Preoperative Contrast-Enhanced Ultrasound Predicts Microvascular Invasion in Hepatocellular Carcinoma as Accurately as Contrast-Enhanced MR.

OBJECTIVES: Both contrast-enhanced ultrasound (CEUS) and contrast-enhanced magnetic resonance (CEMR) are important imaging methods for hepatocellular carcinoma (HCC). This study aimed to establish a model using preoperative CEUS parameters to predict microvascular invasion (MVI) in HCC, and compare its predictive efficiency with that of CEMR model. METHODS: A total of 93 patients with HCC (39 cases in MVI positive group and 54 cases in MVI negative group) who underwent surgery in our hospital from January 2020 to June 2021 were retrospectively analyzed. Their clinical and imaging data were collected to establish CEUS and CEMR models for predicting MVI. The predictive efficiencies of both models were compared. RESULTS: By the univariate and multivariate regression analyses of patients' clinical information, preoperative CEUS static and dynamic images, we found that serrated edge and time to peak were independent predictors of MVI. The CEUS prediction model achieved a sensitivity of 92.3%, a specificity of 83.3%, and an accuracy of 84.6% (Az: 0.934). By analyzing the clinical and CEMR information, we found that tumor morphology, fast-in and fast-out, peritumoral enhancement, and capsule were independent predictors of MVI. The CEMR prediction model achieved a sensitivity of 97.4%, a specificity of 77.8%, and an accuracy of 83.2% (Az: 0.900). The combination of the two models achieved a sensitivity of 84.6%, a specificity of 87.0%, and an accuracy of 86.2% (Az: 0.884). There was no significant statistical difference in the areas under the ROC curve of the three models. CONCLUSION: The CEUS model and the CEMR model have similar predictive efficiencies for MVI of HCC. CEUS is also an effective method to predict MVI before operation.

Engineering and optimization of the 2-phenylethylglucosinolate production in Nicotiana benthamiana by combining biosynthetic genes from Barbarea vulgaris and Arabidopsis thaliana.

2-Phenylethylglucosinolate (2PE) derived from homophenylalanine is present in plants of the Brassicales order as a defense compound. It is associated with multiple biological properties, including deterrent effects on pests and antimicrobial and health-promoting functions, due to its hydrolysis product 2-phenylethyl isothiocyanate, which confers 2PE as a potential application in agriculture and industry. In this study, we characterized the putative key genes for 2PE biosynthesis from Barbarea vulgaris W.T. Aiton and demonstrated the feasibility of engineering 2PE production in Nicotiana benthamiana Domin. We used different combinations of genes from B. vulgaris and Arabidopsis thaliana (L.) Heynh. to demonstrate that: (i) BvBCAT4 performed more efficiently than AtBCAT4 in biosynthesis of both homophenylalanine and dihomomethionine; (ii) MAM1 enzymes were critical for the chain-elongated profile, while CYP79F enzymes accepted both chain-elongated methionine and homophenylalanine; (iii) aliphatic but not aromatic core structure pathway catalyzed the 2PE biosynthesis; (iv) a chimeric pathway containing BvBCAT4, BvMAM1, AtIPMI and AtIPMDH1 resulted in a two-fold increase in 2PE production compared with the B. vulgaris-specific chain elongation pathway; and (v) profiles of chain-elongated products and glucosinolates partially mirrored the profiles in the gene donor plant, but were wider in N. benthamiana than in the native plants. Our study provides a strategy to produce the important homophenylalanine and 2PE in a heterologous host. Furthermore, chimeric engineering of the complex 2PE biosynthetic pathway enabled detailed understanding of catalytic properties of individual enzymes - a prerequisite for understanding biochemical evolution. The new-to-nature gene combinations have the potential for application in biotechnological and plant breeding.

Comparison of Genome and Plasmid-Based Engineering of Multigene Benzylglucosinolate Pathway in Saccharomyces cerevisiae.

Intake of brassicaceous vegetables such as cabbage is associated with numerous health benefits. The major defense compounds in the Brassicales order are the amino acid-derived glucosinolates that have been associated with the health-promoting effects. This has primed a desire to build glucosinolate-producing microbial cell factories as a stable and reliable source. Here, we established-for the first time-production of the phenylalanine-derived benzylglucosinolate (BGLS) in Saccharomyces cerevisiae using two different engineering strategies: stable genome integration versus plasmid-based introduction of the biosynthetic genes. Although the plasmid-engineered strain showed a tendency to generate higher expression level of each gene (except CYP83B1) in the biosynthetic pathway, the genome-engineered strain produced 8.4-fold higher BGLS yield compared to the plasmid-engineered strain. Additionally, we optimized the genome-engineered strain by overexpressing the entry point genes CYP79A2 and CYP83B1, resulting in a 2-fold increase in BGLS production but also a 4.8-fold increase in the level of the last intermediate desulfo-benzylglucosinolate (dsBGLS). We applied several approaches to alleviate the metabolic bottleneck in the step where dsBGLS is converted to BGLS by sulfotransferase, SOT16 dependent on 3'-phosphoadenosine-5'-phosphosulfate (PAPS). BGLS production increased 1.7-fold by overexpressing SOT16 and 1.7-fold by introducing APS kinase, APK1, from Arabidopsis thaliana involved in the PAPS regeneration cycle. Modulating the endogenous sulfur assimilatory pathway through overexpression of MET3 and MET14 resulted in 2.4-fold to 12.81 µmol/L (=5.2 mg/L) for BGLS production. IMPORTANCE Intake of brassicaceous vegetables such as cabbage is associated with numerous health benefits. The major defense compounds in the Brassicales order are the amino acid-derived glucosinolates that have been associated with the health-promoting effects. This has primed a desire to build glucosinolate-producing microbial cell factories as a stable and reliable source. In this study, we engineered for the first time the production of phenylalanine-derived benzylglucosinolate in Saccharomyces cerevisiae with two engineering strategies: stable genome integration versus plasmid-based introduction of the biosynthetic genes. Although the plasmid-engineered strain generally showed higher expression level of each gene (except CYP83B1) in the biosynthetic pathway, the genome-engineered strain produced higher production level of benzylglucosinolate. Based on the genome-engineered strain, the benzylglucosinolate level was improved by optimization. Our study compared different approaches to engineer a multigene pathway for production of the plant natural product benzylglucosinolate. This may provide potential application in industrial biotechnology.

The epidermal bladder cell-free mutant of the salt-tolerant quinoa challenges our understanding of halophyte crop salinity tolerance.

Halophytes tolerate high salinity levels that would kill conventional crops. Understanding salt tolerance mechanisms will provide clues for breeding salt-tolerant plants. Many halophytes, such as quinoa (Chenopodium quinoa), are covered by a layer of epidermal bladder cells (EBCs) that are thought to mediate salt tolerance by serving as salt dumps. We isolated an epidermal bladder cell-free (ebcf) quinoa mutant that completely lacked EBCs and was mutated in REBC and REBC-like1. This mutant showed no loss of salt stress tolerance. When wild-type quinoa plants were exposed to saline soil, EBCs accumulated potassium (K+ ) as the major cation, in quantities far exceeding those of sodium (Na+ ). Emerging leaves densely packed with EBCs had the lowest Na+ content, whereas old leaves with deflated EBCs served as Na+ sinks. When the leaves expanded, K+ was recycled from EBCs, resulting in turgor loss that led to a progressive deflation of EBCs. Our findings suggest that EBCs in young leaves serve as a K+ -powered hydrodynamic system that functions as a water sink for solute storage. Sodium ions accumulate within old leaves that subsequently wilt and are shed. This mechanism improves the survival of quinoa under high salinity conditions.

Donepezil Attenuates Obesity-Associated Oxidative Stress and Central Inflammation and Improves Memory Deficit in Mice Fed a High-Fat Diet.

BACKGROUND/AIMS: Obesity is associated with chronic inflammation and cognitive decline, and is considered a major risk factor for neurodegeneration. Meanwhile, neuroinflammation is important in the pathogenesis and progression of neurodegenerative diseases. METHODS: In this study, we tested the hypothesis that donepezil would attenuate central inflammation and oxidative damage and improve memory deficit in high-fat diet (HFD)-fed mice. After 16 weeks on a HFD, C57BL/6J mice were given either donepezil (3 mg/kg, i.p.) or saline for 4 weeks in parallel to a control diet (CD) group. Thereafter, the step-through test was used to assess learning and memory function. RESULTS: In the brain of HFD-fed mice, levels of the proinflammatory cytokines interleukin 16 and tumor necrosis factor α were reduced by donepezil treatment. Similarly, HFD-induced protein levels of advanced glycation end-products and oxidative stress in the brain were significantly decreased by donepezil treatment. CONCLUSION: Our results indicate that donepezil may reverse obesity-related central inflammation and oxidative damage and improve memory deficit in HFD-fed mice.

Biotechnological approaches in glucosinolate production.

Glucosinolates (GLSs) are sulfur-rich, amino acid-derived defense compounds characteristic of the Brassicales order. In the past, GLSs were mostly known as anti-nutritional factors in fodder, biopesticides in agriculture, and flavors in condiments such as mustard. However, in recent times, GLSs have received increased attention as promoters of human health. This has spurred intensive research towards generating rich sources of health-promoting GLSs. We provide a comprehensive overview of the biotechnological approaches applied to reach this goal. This includes optimization of GLS production and composition in native, GLS-producing plants, including hairy root and cell cultures thereof, as well as synthetic biology approaches in heterologous hosts, such as tobacco and the microbial organisms Escherichia coli and Saccharomyces cerevisiae. The progress using these different approaches is discussed.

Effects of Antiretroviral Therapy and Depressive Symptoms on All-Cause Mortality Among HIV-Infected Women.

Depression affects up to 30% of human immunodeficiency virus (HIV)-infected individuals. We estimated joint effects of antiretroviral therapy (ART) initiation and depressive symptoms on time to death using a joint marginal structural model and data from a cohort of HIV-infected women from the Women's Interagency HIV Study (conducted in the United States) from 1998-2011. Among 848 women contributing 6,721 years of follow-up, 194 participants died during follow-up, resulting in a crude mortality rate of 2.9 per 100 women-years. Cumulative mortality curves indicated greatest mortality for women who reported depressive symptoms and had not initiated ART. The hazard ratio for depressive symptoms was 3.38 (95% confidence interval (CI): 2.15, 5.33) and for ART was 0.47 (95% CI: 0.31, 0.70). Using a reference category of women without depressive symptoms who had initiated ART, the hazard ratio for women with depressive symptoms who had initiated ART was 3.60 (95% CI: 2.02, 6.43). For women without depressive symptoms who had not started ART, the hazard ratio was 2.36 (95% CI: 1.16, 4.81). Among women reporting depressive symptoms who had not started ART, the hazard ratio was 7.47 (95% CI: 3.91, 14.3). We found a protective effect of ART initiation on mortality, as well as a harmful effect of depressive symptoms, in a cohort of HIV-infected women.

Change in patterns of HIV status disclosure in the HAART era and association of HIV status disclosure with depression level among women.

Whether widespread use of HAART changed patterns of HIV status disclosure among women living with HIV is largely unknown. In addition, the association between time to first HIV disclosure and depression has not been fully explored among women. A retrospective cross-sectional survey was conducted among HIV-infected women from the Washington, DC site of the Women's Interagency HIV Study to collect detailed information about their HIV status disclosure behavior. A sample of 202 HIV-positive women, 102 diagnosed prior to and 100 post-HAART era participated in this study. Relationships between treatment era when diagnosed (pre-HAART or HAART era) and patterns of HIV status disclosure, and associations between HIV status disclosure and depression level were examined using generalized linear regression models with generalized estimating equation to adjust for repeated measurements from the same individuals. Our analyses showed that treatment era was not associated with either comfort level of HIV status disclosure or time to first HIV disclosure to either family members or friends. However, women were less likely to disclose HIV status to their family members in the HAART era (P = 0.006) after adjusting for social network type, comfort level of disclosure, time to first disclosure and length of follow-up time. In addition, longer time to first HIV disclosure, but not comfort level or extent of HIV status disclosure, was independently associated with depression levels as measured by CES-D score at study enrollment ("a few months after" vs "within a few days": P = 0.008). More definitive studies utilizing longitudinal designs should be conducted to further examine impact of HAART era on HIV status disclosure and effect of HIV status disclosure on mental health.

CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal Contraception.

Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P < .01 for all comparisons). LNG-IUD and, to a lesser extent, DMPA use were associated with increased peripheral T-cell CCR5 expression.

Trajectory analyses of virologic outcomes reflecting community-based HIV treatment in Washington DC 1994-2012.

BACKGROUND: Effective treatment of HIV since 1996 has reduced morbidity and mortality through virologic suppression. Combination antiretroviral therapy (cART) has been recognized as key to the prevention of drug resistance and the transmission of infection. We used eighteen years of virologic outcomes in a long-standing cohort of women to describe longitudinal viral load trajectories; and examine factors associated with sustained viremia and mortality. METHODS: We analyzed data from DC WIHS women with > four semiannual visits using a group-based logistic trajectory analysis approach to identify patterns of HIV RNA detection (>80 copies/mL or lower assay limit, and >1000 copies/mL). We verified findings using cumulative viral load suppression-years, explored group characteristics using generalized linear modeling with generalized estimating equations for repeated measures, and examined survival using the Kaplan-Meier and Cox proportional hazard analyses. RESULTS: 329 women contributed 6633 visits between 1994 and 2012 and demonstrated high, moderate, and low probability patterns of HIV RNA detection (>80 copies/mL) in 40.7, 35.6, and 23.7% of participant visits, respectively. Analysis of cumulative years of viral load suppression supported these observations. Kaplan-Meier survival analysis demonstrated high mortality of 31.1% with sustained viremia, but no significant difference in mortality between intermittent viremia and non-viremia patterns, 6.9 and 4.9% respectively. Mortality was associated with higher age, lower CD4+ T lymphocyte count, and sustained viremia by Cox multivariate analysis. CONCLUSIONS: This ecologic study demonstrates the effectiveness of viral suppression, and conversely the association between viremia and mortality. In community delivery of cART for HIV care, distinct patterns of sustained viremia, intermittent viremia, and non-viremia were identified over nearly 18 years in the DC WIHS, capturing the dynamics and complexity of sustaining long-term HIV care. Persistent viremia was associated with lower CD4s and mortality, but surprisingly mortality was not different between continuous suppression and intermittent viremia. Classification of long-term virologic patterns such as these observed HIV treatment "careers" may provide a suitable framework to identify modifiable factors associated with treatment resilience and failure. Both individual and population interventions are needed to reduce transmission, prevent the emergence of drug resistance, and improve outcomes of community ART programs.

Fluconazole Resistance Patterns in Candida Species that Colonize Women with HIV Infection.

BACKGROUND: The Women's Interagency HIV Study was established in 1993 to study the natural history of HIV disease among women in the United States. It currently has enrolled 2,895 women testing positive for HIV infection and 972 women without HIV infection recruited from 6 national metropolitan locations. The clinical database information collected for each HIV-positive individual included CD4 cell counts, viral load, and antiviral treatment to evaluate HIV prognosis and related conditions in women. OBJECTIVE: To provide a baseline for fluconazole treatment prospects in women who test positive for HIV infection. As part of the ongoing Women's Interagency HIV Study project, we investigated the fluconazole susceptibility of Candida spp. isolated from women with HIV in comparison to volunteer women without HIV. The implication of antifungal treatment on fluconazole susceptibility was evaluated by reviewing antifungal medication use for the past 2 years in each participant. In addition, genotyping of Candida spp. at oral and vaginal sites was monitored for 4 months in 9 patients. METHODS: In a cohort of 59 women with HIV and 24 women without HIV, colonization by Candida albicans and non-albicans species of the oral and vaginal sites was first determined. Fluconazole susceptibility was surveyed in vitro according to Clinical and Laboratory Standards Institute protocol. Antifungal drug treatment history was investigated for each patient to correspond with fluconazole susceptibility. Finally, series of isolates from several patients were followed for resistance and susceptibility. Their lineage was verified by genotyping multilocus sequence typing (MLST). RESULTS: A total of 280 Candida strains were recovered from oral and vaginal swabs of women with and without HIV infection. We found that patients with HIV were colonized with Candida spp. more frequently than women without HIV. The percent of isolates that were susceptibility dose dependent or resistant to fluconazole was higher in Candida glabrata compared with C. albicans isolates, but higher for C. albicans than other published data. Resistance was noted to be more common in vaginal sites. Fluconazole resistance in either species was not associated with relative CD4 cell counts or viral load. However an association with systemic application of fluconazole and resistance was noted. CONCLUSIONS: Systemic antifungal therapy, including a vaginal topical regimen in women with HIV infection correlated with reduced fluconazole susceptibility of oral and vaginal isolates. Genotype profiling has disclosed that a majority of isolates from the same individual are clustered together, suggesting the likelihood of an original strain with some microevolution. We observed a change from a susceptibility dose dependent to a resistant phenotype of isolates in 2 women with HIV infection, even though no treatments were received during the 4-month study and the prior 2 years.

Effects of highly active antiretroviral therapy and its adherence on herpes zoster incidence: a longitudinal cohort study.

BACKGROUND: Herpes zoster (HZ) is common among HIV-infected individuals, but the impacts of highly active antiretroviral therapy (HAART) and HAART adherence on HZ risk have not been well studied. METHODS: The effects of HAART and HAART adherence on HZ incidence were evaluated by comparing HIV-infected women on HAART (HAART use group) with the HIV-infected women remaining HAART naïve (HAART naïve group) in the Women's Interagency HIV Study (WIHS). A 1:1 matching with propensity score for predicting HAART initiation was conducted to balance background covariates at index visit, including HIV disease stage. Kaplan-Meier method was used to compare the risk of HZ development between the matched pairs. Cox proportional hazard models were used to assess the effects of HAART and HAART adherence on HZ incidence. RESULTS: Through propensity score matching, 389 pairs of participants were identified and they contributed 3,909 person years after matching. The background covariates were similar between the matched pairs at the index visit. The participants had a mean age around 39 years old, and about 61% of them were Black and 22% were Latina. No significant difference in HZ risk was observed between the HAART use group and the HAART naïve group during the first year of follow-up in any analyses. In the univariate analysis, the HAART use group had marginally lower HZ risk (Hazard Ratio (HR): 0.72; 95% Confidence Interval (CI): 0.48-1.1) over the entire follow-up period. However, women with a HAART adherence level of ≥95% had significantly lower HZ risk (HR: 0.54; 95% CI: 0.31, 0.94) compared to the HAART naïve women. The association remained significant after adjusting for quality of life score and acyclovir use, but it attenuated and was no longer statistically significant after adjusting for an intermediate variable, either CD4+ T cell counts or HIV viral load. CONCLUSIONS: Among adult women, we observed a significant preventive effect of long-term HAART use on HZ incidence when a HAART adherence level of ≥95% was attained, and this effect was mediated through reduction of HIV viral load and improvement of CD4+ T cell counts.

Impact of eating probiotic yogurt on colonization by Candida species of the oral and vaginal mucosa in HIV-infected and HIV-uninfected women.

BACKGROUND: Candidiasis in HIV/AIDS patients continues to be a public health problem. Antifungal therapies are not always effective and may result in complications, such as the development of drug-resistant strains of Candida species. OBJECTIVES: This study evaluated the impact of probiotic consumption on Candida colonization of the oral and vaginal mucosa. PATIENTS/METHODS: A pilot study was conducted in 24 women (17 HIV-infected, 7 HIV-uninfected) from the Women's Interagency HIV Study. The women underwent a 60-day initiation period with no probiotic consumption, followed by two 15-day consumption periods, with a different probiotic yogurt (DanActive™ or YoPlus™ yogurt) during each interval. There was a 30-day washout period between the two yogurt consumption periods. Oral and vaginal culture swabs were collected on days 0, 60, 74, and 120. Candida was detected by inoculating each swab in both Sabouraud's dextrose agar with or without chloramphenicol and CHROMagar. RESULTS: Less fungal colonization among women was observed when the women consumed probiotic yogurts (54 % of the women had vaginal fungal colonization during the non-probiotic yogurt consumption period, 29 % during the DanActive™ period, and 38 % during YoPlus™ yogurt consumption period), and HIV-infected women had significantly lower vaginal fungal colonization after they consumed DanActive™ yogurt compared to the non-intervention periods (54 vs 29 %, p = 0.03). CONCLUSIONS: These data are promising, but as expected in a small pilot study, there were some significant changes but also some areas where colonization was not changed. This type of conflicting data is supportive of the need for a larger trial to further elucidate the role of probiotic yogurts in fungal growth in HIV-infected women.

Short-term garlic supplementation and highly active antiretroviral treatment adherence, CD4+ cell counts, and human immunodeficiency virus viral load.

CONTEXT: Human immunodeficiency virus (HIV)-infected individuals frequently have consumed garlic, a popular complementary supplement. Researchers rarely have studied garlic's association with antiretroviral therapies, however, even though that association is very relevant clinically. OBJECTIVE: To examine associations of supplemental use of garlic with highly active antiretroviral treatment (HAART) adherence level and HAART effectiveness (HIV viral load and CD4+ cell counts) in HIV-infected women. DESIGN: The research team carried out a self-controlled, longitudinal study nested within the Women's Interagency HIV Study (WIHS). The team used a paired study design that allowed participants to serve as their own controls. The team first identified all of the studies visits in which the participant self-reported the use of a garlic supplement since her last visit (index visit). Then for each index visit, the team identified a matching visit (a control visit) using the following criteria: (a) the visit must be one for the same participant in which that participant reported no garlic supplementation; (b) the visit must immediately precede the index visit (less than 1 year apart); and (c) at the time of the control visit, the participant must have been using antiretroviral therapy identical to that used at the time of the index visit. PARTICIPANTS: Participants were persons using garlic supplementation who already were participants in the WIHS. OUTCOME MEASURES: The research team used a logistic regression model to examine the association between garlic supplementation and HAART adherence level. The team used a mixed linear model to examine the association of garlic supplementation with HIV viral load and CD4+ cell counts. RESULTS: From October 1994 to April 2009, 390 HIV-infected women in the WIHS made 1112 visits at which they reported using garlic supplements. Seventy-seven HIV-infected women using HAART met the research teams selection criteria and contributed 99 pairs of visits for the study. Among the women who used garlic supplements, 22% were 50 years and older; 58% were black and non-Hispanic; and 23% had less than a high-school education. Neither use of garlic supplementation nor reasons for using garlic supplements were significantly associated with the HAART adherence level, HIV viral load, or CD4+ cell counts; however, use garlic as needed, a potential marker of a disease state, was significantly associated with higher viral load (P=.0003). CONCLUSION: Short-term garlic supplementation did not impact HAART adherence level, HIV viral load, and CD4+ cell counts.

"I Haven't Been Ill, I Know It's There": a Case Study Examination of the Social, Behavioral, Clinical, and Structural Factors that Contribute to Sustained Viremia Among Women Living with HIV.

Compared to their HIV-seropositive male counterparts, HIV-seropositive women are less likely to achieve and retain viral suppression (VS). Data regarding the social, behavioral, clinical, and structural factors that facilitate or impede viral suppression among HIV-seropositive women is needed. This study aims to examine HIV-seropositive women's perceptions regarding factors that contribute to their HIV treatment decisions. Two case studies describe the HIV treatment decision-making of two never suppressed, HIV-seropositive women aged 65 and 54. The framework method of analysis was employed to obtain a descriptive overview of three interrelated areas of inquiry: (1) the meanings women give to VS; (2) social, behavioral, clinical, and structural obstacles related to HIV medication adherence; and (3) women's perceptions of what they need to achieve and sustain (VS). The meaning of VS for both women is influenced by how they currently feel. Women's general feeling of wellness detracts from any sense of urgency that may be associated with engaging in HIV treatment. Mistrust of medical providers and unstable housing/unemployment pose as obstacles to medication adherence. Finally, women's accounts of what they need to achieve and remain virally suppressed are influenced by a gap in understanding related to HIV treatment. HIV clinicians should routinely measure their patients' HIV health literacy to ensure patients understand when to begin and why they should continue an HIV treatment regimen. To increase their capacity to provide appropriate HIV care, providers should take into consideration how patients' life experiences and social locations influence their HIV treatment decision-making.

UnPrEPed for HIV prevention services: Hesitancy among US primary care providers.

Provision of HIV prevention services by primary care (PCP) healthcare providers is critical to reduce the number of new HIV infections. We examined the performance of HIV risk assessments and provision of HIV prevention services by PCPs. In our cohort, less than one-half of respondents asked about sex and drug use all or most of the time, and among those that did not routinely ask about sex and drug use only 66% and 59%, respectively, would ask given more time. Less than a quarter of respondents noted that HIV prevention services were part of their clinical practice. These findings demonstrate gaps in the provision of HIV prevention services by a key population of healthcare providers.

High Provider Trust Associates with High HIV Antiretroviral Adherence Among Women Living with HIV in a Metropolitan Washington, DC Cohort.

Trust in providers and health care systems (HCSs) has been associated with higher HIV antiretroviral (ART) adherence; however, most previous studies enrolled primarily men and did not concurrently assess provider trust, HCS distrust, and clinical/biological outcomes. We enrolled 239 Washington, DC Women's Interagency HIV Study (WIHS) women: 167 with HIV (WWH) and 72 without HIV. In 2006 and 2017-2018, women completed surveys on provider trust and HCS distrust. Clinical, social, and demographic covariates were obtained during the 2017-2018 WIHS study visit. Descriptive analyses included chi-squared and Mann-Whitney tests. Wilcoxon signed-rank tests assessed trust measure change over time. Logistic (provider trust) and linear (HCS distrust) models were constructed in R. The majority of women were African American/Black (76.9%) with a median age of 52 (interquartile range 48, 58) and currently insured (99.6%). In multi-variable analyses, women with HIV (WWH) had higher odds of high provider trust [adjusted odds ratio (aOR) 2.90, 95% confidence interval (CI) 1.34, 6.45], with ≥95% ART adherence associated with high provider trust among only WWH (aOR 4.13, 95% CI 1.14, 15.92). Multi-variable models also showed 3.40-point higher HCS distrust scores among WWH who reported ≥95% ART adherence (p = 0.03). CD4 count and HIV viral load were not associated with provider trust or HCS distrust. Provider (p = 0.67) and HCS (p = 0.65) trust did not significantly change in this population at two time points for 10 years. Self-reported antiretroviral therapy adherence significantly associated with high provider trust, yet also with high HCS distrust, revealing a nuanced relationship to providers and the HCS among WWH.

HIV Related Stigma among Healthcare Providers: Opportunities for Education and Training.

Background: HIV-stigma can influence engagement in care and viral suppression rates among persons living with HIV (PLWH). Understanding HIV-provider level stigma and its associated factors may aid in development of interventions to improve engagement in care. Methods: We assessed HIV-related stigma, provider knowledge, and practices and beliefs among healthcare providers using an online survey tool. Generalized linear modeling was used to determine factors associated with HIV-stigma score. Results: Among 436 participants, the mean age was 42.3 (SD 12.3), 70% female, 62% white, 65% physicians, and 44% worked at an academic center. The mean HIV Health Care Provider Stigma Scale (HPASS) score was 150.5 (SD 18.9, total = 180 [higher score = less stigma]) with factor subscale scores of 67.1 (SD 8.2, total = 78) prejudice, 51.3 (SD 9.7, total = 66) stereotyping, and 32.1 (SD 5, total = 36) discrimination. Female sex and comfort with talking about sex and drug use had 4.97 (95% CI 0.61, 9.32) and 1.99 (95% CI 0.88, 3.10) estimated higher HPASS scores. Disagreement/strong disagreement versus strong agreement with the statement that PLWH should be allowed to have babies and feeling responsible for talking about HIV prevention associated with -17.05 (95% CI -25.96, -8.15) and -2.16 (95% CI -3.43, -0.88) estimated lower HPASS scores. Conclusions: The modifiable factors we identified as associated with higher HIV related stigma may provide opportunities for education that may ameliorate these negative associations.

The evolution of plant proton pump regulation via the R domain may have facilitated plant terrestrialization.

Plasma membrane (PM) H+-ATPases are the electrogenic proton pumps that export H+ from plant and fungal cells to acidify the surroundings and generate a membrane potential. Plant PM H+-ATPases are equipped with a C­terminal autoinhibitory regulatory (R) domain of about 100 amino acid residues, which could not be identified in the PM H+-ATPases of green algae but appeared fully developed in immediate streptophyte algal predecessors of land plants. To explore the physiological significance of this domain, we created in vivo C-terminal truncations of autoinhibited PM H+­ATPase2 (AHA2), one of the two major isoforms in the land plant Arabidopsis thaliana. As more residues were deleted, the mutant plants became progressively more efficient in proton extrusion, concomitant with increased expansion growth and nutrient uptake. However, as the hyperactivated AHA2 also contributed to stomatal pore opening, which provides an exit pathway for water and an entrance pathway for pests, the mutant plants were more susceptible to biotic and abiotic stresses, pathogen invasion and water loss, respectively. Taken together, our results demonstrate that pump regulation through the R domain is crucial for land plant fitness and by controlling growth and nutrient uptake might have been necessary already for the successful water-to-land transition of plants.

Viral Suppression Is Associated with HIV Treatment Self-Efficacy in a Cohort of Women in Washington, DC.

The goal of HIV treatment is viral suppression as it is linked with improved health outcomes and decreased risk of viral transmission. We assessed the sociodemographic, behavioral, and patient-provider interaction associations with viral suppression with an administered survey to HIV-seropositive women in the metropolitan Washington, DC, site of the Women's Interagency HIV Study (WIHS) between 2017 and 2018. Logistic and mixed models were used to explore related factors between HIV viral suppression groups and HIV treatment self-efficacy, respectively. Higher HIV treatment self-efficacy and disclosure concerns were positively associated with viral suppression, while illicit drug use had a negative association. In mixed models, more health care provider trust was associated with higher HIV treatment self-efficacy, while depressive symptoms were associated with lower HIV treatment self-efficacy. Depression, illicit substance use, and HIV treatment self-efficacy are potentially modifiable factors that can influence viral suppression. Implementation studies are needed to determine whether interventions to manage depression or self-efficacy and improve trust in health care providers will influence treatment outcomes.