Polycystic ovary syndrome: clinical and laboratory variables related to new phenotypes using machine-learning models.

PURPOSE: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. Machine learning (ML) is the area of artificial intelligence with a focus on predictive computing algorithms. We aimed to define the most relevant clinical and laboratory variables related to PCOS diagnosis, and to stratify patients into different phenotypic groups (clusters) using ML algorithms. METHODS: Variables from a database comparing 72 patients with PCOS and 73 healthy women were included. The BorutaShap method, followed by the Random Forest algorithm, was applied to prediction and clustering of PCOS. RESULTS: Among the 58 variables investigated, the algorithm selected in decreasing order of importance: lipid accumulation product (LAP); abdominal circumference; thrombin activatable fibrinolysis inhibitor (TAFI) levels; body mass index (BMI); C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c), follicle-stimulating hormone (FSH) and insulin levels; HOMA-IR value; age; prolactin, 17-OH progesterone and triglycerides levels; and family history of diabetes mellitus in first-degree relative as the variables associated to PCOS diagnosis. The combined use of these variables by the algorithm showed an accuracy of 86% and area under the ROC curve of 97%. Next, PCOS patients were gathered into two clusters in the first, the patients had higher BMI, abdominal circumference, LAP and HOMA-IR index, as well as CRP and insulin levels compared to the other cluster. CONCLUSION: The developed algorithm could be applied to select more important clinical and biochemical variables related to PCOS and to classify into phenotypically different clusters. These results could guide more personalized and effective approaches to the treatment of PCOS.

Microparticles: Inflammatory and haemostatic biomarkers in Polycystic Ovary Syndrome.

Polycystic Ovary Syndrome (PCOS) is associated with a chronic low-grade inflammation and predisposition to hemostatic and atherosclerotic complications. This case-control study evaluated the microparticles (MPs) profile in patients with the PCOS and related these MPs to clinical and biochemical parameters. MPs derived from platelets (PMPs), leuckocytes (LMPs) and endothelial cells (EMPs) were evaluated, as well as MPs expressing tissue factor (TFMPs), by flow cytometry, comparing women with PCOS (n = 50) and a healthy control group (n = 50). PCOS women presented increased total MPs, PMPs, LMPs and EMPs levels when compared to control group (all p < 0.05). TFMPs was similar between the groups (p = 0.379). In conclusion, these MPs populations could be useful biomarkers for association with thrombosis and cardiovascular disease in PCOS women.

Estrogen receptor αlpha gene (ESR1) PvuII and XbaI polymorphisms are associated to metabolic and proinflammatory factors in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that involves multiple factors. Although the etiology of PCOS is unknown, there is an involvement of sex steroid hormones in the pathophysiology of this syndrome. Therefore, polymorphisms in genes involved in the action of estrogen may contribute to a woman's susceptibility to PCOS. AIM: This study aimed to evaluate the association between the polymorphisms PvuII and XbaI in the estrogen receptor alpha (ESR1) gene and the occurrence of PCOS. The study also aimed to assess the influence of these polymorphisms on the metabolic and inflammatory profiles of women with PCOS. MATERIAL AND METHODS: This case-control study included 99 women with PCOS, diagnosed according to the Rotterdam criteria, and 104 age-matched healthy women. The polymorphisms were evaluated using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No association between the ESR1 gene polymorphisms and the presence of PCOS was observed. However, we found associations between the PvuII polymorphism and C-reactive protein levels, testosterone levels, family history of diabetes, and waist circumference. The XbaI polymorphism was associated with fasting glucose and a family history of hypertension. CONCLUSION: These polymorphisms are not associated with PCOS development, but they are involved in the phenotype of complications of the syndrome. Therefore, prior knowledge of these genomic variants might contribute to taking preventive measures that could delay the metabolic and reproductive complications commonly seen in women with PCOS.

Correlation between plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G polymorphism and metabolic/proinflammatory factors in polycystic ovary syndrome.

Polycystic Ovary Syndrome (PCOS) is the most common cause of subfertility associated to metabolic disorders. The aim of this study was to correlate metabolic and proinflammatory factors in women with PCOS. The frequency of Plasminogen Activator Inhibitor-1 (PAI-1) promoter 4 G/5 G polymorphism was also compared to healthy controls. We evaluated 79 PCOS and 79 healthy women. PAI-1 levels are positively correlated with proinflammatory factors in PCOS group. 4 G allele in PAI-1 gene was more frequent in PCOS and the 4G/4 G genotype was associated with increased PAI-1 levels. A correlation between insulin resistance and proinflammatory and overweight was also observed. C-reactive protein, serum levels of vascular cell adhesion molecule-1 (sVCAM-1), Lipid Accumulation Product (LAP) and vitamin D are good tools to evaluated factors associated to cardiovascular risk in women with PCOS.

Evaluation of post-surgical cognitive function and protein fingerprints in the cerebro-spinal fluid utilizing surface-enhanced laser Desorption/Ionization time-of-flight mass-spectrometry (SELDI-TOF MS) after coronary artery bypass grafting: review of proteomic analytic tools and introducing a new syndrome.

Cognitive dysfunction following surgery is a common complication, which increases the incidence of other co-morbid conditions, hospital and health-care costs. The reported rate of the occurrence of post-operative cognitive decline varies with different studies, depending on population profile, type of surgery, definition of cognitive disorder and detection methods, design of study, etc. It remains unclear whether these psychiatric signs and symptoms are direct results of the effects of surgery or general anesthesia. Nonetheless they are more frequent after cardiac surgery and are likely to be multi-factorial, but the patho-mechanisms are not yet fully characterized. This communication provides a synopsis of proteomics tools and delineates novel SELDI-TOF results to evaluate biomarkers in this regard. Presented for the first time is a classification of the clinically relevant forms of post-operative cognitive decline with the advent of a novel subclass.

Atheromatosis extent in coronary artery disease is not correlated with apolipoprotein-E polymorphism and its plasma levels, but associated with cognitive decline.

BACKGROUND: Apolipoprotein-E (apoE) ε4 allele is a known risk factor for Alzheimer's disease (AD). Polymorphism of apoE is also one of the most important genetic markers for coronary artery disease (CAD). The allelic variation in the apoE gene has a significant effect on inter-individual variation of lipids and lipoprotein plasma levels as well. This study investigated whether apoE polymorphism affects the plasma levels of apoE and the possible association to CAD extent and cognitive functions. METHODS: Plasma apoE levels and apoE genotypes were evaluated of subjects with normal coronary arteries, and individuals with angiographycally confirmed mild/moderate or severe atheromatosis. The cognitive performance of the volunteers was also measured by mini-mental state examination (MMSE). RESULTS: Out of the 6 expected genotypes, only 5 were detected in participants: E3/3 (56.0%), E3/4 (23.6%), E4/4 (8.2%), E2/4 (3.3%), E2/3 (8.9%). The ε3 allele (72%) was the most frequent, followed by ε4 (22%) and ε2 (6%). No difference was found in plasma levels of either apoE or in apoE genotype frequencies among the groups, however MMSE scores of CAD patients irrespective of their atheromatosis extent were significantly lower than that seen in the normal population. CONCLUSIONS: Although neither apoE plasma levels, nor apoE polymorphism in patients presenting with mild/moderate or severe atheromatosis showed to be associated with CAD severity, the presence of atheromatosis in the heart vessels positively correlated with cognitive dysfunction.

Evaluation of the blood coagulation mechanism and platelet aggregation in individuals with mechanical or biological heart prostheses.

Oral anticoagulants have been widely employed to decrease thrombotic risk by reducing the levels of vitamin K-dependent clotting factors. Paradoxically, the use of oral anticoagulants also decreases the levels of natural anticoagulants (protein C and protein S), which favors the hypercoagulability state. Increased platelet activation has been reported in patients undergoing warfarin treatment. These findings have raised questions about the antagonistic effect of oral anticoagulants and their implications for hemostatic balance. The aim of this study is to determine the relationship between warfarin dosage and prothrombin time [International Normalized Ratio (INR)], platelet aggregation, vitamin K-dependent clotting factors, and protein C and protein S. Blood samples from 27 patients were analyzed, seven with mechanical prostheses and 20 with biological prostheses, and 27 controls. Multiple regression analysis showed that factor II most significantly determines the INR. Results showed that the INR, clotting factors, and protein C and protein S activity did not correlate with warfarin dosage, highlighting the need for accurate laboratory monitoring of those undergoing anticoagulant therapy.