The transcriptome of corona radiata cells from individual MII oocytes that after ICSI developed to embryos selected for transfer: PCOS women compared to healthy women

BACKGROUND: Corona radiata cells (CRCs) refer to the fraction of cumulus cells just adjacent to the oocyte. The CRCs are closely connected to the oocyte throughout maturation and their gene expression profiles might reflect oocyte quality. Polycystic ovary syndrome (PCOS) is a common cause of infertility. It is controversial whether PCOS associate with diminished oocyte quality. The purpose of this study was to compare individual human CRC samples between PCOS patients and controls. METHODS: All patients were stimulated by the long gonadotropin-releasing hormone (GnRH) agonist protocol. The CRC samples originated from individual oocytes developing into embryos selected for transfer. CRCs were isolated in a two-step denudation procedure, separating outer cumulus cells from the inner CRCs. Extracted RNA was amplified and transcriptome profiling was performed with Human Agilent® arrays. RESULTS: The transcriptomes of CRCs showed no individual genes with significant differential expression between PCOS and controls, but gene set enrichment analysis identified several cell cycle- and DNA replication pathways overexpressed in PCOS CRCs (FDR < 0.05). Five of the genes contributing to the up-regulated cell cycle pathways in the PCOS CRCs were selected for qRT-PCR validation in ten PCOS and ten control CRC samples. qRT-PCR confirmed significant up-regulation in PCOS CRCs of cell cycle progression genes HIST1H4C (FC = 2.7), UBE2C (FC = 2.6) and cell cycle related transcription factor E2F4 (FC = 2.5). CONCLUSION: The overexpression of cell cycle-related genes and cell cycle pathways in PCOS CRCs could indicate a disturbed or delayed final maturation and differentiation of the CRCs in response to the human chorionic gonadotropin (hCG) surge. However, this had no effect on the in vitro development of the corresponding embryos. Future studies are needed to clarify whether the up-regulated cell cycle pathways in PCOS CRCs have any clinical implications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13048-014-0110-6) contains supplementary material, which is available to authorized users

Levels of circulating insulin cell-free DNA in women with Polycystic Ovary Syndrome:a longitudinal cohort study

Correlations between clinical measurements and unmethylated and methylated INScfDNA at baseline and at follow-up. (XLSX 14 kb

Motivations for relationships as sources of meaning : Ghanaian and South African experiences

Afrocentric paradigms reflect assumptions of the overarching importance of interconnectedness and social bonds in meaningful experiences. It is, however, not known if types of relatedness vary in importance as meaning sources in the subjective experiences of laypeople, or what the reasons are that they ascribe to the importance of relationships. The empirical and theoretical substantiation of philosophical assumptions is needed to provide a scientific basis for appropriate well-being interventions in African contexts. Therefore, this study aimed to empirically explore the relative importance of various types of relationships as sources of meaning and in particular why relationships are important to laypeople in relatively collectivist African contexts. Using a bottomup qualitative approach with quantification of responses, this study explored how prominently relationships featured as meaning sources compared to other domains of life and then, in particular, the motivations for the importance of various types of relationships as found in four African samples: a Ghanaian urban group (n = 389), a South African multicultural, English-speaking urban group (n = 585), and two South African Setswana-speaking groups (n = 512 rural, n = 380 urban). Findings showed that the relational domains of life, namely, family, interpersonal relations, spirituality/religion, and community/society, made up a large proportion of responses on what provides meaning in life in particular family and spirituality/religion with community/society occurring the least. The reasons for meaning experienced in various relationship types included domain-typical relational descriptors, such as contributions made or rewards received. However, many intrapersonal motives also emerged: inner well-being, happiness, joy, a sense of competence, and own growth. Material needs and harmony also surfaced as motivations for relational importance. Findings are aligned with African philosophical perspectives as far as the importance of relationships and the value attached to spirituality/religion are concerned, but contributed additionally by showing that different types of relationships vary in importance: close relationships are more important than community/societal relationships. Unearthing the reasons for the importance of relationships points toward a dialectic pattern of African individualism– collectivism in which independent and interdependent orientations flow together. Such knowledge is vital for the promotion of mental health and well-being in these contexts.This work from the FORT 3 and PURE-SA projects are based on the research supported in part by the National Research Foundation (NRF) of South Africa (Grant Numbers: 91557, 106050, 2069139, FA2006040700010, FA2007042600011, and 121948). Funding for PURE-SA were also obtained from the SANPAD (South Africa Netherlands Research Programme on Alternatives in Development 08/15), the South African Medical Research Council, the North-West University, South Africa, and the Population Health Research Institute, ON, Canada.http://www.frontiersin.org/Psychologyam2020Psycholog

Hyperandrogenism and Metabolic Syndrome Are Associated With Changes in Serum-Derived microRNAs in Women With Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) remains one of the most common endocrine disorder in premenopausal women with an unfavorable metabolic risk profile. Here, we investigate whether biochemical hyperandrogenism, represented by elevated serum free testosterone, resulted in an aberrant circulating microRNA (miRNAs) expression profile and whether miRNAs can identify those PCOS women with metabolic syndrome (MetS). Accordingly, we measured serum levels of miRNAs as well as biochemical markers related to MetS in a case-control study of 42 PCOS patients and 20 Controls. Patients were diagnosed based on the Rotterdam consensus criteria and stratified based on serum free testosterone levels (≥0.034 nmol/l) into either a normoandrogenic (n = 23) or hyperandrogenic (n = 19) PCOS group. Overall, hyperandrogenic PCOS women were more insulin resistant compared to normoandrogenic PCOS women and had a higher prevalence of MetS. A total of 750 different miRNAs were analyzed using TaqMan Low-Density Arrays. Altered levels of seven miRNAs (miR-485-3p, -1290, -21-3p, -139-3p, -361-5p, -572, and -143-3p) were observed in PCOS patients when compared with healthy Controls. Stratification of PCOS women revealed that 20 miRNAs were differentially expressed between the three groups. Elevated serum free testosterone levels, adjusted for age and BMI, were significantly associated with five miRNAs (miR-1290, -20a-5p, -139-3p, -433-3p, and -361-5p). Using binary logistic regression and receiver operating characteristic curves (ROC), a combination panel of three miRNAs (miR-361-5p, -1225-3p, and -34-3p) could correctly identify all of the MetS cases within the PCOS group. This study is the first to report comprehensive miRNA profiling in different subgroups of PCOS women with respect to MetS and suggests that circulating miRNAs might be useful as diagnostic biomarkers of MetS for a different subset of PCOS

Risk for excessive anticoagulation during hemodialysis is associated with type of vascular access and bedside coagulation testing: Results of a cross-sectional study

BackgroundRecommendations and practice patterns for heparin dosing during hemodialysis show substantial heterogeneity and are scantly supported by evidence. This study assessed the variability in unfractionated heparin (UFH) dosing during hemodialysis and its clinical and biological anticoagulatory effects, and identified explanatory factors of heparin dosing.MethodsCross-sectional study assessing UFH dosing, coagulation tests – activated partial thromboplastin time (aPTT) and activated clotting time (ACT) before dialysis start, 1 h after start and at treatment end (4 h) – and measurement of residual blood compartment volume of used dialyzers.Results101 patients, 58% male, with a median dialysis vintage of 33 (6–71) months received hemodialysis using a total UFH dose of 9,306 ± 4,079 (range 3,000–23,050) IU/session. Use of a dialysis catheter (n = 56, 55%) was associated with a 1.4 times higher UFH dose (p &lt; 0.001) irrespective of prior access function. aPTT increased significantly more than ACT both 1 h and 4 h after dialysis start, independent of the dialysis access used. 53% of patients with catheter access and ACT ratio &lt; 1.5, 1 h after dialysis start had simultaneous aPTT ratios &gt; 2.5. Similar findings were present at 1 h for patients with AVF/AVG and at dialysis end for catheter use. No clinically significant clotting of the extracorporeal circuit was noted during the studied sessions. Dialyzer’s blood compartment volume was reduced with a median of 9% (6–20%) without significant effect of UFH dose, aPTT or ACT measurements and vascular access type.ConclusionUFH dose adaptations based on ACT measurements frequently result in excessive anticoagulation according to aPTT results. Higher doses of UFH are used in patients with hemodialysis catheters without evidence that this reduces dialyzer clotting

Prevention of tunneled cuffed catheter dysfunction with prophylactic use of taurolidine locking solution containing urokinase : a prospective and randomized placebo-controlled trial

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MicroRNAs Related to Polycystic Ovary Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is the most common, though heterogeneous, endocrine aberration in women of reproductive age, with high prevalence and socioeconomic costs. The syndrome is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism, as well as being associated with infertility, insulin resistance, chronic low-grade inflammation and an increased life time risk of type 2 diabetes. MicroRNAs (miRNAs) are small, non-coding RNAs that are able to regulate gene expression at the post-transcriptional level. Altered miRNA levels have been associated with diabetes, insulin resistance, inflammation and various cancers. Studies have shown that circulating miRNAs are present in whole blood, serum, plasma and the follicular fluid of PCOS patients and that they might serve as potential biomarkers and a new approach for the diagnosis of PCOS. In this review, recent work on miRNAs with respect to PCOS will be summarized. Our understanding of miRNAs, particularly in relation to PCOS, is currently at a very early stage, and additional studies will yield important insight into the molecular mechanisms behind this complex and heterogenic syndrome