scholarly journals Effects of FSHR and FSHB Variants on Hormonal Profile and Reproductive Outcomes of Infertile Women With Endometriosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Bianca Bianco ◽  
Flavia Altheman Loureiro ◽  
Camila Martins Trevisan ◽  
Carla Peluso ◽  
Denise Maria Christofolini ◽  
...  
Keyword(s):  
Cross Sectional Study ◽  
Reproductive Outcomes ◽  
Single Nucleotide Variants ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Hormonal Profile ◽  
Ivf Outcomes ◽  
Mild Disease ◽  
Dimensionality Reduction Method

BackgroundSingle nucleotide variants (SNVs) FSHB:c.-211G>T, FSHR:c.919G>A, and FSHR:c.2039G>A were reported to be associated with the variability in FSH and LH levels, and in vitro fertilization (IVF) outcomes. In this study, we aimed to evaluate the effects of FSHB:c.-211G>T, FSHR:c.919G>A, and FSHR:c.2039G>A variants, alone and combined, on the hormonal profile and reproduction outcomes of women with endometriosis.MethodsA cross-sectional study was performed comprising 213 infertile Brazilian women with endometriosis who underwent IVF treatment. Genotyping was performed using TaqMan real-time PCR. Variables were compared according to the genotypes of each variant and genetic models, and the combined effects of the SNVs were evaluated using the multifactorial dimensionality reduction method.ResultsFSHB:c.-211G>T affected LH levels in women with overall endometriosis and minimal/mild disease. FSHR:c.919G>A affected FSH levels in women with overall endometriosis and the number of oocytes retrieved in those with moderate/severe endometriosis. Moreover, the FSHR:c.2039G>A affected FSH levels in women with overall endometriosis, LH levels and total amount of rFSH in those with minimal/mild disease, and number of follicles and number of oocytes retrieved in those with moderate/severe endometriosis. No effect on hormone profile or reproductive outcomes was observed when the genotypes were combined.ConclusionsVariants of the FSHB and FSHR genes separately interfered with the hormonal profiles and IVF outcomes of women with endometriosis.

scholarly journals Genetic Variants in Smoking-Related Genes in Two Smoking Cessation Programs: A Cross-Sectional Study

2021 ◽  
Vol 18 (12) ◽  
pp. 6597
Author(s):  
Gloria Pérez-Rubio ◽  
Luis Alberto López-Flores ◽  
Ana Paula Cupertino ◽  
Francisco Cartujano-Barrera ◽  
Luz Myriam Reynales-Shigematsu ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Cross Sectional Study ◽  
Nucleotide Polymorphisms ◽  
Sectional Study ◽  
Cross Sectional ◽  
Single Nucleotide ◽  
Genotype Frequencies ◽  
Quitting Smoking ◽  
Genes Encoding ◽  
Genomic Regions

Previous studies have identified variants in genes encoding proteins associated with the degree of addiction, smoking onset, and cessation. We aimed to describe thirty-one single nucleotide polymorphisms (SNPs) in seven candidate genomic regions spanning six genes associated with tobacco-smoking in a cross-sectional study from two different interventions for quitting smoking: (1) thirty-eight smokers were recruited via multimedia to participate in e-Decídete! program (e-Dec) and (2) ninety-four attended an institutional smoking cessation program on-site. SNPs genotyping was done by real-time PCR using TaqMan probes. The analysis of alleles and genotypes was carried out using the EpiInfo v7. on-site subjects had more years smoking and tobacco index than e-Dec smokers (p < 0.05, both); in CYP2A6 we found differences in the rs28399433 (p < 0.01), the e-Dec group had a higher frequency of TT genotype (0.78 vs. 0.35), and TG genotype frequency was higher in the on-site group (0.63 vs. 0.18), same as GG genotype (0.03 vs. 0.02). Moreover, three SNPs in NRXN1, two in CHRNA3, and two in CHRNA5 had differences in genotype frequencies (p < 0.01). Cigarettes per day were different (p < 0.05) in the metabolizer classification by CYP2A6 alleles. In conclusion, subjects attending a mobile smoking cessation intervention smoked fewer cigarettes per day, by fewer years, and by fewer cumulative pack-years. There were differences in the genotype frequencies of SNPs in genes related to nicotine metabolism and nicotine dependence. Slow metabolizers smoked more cigarettes per day than intermediate and normal metabolizers.

scholarly journals Association between HOX Transcript Antisense RNA Single-Nucleotide Variants and Recurrent Implantation Failure

2021 ◽  
Vol 22 (6) ◽  
pp. 3021
Author(s):  
Jeong Yong Lee ◽  
Eun Hee Ahn ◽  
Hyeon Woo Park ◽  
Ji Hyang Kim ◽  
Young Ran Kim ◽  
...  
Keyword(s):  
Antisense Rna ◽  
Coagulation Factors ◽  
Healthy Controls ◽  
Implantation Failure ◽  
Single Nucleotide Variants ◽  
Recurrent Implantation Failure ◽  
Single Nucleotide ◽  
Vitro Fertilization ◽  
And Control

Recurrent implantation failure (RIF) refers to the occurrence of more than two failed in vitro fertilization–embryo transfers (IVF-ETs) in the same individual. RIF can occur for many reasons, including embryo characteristics, immunological factors, and coagulation factors. Genetics can also contribute to RIF, with some single-nucleotide variants (SNVs) reported to be associated with RIF occurrence. We examined SNVs in a long non-coding RNA, homeobox (HOX) transcript antisense RNA (HOTAIR), which is known to affect cancer development. HOTAIR regulates epigenetic outcomes through histone modifications and chromatin remodeling. We recruited 155 female RIF patients and 330 healthy controls, and genotyped HOTAIR SNVs, including rs4759314, rs920778, rs7958904, and rs1899663, in all participants. Differences in these SNVs were compared between the patient and control groups. We identified significant differences in the occurrence of heterozygous genotypes and the dominant expression model for the rs1899663 and rs7958904 SNVs between RIF patients and control subjects. These HOTAIR variants were associated with serum hemoglobin (Hgb), luteinizing hormone (LH), total cholesterol (T. chol), and blood urea nitrogen (BUN) levels, as assessed by analysis of variance (ANOVA). We analyzed the four HOTAIR SNVs and found significant differences in haplotype patterns between RIF patients and healthy controls. The results of this study showed that HOTAIR is not only associated with the development of cancer but also with pregnancy-associated diseases. This study represents the first report showing that HOTAIR is correlated with RIF.

Time to Positivity of Bacteria Cultures in Peritoneal Dialysis Fluid: Evaluation of Different Laboratory Techniques

2017 ◽  
Vol 37 (3) ◽  
pp. 342-344
Author(s):  
Roberta M. Katzap ◽  
Vany Elisa Pagnussatti ◽  
Ana Elizabeth Figueiredo ◽  
Julia Gabriela Motta ◽  
Domingos O. d'Avila ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Fluid ◽  
Antibiotic Sensitivity ◽  
Positive Culture ◽  
Cross Sectional Study ◽  
Essential Elements ◽  
Coagulase Negative Staphylococcus ◽  
Cross Sectional ◽  
Peritoneal Dialysis Fluid

Patients with chronic kidney disease on peritoneal dialysis (PD) are susceptible to infections, with peritonitis being the primary cause of dropout. Peritoneal fluid culture is one of the essential elements for proper diagnosis and peritonitis treatment. The aim of this study was to compare the time required to obtain a positive culture using different laboratory methods. An in vitro cross-sectional study was conducted comparing different techniques for preparation and culture of bacteria in peritoneal fluid. The research was carried out with 21 sterile dialysis bags and 21 PD bags containing peritoneal fluid drained from patients without peritonitis. Fluids from the 42 PD bags were contaminated by injecting a coagulase-negative Staphylococcus suspension and then prepared for culture using 4 distinct techniques: A - direct culture; B - post-centrifugation culture; C - direct culture after 4 h sedimentation; and D - culture after 4 h sedimentation and centrifugation. This was followed by seeding. In the 21 contaminated sterile bags, mean times to obtain a positive culture with techniques D (19.6 h ± 2.6) and C (19.1 h ± 2.3) were longer than with technique A (15.8 h ± 3.0; p < 0.01), but not statistically different from group B (19.0 h ± 3.2). The same occurred in the 21 bags drained from patients, with mean times for techniques D (14.0 h ± 1.9) and C (14.5 h ± 1.7) being longer than technique A (12.22 h ± 1.94; p < 0.05) but not statistically different from technique B (13.2 h ± 1.3). The sedimentation and centrifugation steps seem to be unnecessary and may delay antibiotic sensitivity test results by approximately 8 hours.

scholarly journals An efficient and adaptable workflow for editing disease-relevant single nucleotide variants using CRISPR/Cas9

2021 ◽  
Author(s):  
Inga Usher ◽  
Lorena Ligammari ◽  
Sara Ahrabi ◽  
Emily Hepburn ◽  
Calum Connolly ◽  
...  
Keyword(s):  
Genetic Research ◽  
Bone Cancer ◽  
Illumina Miseq ◽  
Genetic Alterations ◽  
Single Nucleotide Variants ◽  
Experimental Conditions ◽  
Single Nucleotide ◽  
Droplet Pcr ◽  
Low Efficiency

Single nucleotide variants are the commonest genetic alterations in the human genome. At least 60,000 have been reported to be associated with disease. The CRISPR/Cas9 system has transformed genetic research, making it possible to edit single nucleotides and study the function of genetic variants in vitro. While significant advances have improved the efficiency of CRISPR/Cas9, the editing of single nucleotides remains challenging. There are two major obstacles: low efficiency of accurate editing and the isolation of these cells from a pool of cells with other editing outcomes. We present data from 85 transfections of induced pluripotent stem cells and an immortalised cell line, comparing the effects of altering CRISPR/Cas9 design and experimental conditions on rates of single nucleotide substitution. We targeted variants in TP53, which predispose to several cancers, and in TBXT which is implicated in the pathogenesis of the bone cancer, chordoma. We describe a scalable and adaptable workflow for single nucleotide editing that incorporates contemporary techniques including Illumina MiSeq sequencing, TaqMan qPCR and digital droplet PCR for screening transfected cells as well as quality control steps to mitigate against common pitfalls. This workflow can be applied to CRISPR/Cas9 and other genome editing systems to maximise experimental efficiency.

scholarly journals HIV infection is associated with reduced serum alpha-1-antitrypsin concentrations

2010 ◽  
Vol 33 (6) ◽  
pp. 384 ◽  
Author(s):  
Courtney L Bryan ◽  
K Scott Beard ◽  
Gregory B Pott ◽  
Jeremy Rahkola ◽  
Edward M Gardner ◽  
...  
Keyword(s):  
T Cell ◽  
Hiv Infection ◽  
Fluid Phase ◽  
Cross Sectional Study ◽  
Infected Group ◽  
Cd4 T Cell ◽  
Cross Sectional ◽  
Clinically Significant ◽  
Alpha 1 Antitrypsin

Purpose: Several observations suggest the presence of HIV-suppressive factors in the fluid phase of blood. Alpha-1-antitrypsin (AAT), the most abundant serine protease inhibitor in the circulation, has potent anti-HIV activity in vitro, and may function as an endogenous HIV suppressor. Therefore, we assessed serum AAT concentrations for association with HIV infection. Methods: In this cross-sectional study, serum AAT concentrations were measured in 66 persons with HIV infection and in 45 healthy persons (Controls). In the HIV-infected group, antiretroviral therapy (ART) use was assessed and CD4+ T cell levels and plasma HIV RNA were quantified. Results: Median AAT concentration was significantly lower in the HIV-infected group (1.64 mg/mL) in comparison with Controls (1.94 mg/mL; p=0.001). AAT reduction was most pronounced in the HIV-infected subgroup with CD4+ T cell levels > 200 cells/µL in comparison with Controls (p < 0.01). Serum AAT concentrations < 1.0 mg/mL are clinically significant, and concentrations below this level were identified in 4.5% of the HIV-infected group and in no Control subjects. No association between AAT levels and viral load or use of ART was observed in HIV-infected subjects. Conclusion: The association between reduced serum AAT concentration and HIV infection is consistent with a role for AAT as an endogenous HIV suppressor.

scholarly journals Identification of Novel Classes for Patients With Lupus Nephritis Using Two-step Cluster Model

2021 ◽  
Author(s):  
Ting Huang ◽  
Shasha Xie ◽  
Liqing Ding ◽  
Hui Luo
Keyword(s):  
Cluster Analysis ◽  
Evaluation System ◽  
Demographic Data ◽  
White Blood Cells ◽  
Damage Index ◽  
Cross Sectional Study ◽  
Laboratory Findings ◽  
Cross Sectional ◽  
Mild Disease ◽  
Cluster 2

Abstract Objectives: To identify and reclassify the patients in the LN cohort, and to further analyze the prominent clinical features and clinical significance of each cluster of patients.Methods: This is a cross-sectional study of a cohort of 635 LN patients from the Rheumatology Department of Xiangya Hospital of Central South University. Demographic data, laboratory findings and clinical evaluation system include physician’s global assessment and the SLICC/ACR Damage Index were collected. Using two-step cluster analysis, patients with similar clinical property were identified and compared.Results: Among the 635 LN patients, 599 patients (94.3%) were female. The mean age of the patients were 33.8 ± 10.4 years. Three subgroups were identified by two-step cluster analysis. Cluster 1 included 130 (20.5%) patients, Cluster 2 included 132(20.8%) patients and Cluster 3 included 373 (58.7%) patients. Cluster 3 was the largest group of mild disease activity, patients in this cluster had lower white blood cells, neutrophils, lymphocytes and mean SDI scores compared to those in the other two clusters. Cluster 1 was the smallest group of severe damage, patients in this cluster had multiple positive auto-antibodies, higher SDI scores and lower complement level. Patients of cluster 2 had the highest levels of granulocytes, but the results of other laboratory tests were roughly between the cluster 1 and cluster 3.Conclusions: This study reclassified three groups of LN patients in a large cohort. Our research shows that the multiple positive ANA antibody may be related to the high SDI score of LN patients. Clinicians can identify patients at different stages through cluster analysis to better implement prognosis.

scholarly journals Transferrin and antioxidants partly prevented mouse oocyte oxidative damage induced by exposure of cumulus-oocyte complexes to endometrioma fluid

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Zi Ren ◽  
Jiana Huang ◽  
Chuanchuan Zhou ◽  
Lei Jia ◽  
Manchao Li ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Oocyte Retrieval ◽  
Cross Sectional Study ◽  
Human Oocyte ◽  
Cross Sectional ◽  
Vitro Fertilization ◽  
Good Quality Embryo ◽  
Damage Process ◽  
Human And Mouse

Abstract Background Exposure of oocytes to the endometrioma fluid has an adverse effect on embryonic quality. To determine whether adding transferrin and antioxidants to culture medium could counteract detrimental effects on mouse cumulus-oocyte complexes (COCs) induced by exposure to endometrioma fluid or not, we conducted an in vitro cross-sectional study using human and mouse COCs. Methods Eighteen women who had their oocytes exposed to endometrioma fluid during oocyte retrieval were enrolled. COCs from superovulated ICR female mice were collected. They were first exposed to human endometrioma fluid and then treated by transferrin and/or antioxidants (cysteamine + cystine). Subsequently, COCs function was assessed by molecular methods. Results This study observed that human COCs inadvertently exposed to endometrioma fluid in the in vitro fertilization (IVF) group led to a lower good quality embryo rate compared to intracytoplasmic sperm injection (ICSI) group. Exposure of mouse COCs to endometrioma fluid accelerated oocyte oxidative damage, evidenced by significantly reduced CCs viability, defective mitochondrial function, decreased GSH content and increased ROS level, associated with the significantly higher pro-portion of abnormal spindles and lower blastocyst formation (p < 0.05, respectively). This damage could be recovered partly by treating COCs with transferrin and antioxidants (cysteamine + cystine). Conclusions Transferrin and antioxidants could reduce the oxidative damage caused by COCs exposure to endometrioma fluid. This finding provides a promising new possibility for intervention in the human oocyte oxidative damage process induced by endometrioma fluid during oocyte pick-up.

scholarly journals Rare single-nucleotide DAB1 variants and their contribution to Schizophrenia and autism spectrum disorder susceptibility

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Yoshihiro Nawa ◽  
Hiroki Kimura ◽  
Daisuke Mori ◽  
Hidekazu Kato ◽  
Miho Toyama ◽  
...  
Keyword(s):  
Rare Variants ◽  
Adaptor Protein ◽  
Autism Spectrum ◽  
Case Group ◽  
Missense Mutations ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Next Generation Sequencing Technology ◽  
A Minor

AbstractDisabled 1 (DAB1) is an intracellular adaptor protein in the Reelin signaling pathway and plays an essential role in correct neuronal migration and layer formation in the developing brain. DAB1 has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in genetic, animal, and postmortem studies. Recently, increasing attention has been given to rare single-nucleotide variants (SNVs) found by deep sequencing of candidate genes. In this study, we performed exon-targeted resequencing of DAB1 in 370 SCZ and 192 ASD patients using next-generation sequencing technology to identify rare SNVs with a minor allele frequency <1%. We detected two rare missense mutations (G382C, V129I) and then performed a genetic association study in a sample comprising 1763 SCZ, 380 ASD, and 2190 healthy control subjects. Although no statistically significant association with the detected mutations was observed for either SCZ or ASD, G382C was found only in the case group, and in silico analyses and in vitro functional assays suggested that G382C alters the function of the DAB1 protein. The rare variants of DAB1 found in the present study should be studied further to elucidate their potential functional relevance to the pathophysiology of SCZ and ASD.

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