Men have a universal protection tool (male condom) under their control to protect themselves against sexually transmitted infections (STIs) including HIV/AIDS, and to avoid unintended pregnancy. Unfortunately, it is not consistently used. Male condom is used in only one-third of at-risk sexual intercourse by men 15–44 years of age. On the other hand, despite being up to 8 times more at risk of getting STIs during an unprotected vaginal intercourse, women have no means under their control to protect themselves as men do. In addition, they are vulnerable to unintended pregnancy that represents about 45% of all pregnancies (of more than 200 million pregnancies annually) around the globe. It is primordial to empower women with vaginal multipurpose prevention technologies (MPTs) to protect themselves during sexual intercourse when men do not use means of protection. Women need safe, effective, affordable and accessible vaginal protection. Protecting women will be beneficial, not only for them, but also for the whole society as well.

In this concise communication, we shed some light on the urgent need to support and fund women’s sexual and reproductive health research in the area of STIs/HIV/unintended pregnancy prevention that is largely underserved. We stress the need for developing affordable safe and effective innovative vaginal products under the control of women to protect themselves against unintended pregnancy and sexually transmitted infections (STIs). We highlight the importance of complete and homogenous coverage of the vaginal and cervical mucosae of women by the vaginal product for optimal protection, especially against biofilm vaginal infections. Finally, we focus on the necessity of equity for women and the ease of access to such woman-controlled products for the benefit of the whole society.

HIV-1 infection in the central nervous system (CNS) causes the release of neurotoxic products from infected cells which trigger extensive neuronal loss. Clinically, this results in HIV-1-associated neurocognitive disorders (HAND). However, the effects on neuroprotective factors in the brain remain poorly understood and understudied in this situation. HAND is a multifactorial process involving several players, and the complex cellular mechanisms have not been fully elucidated yet. In this study, we reported that HIV-1 infection of astrocytes limits their potential to express the protective chemokine fractalkine in response to an inflammatory environment. We next confirmed that this effect was not due to a default in its shedding from the cell surface. We then investigated the biological mechanism responsible for this reduced fractalkine expression and found that HIV-1 infection specifically blocks the interaction of transcription factor NF-κB on its promoter with no effect on other cytokines. Moreover, we demonstrated that fractalkine production in astrocytes is regulated in response to immune factors secreted by infected/activated microglia and macrophages. In contrast, we observed that conditioned media from these infected cells also trigger neuronal apoptosis. At last, we demonstrated a strong neuroprotective action of fractalkine on human neurons by reducing neuronal damages. Taken together, our results indicate new relevant interactions between HIV-1 and fractalkine signaling in the CNS. This study provides new information to broaden the understanding of HAND and possibly foresee new therapeutic strategies. Considering its neuro-protective functions, reducing its production from astrocytes could have important outcomes in chronic neuroinflammation and in HIV-1 neuropathogenesis.

Objectives: To evaluate the spermicidal efficacy of non-hormonal vaginal gel in vitro and in a post-coital test, and to evaluate its contraceptive efficacy in Canadian women of childbearing age. Methods: We conducted single-centre trial to assess spermicidal and contraceptive efficacy of vaginal gel. Participants were healthy, sexually active women aged 18-49 years and their regular male sexual partners (30 couples). Measured outcomes included effect of vaginal gel on sperm motility in vitro, its effect on sperm in a post coital test, and its effect on pregnancy prevention over 3 months. Results: For in vitro spermicidal effect, 98% and 67% of sperm were immotile in the presence of the gel with sodium lauryl sulfate (gelSLS) and gel alone, respectively. For the post-coital test, 99% and 93% of sperm were immotile in the presence of gel-SLS and gel alone, respectively. In the second part of trial, a total of 410 instances of vaginal intercourse in 95 menstrual cycles were protected (during 3-month period of gel-SLS use before each sexual intercourse with probability of 24 conceptions prevented according to Wilcox's table). Four women became pregnant during the study period; 2 during unprotected vaginal intercourse around the time of ovulation, and 2 attributed to user failure. Conclusion: Based on our results, the vaginal gel demonstrated important spermicidal and contraceptive effect. A larger phase III contraceptive efficacy trial is warranted. The vaginal gel may represent a non-hormonal spermicide/contraceptive option for women. (C) 2021 The Society of Obstetricians and Gynaecologists of Canada/La Societe des obstetriciens et gynecologues du Canada. Published by Elsevier Inc. All rights reserved.

Since the introduction of the combined antiretroviral therapy, HIV-1 infection has become a manageable chronic disease in which patients display a life expectancy almost identical to the general population. Nevertheless, various age-related pathologies such as neurocognitive disorders have emerged as serious complications. A "shock and kill" strategy using latency-reversing agents (LRA) to reactivate HIV-1 has been proposed to eliminate the viral reservoir in such chronically infected patients. However, the impact of LRA on the central nervous system remains elusive. Given that an increased amyloid beta (Aβ) deposition is a feature of HIV-1-infected brains, we investigated the consequences of HIV-1 infection and treatment with two LRA (bryostatin-1 and JQ1) on the capacity of human astrocytes to engulf and clear Aβ. We show here that HIV-1-infected astrocytes accumulate a very high amount of Aβ compared to uninfected cells, but the engulfed peptide in degraded very slowly. The LRA bryostatin-1 induces a reduction in Aβ endocytosis, whereas JQ1 treatment results in a very slow degradation of the ingested material associated with a reduced expression of the endopeptidase neprilysin. An exposure to JQ1 also induces a sustained release of Aβ-loaded microvesicles. Thus, both HIV-1 infection and treatment with some LRA could contribute to the reported Aβ accumulation in the brain of HIV-1-infected persons.

Objective Contraception is an important issue in the lives of women, their partners, and society. Canadians and their health care providers play a critical role in contraceptive decision making that influences individuals and Canadian society. The purpose of this study was to gather data on contraception-related knowledge, counselling, and prescribing practices of Canadian health care providers. Methods This project reported on the outcomes of an educational initiative, designed as a quality improvement initiative (time series level II-3), focused on Canadian health care providers' contraception-related knowledge, counselling, and prescribing practices. Outcomes were intended to inform the development of tools, resources, and educational programming. Part 1 was an online program to identify educational and knowledge gaps for health care providers. Part 2 was a practice assessment exploring and measuring health care providers' contraceptive counselling and prescribing practices. Results A total of 4300 health care providers completed the program between July 6, 2015 and August 30, 2016. Knowledge significantly increased; post-test scores were higher than pretest scores. After completion, all participants felt more comfortable, knowledgeable, and inclined to change their practice around prescribing intrauterine contraception (IUC). The 4300 providers reported on their contraception counselling experiences with 10 patients following participation in Part 1. Forty percent of patients were using oral contraceptives, and 53% were dissatisfied with their current type of contraception. After counselling, patients reported being most comfortable with IUC (55%). Both short- and long-acting types of contraception were most often discussed or offered (74% of the time), followed by long-acting reversible contraception only (21%) and short-acting methods only (5%). Conclusion This training program filled an education need for patients and gave providers tools to change their behaviour and practice around IUC prescribing. On the basis of these data, a practice assessment model was deemed a successful way to change behaviour.

The "shock and kill" HIV-1 cure strategy proposes eradication of stable cellular reservoirs by clinical treatment with latency-reversing agents (LRAs). Although resting CD4+ T cells latently infected with HIV-1 constitute the main reservoir that is targeted by these approaches, their consequences on other reservoirs such as the central nervous system are still unknown and should be taken into consideration. We performed experiments aimed at defining the possible role of astrocytes in HIV-1 persistence in the brain and the effect of LRA treatments on this viral sanctuary. We first demonstrate that the diminished HIV-1 production in a proliferating astrocyte culture is due to a reduced proliferative capacity of virus-infected cells compared with uninfected astrocytes. In contrast, infection of non-proliferating astrocytes led to a robust HIV-1 infection that was sustained for over 60 days. To identify astrocytes latently infected with HIV-1, we designed a new dual-color reporter virus called NL4.3 eGFP-IRES-Crimson that is fully infectious and encodes for all viral proteins. Although we detected a small fraction of astrocytes carrying silent HIV-1 proviruses, we did not observe any reactivation using various LRAs and even strong inducers such as tumor necrosis factor, thus suggesting that these proviruses were either not transcriptionally competent or in a state of deep latency. Our findings imply that astrocytes might not constitute a latent reservoir per se but that relentless virus production by this brain cell population could contribute to the neurological disorders seen in HIV-1-infected persons subjected to combination antiretroviral therapy.

“We hold these truths to be self-evident: that all men and women are created equal… .”1 Nearly 170 years after the Seneca Falls Convention, the call for gender parity remains necessary. However, the anatomy and physiology of both genders are different, so is the vulnerability to disease. There are also important differences between men and women in psychosocial health and behaviour. In this article, we hope to increase awareness about the gender gap in medical technologies for women, especially with regard to sexual and reproductive health.

Background: Despite effectiveness of the combined antiretroviral therapy, HIV-1 persists in long-lived latently infected cells. Consequently, new therapeutic approaches aimed at eliminating this latent reservoir are currently being developed. A "shock and kill" strategy using latency-reversing agents (LRA) to reactivate HIV-1 has been proposed. However, the impact of LRA on the central nervous system (CNS) remains elusive. Methods: We used human fetal astrocytes and investigated the effects of several LRA on their functional and secretory activities. Astrocytes were infected with VSV-G-pseudotyped HIV-1 before treatment with various bloodbrain barrier (BBB)-permeable LRA at subcytotoxic doses, which allow HIV-1 reactivation based on previous in vitro and clinical studies. Cells and supernatants were then used to evaluate effects of infection and LRA on (i) viability and metabolic activity of astrocytes using a colorimetric MTS assay; (ii) chemokines and proinflammatory cytokines secretion and gene expression by astrocytes using ELISA and RT-qPCR, respectively; (iii) expression of complement component 3 (C3), a proxy for astrogliosis, by RT-qPCR; (iv) glutamate uptake capacity by a fluorometric assay; and (v) modulation of neutrophil transmigration across an in vitro BBB model. Results: We demonstrate that bryostatin-1 induces secretion of chemokines CCL2 and IL-8 and proinflammatory cytokines IL-6 and GM-CSF, whereas their production is repressed by JQ1. Bryostatin-1 also increases expression of complement component 3 and perturbs astrocyte glutamate homeostasis. Lastly, bryostatin-1 enhances transmigration of neutrophils across an in vitro blood-brain barrier model and induces formation of neutrophil extracellular traps. Conclusions: These observations highlight the need to carefully assess the potential harmful effect to the CNS when selecting LRA for HIV-1 reactivation strategies.

Objective: To assess the ability of CT-derived measurements including adipose tissue attenuation and area to predict fat cell hypertrophy and related cardiometabolic risk. Methods: Abdominal adipose tissue areas and radiologic attenuation were assessed using 4 CT images in 241 women (age: 47 years, BMI: 26.5 kg/m2). Fat cell weight was measured in paired VAT and SAT samples. Fasting plasma lipids, glucose and insulin levels were measured. Results: Adipose tissue attenuation was negatively correlated with SAT (r=-0.46) and VAT (r=-0.67) fat cell weight in the corresponding depot (p<0.0001 for both). Women with visceral adipocyte hypertrophy had higher total-, VLDL-, LDL- and HDL-triglyceride and apoB levels as well as a higher cholesterol/HDL-cholesterol ratio, fasting glucose and insulin levels compared to women with smaller visceral adipocytes. Adjustment for VAT area minimized these differences while subsequent adjustment for attenuation eliminated all differences, with the exception of fasting glycaemia. In SAT, adjustment for VAT area and attenuation eliminated all adipocyte hypertrophy-related alterations except for fasting hyperglycaemia. Conclusion: CT-derived adipose tissue attenuation and area both contribute to explain variation in the cardiometabolic risk profile associated with the same biological parameter: visceral fat cell hypertrophy.

Background Approximately 2.1% to 8.6% of all pregnancies after IVF with embryo transfer have been reported to be ectopic. In this report, we present a case of presumed intestinal microperforation caused by an ectopic pregnancy following IVF. Case A 29-year-old woman presented with rectal bleeding. She had previously been treated for an ectopic pregnancy for which she had received two doses of methotrexate. Colonoscopy and abdominal CT angiography were performed and showed that the ectopic pregnancy was attached to the sigmoid colon. Surgery was performed to remove the ectopic pregnancy. Because intestinal microperforations were suspected, the patient received intravenous antibiotic therapy during her hospitalization. Conclusion In cases of intestinal bleeding, clinicians should consider the possibility of intestinal involvement of an ectopic pregnancy, even if the response to treatment for the ectopic pregnancy has been appropriate.

BACKGROUND Visceral obesity is independently related to numerous cardiometabolic alterations, with adipose tissue dysfunction as a central feature. OBJECTIVE To examine whether omental (OM) and subcutaneous (SC) adipocyte size populations in women relate to visceral obesity, cardiometabolic risk factors and adipocyte lipolysis independent of total adiposity. DESIGN AND METHODS OM and SC fat samples were obtained during gynecological surgery in 60 women (mean age, 46.1±5.9 years; mean BMI, 27.1±4.5 kg/m² (range, 20.3-41.  kg/m²)). Fresh samples were treated with osmium tetroxide and were analyzed with a Multisizer Coulter. Cell size distributions were computed for each sample with exponential and Gaussian function fits. RESULTS Computed tomography-measured visceral fat accumulation was the best predictor of larger cell populations as well as the percentage of small cells in both OM and SC fat (P<0.0001 for all). Accordingly, women with visceral obesity had larger cells in the main population and higher proportion of small adipocytes independent of total adiposity (P≤0.05). Using linear regression analysis, we found that women characterized by larger-than-predicted adipocytes in either OM or SC adipose tissue presented higher visceral adipose tissue area, increased percentage of small cells and homeostasis model assessment insulin resistance index as well as higher OM adipocyte isoproterenol-, forskolin- and dbcAMP-stimulated lipolysis compared to women with smaller-than-predicted adipocytes, independent of total adiposity (P≤0.05). CONCLUSION Excess visceral adipose tissue accumulation is a strong marker of both adipocyte hypertrophy and increased number of small cells in either fat compartment, which relates to higher insulin resistance index and lipolytic response, independent of total adiposity.

Studies have long sought specific cytokines that could characterize endometriosis. Either due to variations between study designs regarding the assessment criteria for the cytokine or to low power resulting from small sample size, no factor proved to be sufficiently specific to endometriosis. In other clinical fields, a combination of several markers proved to be more powerful than a single:molecule approach. As well, in the context of endometriosis, simultaneous assessment of several cytokines present in the peritoneal fluid might help in unveiling patho-physiological processes, thus contributing to a better understanding of the condition. Therefore, the objective of this study was to investigate peritoneal fluid cytokines-derived of endometriotic women. For this retrospective case-control study, peritoneal fluid samples were obtained at laparoscopy and assessed by multiplex. Our data showed distinct patterns of peritoneal fluid cytokine concentrations in endometriotic women most notably a marked increase in EGF, FGF-2, IL-1 alpha, MIP-1 beta, TGF alpha, PDGF-AA, PDGF-BB, MCP-3, sCD40L, Gro Pan, IL-17 alpha, MDC and Rantes. The overall effect of fertility status revealed a significant difference for only one cytokine, namely MDC. Furthermore, FLT-3L and IP-10 levels were decreased in endometriosis patients, the former in both menstrual cycle phases and the latter in the secretory phase. A significant inverse Pearson correlation (p<0.05) was noted between proangiogenic cytokines EGF and FGF and the anti-angiogenic cytokine IP-10 in endometriosis patients at stages III-IV and in the secretory phase. These changes may exacerbate the local peritoneal angiogenic and proliferative reaction observed in women with endometriosis, and contributes to its pathophysiology. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

CONTEXTAngiogenesis is required for ectopic endometrial tissue growth. Our previous studies showed that prostaglandin F2α (PGF2α) biosynthetic enzymes and receptor were markedly elevated in endometriotic lesions and that PGF2α is a potent angiogenic factor in endothelial cells.OBJECTIVEWe sought to determine whether or not the F-prostanoid receptor modulates angiogenesis in ectopic stromal cells.DESIGNRelease of angiogenic factors by ectopic endometrial stromal cell primary cultures stimulated with PGF2αand exposed to agents that target PGF2α signaling was assessed.SETTINGThe study was conducted in an immunology laboratory at the Centre Hospitalier Universitaire (Québec City) medical research center.PATIENTSWomen found to have peritoneal endometriosis during laparoscopy were included in this study.MAIN OUTCOME MEASURE(S)Prostaglandin E2, PGF2α, vascular endothelial cell growth factor, and CXC chemokine ligand 8 mRNA and protein; FP prostanoid receptor expression.RESULTSPGF2α markedly up-regulated prostaglandin E2, CXC chemokine ligand 8 and vascular endothelial cell growth factor secretion in endometriotic cells. This effect was suppressed in the presence of a specific F-prostanoid antagonist (AL8810) and its signaling pathway was dependent on F-prostanoid receptor variant. PGF2α can exert its proliferative and angiogenic activities either directly by stimulating endothelial cell proliferation, migration and angiogenesis through F-prostanoid receptor, or indirectly, by stimulating endometriotic stromal cells to produce potent angiogenic factors through either receptor variant.CONCLUSIONThese results show for the first time that PGF2α exerts an angiogenic effect on ectopic stromal cells, inducing the secretion of major angiogenic factors via different F-prostanoid signaling pathways. This study suggests a new interpretation of the mechanism underlying endometriosis development involving PGF2α in endometriosis-associated angio-inflammatory changes.

To investigate interleukin-8 (CXCL8) and vascular endothelial growth factor (VEGF) expressions (potent angiogenic factors) in endometrial stromal cells of women with endometriosis compared with controls in response to Prostaglandin F2a (PGF2a), an important regulators of female reproductive function. Primary cultures of eutopic and ectopic endometrial stromal cells isolated from endometrial biopsies of endometriosis patients (n = 9), as well as eutopic endometrium of control patients (n=5) in proliferative and secretory cycle phases exposed to PGF2a, with assessment of CXCL8 and VEGF expression. Cells were cultured in DMEM-F12 medium with 10% FBS, 1% antibiotics, 5 μg/mL insulin and 5μg/mL transferrin. Cells grown to confluence were preincubated for 1 h with PGF2a-FP receptor antagonist (AL8810) (50ug/mL) or cyclo-oxygenase-2 (cox-2) inhibitor (NS398) (50 ug/mL) and stimulated with different concentrations of PGF2a (0-1000ng/mL) or PGF2a analog (Fluprostenol) (0-1000 ng/mL) for different periods of time (0-48 h). PGF2a biosynthetic pathways were analyzed by RT-qPCR and Western blot. While, CXCL8 and VEGF secretions were analyzed by ELISAs. An unpaired t test and one-way ANOVA followed by the Dunnett's test were performed for this study. Our study showed that PGF2a stimulated CXCL8 and VEGF expressions in ectopic endometrial stromal cells of women with endometriosis in the proliferative and the secretory phases of the menstrual cycle, without noticeable change in eutopic endometrial stromal cells of women with or without endometriosis. Cell exposure to PGF2a analog (Fluprostenol) confirmed these previous observations. After 24h of stimulation, diminutions of CXCL8 and VEGF were significant when PGF2a receptor (FP) antagonist was added with either PGF2a or Fluprostenol. Meanwhile, we observed that PGF2a increased significantly cox-2 expression while its other biosynthetic enzymes showed no statistical difference. We, therefore, used cox-2 inhibitor (NS398) which correlated a statistical decrease for both VEGF and IL-8 secretions. This study showed that angiogenic pathways are involved in PGF2a-mediated activation through FP and Cox-2 in ectopic endometrial stromal cells of women with endometriosis. This is in keeping with our previous data showing multiple abnormalities in PGF2a pathways in ectopic endometrial tissue, leading to an abnormal behavior. Expression of CXCL8 and VEGF in ectopic endometrial cells throughout the menstrual cycle of women with endometriosis may, considering the role of these cytokines in cell growth and angiogenesis, play an important role in the capability of endometrial cells to develop and to survive in ectopic locations.

An unintended pregnancy can have significant effects on a patient with MS, particularly if she has uncontrolled MS. Family planning is an important part of managing your MS, and there are many available birth control methods to assist with this. Sterilization and long-acting reversible contraceptives (implants and intrauterine devices [IUDs]) result in less than 1 pregnancy per 100 women. Long-acting reversible contraceptives are encouraged as a first-line option for most women (including those with MS). They have a high satisfaction rate and are effective for several years before they must be replaced. Hormonal injections, pills, patch, and vaginal ring are not quite as effective, resulting in an average of 5 pregnancies per 100 women. The rhythm method, withdrawal, spermicides, sponges, diaphragms, and male and female condoms are the least effective of these methods, resulting in more than 15 pregnancies in 100 women.