Women Want Choices: Opinions from the Share.Learn.Shape Global Internet Survey About Multipurpose Prevention Technology (MPT) Products in Development.

Women need multipurpose prevention technologies (MPTs) to simultaneously prevent sexually transmitted infections (STIs), including HIV, with or without contraception. User feedback early in product development is critical for maximizing uptake and continuation. Our global online survey (April 2017-December 2018) explored women's opinions about MPT formulations in development (e.g., fast-dissolving vaginal inserts, vaginal films, intravaginal rings, injectables, implants), preferences for long-acting or "on-demand" methods, and interest in a contraceptive MPT versus products for HIV/STI prevention alone. Of the 630 women in our final analysis (mean 30 years old; range 18-49), 68% were monogamous, 79% completed secondary education, 58% had ≥ 1 child, 56% were from sub-Saharan Africa and 82% preferred a cMPT versus HIV/STI prevention alone. There were no clear preferences for any specific product or product type (long-acting, on-demand, daily). No single product will appeal everyone, however, adding contraception is likely to increase uptake of HIV/STI prevention methods for most women.

RESUMEN: Las mujeres necesitan tecnologías de prevención multipropósito (TPM) para prevenir simultáneamente las infecciones de transmisión sexual (ITS), incluido el VIH, con o sin anticoncepción. Las opiniones de los usuarios cuando un producto comienza a desarrollarse son fundamentales para maximizar la adopción y continuación de dicho producto. Nuestra encuesta global realizada en internet (abril de 2017­diciembre de 2018) exploró las opiniones de las mujeres sobre diferentes fórmulas o dispositivos de TPM que se están desarrollando (ej., insertos vaginales de disolución rápida, láminas vaginales, anillos intravaginales, inyectables, implantes). En esta encuesta se indagó acerca de las preferencias en términos de período de acción (prolongado o breve) y propósito del uso (anticonceptivo, productos para la prevención del VIH/ITS, o ambos). De las 630 mujeres (media de 30 años; rango 18­49) en el análisis final, el 68% eran monógamas, el 79% completaron la educación secundaria, el 58% tenían ≥ 1 hijo, el 56% eran del África subsahariana y el 82% preferían una TPM con componente anticonceptivo en vez de un producto para la prevención de VIH/ITS exclusivamente. No hubo preferencias claras por ningún producto o tipo de producto específico (de acción prolongada, de acción breve, de uso diario). Ningún producto por sí solo logró abarcar todas las preferencias; sin embargo, es probable que la inclusión de métodos anticonceptivos en una TPM aumente el uso de métodos de prevención del VIH/ITS en la mayoría de las mujeres.

Drug interactions between rifamycin antibiotics and hormonal contraception: a systematic review.

BACKGROUND: Rifamycin antibiotics are commonly used for treatment of tuberculosis, but may reduce the effectiveness of hormonal contraception (HC). OBJECTIVES: To determine whether interactions between rifamycins and HC result in decreased effectiveness or increased toxicity of either therapy. SEARCH STRATEGY: We searched MEDLINE, Embase, Cochrane and clinicaltrials.gov through May 2017. SELECTION CRITERIA: We included trials, cohort, and case-control studies addressing pregnancy rates, pharmacodynamics or pharmacokinetic (PK) outcomes when HC and rifamycins were administered together versus apart. Of 7291 original records identified, 11 met inclusion criteria after independent review by two authors. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted study details and assessed study quality using the United States Preventive Services Task Force grading system. Findings are reported descriptively. MAIN RESULTS: Studies only addressed combined oral contraceptives (COCs) and none reported pregnancy rates. Quality ranged from good to poor. Rifampin increased the frequency of ovulation in two of four studies, and reduced estrogen and/or progestin exposure in five studies. Rifabutin led to smaller PK changes than rifampin in two studies. In one study each, rifaximin and rifalazil did not alter hormone PK. CONCLUSIONS: No studies evaluated pregnancy risk or non-oral HCs. PK and ovulation outcomes support a clinically concerning drug interaction between COCs and rifampin, and to a lesser extent rifabutin. Data are limited for other rifamycins. TWEETABLE ABSTRACT: Rifampin and rifabutin reduce systemic exposure of oral contraceptives, but no studies have evaluated pregnancy risk.

M2000 (ß-D-Mannuronic Acid) as a Novel Antagonist for Blocking the TLR2 and TLR4 Downstream Signalling Pathway.

To date, selective blockade of Toll-like receptor (TLR) signalling has been developed as a new approach for treatment for many inflammatory diseases. As ß-D-mannuronic acid (M2000) has been known as an anti-inflammatory molecule in several experimental models, we investigated the antagonistic effects of M2000 on TLR2 and TLR4 downstream signalling transduction pathway in human embryonic kidney (HEK) 293 cell lines overexpressing TLR2/CD14 and the TLR4/MD2/CD14 complex, respectively. M2000 effectively inhibited mRNA expression of MyD88 and p65, major subunit of nuclear factor-κB, in HEK293 cells stimulated by lipoteichoic acid (LTA, a TLR2 agonist) and lipopolysaccharide (LPS, a TLR4 agonist) with no evidence of cytotoxicity. In addition, M2000 also suppressed LTA and LPS-induced production of TNF-α and IL-6 inflammatory cytokines in these cells. Furthermore, the results revealed that M2000 had no significant effect on Tollip mRNA expression as a negative regulator of TLR signalling in aforesaid cells. Overall, these data point to M2000 inhibitory effect on Toll-like receptor (TLR) 2, 4 signalling in HEK293 cells. This information might provide new insights into the possible roles of this small drug in order to introduce it as a TLR signalling pathway inhibitor. However, more studies are needed to confirm ß-D-mannuronic acid antagonistic effects including the effects of M2000 on peritoneal isolated macrophages and also on blood cells in patients with inflammatory diseases such as ankylosing spondylitis.

Factors associated with sterilization among HIV-positive US women in an urban outpatient clinic.

This cross-sectional study sought to determine factors associated with sterilization among HIV-positive US women. HIV-positive women aged 18-45 completed an Audio Computer Assisted Self Interview (ACASI) questionnaire. Chi-square tests and multivariable logistic regression evaluated factors associated with sterilization. The median age of the 187 participants was 37, the majority had at least a high school education, and 88% were African American. Nearly a quarter (22%) of women had undergone sterilization at an average age of 25; of these women, 71% cited their HIV-positive status as an important factor in deciding to have a tubal ligation, 22% expressed desire for future children, 32% reported sterilization regret, and 20% reported feeling pressure to undergo sterilization. In multivariable analysis, factors significantly associated with sterilization included non-African American race, no desire for future pregnancy, having heard of any birth control methods making it harder to get pregnant in the future, belief that women should take a break from hormonal methods every few years, and having had a child born with HIV. While almost a quarter of this HIV-positive group was sterilized, many during the height of the early HIV epidemic, a large proportion of sterilized women expressed sterilization regret. Counseling messages for sterilized HIV-positive women should be sensitive to the fact that women may have regret regarding a decision that, in some cases, may historically have been part of provider recommendations to prevent vertical transmission of HIV. Improved knowledge about contraceptive options such as the IUD and implant is needed among HIV-positive women.

Simultaneous laparoscopic resection of primary colorectal cancer and associated liver metastases: a systematic review.

As many as 25 % of colorectal cancer (CRC) patients have liver metastases at presentation. However, the optimal strategy for resectable synchronous colorectal liver metastasis remains controversial. Despite the increasing use of laparoscopy in colorectal and liver resections, combined laparoscopic resection of the primary CRC and synchronous liver metastasis is rarely performed. The potential benefits of this approach are the possibility to perform a radical operation with small incisions, earlier recovery, and reduction in costs. The aim of this study was to review the literature on feasibility and short-term results of simultaneous laparoscopic resection. We conducted a systematic search of all articles published until February 2013. Search terms included: hepatectomy [Mesh], "liver resection," laparoscopy [Mesh], hand-assisted laparoscopy [Mesh], surgical procedures, minimally invasive [Mesh], colectomy [Mesh], colorectal neoplasms [Mesh], and "colorectal resections." No randomized trials are available. All data have been reported as case reports, case series, or case-control studies. Thirty-nine minimally invasive simultaneous resections were identified in 14 different articles. There were 9 (23 %) major hepatic resections. The most performed liver resection was left lateral sectionectomy in 26 (67 %) patients. Colorectal resections included low rectal resections with total mesorectal excision, right and left hemicolectomies, and anterior resections. Despite the lack of high-quality evidence, the laparoscopic combined procedure appeared to be feasible and safe, even with major hepatectomies. Good patient selection and refined surgical technique are the keys to successful simultaneous resection. Simultaneous left lateral sectionectomy associated with colorectal resection should be routinely proposed.

[Social environmental risk factors and mental disorders: insights into underlying neural mechanisms drawing on the example of urbanicity]. / Soziale Umweltrisikofaktoren und psychische Erkrankungen : Einblicke in zugrunde liegende Gehirnmechanismen am Beispiel der Urbanizität.

The importance of social environmental factors for mental disorders is well known; nonetheless explanations of the underlying associations are still incomplete. For example this holds true for the schizophrenia risk factor urban upbringing (early urbanicity), which puzzled researchers for a long time. This article reports on recently identified neural correlates of this factor in the context of social stress processing. Drawing on this example, it is demonstrated how the identification of such correlates can contribute to the etiological understanding of mental disorders. While including genetic risk mechanisms and gene-environment interactions, a theoretical model is specified that postulates changes in the perigenual anterior cingulate cortex (pACC) and a heightened sensitivity towards social stressors as the relevant link between risk of schizophrenia and early urbanicity.

Fibrosis assessment in patients with nonalcoholic fatty liver disease: Adherence to proposed algorithms and barriers to complying with them.

INTRODUCTION AND AIMS: Fibrosis staging in patients with nonalcoholic fatty liver disease (NAFLD) is carried out through the application of stepwise algorithms but there is little real-world data on their use. Our aim was to calculate the number of patients with NAFLD and indeterminate or high risk for fibrosis, assessed through noninvasive scores, that consequently underwent further staging evaluation. MATERIALS AND METHODS: A cross-sectional multicenter cohort study was conducted on patients with NAFLD evaluated by hepatologists within the time frame of June 1 and July 31, 2018. The FIB-4 and NAFLD fibrosis scores were calculated in all the patients, and if at least one of the scores suggested indeterminate or high risk for fibrosis, we believed the patient should have undergone additional fibrosis staging assessment. RESULTS: The study included 238 patients. The median time interval from NAFLD diagnosis and inclusion in the analysis was 12.2 months (IQR 3.0-36.5). A total of 128 (54%) patients had at least one noninvasive score that suggested indeterminate or high risk for fibrosis but studies to confirm the fibrosis grade (elastography, biopsy, etc.) were performed on only 72 (56%). The main barriers encountered by the physicians for applying the staging algorithms were related to health insurance coverage and imaging study costs. CONCLUSIONS: A high percentage of patients with NAFLD were at indeterminate or high risk for fibrosis, according to noninvasive scores, but additional studies were carried out on only half of them, showing low adherence to current recommendations.

Cochlea cell-specific marker expression upon in vitro Hes1 knockdown.

NOTCH pathway proteins, including the transcriptional factor HES1, play crucial roles in the development of the inner ear by means of the lateral inhibition mechanism, in which supporting cells have their phenotype preserved while they are prevented from becoming hair cells. Genetic manipulation of this pathway has been demonstrated to increase hair cell number. The present study aimed to investigate gene expression effects in hair cells and supporting cells after Hes1-shRNA lentivirus transduction in organotypic cultures of the organ of Corti from postnatal-day-3 mice. Forty-eight hours after in vitro knockdown, Hes1 gene expression was reduced at both mRNA and protein levels. Myo7a (hair cell marker) and Sox2 (progenitor cell marker) mRNA levels also significantly increased. The modulation of gene expression in the organ of Corti upon Hes1 knockdown is consistent with cell phenotypes related to lateral inhibition mechanism interference in the inner ear. The lentivirus-based expression of Hes1-shRNA is a valuable strategy for genetic interference in the organ of Corti and for future evaluation of its efficacy in protocols aiming at the regeneration of hair cells in vivo.

Steroidome and metabolome analysis in gilt saliva to identify potential biomarkers of boar effect receptivity.

Optimal management of gilt reproduction requires oestrus synchronization. Hormonal treatments are used for this purpose, but there is a growing demand for non-hormonal alternatives, especially in organic farms. The boar effect is an important alternative opportunity to induce and synchronize oestrus without hormones. Before puberty, gilts exhibit a 'waiting period' during which boar exposure could induce and synchronize the first ovulation. We searched for salivary biomarkers of this period of boar effect receptivity to improve detection of the gilts to stimulate with the perspective of enhancing the efficacy of the boar effect. Saliva samples were collected from 30 Large-White×Landrace crossbred gilts between 140 and 175 days of age. Gilts were exposed twice a day to a boar and subjected to oestrus detection from 150 to 175 days of age. Among the 30 gilts, 10 were detected in oestrus 4 to 7 days after the first introduction of the boar and were considered receptive to the boar effect, 14 were detected in oestrus more than 8 days after first boar contact, and six did not show oestrus and were considered non-receptive. Saliva samples from six receptive and six non-receptive gilts were analyzed for steroidome and for metabolome using gas chromatography coupled to tandem mass spectrometry and 1H nuclear magnetic resonance spectroscopy, respectively. Four saliva samples per gilt were analyzed: 25 days and 11 days before boar introduction, the day of boar introduction, 3 days later for receptive gilts or 7 days later for non-receptive gilts. Twenty-nine steroids and 31 metabolites were detected in gilt saliva. Salivary concentrations of six steroids and three metabolites were significantly different between receptive and non-receptive gilts: progesterone and glycolate 25 days before boar introduction, 3α5ß20α- and 3ß5α20ß-hexahydroprogesterone, dehydroepiandrosterone, androstenediol, succinate, and butyrate 11 days before boar introduction, and 3ß5α-tetrahydroprogesterone on the day of boar introduction. Thus, nine potential salivary biomarkers of boar effect receptivity were identified in our experimental conditions. Further studies with higher numbers of gilts and salivary sampling points are necessary to ascertain their reliability.

Fibrosis assessment in patients with nonalcoholic fatty liver disease: Adherence to proposed algorithms and barriers to complying with them. / Evaluación de fibrosis en pacientes con enfermedad por hígado graso no alcohólico: adherencia a los algoritmos propuestos y barreras para cumplir con ellos.

INTRODUCTION AND AIMS: Fibrosis staging in patients with nonalcoholic fatty liver disease (NAFLD) is carried out through the application of stepwise algorithms but there is little real-world data on their use. Our aim was to calculate the number of patients with NAFLD and indeterminate or high risk for fibrosis, assessed through noninvasive scores, that consequently underwent further staging evaluation. MATERIALS AND METHODS: A cross-sectional multicenter cohort study was conducted on patients with NAFLD evaluated by hepatologists within the time frame of June 1 and July 31, 2018. The FIB-4 and NAFLD fibrosis scores were calculated in all the patients, and if at least one of the scores suggested indeterminate or high risk for fibrosis, we believed the patient should have undergone additional fibrosis staging assessment. RESULTS: The study included 238 patients. The median time interval from NAFLD diagnosis and inclusion in the analysis was 12.2months (IQR 3.0-36.5). A total of 128 (54%) patients had at least one noninvasive score that suggested indeterminate or high risk for fibrosis but studies to confirm the fibrosis grade (elastography, biopsy, etc.) were performed on only 72 (56%). The main barriers encountered by the physicians for applying the staging algorithms were related to health insurance coverage and imaging study costs. CONCLUSIONS: A high percentage of patients with NAFLD were at indeterminate or high risk for fibrosis, according to noninvasive scores, but additional studies were carried out on only half of them, showing low adherence to current recommendations.

Contraceptive method use among HIV-positive women in a US urban outpatient clinic: an exploratory cross-sectional study.

OBJECTIVE(S): Effective contraceptive method use is important for HIV-positive women to meet fertility goals, prevent unintended pregnancy and reduce risk of vertical HIV transmission. Our objective was to evaluate factors associated with HIV-positive women's contraceptive method use at last coitus defined as more effective [Tier 1 and 2 methods (T1/2)] versus less effective [Tier 3 or no method (T3/none)] by the US Medical Eligibility Criteria for contraception use. STUDY DESIGN: HIV-positive women, recruited from an HIV clinic in Atlanta, Georgia, between 2013 and 2014, completed a survey of demographic, clinical and reproductive health characteristics surrounding contraception. We examined the relationship between survey responses and contraceptive method use at last coitus using χ2 tests and multivariate logistic regression. RESULTS: Thirty-one percent of this HIV-positive and predominantly African-American (90%) cohort reported usage of T1/2 methods. T1/2 methods use was higher among younger women [adjusted odds ratio (aOR)=.90, p=.008] and those in noncommitted relationships (aOR =.32, p=.027). Only 21% reported dual method use at last intercourse. Fifty-three percent and 31% reported having heard of the intrauterine device and implant, respectively. Misconceptions about contraception were common. CONCLUSIONS: The use of T1/2 methods was more common in this cohort than in the general African-American population, but overall use and dual method use can still be improved, particularly among older women and those in noncommitted relationships. IMPLICATIONS: As this population had low awareness and usage of T1/2 methods and expressed many misconceptions, reoccurring contraceptive counseling may be helpful. Providers should address patient-level barriers, pregnancy intentions, and the importance of dual method and T1/2 method use.

Characteristics of Liver Transplantation in Argentina: A Multicenter Study.

INTRODUCTION: There is a lack of information regarding outcomes after liver transplant in Latin America. OBJECTIVES: This study sought to describe outcomes after liver transplant in adult patients from Argentina. METHODS: We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. RESULTS: A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. CONCLUSIONS: We believe the information contained in this article might be of value for reviewing current practices and developing local policies.