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Despite being a physiological condition, human pregnancy is known to cause numerous complications that can endanger the life of the mother and the fetus alike. While the majority of complications are mostly limited within the peripartum period, more and more information is available about persistently higher short- and long-term cardiovascular risk after a pregnancy complicated by a hypertensive disorder. There is evidence that women after gestational hypertension or preeclampsia are more likely to develop arterial hypertension, coronary atherosclerosis, myocardial infarction, stroke, peripheral artery disease, and even diabetes mellitus and venous thromboembolism years after the target pregnancy. This has urged some authors to view hypertensive disorders of pregnancy as a “stress test” for the maternal organism that unmasks latent endothelial dysfunction. An explanation is sought in the presence of common risk factors and underlying pathological pathways with cardiovascular diseases, although a certain etiological mechanism for the development of hypertensive disorders in pregnancy has not been established yet. More attention is needed towards the follow-up of women after a hypertensive pregnancy as it could be an opportunity for early prevention of cardiovascular diseases.

Introduction: Gestational hypertension is a less investigated hypertensive disorder of pregnancy than preeclampsia, but evidence exists of an unfavourable cardiovascular profile for women after such a pregnancy.Aim: To determine serum high-sensitivity C-reactive protein (hs-CRP) levels in women with preeclampsia, gestational hypertension, and in normotensive pregnancy in order to assess the cardiovascular implications and to examine its correlations with some characteristics of women.Materials and methods: Thirty-six women with gestational hypertension, thirty-seven with preeclampsia, and fifty maternal and gestational age-matched controls were included in a single-center prospective clinical-epidemiological study. Serum hs-CRP levels were determined using ELISA method.Results: Significantly higher hs-CRP levels were found in the gestational hypertension group than in the controls (p=0.043), but not in the preeclampsia group (p=0.445). The levels between the two pathological groups did not differ significantly (p=0.247). Odds ratio for hs-CRP levels higher than the provided cut-off was 3.31 (95% CI 1.32–8.29) for the presence of gestational hypertension. In the normotensive pregnant women, the hs-CRP levels had a positive correlation with BSA, pre-pregnancy and current BMI, but such correlations were absent in the hypertensive groups. There were no correlations with the maternal or gestational age, current weight gain in any of the groups or with the highest detected blood pressure in the pathological groups. These levels did not differ according to gravidity, smoking status and smoking during pregnancy.Conclusions: Elevation of hs-CRP was more pronounced in women with gestational hypertension than in women with preeclampsia, which could indicate a different pathophysiological mechanism and a higher cardiovascular risk for those women.

Edmund J Pezalla,1 David Rosen,2 Jennifer G Erensen,2 J David Haddox,2,3 Tracy J Mayne2 1Bioconsult, LLC, Wethersfield, 2Purdue Pharma L.P., Stamford, CT, 3Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA Abstract: Opioid abuse and misuse in the USA is a public health crisis. The use of prescription opioid analgesics increased substantially from 2002 through 2010, then plateaued and began to decrease in 2011. This study examined prescriptions of branded and generic immediate- and extended-release opioid analgesics from 1992 to 2016. This was juxtaposed against state and federal policies designed to decrease overutilization and abuse, as well as the launch of new opioid products, including opioids with abuse-deterrent properties (OADPs). The data indicate that these health policies, including the utilization and reimbursement of OADPs, have coincided with decreased opioid utilization. The hypothesis that OADPs will paradoxically increase opioid prescribing is not supported. Keywords: OADP, prescription, utilization trends, legislation, opioids

Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), termed bipolar androgen therapy (BAT), can result in tumor regression and clinical benefit for patients with castrationresistant prostate cancer. However, predictors and mechanisms of response and resistance have been ill defined. Here, we show that growth inhibition of prostate cancer models by SPA required high androgen receptor (AR) activity and were driven in part by downregulation of MYC. Using matched sequential patient biopsies, we show that high pretreatment AR activity predicted downregulation of MYC, improved clinical response, and prolonged progression-free and overall survival for patients on BAT. BAT induced strong downregulation of AR in all patients, which is shown to be a primary mechanism of acquired resistance to SPA. Acquired resistance was overcome by alternating SPA with the AR inhibitor enzalutamide, which induced adaptive upregulation of AR and resensitized prostate cancer to SPA. This work identifies high AR activity as a predictive biomarker of response to BAT and supports a treatment paradigm for prostate cancer involving alternating between AR inhibition and activation., Introduction Signaling through the androgen receptor (AR) is the primary oncogenic driver of prostate adenocarcinoma. Inhibition of AR signaling by androgen deprivation and AR inhibitors produces significant therapeutic and palliative [...]

The article titled "GORGETS: trans hummingbirds and iridescent echos" explores the concept of gorgets, which are the plumage lining the throats of trans Sunangel Hummingbirds. The author uses an intersectional assemblage of queer theory to examine the linguistic fashioning of gendered categories. The article discusses the disruption of normative linguistic frameworks and the refashioning of categories of being through polyvocality. It also explores the limits of language and the importance of recognizing the interdependent fashioning of gendered categories. The text does not discuss masculinity in contemporary films or the character of James Bond. [Extracted from the article]

Intratumor heterogeneity is an important mediator of poor outcomes in many cancers, including breast cancer. Genetic subclones frequently contribute to this heterogeneity; however, their growth dynamics and interactions remain poorly understood. PIK3CA and HER2 alterations are known to coexist in breast and other cancers. Herein, we present data that describe the ability of oncogenic PIK3CA mutant cells to induce the proliferation of quiescent HER2 mutant cells through a cell contact-mediated mechanism. Interestingly, the HER2 cells proliferated to become the major subclone over PIK3CA counterparts both in vitro and in vivo. Furthermore, this phenotype was observed in both hormone receptor-positive and -negative cell lines, and was dependent on the expression of fibronectin from mutant PIK3CA cells. Analysis of human tumors demonstrated similar HER2:PIK3CA clonal dynamics and fibronectin expression. Our study provides insight into nonrandom subclonal architecture of heterogenous tumors, which may aid the understanding of tumor evolution and inform future strategies for personalized medicine., Introduction Breast cancer is the most common cancer among women worldwide and the second leading cause of cancer related deaths (1). Like many other cancers, breast cancer has been shown [...]

Aim: This study aimed at identifying factors that worsen the prognosis of diabetic foot, one of the most common complications seen in patients with diabetes. Materials and patients: The sample included 230 patients treated in the Department of Surgery at Kaspela University Hospital in Plovdiv, Bulgaria, between January 2016 and May 2022. Of them, 55.65% were men, and 44.35% were women. The age of the patients ranged from 18 to 77 years, with a mean age of 44.4±14.7 years. Results: Diabetic foot patients of grade ≥4 were 1.8 times more likely to be amputated than the rest of the patients (AOR=1.6; 95% CI: 1.504, 4.683). The utilization of inappropriate antibiotics was associated with a 9.47-fold increased risk of amputation (p