Search

BACKGROUND:Men who have sex with men (MSM) continue to be disproportionately impacted globally by the HIV epidemic. Studies suggest that HIV self-testing (HIVST) is highly acceptable among MSM. Social network strategies to increase testing are effective in reaching MSM, particularly MSM of color, who may not otherwise test. We tested a social network-based strategy to distribute HIVST kits to African American MSM (AAMSM) and Latino MSM (LMSM). SETTING:This study was conducted in Alameda County, California, a large, urban/suburban county with an HIV epidemic mirroring the national HIV epidemic. METHODS:From January 2016 to March 2017, 30 AAMSM, LMSM, and transgender women were trained as peer recruiters and asked to distribute 5 self-test kits to MSM social network members and support those who test positive in linking to care. Testers completed an online survey after their test. We compared peer-distributed HIVST testing outcomes to outcomes from Alameda County's targeted, community-based HIV testing programs using χ tests. RESULTS:Peer-distributed HIVST to 143 social and sexual network members, of whom 110 completed the online survey. Compared with MSM who used the County's sponsored testing programs, individuals reached through the peer-based self-testing strategy were significantly more likely to have never tested for HIV (3.51% vs. 0.41%, P < 0.01) and to report a positive test result (6.14% vs. 1.49%, P < 0.01). CONCLUSION:Findings suggest that a network-based strategy for self-test distribution is a promising intervention to increase testing uptake and reduce undiagnosed infections among AAMSM and LMSM.

More than 30 years into the HIV epidemic, men who have sex with men (MSM) continue to be disproportionately impacted. It is estimated that worldwide nearly half of MSM infected with HIV are unaware of their status, making HIV testing along with early linkage to care crucial to HIV prevention efforts. However, there remain significant barriers to HIV testing among MSM, due largely to complex issues of layered stigma that deter MSM from accessing traditional, clinic-based testing. We conducted a review and synthesis of the literature on strategies to increase uptake of HIV testing among MSM. We found that social network-based strategies, community-based testing, HIV self-testing, and modifications to the traditional clinic-based model can effectively reach a subset of MSM, but success was often context-specific and there are significant gaps in evidence. We provide recommendations for increasing HIV testing rates and status awareness among MSM.

BackgroundNeonatal herpes is a potentially devastating infection that results from acquisition of herpes simplex virus (HSV) type 1 or 2 from the maternal genital tract at the time of vaginal delivery. Current guidelines recommend (1) cesarean delivery if maternal genital HSV lesions are present at the time of labor and (2) antiviral suppressive therapy for women with known genital herpes to decrease HSV shedding from the genital tract at the time of vaginal delivery. However, most neonatal infections occur in infants born to women without a history of genital HSV, making current prevention efforts ineffective for this group. Although routine serologic HSV testing of women during pregnancy could identify women at higher risk of intrapartum viral shedding, it is uncertain how this knowledge might impact intrapartum management, and a potential concern is a higher rate of cesarean sections among women known to be HSV-2 seropositive.MethodsTo assess the effects of prenatal HSV-2 antibody testing, history of genital herpes, and use of suppressive antiviral medication on the intrapartum management of women, we investigated the frequency of invasive obstetric procedures and cesarean deliveries. We conducted a retrospective cohort study of pregnant women delivering at the University of Washington Medical center in Seattle, Washington. We defined the exposure of interest as HSV-2 antibody positivity or known history of genital herpes noted in prenatal records. The primary outcome was intrapartum procedures including fetal scalp electrode, artificial rupture of membranes, intrauterine pressure catheter, or operative vaginal delivery (vacuum or forceps). The secondary outcome was incidence of cesarean birth. Univariate and multivariable logistic regressions were performed.ResultsFrom a total of 449 women included in the analysis, 97 (21.6%) were HSV-2 seropositive or had a history of genital herpes (HSV-2/GH). Herpes simplex virus-2/GH women not using suppressive antiviral therapy were less likely to undergo intrapartum procedures than women without HSV-2/GH (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0.95; P = .036), but this relationship was attenuated after adjustment for potential confounders (adjusted OR, 0.69; 95% CI, 0.34-1.41; P = .31). There was no difference in intrapartum procedures for women on suppressive therapy versus women without HSV-2/GH (OR, 1.17; 95% CI, 0.66-2.07; P = .60). Similar proportions of cesarean sections were performed within each group of women: 25% without history of HSV-2/GH, 30% on suppressive treatment, and 28.1% without suppressive treatment (global, P = .73).ConclusionsIn this single-site study, provider awareness of genital herpes infection either by HSV serotesting or history was associated with fewer invasive obstetric procedures shown to be associated with neonatal herpes, but it was not associated with an increased rate of cesarean birth.

BackgroundNeonatal herpes is a potentially devastating infection that results from acquisition of herpes simplex virus (HSV) type 1 or 2 from the maternal genital tract at the time of vaginal delivery. Current guidelines recommend (1) cesarean delivery if maternal genital HSV lesions are present at the time of labor and (2) antiviral suppressive therapy for women with known genital herpes to decrease HSV shedding from the genital tract at the time of vaginal delivery. However, most neonatal infections occur in infants born to women without a history of genital HSV, making current prevention efforts ineffective for this group. Although routine serologic HSV testing of women during pregnancy could identify women at higher risk of intrapartum viral shedding, it is uncertain how this knowledge might impact intrapartum management, and a potential concern is a higher rate of cesarean sections among women known to be HSV-2 seropositive.MethodsTo assess the effects of prenatal HSV-2 antibody testing, history of genital herpes, and use of suppressive antiviral medication on the intrapartum management of women, we investigated the frequency of invasive obstetric procedures and cesarean deliveries. We conducted a retrospective cohort study of pregnant women delivering at the University of Washington Medical center in Seattle, Washington. We defined the exposure of interest as HSV-2 antibody positivity or known history of genital herpes noted in prenatal records. The primary outcome was intrapartum procedures including fetal scalp electrode, artificial rupture of membranes, intrauterine pressure catheter, or operative vaginal delivery (vacuum or forceps). The secondary outcome was incidence of cesarean birth. Univariate and multivariable logistic regressions were performed.ResultsFrom a total of 449 women included in the analysis, 97 (21.6%) were HSV-2 seropositive or had a history of genital herpes (HSV-2/GH). Herpes simplex virus-2/GH women not using suppressive antiviral therapy were less likely to undergo intrapartum procedures than women without HSV-2/GH (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0.95; P = .036), but this relationship was attenuated after adjustment for potential confounders (adjusted OR, 0.69; 95% CI, 0.34-1.41; P = .31). There was no difference in intrapartum procedures for women on suppressive therapy versus women without HSV-2/GH (OR, 1.17; 95% CI, 0.66-2.07; P = .60). Similar proportions of cesarean sections were performed within each group of women: 25% without history of HSV-2/GH, 30% on suppressive treatment, and 28.1% without suppressive treatment (global, P = .73).ConclusionsIn this single-site study, provider awareness of genital herpes infection either by HSV serotesting or history was associated with fewer invasive obstetric procedures shown to be associated with neonatal herpes, but it was not associated with an increased rate of cesarean birth.

BackgroundPersons with unsuppressed HIV viral load (VL) who disengage from care may experience poor clinical outcomes and potentially transmit HIV. We assessed the feasibility and yield of using the San Francisco Department of Public Health (SFDPH) enhanced HIV surveillance system (eHARS) to identify and re-engage such persons in care.MethodsUsing SFDPH eHARS data as of 4/20/2012 (index date), we selected HIV-infected adults who were alive, had no reported VL or CD4 cell count results in the past nine months (proxy for "out-of-care") and a VL >200 copies/mL drawn nine to 15 months earlier. We prioritized cases residing locally for investigation, and used information from eHARS and medical and public health databases to contact them for interview and referral to the SFDPH linkage services (LINCS). Twelve months later, we matched-back to eHARS data to assess how HIV laboratory reporting delays affected original eligibility, and if persons had any HIV laboratory results performed and reported within 12 months after index date ('new labs').ResultsAmong 434 eligible persons, 282 were prioritized for investigation, of whom 75 (27%) were interviewed, 79 (28%) could not be located, and 48 (17%) were located out of the area. Among the interviewed, 54 (72%) persons accepted referral to LINCS. Upon match-back to eHARS data, 324 (75%) in total were confirmed as eligible, including 221 (78%) of the investigated; most had new labs.ConclusionsAmong the investigated persons presumed out-of-care, we interviewed and offered LINCS referral to about one-quarter, demonstrating the feasibility but limited yield of our project. Matching to updated surveillance data revealed that a substantial minority did not disengage from care and that most re-engaged in HIV care. Verifying persons' HIV care status with medical providers and improving timeliness of transfer and cross-jurisdictional sharing of HIV laboratory data may aid future efforts.

In this article, we describe a process of the San Francisco collaboration to select optimal measures of linkage to care in response to the Enhanced Comprehensive HIV Prevention Planning program of the Centers for Disease Control and Prevention and to understand the implications of measure selection and the challenges of accessing data sources to measure outcomes along the HIV care continuum. Challenges identified are the variety of definitions of linkage to care and the nonintegrative nature of the multiple data systems necessary to measure linkage to care and other continuum outcomes. The choice of linkage measures, which at the extremes is a choice between higher-resolution measures based on clinical visit data in a subset of patients vs. a lower-resolution proxy measure based on surveillance data, has key implications. Choosing between the options needs to be informed by the primary use of the measure. For representing trends in the overall performance and response to interventions, more generalizable measures based on surveillance data are optimal. For identifying barriers to linkage to care for specific populations and potential intervention targets within the linkage process, higher-resolution measures of linkage that include clinical, laboratory, and social work visit information are optimal. Cataloging the different data systems along the continuum and observations of challenges of data sharing between the systems highlighted the promise of integrated data management systems that span HIV surveillance and care systems. Such integrated data management systems would have the ability to support detailed investigation and would provide simplified data to match newly developed, cross-agency Health and Human Service measures of HIV care continuum outcomes.

BackgroundYoung women receiving family planning services are at risk for both unintended pregnancy and herpes simplex virus type 2 (HSV-2) infection.MethodsWe performed a secondary analysis using data from a previously published randomized controlled trial evaluating access to emergency contraception on reproductive health outcomes. Women aged 15 to 24 years were recruited from two Planned Parenthood clinics and two community health clinics in San Francisco. Demographic information and sexual history were obtained by interview. HSV-2 seropositivity was determined by fingerstick blood test. New pregnancies were measured by self-report, urine testing and medical chart review. Subjects were evaluated for incident HSV-2 infection and pregnancy at a 6-month follow-up appointment. Women who were pregnant or intending to become pregnant at enrolment were excluded.ResultsAt enrolment 2,104 women were screened for HSV-2 and 170 (8.1%) were seropositive. Eighty-seven percent of initially seronegative women completed the study (n = 1,672) and 73 (4.4%) became HSV-2 seropositive. HSV-2 seroincidence was 7.8 cases per 100 person-years. One hundred and seventeen women (7%) became pregnant and 7 (6%) of these had a seroincident HSV-2 infection during the study. After adjustment for confounders, predictors of incident HSV-2 infection were African American race and having multiple partners in the last six months. Condom use at last sexual encounter was protective.ConclusionHSV-2 seroincidence and the unintended pregnancy rate in young women were high. Providers who counsel women on contraceptive services and sexually transmitted infection prevention could play an expanded role in counselling women about HSV-2 prevention given the potential sequelae in pregnancy. The potential benefit of targeted screening and future vaccination against HSV-2 needs to be assessed in this population.

The loss of insulin-secreting [beta] cells is characteristic among type I and type II diabetes. Stimulating proliferation to expand sources of [beta] cells for transplantation remains a challenge because adult [beta] cells do not proliferate readily. The cell cycle inhibitor p57 has been shown to control cell division in human [beta] cells. Expression of p57 is regulated by the DNA methylation status of the imprinting control region 2 (ICR2), which is commonly hypomethylated in Beckwith-Wiedemann syndrome patients who exhibit massive [beta] cell proliferation. We hypothesized that targeted demethylation of the ICR2 using a transcription activator-like effector protein fused to the catalytic domain of TET1 (ICR2-TET1) would repress p57 expression and promote cell proliferation. We report here that overexpression of ICR2-TET1 in human fibroblasts reduces p57 expression levels and increases proliferation. Furthermore, human islets overexpressing ICR2-TET1 exhibit repression of p57 with concomitant upregulation of Ki-67 while maintaining glucose-sensing functionality. When transplanted into diabetic, immunodeficient mice, the epigenetically edited islets show increased [beta] cell replication compared with control islets. These findings demonstrate that epigenetic editing is a promising tool for inducing [beta] cell proliferation, which may one day alleviate the scarcity of transplantable [beta] cells for the treatment of diabetes., IntroductionIn 2014, 422 million people worldwide lived with diabetes (1). While patients with type I or severe forms of type II diabetes can manage extreme glucose excursions by administering insulin [...]

Understanding the molecular basis of the regenerative response following hepatic injury holds promise for improved treatment of liver diseases. Here, we report an innovative method to profile gene expression specifically in the hepatocytes that regenerate the liver following toxic injury. We used the [Fah.sup.-/-] mouse, a model of hereditary tyrosinemia, which conditionally undergoes severe liver injury unless fumarylacetoacetate hydrolase (FAH) expression is reconstituted ectopically. We used translating ribosome affinity purification followed by high-throughput RNA sequencing (TRAP-seq) to isolate mRNAs specific to repopulating hepatocytes. We uncovered upstream regulators and important signaling pathways that are highly enriched in genes changed in regenerating hepatocytes. Specifically, we found that glutathione metabolism, particularly the gene Slc7a11 encoding the cystine/glutamate antiporter (xCT), is massively upregulated during liver regeneration. Furthermore, we show that Slc7a11 overexpression in hepatocytes enhances, and its suppression inhibits, repopulation following toxic injury. TRAP-seq allows cell type-specific expression profiling in repopulating hepatocytes and identified xCT, a factor that supports antioxidant responses during liver regeneration. xCT has potential as a therapeutic target for enhancing liver regeneration in response to liver injury., Introduction The liver is the main metabolic organ in the body; it is the nexus for homeostasis of carbohydrates, proteins, and lipids, and it eliminates waste products by oxidation and [...]

Family-owned businesses have their unique strategic advantages and challenges. One of the challenges encountered in the dynamics of a family business is the development of its business strategy. Business strategy plays a key role in helping companies to achieve and sustain competitive advantage. A board including outside directors could aid family businesses with its expertise to craft and implement resilient strategies. Within this context, this paper aims to critically analyse the role of governance in family businesses using an agribusiness case study from Kenia. This study uses a qualitative research approach. Primary data were collected from board members and shareholders working at Kisima farm. The results of this study indicate that having a board of directors have helped the selected agribusiness enterprise to develop successful strategies in a very competitive environment. Findings have revealed that when managed infectively, a board may become a liability. The findings of this research make a contribution to the existing literature by extending current knowledge within this domain and identifying the key issues surrounding the use of a board of directors in an agribusiness enterprise. [ABSTRACT FROM AUTHOR]

The e-syllabus is a set of Web pages in which each course in the curriculum is assigned a "course page" and multiple "session pages." Course pages have a standardized format that provides course objectives, course policies, required or recommended textbooks, grading scales, and faculty listings. A separate session page is created for each lecture/lab session conducted within the course. Together with specific objectives for each lecture or lab, these pages provide links to handout material (in PDF format) for use in that session, to supplemental Web resources maintained within the e-syllabus, and to outside Web sites. Session pages are accessed from links on the course page and from electronic calendar pages, one for each of the four years in the curriculum. In this article, the author provides an overview of the e-syllabus framework as it evolved through several different stages at the University of North Carolina (UNC) dental school. In particular, this article describes his attempts to bring more student involvement and educational relevance to the e-syllabus in the first-year curriculum. This initially entailed the creation of an online syllabus with a Web site development program, and eventually led to implementing rich media presentations that enhanced the interactive component of the syllabus. By tracing these steps, the author hopes to show how online technology in lecture-based courses can be utilized in ways that go beyond the mere presentation of supplemental course materials, such that it may promote active student learning.

Activation of NADPH oxidase (NOX) enzymes and the generation of reactive oxygen species and oxidative stress regulate vascular and renal function and contribute to the pathogenesis of hypertension. The present study examined the role of NOXA1/NOX1 function in vascular reactivity of renal and mesenteric resistance arteries/arterioles of wild-type and Noxa1-/- mice. A major finding was that renal blood flow is less sensitive to acute stimulation by angiotensin II (ANG II) in Noxa1-/- mice compared with wild-type mice, with a direct action on resistance arterioles independent of nitric oxide (NO) bioavailability. These functional results were reinforced by immunofluorescence evidence of NOXA1/NOX1 protein presence in renal arteries, afferent arterioles, and glomeruli as well as their upregulation by ANG II. In contrast, the renal vascular response to the thromboxane mimetic U46619 was effectively blunted by NO and was similar in both mouse genotypes and thus independent of NOXA1/NOX1 signaling. However, phenylephrine- and ANG II-induced contraction of isolated mesenteric arteries was less pronounced and buffering of vasoconstriction after acetylcholine and nitroprusside stimulation was reduced in Noxa1-/- mice, suggesting endothelial NO-dependent mechanisms. An involvement of NOXA1/NOX1/O2•- signaling in response to ANG II was demonstrated with the specific NOXA1/NOX1 assembly inhibitor C25 and the nonspecific NOX inhibitor diphenyleneiodonium chloride in cultured vascular smooth muscle cells and isolated mesenteric resistance arteries. Collectively, our data indicate that the NOX1/NOXA1/O2•- pathway contributes to acute vasoconstriction induced by ANG II in renal and mesenteric vascular beds and may contribute to ANG II-induced hypertension. [ABSTRACT FROM AUTHOR]

The peptide uroguanylin (Ugn) is stored and released as a propeptide (proUgn) by enterochromaffin cells in the intestine, and converted to Ugn and other metabolites in the renal tubules. Both proUgn and Ugn are natriuretic, although the response to proUgn is thought to depend on its conversion to Ugn within nephrons. To assess the efficiency of intrarenal conversion of proUgn to Ugn, we measured urinary Ugn excretion in rats following intravenous infusions of proUgn or Ugn. Infusion of 2 and 10 nmol proUgn/kg body wt increased plasma proUgn concentration from 2.2 [+ or -] 0.3 to 5.6 [+ or -] 1.3 pmol/ml and to 37 [+ or -] 9.6 pmol/ml, respectively. No proUgn was detected in urine before, during, or after proUgn infusions. These two proUgn infusion doses resulted in total Ugh recovery in urine of 162 [+ or -] 64 and 206 [+ or -] 39 pmol/kg body wt (9 and 2% of the infused amount, respectively). By contrast, the same molar amounts of Ugh resulted in 1,009 [+ or -] 477 and 5,352 [+ or -] 2,133 pmol/kg body wt of Ugh in urine (recoveries of ~50%). Unexpectedly, comparisons of natriuretic dose-response curves for each peptide showed proUgn to be about five times more potent than Ugh, despite the relatively modest amount of Ugn generated from infused proUgn. In addition, both peptides were antikaliuretic at low doses, but in this case Ugn showed greater potency than proUgn. These data do not support Ugn as the primary active principle of proUgn for regulation of renal sodium excretion. Instead, an alternative peptide fragment produced from proUgn may be responsible for natriuretic activity in the kidney, whereas Ugh itself may play an antikaliuretic role. renal function; sodium excretion; intestinal peptides doi: 10.1152/ajprenal.00281.2010

Chlamydia and gonorrhea rates among African American youths in San Francisco are far higher than those among young people of the city's other racial and ethnic groups. A geographically targeted sexually transmitted disease education and screening intervention performed in collaboration with a local faith-based organization was able to screen hundreds of at-risk youths. The screened individuals included friends and sex partners from an extensive social-sexual network that transcended the boundaries of the target population. The intervention also provided an excellent opportunity to practice 'street medicine,' in which all screening and treatment was effectively conducted in the field.

The pelvic and hypogastric nerves of anesthetized rats were analyzed to determine the properties of the chemoreceptive renal afferent nerves of rodent urinary bladder. Analysis of bladder afferent nerve activity in rodent pelvic and hypogastric nerves indicated the presence of a chemoreceptive component in the afferent innervation of the urinary bladder of rats. The chemosensitive afferent nerves were activated during bladder filling by increasing concentration of KCl in a dose-dependent manner.