scholarly journals Early Phenotypes in Girls at Risk for PCOS Replicate Metabolic and Reproductive Subtypes: An Unsupervised Clustering Analysis

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A739-A739
Author(s):  
Laura Christine Torchen ◽  
Ryan Sisk ◽  
Sarayu Ratnam ◽  
Andrea Elizabeth Dunaif

Abstract Both daughters of women with PCOS (PCOS-d) and overweight girls (OW-g) are proposed to be at increased risk of PCOS because they have peripubertal increases in testosterone (T) levels, a cardinal feature of PCOS. We are testing this hypothesis by performing longitudinal studies in these girls after menarche. In adult women with PCOS, we have recently identified reproductive and metabolic subtypes using unsupervised cluster analyses. These subtypes were associated with novel PCOS susceptibility genetic loci suggesting that the subtypes reflect biologically discrete entities. We performed similar analyses in our cohort of early postmenarchal PCOS-d and OW-g to test the hypothesis that these subtypes are present in girls at risk for PCOS. Fifteen PCOS-d and 10 OW-g aged 11-16 years and with postmenarchal age less than 2 years were studied. Mothers of PCOS-d fulfilled NIH criteria for PCOS, mothers of OW-g were reproductively normal with no history of irregular menses or clinical hyperandrogenism. OW-g had a BMI above the 85th percentile for age. There was no BMI inclusion criterion for PCOS-d; four PCOS-d had a BMI above the 85th percentile. The girls were of comparable age, post-menarchal age and BMI z score. A fasting morning blood sample was drawn for T, SHBG, DHEAS, glucose and insulin. Leuprolide 10 mcg/kg SC was administered. LH and FSH levels were measured at baseline, 30 min, and 60 min following leuprolide. Unsupervised hierarchical cluster analysis adjusted for age was performed on quantitative traits including BMI, T, fasting insulin, fasting glucose, DHEAS, SHBG, and LH and FSH. These are the same quantitative traits used for clustering in adult PCOS. The clustering revealed 2 distinct PCOS subtypes: a reproductive group (41%), characterized by higher SHBG levels, LH and FSH with relatively low BMI and insulin levels, and a metabolic group (41%), characterized by higher BMI and insulin levels and lower SHBG, LH, and FSH. Jaccard coefficients indicated cluster stability (0.70 reproductive, 0.69 metabolic). There was a significant difference in the distribution of the two subgroups in PCOS-d and OW-g: PCOS-d 60% reproductive, 13% metabolic, 27% indeterminate; OW-g 25% reproductive, 50% metabolic, 25% indeterminate (Chi Sq P=0.05). We found that early postmenarchal PCOS-d and OW-g demonstrate reproductive and metabolic subtypes similar to those identified in adult women with PCOS. The majority of PCOS-d had the reproductive subtype. These findings suggest that this subtype, which is characterized by disordered gonadotropin secretion, is an early harbinger of PCOS. Longitudinal studies are ongoing to test this hypothesis.

Author(s):  
Salwa Abdelmaged Elraey ◽  
Mohammed Mohsen Elnamoury ◽  
Ahmed Mohammed Othman ◽  
Ahmed Mahmoud Awara

Background: Doppler velocimetry is the best method of surveillance for fetal hypoxemia during pregnancy. Cerebroplacental ratio (CPR), has been suggested as a useful clinical simplification. It is believed that the CPR better predicts adverse perinatal outcomes than its individual components and better than conventional anthropometric models. Therefore, the aim of this study is to evaluate the significance of the cerebroplacental 10th centile threshold measured weekly from 36 weeks of gestation till delivery as a screening test for prediction of need for Cesarean section for intrapartum fetal compromise and the adverse neonatal outcome in women with normally grown fetuses and uncomplicated pregnancy. Methods: This study was carried out on 40 pregnant women uncomplicated, singleton pregnancy with appropriately grown fetuses on clinical assessment. The last Doppler indices including cerebroplacental ratio measurement obtained before labor was reported. CPR values below 1.1 were reported as abnormal. Various studies have variably defined the threshold of abnormal CPR ratio as <1.08. Results: There was significant decrease in the Mean of CPR among patients who had anemia compared to those without anemia. In addition, there was no significant association seen between low CPR and having previous history of abortion or IUGR as well as being a smoker. There was no significant difference between cases who had normal and abnormal CPR regarding gestational age at delivery. There was no difference between cases who had normal and abnormal cerebroplacental ratio regarding mode of delivery. there was significant decrease in the prevalence of low birth weight among group who had CPR≥1.08. CPR <1.08 was significantly associated with neonatal complication like NICU admission, and neonatal death. There was no statistically significant relationship between cerebroplacental ratio and neonatal complication like IUFD, and neonatal sepsis. There was no statistically significant association between the mean cerebroplacental ratio and IUFD. There was statistically significant association between the mean cerebroplacental ratio and NICU. There was no statistically significant association between the mean cerebroplacental ratio and neonatal sepsis. The mean cerebroplacental ratio of 0.93± 0.22 has a significant association with neonatal death. Conclusion: A low cerebroplacental ratio reflects redistribution of the cardiac output to the cerebral circulation and has been shown to improve accuracy in predicting adverse outcome compared with Middle cerebral artery (MCA) or Umbilical artery (UA) Doppler alone. Therefore, integrating CPR in clinical management may help to better identify fetuses at risk for adverse perinatal events, since abnormal CPR has been associated with an increased risk of perinatal complications.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7150 ◽  
Author(s):  
Yun Shen ◽  
Deepthi S. Varma ◽  
Yi Zheng ◽  
Jenny Boc ◽  
Hui Hu

Objective The association between early age at menarche and depression among adolescent girls and adult women has been examined in many studies. However, inconsistent results and limitations such as small sample size, low generalizability, and measurement error exist. We aimed to address these issues to assess the association between age at menarche and depressive symptoms in a nationally representative sample of US women aged 18 years and older. Methods We used the 2005–2016 National Health and Nutrition Examination Survey (NHANES) data with a total of 15,674 women aged 18 years and older included in our study. Logistic regression models were used after adjusting for sociodemographic and health-related factors. Results The crude-adjusted model suggests that women with early age of menarche had 1.36 (95% CI [1.16–1.61]) times the odds of current depressive symptoms compared with the normal menarche group, after controlling for age, race/ethnicity, education, poverty income ratio (PIR) and marital status. In the fully-adjusted model, women with early menarche had 1.25 (95% CI [1.05–1.48]) times the odds of current depressive symptoms, after additionally adjusting for smoking status and body mass index (BMI). However, no significant difference was observed between the normal and late menarche groups. Conclusion Further studies are warranted to determine the causal relationship and mechanisms between early menarche and increased risk of depression.


Medicina ◽  
2021 ◽  
Vol 58 (1) ◽  
pp. 9
Author(s):  
Igor Lukic ◽  
Nikola Savic ◽  
Maja Simic ◽  
Nevena Rankovic ◽  
Dragica Rankovic ◽  
...  

Background and Objectives: Hyperinsulinemia and insulin resistance are not synonymous; if the risk of developing insulin resistance in adolescents is monitored, they do not necessarily have hyperinsulinemia. It is considered a condition of pre-diabetes and represents a condition of increased risk of developing DM (diabetes mellitus); it can exist for many years without people having the appropriate symptoms. This study aims to determine the risk of developing hyperinsulinemia at an early age in adolescents by examining which factors are crucial for its occurrence. Materials and Methods: The cross-sectional study lasting from 2019 to 2021 (2 years) was realized at the school children’s department in the Valjevo Health Center, which included a total of 822 respondents (392 male and 430 female) children and adolescents aged 12 to 17. All respondents underwent a regular, systematic examination scheduled for school children. BMI is a criterion according to which respondents are divided into three groups. Results: After summary analyzes of OGTT test respondents and calculated values of HOMA-IR (homeostatic model assessment for insulin resistance), the study showed that a large percentage of respondents, a total of 12.7%, are at risk for hyperinsulinemia. The research described in this paper aimed to use the most popular AI (artificial intelligence) model, ANN (artificial neural network), to show that 13.1% of adolescents are at risk, i.e., the risk is higher by 0.4%, which was shown by statistical tests as a significant difference. Conclusions: It is estimated that a model using three different ANN architectures, based on Taguchi’s orthogonal vector plans, gives more precise and accurate results with much less error. In addition to monitoring changes in each individual’s risk, the risk assessment of the entire monitored group is updated without having to analyze all data.


2012 ◽  
Vol 49 (2) ◽  
pp. 115-124 ◽  
Author(s):  
Valentina Vaira ◽  
Francesca Elli ◽  
Irene Forno ◽  
Vito Guarnieri ◽  
Chiara Verdelli ◽  
...  

A subset of over-expressed microRNAs (miRNAs) identified in parathyroid carcinomas (Ca) compared to normal glands belongs to C19MC, a cluster on chromosome 19q13.4 involved in stem cell biology and tumourigenesis. In this study, the expression of C19MC–MIR371–3 clusters and the molecular mechanisms presiding their modulation were investigated in a series of six normal parathyroids, 24 adenomas (Ad), 15 Ca and five matched metastases. The general expression levels of C19MC or MIR371–3 clusters in Ad lesions did not differ from normal glands, while they distinguished Ad from Ca at unsupervised hierarchical cluster analysis (P=0.0008). MIR517C showed the most significant difference in expression between Ca and Ad (P=0.0003) and it positively correlated with serum calcium, parathormone and tumour weight. In regard to the molecular mechanism determining C19MC cluster activation, we could detect C19MC copy number (CN) gain in ten Ca (67%) extending distal to the MIR371–3 cluster in almost all samples. Conversely, only four Ad (16%) showed C19MC amplification, with one case presenting distal genomic aberration to MIR371–3. Globally, CN variations of 19q13.4 loci were significantly associated with MIR517C up-regulation (P=0.006). Opposite to normal glands where C19MC promoter was methylated, hypomethylation occurred in 15 out of 30 analysed tumours. Though the epigenetic status did not correlate with C19MC miRNA expression levels, loss of C19MC promoter methylation was significantly associated with Ca and metastatic disease (P=0.01). In conclusion, C19MC cluster aberrations are a characteristic of Ca with respect to Ad. Altogether, these evidences point towards a role for 19q13.4 miRNA clusters as oncogenes in parathyroid tumourigenesis.


Sarcoma ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Josefin Fernebro ◽  
Ana Carneiro ◽  
Anders Rydholm ◽  
Henryk A. Domanski ◽  
Anna Karlsson ◽  
...  

Purpose. Patients with soft tissue sarcomas (STS) are at increased risk of second primary malignancies, including a second STS, but distinction between metastases and a second primary STS is difficult.Patients and Methods. Array-based comparative genomic hybridization (aCGH) was applied to 30 multiple STS of the extremities and the trunk wall from 13 patients. Different histotypes were present with malignant fibrous histiocytomas/undifferentiated pleomorphic sarcomas being the predominant subtype.Results. aCGH profiling revealed genetic complexity with multiple gains and losses in all tumors. In an unsupervised hierarchical cluster analysis, similar genomic profiles and close clustering between the first and subsequent STS were identified in 5 cases, suggesting metastatic disease, whereas the tumors from the remaining 8 patients did not cluster and showed only weak pairwise correlation, suggesting development of second primary STS.Discussion. The similarities and dissimilarities identified in the first and second STS suggest that genetic profiles can be used to distinguish soft tissue metastases from second primary STS. The demonstration of genetically different soft tissue sarcomas in the same patient suggests independent tumor origin and serves as a reminder to consider development of second primary STS, which has prognostic and therapeutic implications.


Neurology ◽  
2019 ◽  
Vol 92 (24) ◽  
pp. e2815-e2821 ◽  
Author(s):  
Andrew G. Herzog ◽  
Hannah B. Mandle ◽  
Devon B. MacEachern

ObjectiveTo determine (1) the proportion of women with epilepsy (WWE) at risk of unintended pregnancy who use highly effective contraception, (2) demographic predictors, and (3) folic acid (FA) use.MethodsThese cross-sectional data come from 311 US WWE, 18–47 years, who participated in the Epilepsy Birth Control Registry (EBCR) web-based survey in 2017. They provided demographic, epilepsy, antiepileptic drug (AED), contraceptive, and FA data. We report frequencies of highly effective contraception use and use logistic regression to determine demographic predictors. We report the proportion who take FA.ResultsA total of 186 (59.8%) of the 311 WWE were at risk of unintended pregnancy. A total of 131 (70.4%) used a highly effective contraceptive category; 55 (29.6%) did not. An additional 13 (7.0%) used a combination of generally effective hormonal contraception with an enzyme-inducing AED, which poses increased risk of unintended pregnancy. Overall, 68 (36.6%) of the 186 WWE at risk did not use highly effective contraception. Increasing income (p = 0.004) and having insurance (p = 0.048) were predictors of highly effective contraception. A total of 50.0% took FA supplement. There was no significant difference in relation to the use or lack of use of highly effective contraception.ConclusionA total of 36.6% of WWE in the EBCR did not use highly effective contraception and 50.0% did not take FA in 2017 despite the important negative consequences of unintended pregnancy on pregnancy outcomes. There is a need for more readily available information and counseling on safe and effective contraception and FA use for this community.


VASA ◽  
2017 ◽  
Vol 46 (6) ◽  
pp. 484-489 ◽  
Author(s):  
Tom Barker ◽  
Felicity Evison ◽  
Ruth Benson ◽  
Alok Tiwari

Abstract. Background: The invasive management of varicose veins has a known risk of post-operative deep venous thrombosis and subsequent pulmonary embolism. The aim of this study was to evaluate absolute and relative risk of venous thromboembolism (VTE) following commonly used varicose vein procedures. Patients and methods: A retrospective analysis of secondary data using Hospital Episode Statistics database was performed for all varicose vein procedures performed between 2003 and 2013 and all readmissions for VTE in the same patients within 30 days, 90 days, and one year. Comparison of the incidence of VTEs between procedures was performed using a Pearson’s Chi-squared test. Results: In total, 261,169 varicose vein procedures were performed during the period studied. There were 686 VTEs recorded at 30 days (0.26 % incidence), 884 at 90 days (0.34 % incidence), and 1,246 at one year (0.48 % incidence). The VTE incidence for different procedures was between 0.15–0.35 % at 30 days, 0.26–0.50 % at 90 days, and 0.46–0.58 % at one year. At 30 days there was a significantly lower incidence of VTEs for foam sclerotherapy compared to other procedures (p = 0.01). There was no difference in VTE incidence between procedures at 90 days (p = 0.13) or one year (p = 0.16). Conclusions: Patients undergoing varicose vein procedures have a small but appreciable increased risk of VTE compared to the general population, with the effect persisting at one year. Foam sclerotherapy had a lower incidence of VTE compared to other procedures at 30 days, but this effect did not persist at 90 days or at one year. There was no other significant difference in the incidence of VTE between open, endovenous, and foam sclerotherapy treatments.


Crisis ◽  
2017 ◽  
Vol 38 (6) ◽  
pp. 433-442 ◽  
Author(s):  
Kim Gryglewicz ◽  
Melanie Bozzay ◽  
Brittany Arthur-Jordon ◽  
Gabriela D. Romero ◽  
Melissa Witmeier ◽  
...  

Abstract. Background: Given challenges that exceed the normal developmental requirements of adolescence, deaf and hard-of-hearing (DHH) youth are believed to be at elevated risk for engaging in suicide-related behavior (SRB). Unfortunately, little is known about the mechanisms that put these youth potentially at risk. Aims: To determine whether peer relationship difficulties are related to increased risk of SRB in DHH youth. Method: Student records (n = 74) were retrieved from an accredited educational center for deaf and blind students in the United States. Results: Peer relationship difficulties were found to be significantly associated with engagement in SRB but not when accounting for depressive symptomatology. Limitations: The restricted sample limits generalizability. Conclusions regarding risk causation cannot be made due to the cross-sectional nature of the study. Conclusion: These results suggest the need for future research that examines the mechanisms of the relationship between peer relationship difficulties, depression, and suicide risk in DHH youth and potential preventive interventions to ameliorate the risks for these at-risk youth.


Author(s):  
Judd Sher ◽  
Kate Kirkham-Ali ◽  
Denny Luo ◽  
Catherine Miller ◽  
Dileep Sharma

The present systematic review evaluates the safety of placing dental implants in patients with a history of antiresorptive or antiangiogenic drug therapy. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and OpenGrey databases were used to search for clinical studies (English only) to July 16, 2019. Study quality was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases using a modified Newcastle-Ottawa scale and the Joanna Briggs Institute critical appraisal checklist for case series. A broad search strategy resulted in the identification of 7542 studies. There were 28 studies reporting on bisphosphonates (5 cohort, 6 case control, and 17 case series) and one study reporting on denosumab (case series) that met the inclusion criteria and were included in the qualitative synthesis. The quality assessment revealed an overall moderate quality of evidence among the studies. Results demonstrated that patients with a history of bisphosphonate treatment for osteoporosis are not at increased risk of implant failure in terms of osseointegration. However, all patients with a history of bisphosphonate treatment, whether taken orally for osteoporosis or intravenously for malignancy, appear to be at risk of ‘implant surgery-triggered’ MRONJ. In contrast, the risk of MRONJ in patients treated with denosumab for osteoporosis was found to be negligible. In conclusion, general and specialist dentists should exercise caution when planning dental implant therapy in patients with a history of bisphosphonate and denosumab drug therapy. Importantly, all patients with a history of bisphosphonates are at risk of MRONJ, necessitating this to be included in the informed consent obtained prior to implant placement. The James Cook University College of Medicine and Dentistry Honours program and the Australian Dental Research Foundation Colin Cormie Grant were the primary sources of funding for this systematic review.


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