, as they showed promising shattering resistance as well as enhanced growth and yield.

Molecular characterisation of 36 multilocus imprinting disturbance (MLID) patients: a comprehensive approach.

BACKGROUND: Imprinting disorders (ImpDis) comprise diseases which are caused by aberrant regulation of monoallelically and parent-of-origin-dependent expressed genes. A characteristic molecular change in ImpDis patients is aberrant methylation signatures at disease-specific loci, without an obvious DNA change at the specific differentially methylated region (DMR). However, there is a growing number of reports on multilocus imprinting disturbances (MLIDs), i.e. aberrant methylation at different DMRs in the same patient. These MLIDs account for a significant number of patients with specific ImpDis, and several reports indicate a central role of pathogenic maternal effect variants in their aetiology by affecting the maturation of the oocyte and the early embryo. Though several studies on the prevalence and the molecular causes of MLID have been conducted, homogeneous datasets comprising both genomic and methylation data are still lacking. RESULTS: Based on a cohort of 36 MLID patients, we here present both methylation data obtained from next-generation sequencing (NGS, ImprintSeq) approaches and whole-exome sequencing (WES). The compilation of methylation data did not reveal a disease-specific MLID episignature, and a predisposition for the phenotypic modification was not obvious as well. In fact, this lack of epigenotype-phenotype correlation might be related to the mosaic distribution of imprinting defects and their functional relevance in specific tissues. CONCLUSIONS: Due to the higher sensitivity of NGS-based approaches, we suggest that ImprintSeq might be offered at reference centres in case of ImpDis patients with unusual phenotypes but MLID negative by conventional tests. By WES, additional MLID causes than the already known maternal effect variants could not be identified, neither in the patients nor in the maternal exomes. In cases with negative WES results, it is currently unclear to what extent either environmental factors or undetected genetic variants contribute to MLID.

Rs28446116 in PTCH1 is associated with non-syndromic cleft lip with or without palate in the Ningxia population, China.

OBJECTIVES: To investigate the association between PTCH1 single nucleotide polymorphism(SNP) and non-syndromic cleft lip with or without palate (NSCL/P) in the Ningxia Hui Autonomous region and predict the function of single nucleotide polymorphism through bioinformatics analysis. DESIGN: A case-control analysis of 31 single nucleotide polymorphism locus alleles on PTCH1 gene (504 cases and 455 controls) was performed to explore the association between PTCH1 gene polymorphisms and non-syndromic cleft lip with or without palate in Ningxia region. Transcription factors, 3D single nucleotide polymorphism and other related information of single nucleotide polymorphism loci with statistical significance were screened by the case-control experiments, and then analyzed the corresponding transcription factors through the NCBI database. RESULTS: The case-control study showed that 5 of the 31 single nucleotide polymorphism loci rs357564 (P = 0.0233), rs1805155 (P = 0.0371), rs28446116 (P = 0.0408), rs2282041 (P = 0.0439), rs56119276 (P = 0.0256) had statistically significant differences in allele frequencies between the case and control groups. Bioinformatics analysis revealed that EP300 and RUNX3, among the transcription factors associated with rs28446116, may be associated with the development of non-syndromic cleft lip with or without palate. CONCLUSION: PTCH1 gene may be associated with the occurrence of non-syndromic cleft lip with or without palate in the Ningxia region, which may be related to the role of EP300 and RUNX3 in the development of cleft lip and palate.

Inflammasome genes polymorphisms are associated with progression to mechanical ventilation and death in a cohort of hospitalized COVID-19 patients in a reference hospital in Rio de Janeiro, Brazil.

COVID-19 has a broad spectrum of clinical manifestations. We assessed the impact of single nucleotide polymorphisms (SNPs) of inflammasome genesas risk factors for progression toCOVID-19 critical outcomes, such as mechanical ventilation support (MVS) or death.The study included 451 hospitalized individuals followed up at the INI/FIOCRUZ, Rio de Janeiro, Brazil, from 06/2020 to 03/2021. SNPs genotyping was determined by Real-Time PCR. We analyzed risk factors for progression to MVS (n = 174[38.6 %]) or death (n = 175[38.8 %])as a result of COVID-19 by Cox proportional hazardmodels.Slower progression toMVSwas associated with allele G (aHR = 0.66;P = 0.005) or the genotype G/G (aHR = 0.391;P = 0.006) in the NLRP3 rs10754558 or the allele G (aHR = 0.309;P = 0.004) in the IL1ßrs1143634, while C allele in the NLRP3 rs4612666 (aHR = 2.342;P = 0.006) or in the rs10754558 (aHR = 2.957;P = 0.005) were associated with faster progression to death. Slower progression to death was associated to allele G (aHR = 0.563;P = 0.006) or the genotype A/G (aHR = 0.537;P = 0.005) in the CARD8 rs6509365; the genotype A/C in the IFI16 rs1101996 (aHR = 0.569;P = 0.011); the genotype T/T (aHR = 0.394;P = 0.004) or allele T (aHR = 0.68;P = 0.006) in the NLRP3 rs4612666, and the genotype G/G (aHR = 0.326;P = 0.005) or allele G (aHR = 0,68;P = 0.014) in the NLRP3 rs10754558. Our results suggest that inflammasome genetic variations might influence the critical clinical course of COVID-19.

Identification of microbiological factors associated with periodontal health disparities.

The present study aimed at identifying risk factors associated with periodontitis development and periodontal health disparities with emphasis on differential oral microbiota. The prevalence of periodontitis is recently rising dentate adults in the US, which presents a challenge to oral health and overall health. The risk of developing periodontitis is higher in African Americans (AAs), and Hispanic Americans (HAs) than in Caucasian Americans (CAs). To identify potentially microbiological determinations of periodontal health disparities, we examined the distribution of several potentially beneficial and pathogenic bacteria in the oral cavities of AA, CA, and HA study participants. Dental plaque samples from 340 individuals with intact periodontium were collected prior to any dental treatment, and levels of some key oral bacteria were quantitated using qPCR, and the medical and dental histories of participants were obtained retrospectively from axiUm. Data were analyzed statistically using SAS 9.4, IBM SPSS version 28, and R/RStudio version 4.1.2. Amongst racial/ethnic groups: 1) neighborhood medium incomes were significantly higher in the CA participants than the AA and the HA participants; 2) levels of bleeding on probing (BOP) were higher in the AAs than in the CAs and HAs; 3) Porphyromonas gingivalis levels were higher in the HAs compared to that in the CAs; 4) most P. gingivalis detected in the AAs were the fimA genotype II strain that was significantly associated with higher BOP indexes along with the fimA type IV strain. Our results suggest that socioeconomic disadvantages, higher level of P. gingivalis, and specific types of P. gingivalis fimbriae, particularly type II FimA, contribute to risks for development of periodontitis and periodontal health disparities.

The Investigation of MAPK7 Gene Variations in Colorectal Cancer Risk.

BACKGROUND/AIM: Mitogen-activated protein kinases (MAPKs) are important regulatory molecules, which have essential roles in physiology and pathology. In the present study, we examined the possible correlation between the MAPK7 gene and colorectal cancer risk in the Turkish population. MATERIALS AND METHODS: A total of 100 human DNA samples (50 colorectal cancer patients and 50 healthy individuals) were sequenced using next-generation sequencing to define the potential genetic variations in the MAPK7 gene. RESULTS: Five genetic variations (MAPK7; rs2233072, rs2233076, rs181138364, rs34984998, rs148989290) were detected in our study group. The G (variant) allele of the MAPK7; rs2233072 (T>G) gene polymorphism was found in 76% of colorectal cancer cases, and 66% of controls. The prevalence of rs2233076, rs181138364, rs34984998, and rs148989290 gene variations was quite rare in the subjects and no significant association in terms of genotype and allele frequencies was observed between the cases and controls. CONCLUSION: No statistically significant correlation between the MAP7 kinase gene variations and colorectal cancer risk was observed. This is the first investigation in the Turkish population that may initiate additional studies in larger populations to analyze the effect of MAPK7 gene on the colorectal cancer risk.

Fulminant Adenoid Cystic Carcinoma of the Maxillary Sinus - A Rare Finding: Case Report.

BACKGROUND: The most common malignant tumor of the small salivary glands in the head and neck region is adenoid cystic carcinoma (ACK). The most common localization of ACK is the hard palate. ACK does not show any sex predisposition and is mainly diagnosed in middle-aged patients. CASE REPORT: The present case report describes a fulminant ACK in the rare localization of maxillary sinus in a 36-year old male. The subsequent surgical treatment consisted of a radical hemimaxillectomy using an extraoral approach according to Weber-Fergusson-Dieffenbach and ipsilateral neck dissection. A magnetic epithesis was used for initial defect coverage of the maxillary bone accompanied by an obturator prosthesis. The surgical treatment was then followed by adjuvant proton therapy. CONCLUSION: This case report shows how individual patient care can be provided according to the latest therapy standards of ACK in the rare localization of the maxillary sinus.