A study on the effect of mifepristone on uterine fibroids

Background: Uterine fibroids are the most common pelvic tumors and most common benign tumors in women. Abnormal uterine bleeding and pain are common symptoms of fibroids. The objective of study was to study the effect of mifepristone on uterine fibroids on the basis of change in menstrual pattern, hemoglobin level, fibroid volume and alleviation of pain. Methods: This prospective study had sample size of 40 subjects with uterine leiomyomas who were recruited from OPD after taking an informed written consent. Follow up of each subject was done after 3 months to see changes in various parameters after giving 3 months of mifepristone 25 mg once daily. Study tools included case reporting form, ultrasonography, blood investigations, pictorial blood loss assessment chart (PBAC) to compare change in menstrual pattern and visual analogue pain scale for comparing alleviation in pain. Results: In this study, the majority of patients belonged to 41-45 years of age and were para 1 with dominant symptom of menorrhagia. At the end of 3 months the mean baseline fibroid volume decreased by 37.5%, mean hemoglobin improved from 9.37 to 11.05 gm/dl, mean PBAC score reduced from 90.6 to 8.9, 25% of patients had no pain and pain score in 32.5% patients was 1 and in 32.5% patients pain score was 2. Conclusions: Three months treatment with 25 mg mifepristone daily, effectively controls bleeding, reduces fibroid volume ameliorates pain and abnormal bleeding, improves hemoglobin. It can be recommended as the optimum clinical treatment of fibroids in this dose.

Pre-exposure prophylaxis for HIV prevention (PrEP) among young women at high risk for HIV in South Africa: longitudinal patterns of use and strategies to improve persistence

Background. Adolescent girls and young women (AGYW) and female sex workers (FSW) make up a disproportionate share of HIV infections in South Africa. Oral pre-exposure prophylaxis for HIV prevention (PrEP) can prevent new infections, but low levels of persistence limit its real-world impact. We aimed to characterize patterns of PrEP use, including initiation, discontinuation, and cycling, and to identify implementation strategies that may improve PrEP persistence. Methods. We worked with a South African non-profit, TB HIV Care, to create a cohort of AGYW and FSW eligible for PrEP using routinely collected data. First, we described persistence on PrEP among FSW in eThekwini using a discrete time-to-event survival analysis. Discontinuation was defined as a composite outcome based on 1) two months of not returning for PrEP, 2) client discontinuation, or 3) provider discontinuation. Second, we used discrete time-to-event survival analyses and group-based trajectory modeling to describe the longitudinal patterns of PrEP initiation, discontinuation, and re-initiation across both AGYW and FSW. Eligibility for PrEP initiation was defined as testing negative for HIV. Re-initiation was defined as a new PrEP initiation within 12 months of an initial PrEP prescription, following a 3-month gap in PrEP. Third, we used an interrupted time-series design to evaluate the impact of PrEP delivery strategies, including clinical mentoring for providers, SMS PrEP refill reminders and support texts, case management, and a loyalty rewards program, on 1-month PrEP persistence. Results. Persistence at one month for AGYW (0.38, 95%CI [0.37-0.38]) and FSW (0.41, 95%CI [0.40-0.42]) was low. PrEP cycling was common, with close to half of FSW (22% “Early Cycling”; 21% “Ongoing Cycling”) and one third of AGYW (34% “Ongoing Cycling”) experiencing some form of cycling during the year following initiation. SMS support and refill reminders and provider training had a positive impact on 1-month persistence among FSW. Conclusions. PrEP-delivery programs have focused a large portion of available resources on promoting uptake; however, low PrEP persistence and inadequate understanding of cycling will undermine PrEP as a prevention tool. SMS support, refill reminders, and provider training show promise for improving immediate PrEP persistence, but strategies to augment these are needed for sustained PrEP use

Risk factors for poor adherence to antiretroviral therapy by pregnancy status in two urban cohorts of women living with HIV in the United States and South Africa

Introduction: Many women living with HIV around the world are in their reproductive years. Adherence to antiretroviral therapy (ART) and viral suppression are of particular importance before, during, and after pregnancy to maintain maternal health and limit vertical transmission. It is important to understand what factors prevent women from adhering to their medications. Risk factors for poor adherence in pregnant and non-pregnant women were examined in two different contexts. Methods: Cohorts of HIV-infected women on ART in the United States and in South Africa were examined. Pregnancy experience in the last six months in the Unites States cohort and becoming pregnant during follow-up in the South African cohort were assessed among various other risk factors for poor adherence. Prevalence of poor adherence at baseline and endline in the South African cohort was examined; estimates were stratified by pregnancy and fertility intentions and compared using equality of proportions tests. Poisson regression models with robust variance (as an approximation of log binomial models) were used to estimate crude (PR) and adjusted (aPR) prevalence ratios and 95% confidence intervals ([,]) of risks factors for poor adherence, separately in each of the cohorts and also stratified by pregnancy status. Results: Prevalence of poor adherence declined between baseline and endline for the South African cohort of women. The greatest reduction was seen in those who had pregnancy intentions at baseline and were pregnant during follow-up (difference in percentages: 12.5% [8.5, 16.5]). The independent risk factors for poor adherence to ART among the US cohort were low CD4 count and lower level of completed education. From the analyses stratified by pregnancy status, risk factors that were different between those who experienced a pregnancy outcome and those who did not included age, race, relationship status, parity, and illicit drug use. The main risk factor for the cohort of women from South Africa was trying to conceive (aPrR=1.54 [1.10, 0.94]). Risk factors that were different between those who experienced a pregnancy during follow-up and those who did not were level of education completed, partner HIV status, parity, ability to talk to a provider, and time on HAART. Conclusions: Risk factors for poor adherence appear to differ between pregnant and non-pregnant women of reproductive age in the United States and South Africa. Self-reported poor adherence was associated with pregnancy intentions in the South African context, and further research should be conducted to assess this relationship and to develop strategies for promoting adherence in this important population

Pharmaceutico analytical study of Ashwagandha Ghrita

Ashwagandha (Withania somnifera (L) Family - Solanaceae) known as Indian ginseng is an effective immunomodulator, aphrodisiac, sedative and adaptogen. Ashwagandha Ghrita is a ghee based Ayurvedic formulation which is available in the market, but Ashwagandha Ghrita containing Rasasindura and Tamra Bhasma along with Ashwagandha and Musta Churna is also mentioned in classical text which many of us are not aware of. As we all know that the action of Rasaushadhis are quick and require very less dose the one mentioned by Vagbhatacharya (author of Rasaratnasamuchaya) is the need of the hour for the immunomodulation. The current trend in applied instrumental medical research encourages good medical practice, clinical and research based drug analysis. The main aim of analytical study is to find out working standards for the formulations and safe use of therapeutics

A Review on Ashwagandha Ghrita

Ashwagandha (Withania somnifera (L) Family - Solanaceae) known as Indian ginseng is an effective immunomodulator, aphrodisiac, sedative and adaptogen. Ashwagandha Ghrita is a ghee based Ayurvedic formulation which is available in the market, but Ashwagandha Ghrita containing Rasasindura and Tamra Bhasma along with Ashwagandha and Musta Churna is also mentioned in classical text which many of us are not aware of. As we all know that the action of Rasaushadhis are quick and require very less dose the one mentioned by Vagbhatacharya (author of Rasaratnasamuchaya) is the need of the hour for the immunomodulation

Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1-expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan- And dose-dependent. At concentrations ≤0.25 μM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1-induced migration. Exposure to concentrations ≥1 μM resulted in ERK(1/2)- dependent apoptosis and disruption of the F- Actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1-deficient mice exhibited increased recruitment of eosinophils and CD3+ T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis.Fil: Ge, Xiao Na. University of Minnesota; Estados UnidosFil: Ha, Sung Gil. University of Minnesota; Estados UnidosFil: Greenberg, Yana G.. University of Minnesota; Estados UnidosFil: Rao, Amrita. University of Minnesota; Estados UnidosFil: Bastan, Idil. University of Minnesota; Estados UnidosFil: Blidner, Ada Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rao, Savita P.. University of Minnesota; Estados UnidosFil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sriramarao, P.. University of Minnesota; Estados Unido

Strengthening capacity for assessment of HIV-related data needs among key populations to inform evidence-based responses

Defining the HIV prevention and treatment needs of key populations who have disproportionate HIV acquisition and transmission risks has been particularly difficult in the context of generalized HIV epidemics where less attention has historically been placed on the HIV prevention and treatment needs of these groups. There is a gap in our understanding of the specific needs of—and ultimately the investment case for the added value of supporting—disproportionately burdened key populations in these settings. In response to this gap, Johns Hopkins University under the United States Agency for International Development (USAID)-funded Project SOAR implemented a project in partnership with collaborators, with two primary purposes: synthesizing and assessing the quality of available data for key populations; and leveraging these data to strengthen capacity of a strategic group of governmental, nongovernmental, and community stakeholders to effectively use these data to prioritize rights-based, comprehensive data-collection efforts and programmatic responses. This Project SOAR final report summarizes that work

Crystal structure of binary and ternary complexes of serine hydroxymethyltransferase from Bacillus stearothermophilus

Serine hydroxymethyltransferase (SHMT), a member of the α-class of pyridoxal phosphate-dependent enzymes, catalyzes the reversible conversion of serine to glycine and tetrahydrofolate to 5,10-methylene tetrahydrofolate. We present here the crystal structures of the native enzyme and its complexes with serine, glycine, glycine, and 5-formyl tetrahydrofolate (FTHF) from Bacillus stearothermophilus. The first structure of the serine-bound form of SHMT allows identification of residues involved in serine binding and catalysis. The SHMT-serine complex does not show any significant conformational change compared with the native enzyme, contrary to that expected for a conversion from an "open" to "closed" form of the enzyme. However, the ternary complex with FTHF and glycine shows the reported conformational changes. In contrast to the Escherichia coli enzyme, this complex shows asymmetric binding of the FTHF to the two monomers within the dimer in a way similar to the murine SHMT. Comparison of the ternary complex with the native enzyme reveals the structural basis for the conformational change and asymmetric binding of FTHF. The four structures presented here correspond to the various reaction intermediates of the catalytic pathway and provide evidence for a direct displacement mechanism for the hydroxymethyl transfer rather than a retroaldol cleavage

Sampling Key Populations for HIV Surveillance: Results From Eight Cross-Sectional Studies Using Respondent-Driven Sampling and Venue-Based Snowball Sampling.

BACKGROUND: In using regularly collected or existing surveillance data to characterize engagement in human immunodeficiency virus (HIV) services among marginalized populations, differences in sampling methods may produce different pictures of the target population and may therefore result in different priorities for response. OBJECTIVE: The objective of this study was to use existing data to evaluate the sample distribution of eight studies of female sex workers (FSW) and men who have sex with men (MSM), who were recruited using different sampling approaches in two locations within Sub-Saharan Africa: Manzini, Swaziland and Yaoundé, Cameroon. METHODS: MSM and FSW participants were recruited using either respondent-driven sampling (RDS) or venue-based snowball sampling. Recruitment took place between 2011 and 2016. Participants at each study site were administered a face-to-face survey to assess sociodemographics, along with the prevalence of self-reported HIV status, frequency of HIV testing, stigma, and other HIV-related characteristics. Crude and RDS-adjusted prevalence estimates were calculated. Crude prevalence estimates from the venue-based snowball samples were compared with the overlap of the RDS-adjusted prevalence estimates, between both FSW and MSM in Cameroon and Swaziland. RESULTS: RDS samples tended to be younger (MSM aged 18-21 years in Swaziland: 47.6% [139/310] in RDS vs 24.3% [42/173] in Snowball, in Cameroon: 47.9% [99/306] in RDS vs 20.1% [52/259] in Snowball; FSW aged 18-21 years in Swaziland 42.5% [82/325] in RDS vs 8.0% [20/249] in Snowball; in Cameroon 15.6% [75/576] in RDS vs 8.1% [25/306] in Snowball). They were less educated (MSM: primary school completed or less in Swaziland 42.6% [109/310] in RDS vs 4.0% [7/173] in Snowball, in Cameroon 46.2% [138/306] in RDS vs 14.3% [37/259] in Snowball; FSW: primary school completed or less in Swaziland 86.6% [281/325] in RDS vs 23.9% [59/247] in Snowball, in Cameroon 87.4% [520/576] in RDS vs 77.5% [238/307] in Snowball) than the snowball samples. In addition, RDS samples indicated lower exposure to HIV prevention information, less knowledge about HIV prevention, limited access to HIV prevention tools such as condoms, and less-reported frequency of sexually transmitted infections (STI) and HIV testing as compared with the venue-based samples. Findings pertaining to the level of disclosure of sexual practices and sexual practice-related stigma were mixed. CONCLUSIONS: Samples generated by RDS and venue-based snowball sampling produced significantly different prevalence estimates of several important characteristics. These findings are tempered by limitations to the application of both approaches in practice. Ultimately, these findings provide further context for understanding existing surveillance data and how differences in methods of sampling can influence both the type of individuals captured and whether or not these individuals are representative of the larger target population. These data highlight the need to consider how program coverage estimates of marginalized populations are determined when characterizing the level of unmet need

HIV-related data among key populations to inform evidence-based responses: protocol of a systematic review.

BACKGROUND: Key populations who bear a disproportionate burden of HIV, including female sex workers, men who have sex with men, people who use drugs, transgender people, and incarcerated populations, have been understudied, especially in the context of broadly generalized HIV epidemics. Program and investment planning documents often do not take into account the data that do exist. Prior systematic reviews have been comprehensive, but lack sustainability and relevance over time. This review aims to synthesize all available data for key populations and present the data through an accessible, updatable user-friendly graphic interface. The outputs of this systematic review will serve as a resource for decision-makers, providing government stakeholders and donors with the tools to make evidence-based decisions for national planning. METHODS: We will conduct a systematic review of data published or made available between January 1, 2006, and January 1, 2019, that captures the burden of HIV, both prevalence and incidence estimates, HIV prevention and treatment cascades, key population size estimates, experienced violence, consistent condom use, and engagement with healthcare systems for female sex workers, men who have sex with men, people who use drugs, transgender people, and incarcerated populations. A team of reviewers will use Covidence to conduct two independent reviews of both title/abstract and full text for each article. REDCap will be used for data abstraction and storage. DISCUSSION: Findings from this systematic review and the development of the enhanced graphical interface to display data, along with ongoing efforts to build capacity among key stakeholders to better use and interpret available data, will help ensure that available epidemiologic data related to key populations can be appropriately used to guide large-scale HIV funding and programmatic responses. SYSTEMATIC REVIEW REGISTRATION: PROPSERO CRD42016047259