A Systematic Review of Implementation Research on Determinants and Strategies of Effective HIV Interventions for Men Who Have Sex with Men in the United States.

Men who have sex with men (MSM) are disproportionately affected by HIV, accounting for two-thirds of HIV cases in the United States despite representing ∼5% of the adult population. Delivery and use of existing and highly effective HIV prevention and treatment strategies remain suboptimal among MSM. To summarize the state of the science, we systematically review implementation determinants and strategies of HIV-related health interventions using implementation science frameworks. Research on implementation barriers has focused predominantly on characteristics of individual recipients (e.g., ethnicity, age, drug use) and less so on deliverers (e.g., nurses, physicians), with little focus on system-level factors. Similarly, most strategies target recipients to influence their uptake and adherence, rather than improving and supporting implementation systems. HIV implementation research is burgeoning; future research is needed to broaden the examination of barriers at the provider and system levels, as well as expand knowledge on how to match strategies to barriers-particularly to address stigma. Collaboration and coordination among federal, state, and local public health agencies; community-based organizations; health care providers; and scientists are important for successful implementation of HIV-related health innovations.

Soil bacteria and fungi communities are shaped by elevation influences in Colombian forest and páramo natural ecosystems.

The influence of elevation on natural terrestrial ecosystems determines the arrangements of microbial communities in soils to be associated with biotic and abiotic factors. To evaluate changes of fungi and bacteria at the community level along an elevational gradient (between 1000 and 3800 m.a.s.l.), physicochemical measurements of soils, taxonomic identifications of plants, and metabarcoding sequences of the 16S rRNA gene for bacteria and the ITS1 region for fungi were obtained. The bacterial taxonomic composition showed that Acidobacteriota increased in abundance with elevation, while Actinobacteriota and Verrucomicrobiota decreased. Furthermore, Firmicutes and Proteobacteria maintained maximum levels of abundance at intermediate elevations (1200 and 2400 m.a.s.l.). In fungi, Ascomycota was more abundant at higher elevations, Basidiomycota tended to dominate at lower elevations, and Mortierellomycota had a greater presence at intermediate sites. These results correlated with the edaphic parameters of decreasing pH and increasing organic carbon and available nitrogen with elevation. In addition, the Shannon index found a greater diversity in bacteria than fungi, but both showed a unimodal pattern with maximum values in the Andean Forest at 2400 m.a.s.l. Through the microbial characterization of the ecosystems, the elevational gradient, soil properties, and vegetation were found to exert significant effects on microbial communities and alpha diversity indices. We conclude that the most abundant soil microorganisms at the sampling points differed in abundance and diversity according to the variations in factors influencing ecological communities.

Factors Associated with HIV Testing Among Spanish and English-Speaking Latino Adolescents Aged 13-18.

Adolescent Latino men who have sex with men (LMSM) in the U.S. are disproportionately impacted by HIV. However, there has been limited focus on their HIV prevention and risk behaviors. In this study, we examine the rates of HIV testing and explore the significant demographic and healthcare factors that influence HIV prevention among adolescent LMSM. The analysis for this study utilized data collected during the baseline assessment of SMART, a pragmatic trial aimed at evaluating the effectiveness of an online HIV prevention intervention for adolescent LMSM (N = 524). Only 35.5% of participants had ever had an HIV test in their lifetime. Rates of testing increased among adolescent LMSM who had a doctor with whom they spoke about their sexual health (odds ratio: 4.0; 95% confidence interval: 2.1-8.4; P < 0.001) or HIV testing (odds ratio: 5.8; 95% confidence interval: 3.1-10.7; P < 0.001). Out of the 61 participants who took part in the survey conducted in Spanish, only 26% reported ever having an HIV test. Additionally, 24.5% stated that they had discussed their sexual orientation with a doctor, and only 8.2% had undergone HIV testing. Spanish-speaking adolescents who completed the SMART survey were less likely to openly discuss their sexual orientation or sexual health with most people or have a doctor with whom they discussed these topics, compared to those who completed the survey in English. These findings suggest that Spanish-speaking adolescent LMSM may face obstacles in accessing HIV prevention services in the U.S.

RESUMEN: Los adolescentes latinos hombres que tienen sexo con otros hombres (LHSH) tienen mayor probabilidad de recibir tratamiento para el VIH más tarde en comparación con todos los casos nuevos del VIH en los Estados Unidos. Sin embargo, se ha estudiado muy poco sus prácticas de prevención de VIH o prácticas de riesgo, que similar a la de jóvenes no latinos, es determinada por múltiples factores. En este estudio describimos las tasas de pruebas para el VIH e identificamos los factores lingüísticos, individuales, familiares, escolares y de cuidado de salud que influencian a los adolescentes LHSH. Los datos provinieron de la evaluación inicial para SMART, un ensayo práctico de una intervención en línea para prevenir el VIH entre adolescentes LHSH (N = 524). Las medidas incluían la experiencia de hacerse la prueba del VIH a lo largo de la vida, factores de aculturación, datos demográficos, prácticas sexuales, educación sobre el VIH en la escuela y el hogar, comunicación sobre salud sexual con los médicos, conocimiento sobre el VIH y actitudes de riesgo. Solo 35.5% de los participantes se han realizado la prueba de VIH al menos una vez en su vida. La tasa de pruebas del VIH fue más alta entre los adolescentes LHSH que indicaron haber hablado con su médico sobre su salud sexual (odds ratio: 4.0; intervalo de confianza del 95%: 2.1­8.4; P < 0.001) o de la prueba del VIH (odds ratio: 5.8; intervalo de confianza del 95%: 3.1­10.7; P < 0.001). Más de 60 participantes completaron la encuesta en español. De estos, pocos reportaron alguna vez haberse hecho la prueba del HIV (26%), tener un médico con quien hablar sobre su orientación sexual (24.5%) o hablar sobre la prueba del VIH (8.2%). Estas cifras son significativamente más bajas que las obtenidas en la encuesta en inglés. Este estudio es uno de los primeros en evaluar los factores para hacerse la prueba del VIH entre adolescentes latinos que hablan inglés y español con edades entre 13 y 18 años. Los adolescentes latinos que completaron SMART en español tuvieron menos probabilidad de haber compartido sobre su orientación sexual con la mayoría de las personas o tener un médico con quien hablar sobre su orientación sexual o su salud sexual, en comparación con aquellos que completaron SMART en inglés, lo que sugiere que los jóvenes latinos que prefieren comunicarse en español pueden experimentar mayores barreras para acceder a los servicios de prevención del VIH en los Estados Unidos.

Barriers and Facilitators to Implementing Keep It Up!, A Digital Health Intervention, in Community-Based Organizations.

Despite ongoing investments in the development and testing of new digital interventions for HIV prevention, the widespread use of interventions with proven effectiveness remains limited. This study assessed real-world implementation of a digital HIV prevention intervention, Keep It Up!. The study aimed to identify barriers and facilitators to implementing Keep It Up! within community-based organizations (CBOs) serving racially diverse sexual and gender minoritized populations. The Keep It Up! trial is a type III effectiveness-implementation hybrid trial to compare two delivery approaches: direct-to-consumer and CBO-based implementation. This manuscript focuses on the CBO-based approach through interviews with CBO staff members before and during implementation (n = 37 and n = 25, respectively). Interviews were coded according to the Consolidated Framework for Implementation Research and thematically analyzed. Staff highlighted adaptability, leadership engagement, compatibility, and organizational culture as facilitators of Keep It Up! implementation. Identified barriers included self-efficacy, motivation, staff turnover, and partnerships and connections. CBO infrastructure, capacity, research experience, and processes influenced the relative importance of these barriers and facilitators. This study is one of the first to detail barriers and facilitators experienced by staff implementing a digital HIV prevention intervention in CBOs. Interviews illuminated the need for interventions like Keep It Up! for young men who have sex with men and detailed the need for additional strategies to assist CBOs unfamiliar with implementing digital health interventions. Trial Registration Number: NCT03896776.

RESUMEN: A pesar de a las inversiones hechas en el desarrollo y prueba de nuevas intervenciones digitales para prevenir el VIH, el uso generalizado de intervenciones eficaces aun es limitado. Este estudio evaluó la implementación en el mundo real de una intervención digital de prevención del VIH, Keep It Up!. El estudio identificó barreras y facilitadores para implementar Keep It Up! dentro de organizaciones comunitarias que atienden a personas minorizadas por género y sexualidad. El ensayo de Keep It Up! es un ensayo híbrido de efectividad-implementación de tipo III para comparar dos enfoques de entrega: implementación directa al consumidor e implementación en organizaciones comunitarias. Este manuscrito se centra en la implementación en organizaciones comunitarias a través de entrevistas con miembros del personal de las organizaciones antes y durante la implementación (n = 37 y n = 25, respectivamente). Las entrevistas se codificaron de acuerdo con el Marco Conceptual Consolidado para la Investigación de Implementación y se analizaron temáticamente. El personal destacó la adaptabilidad, el compromiso del liderazgo, la compatibilidad, y la cultura organizacional como facilitadores de la implementación de Keep It Up!. Las barreras identificadas incluyeron la autoeficacia, la motivación, la rotación de personal, y las asociaciones y conexiones. La infraestructura, capacidad, experiencia en investigación, y procesos de las organizaciones comunitarias influyeron en la importancia relativa de estas barreras y facilitadores. Este estudio es uno de los primeros en detallar las barreras y los facilitadores que experimenta el personal que implementa una intervención digital de prevención del VIH en las organizaciones comunitarias. Las entrevistas iluminaron la necesidad de intervenciones como Keep It Up! para hombres jóvenes que tienen sexo con hombres y detalló la necesidad de estrategias adicionales para ayudar a las organizaciones comunitarias que no están familiarizadas con la implementación de intervenciones de salud digitales.

Factors Influencing Engagement Across the Motivational PrEP Cascade Among Latino SMM: A Mixed-Methods Analysis from the Perspectives of Community Providers and Latino SMM.

Latino sexual minority men (SMM) are a highly vulnerable population to HIV, and while pre-exposure prophylaxis (PrEP) has emerged as a promising biomedical tool for HIV prevention among them, its utilization remains disproportionately low in this community despite its potential. Understanding the barriers along the PrEP continuum of care, known as the "PrEP cascade," is crucial for effectively implementing PrEP interventions. Therefore, the objective of our study was twofold: first, to explore the stage of Latino SMM in the PrEP cascade by examining disparities in demographics, social factors, and healthcare aspects; second, to gain insights from healthcare providers who have direct clinical experience with our population regarding the challenges faced by Latino SMM in accessing and adhering to PrEP. Based on the study findings, the majority of participants (n = 74; 49%) were in the contemplation stage, and only one in ten Latino SMM (10.6%) were currently adherent to PrEP. Compared to those who were at least second-generation, first-generation status had a positive association (B = 0.699, SE = 0.208, ß = 0.351, p < .001) with engagement along the PrEP Contemplation Ladder. Conversely, having at least one parent who did not have legal residency, relative to those whose parents were both U.S. citizens or held legal residency documentation, was found to have a negative association (B = - 0.689, SE = 0.245, ß = 0.245, p = .006) with engagement along the PrEP Contemplation Ladder. Additionally, discussing PrEP with a healthcare provider had a positive association (B = 0.374, SE = 0.179, ß = 0.185, p = .038) with engagement along the PrEP Contemplation Ladder. Qualitative results from our study suggest that some Latinos who initially agreed to start using PrEP ended up getting lost in the care pipeline and failed to attend their scheduled appointments. Providers also noted that many patients lacked access to a pharmacy where they felt comfortable obtaining their PrEP prescription, leading them to discontinue use after only a few months. These findings emphasize the importance of considering the unique needs, culture, and background of Latinos, including care delivery and provider attitudes that can facilitate progress through the PrEP cascade.

Improving Delivery and Use of HIV Pre-Exposure Prophylaxis in the US: A Systematic Review of Implementation Strategies and Adjunctive Interventions.

Implementation of pre-exposure prophylaxis (PrEP) to prevent HIV transmission is suboptimal in the United States. To date, the literature has focused on identifying determinants of PrEP use, with a lesser focus on developing and testing change methods to improve PrEP implementation. Moreover, the change methods available for improving the uptake and sustained use of PrEP have not been systematically categorized. To summarize the state of the literature, we conducted a systematic review of the implementation strategies used to improve PrEP implementation among delivery systems and providers, as well as the adjunctive interventions used to improve the uptake and persistent adherence to PrEP among patients. Between November 2020 and January 2021, we searched Ovid MEDLINE, PsycINFO, and Web of Science for peer reviewed articles. We identified 44 change methods (18 implementation strategies and 26 adjunctive interventions) across a variety of clinical and community-based service settings. We coded implementation strategies and adjunctive interventions in accordance with established taxonomies and reporting guidelines. Most studies focused on improving patient adherence to PrEP and most conducted pilot trials. Just over one-third of included studies demonstrated a positive effect on outcomes. In order to end the human immunodeficiency virus (HIV) epidemic in the U.S., future, large scale HIV prevention research is needed that develops and evaluates implementation strategies and adjunctive interventions for target populations disproportionately affected by HIV.

Application of real-time PCR for the identification of the endangered species Galemys pyrenaicus through faecal samples.

BACKGROUND: Currently, many micromammals are important targets for study. The endangered Galemys pyrenaicus is an outstanding example. Globally, their populations have suffered a substantial decline in last 20 years. In the surveyed area, the capture of desman is legally forbidden due to the high conservation concerns. Reason by non-invasive sampling through faeces is proposed for its monitoring. Furthermore, the confusion between faeces from desman and Mediterranean water shrews must be considered. Thus, the aim of this study was focused on developing RT-PCR assays to determine the presence of Galemys pyrenaicus and N. a. anomalus from non-invasive samples. METHODS AND RESULTS: The study was conducted in the mountains of the System Central of Extremadura (Spain). A total of 186 samples were collected from 2018 to 2021 by experts where historically reported and/or our previous studies confirmed their presence. RT-PCR assays using hydrolysis probes were designed to detect genetic material from both desman and Mediterranean water shrews and its specificity was confirmed. The reliability of the method was further assessed by PCR sequencing of mitochondrial Cyb and d-loop, resulting fully compatible with the RT-PCR approach. Intraspecific phylogenetic relationship was reported to improve knowledge about mtDNA variability in the desman from the Central System. CONCLUSIONS: We demonstrated that RT-PCR gives a gold opportunity to further map the species using faeces which minimizes disturbance and reports both population status and individual presence. Cost-effective RT-PCR combined with field-collected faeces allows us to better investigate the full range of occurrence of the species.

The Impact of Sibling Relationships on Behavioral and Sexual Health among Latino Sexual Minority Men.

Pre-exposure prophylaxis (PrEP) is a highly effective method for preventing HIV acquisition and plays a crucial role in the Ending the HIV Epidemic in the US initiative. However, there are various barriers that hinder the access and uptake of PrEP among Latino sexual minority men (SMM) at individual, interpersonal, and cultural levels. While the significance of cultural factors in designing and implementing HIV prevention programs for Latino populations has been consistently emphasized in the literature and prioritized by the Centers for Disease Control and Prevention, few studies have directly integrated these cultural factors into their programs. Our study aimed to investigate the potential influence of siblings in promoting the utilization of PrEP for HIV prevention, an area that has received limited attention. We conducted interviews with 31 pairs of siblings between December 2020 and January 2021, which were held in either English or Spanish and lasted approximately 45-60 min. The data were analyzed using a deductive thematic content analysis approach. The interviews revealed several key themes and categories, including: (1) Sibling support for coming out; (2) Types of support that siblings provide to each other for behavior change; (3) Sibling support for PrEP; and (4) The impact of the study interview on the quality of the sibling relationships. Our findings indicated that siblings were willing to provide support for PrEP in various ways, ranging from emotional support for brothers who may be concerned about potential rejection to practical support such as transportation or financial assistance. These results have significant implications for the design of HIV prevention interventions for Latinos. Incorporating siblings or other extended family members into these interventions can facilitate communication between siblings and their brothers, ultimately encouraging the use of PrEP or similar prevention methods. By considering the unique dynamics and support systems within Latino communities, researchers can develop more effective strategies to promote HIV prevention and support the well-being of Latino SMM.

Practices for Promoting Affirming Health Care for Transgender and Gender Diverse Youth.

Transgender and gender diverse (TGD) youth, particularly transgender youth of color, experience barriers to most, if not all, types of care across the United States. Consequently, clinicians are concerned about the increase of anti-transgender policies in the United States, with many states now restricting gender-affirming care. In this manuscript, we suggest several empirically based techniques to provide quality clinical care. We also share resources to support TGD youth and their families, while accommodating for some of these newer restrictions on the care that clinicians are able to provide. Ongoing training and awareness in these techniques will allow clinicians and their health care institutions to more effectively and immediately respond to anti-transgender policies and be able to provide care. By continuing to advocate for some of these strategies, there is potential to reduce the health inequities that many TGD youth experience. Prioritizing screening for gender discrimination, creating a safe space for TGD youth, and providing immediate clinical strategies to reduce distress can reduce symptoms of depression and suicide. These changes, albeit small, will allow clinicians to feel more comfortable providing gender affirming care through holistic changes in clinical practices and care.

COVID-19-Related Disruptions to HIV Testing and Prevention Among Young Sexual Minority Men 17-24 Years Old: A Qualitative Study Using Synchronous Online Focus Groups, April-September 2020.

Prior research has highlighted the impact of the COVID-19 pandemic on HIV prevention services within the U.S., but few studies have explored this impact through an exploratory, qualitative lens. In this study, we sought to highlight the voices of young sexual minority men (YSMM) 17-24 years old and explored the perceived impact of the pandemic on HIV prevention among a diverse, nationwide sample of YSMM who participated in synchronous online focus group discussions between April and September 2020. Forty-one YSMM described the negative effects of the COVID-19 pandemic on HIV testing and prevention services, including limited and disrupted access to HIV testing, HIV pre-exposure prophylaxis (PrEP), and HIV post-exposure prophylaxis. COVID-19-related challenges were compounded by ongoing, pre-COVID-19 barriers experienced by YSMM in the U.S. For instance, many YSMM relocated back home with family, causing men to avoid HIV prevention services for fear of outing themselves to relatives. YSMM also worried about placing their family at increased risk of COVID-19 by attending clinical appointments. YSMM who did seek HIV prevention services, including access to PrEP, experienced significant barriers, including limited appointment availability and services not tailored to YSMM. Further efforts are needed to support YSMM re-engaging in HIV prevention during and after the COVID-19 era.

Sono-Enzymatically Embedded Antibacterial Silver-Lignin Nanoparticles on Cork Filter Material for Water Disinfection.

Providing clean drinking water is a great challenge worldwide, especially for low-income countries where the access to safe water is limited. During the last decade, new biotechnological approaches have been explored to improve water management. Among them, the use of antimicrobial nanoparticles for designing innovative centralized and decentralized (point-of-use) water treatment systems for microbial decontamination has received considerable attention. Herein, antimicrobial lignin capped silver nanoparticles (AgLNP) were embedded on residual cork pieces using high-intensity ultrasound coupled with laccase-mediated grafting to obtain biofunctionalized nanomaterial. The developed AgLNP-coated cork proved to be highly efficient to drastically reduce the number of viable Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus in liquid medium. Additionally, the coated-cork was characterized using FTIR-ATR spectroscopy and SEM imaging, and further used as a filter bed in a point-of-use device for water disinfection. The constructed water filtering system significantly reduced the amount of viable E. coli and resistant Bacillus cereus spores from filtered water operating at increasing residence times of 1, 4, 6, 16, 24, and 48 h. Therefore, the presented results prove that the obtained cork-based antimicrobial nanocomposite material could be used as a filtering medium for the development of water filtration system to control pathogen dissemination.

Chest pain and acute coronary syndrome in octogenarians admitted to the Emergency Department.

BACKGROUND: Although chest pain and acute coronary syndrome (ACS) are among the most common complaints in the Emergency Departments (ED), little is known about this topic in the octogenarian population. OBJECTIVES: This study aimed to describe the clinical presentation and to evaluate survival time according to the ACS type in a group of 80-year-old or over patients admitted for chest pain to an ED. METHODS: Patients were classified according to the discharge diagnosis. A multivariable Cox regression analysis was done to assess the association between ACS type and mortality with the non-ACS chest pain group as the reference category. RESULTS: ACS was diagnosed in 170 of the 391 patients analyzed and 51% of ACS patients were female. Within the ACS patients, 18.8% presented STEMI, 57% NSTEMI, and 24% unstable angina (UA). Most of the patients were treated conservatively. In the adjusted analysis, the incidence of death at 40 months of follow-up was higher in patients with STEMI (HR 3.24; CI 1.59-6.56) than NSTEMI (HR 2.53; CI 1.56-4.11). There was no difference between patients with UA and the non-ACS group (HR 0.64; CI 0.26-1.58), and myocardial revascularization was associated with reduced mortality risk (HR 0.45; CI 0.22-0.92). CONCLUSIONS: A high prevalence of ACS was found among octogenarians admitted to the ED with chest pain, and the ACS type behaved as an independent predictor of mortality. Patients with UA diagnosis had a similar prognosis to patients with non-ACS chest pain, but this needs to be demonstrated by a prospective study.

A Taxonomy of Food Supply Chain Problems from a Computational Intelligence Perspective.

In the last few years, the Internet of Things, and other enabling technologies, have been progressively used for digitizing Food Supply Chains (FSC). These and other digitalization-enabling technologies are generating a massive amount of data with enormous potential to manage supply chains more efficiently and sustainably. Nevertheless, the intricate patterns and complexity embedded in large volumes of data present a challenge for systematic human expert analysis. In such a data-driven context, Computational Intelligence (CI) has achieved significant momentum to analyze, mine, and extract the underlying data information, or solve complex optimization problems, striking a balance between productive efficiency and sustainability of food supply systems. Although some recent studies have sorted the CI literature in this field, they are mainly oriented towards a single family of CI methods (a group of methods that share common characteristics) and review their application in specific FSC stages. As such, there is a gap in identifying and classifying FSC problems from a broader perspective, encompassing the various families of CI methods that can be applied in different stages (from production to retailing) and identifying the problems that arise in these stages from a CI perspective. This paper presents a new and comprehensive taxonomy of FSC problems (associated with agriculture, fish farming, and livestock) from a CI approach; that is, it defines FSC problems (from production to retail) and categorizes them based on how they can be modeled from a CI point of view. Furthermore, we review the CI approaches that are more commonly used in each stage of the FSC and in their corresponding categories of problems. We also introduce a set of guidelines to help FSC researchers and practitioners to decide on suitable families of methods when addressing any particular problems they might encounter. Finally, based on the proposed taxonomy, we identify and discuss challenges and research opportunities that the community should explore to enhance the contributions that CI can bring to the digitization of the FSC.

A Bibliometric Analysis and Benchmark of Machine Learning and AutoML in Crash Severity Prediction: The Case Study of Three Colombian Cities.

Traffic accidents are of worldwide concern, as they are one of the leading causes of death globally. One policy designed to cope with them is the design and deployment of road safety systems. These aim to predict crashes based on historical records, provided by new Internet of Things (IoT) technologies, to enhance traffic flow management and promote safer roads. Increasing data availability has helped machine learning (ML) to address the prediction of crashes and their severity. The literature reports numerous contributions regarding survey papers, experimental comparisons of various techniques, and the design of new methods at the point where crash severity prediction (CSP) and ML converge. Despite such progress, and as far as we know, there are no comprehensive research articles that theoretically and practically approach the model selection problem (MSP) in CSP. Thus, this paper introduces a bibliometric analysis and experimental benchmark of ML and automated machine learning (AutoML) as a suitable approach to automatically address the MSP in CSP. Firstly, 2318 bibliographic references were consulted to identify relevant authors, trending topics, keywords evolution, and the most common ML methods used in related-case studies, which revealed an opportunity for the use AutoML in the transportation field. Then, we compared AutoML (AutoGluon, Auto-sklearn, TPOT) and ML (CatBoost, Decision Tree, Extra Trees, Gradient Boosting, Gaussian Naive Bayes, Light Gradient Boosting Machine, Random Forest) methods in three case studies using open data portals belonging to the cities of Medellín, Bogotá, and Bucaramanga in Colombia. Our experimentation reveals that AutoGluon and CatBoost are competitive and robust ML approaches to deal with various CSP problems. In addition, we concluded that general-purpose AutoML effectively supports the MSP in CSP without developing domain-focused AutoML methods for this supervised learning problem. Finally, based on the results obtained, we introduce challenges and research opportunities that the community should explore to enhance the contributions that ML and AutoML can bring to CSP and other transportation areas.

The HIV-1 Antisense Protein ASP Is a Transmembrane Protein of the Cell Surface and an Integral Protein of the Viral Envelope.

The negative strand of HIV-1 encodes a highly hydrophobic antisense protein (ASP) with no known homologs. The presence of humoral and cellular immune responses to ASP in HIV-1 patients indicates that ASP is expressed in vivo, but its role in HIV-1 replication remains unknown. We investigated ASP expression in multiple chronically infected myeloid and lymphoid cell lines using an anti-ASP monoclonal antibody (324.6) in combination with flow cytometry and microscopy approaches. At baseline and in the absence of stimuli, ASP shows polarized subnuclear distribution, preferentially in areas with low content of suppressive epigenetic marks. However, following treatment with phorbol 12-myristate 13-acetate (PMA), ASP translocates to the cytoplasm and is detectable on the cell surface, even in the absence of membrane permeabilization, indicating that 324.6 recognizes an ASP epitope that is exposed extracellularly. Further, surface staining with 324.6 and anti-gp120 antibodies showed that ASP and gp120 colocalize, suggesting that ASP might become incorporated in the membranes of budding virions. Indeed, fluorescence correlation spectroscopy studies showed binding of 324.6 to cell-free HIV-1 particles. Moreover, 324.6 was able to capture and retain HIV-1 virions with efficiency similar to that of the anti-gp120 antibody VRC01. Our studies indicate that ASP is an integral protein of the plasma membranes of chronically infected cells stimulated with PMA, and upon viral budding, ASP becomes a structural protein of the HIV-1 envelope. These results may provide leads to investigate the possible role of ASP in the virus replication cycle and suggest that ASP may represent a new therapeutic or vaccine target.IMPORTANCE The HIV-1 genome contains a gene expressed in the opposite, or antisense, direction to all other genes. The protein product of this antisense gene, called ASP, is poorly characterized, and its role in viral replication remains unknown. We provide evidence that the antisense protein, ASP, of HIV-1 is found within the cell nucleus in unstimulated cells. In addition, we show that after PMA treatment, ASP exits the nucleus and localizes on the cell membrane. Moreover, we demonstrate that ASP is present on the surfaces of viral particles. Altogether, our studies identify ASP as a new structural component of HIV-1 and show that ASP is an accessory protein that promotes viral replication. The presence of ASP on the surfaces of both infected cells and viral particles might be exploited therapeutically.

Computation of Dipole Moments: A Recommendation on the Choice of the Basis Set and the Level of Theory.

Together with experimental data, theoretically predicted dipole moments represent a valuable tool for different branches in the chemical and physical sciences. With the diversity of levels of theory and basis sets available, a reliable combination must be carefully chosen in order to achieve accurate predictions. In a recent publication (J. Chem. Theory Comput. 2018, 14 (4), 1969-1981), Hait and Head-Gordon took a first step in this regard by providing recommendations on the best density functionals suitable for these purposes. However, no extensive study has been performed to provide recommendations on the basis set choice. Here, we shed some light into this matter by evaluating the performance of 38 general-purpose basis sets of single- up to triple-ζ-quality, when coupled with nine different levels of theory, in the computation of dipole moments. The calculations were performed on a data set with 114 small molecules containing second- and third-row elements. We based our analysis in regularized root-mean-square errors (regularized RMSE), in which the difference between the calculated µcalc and benchmark µbmk dipole moment values is derived as (µcalc[D] - µbmk[D])/(max(µbmk[D],1[D])). This procedure ensures relative errors for ionic species and absolute errors for species with small dipole moment values. Our results indicate that the best compromise between accuracy and computational efficiency is achieved by performing the computations with an augmented double-ζ-quality basis set (i.e., aug-pc-1, aug-pcseg-1, aug-cc-pVDZ) together with a hybrid functional (e.g., ωB97X-V, SOGGA11-X). Augmented triple-ζ basis sets could enhance the accuracy of the computations, but the computational cost of introducing such a basis set is substantial compared with the small improvement provided. These findings also highlight the crucial role that augmentation of the basis set with diffuse functions on both hydrogen and non-hydrogen atoms plays in the computation of dipole moments.

Nonparametric Population Pharmacokinetic Modeling of Isoniazid in Colombian Patients With Tuberculosis.

BACKGROUND: Isoniazid (INH) is a first-line antituberculosis (TB) agent with a pharmacokinetic profile characterized by high interindividual variation; however, population pharmacokinetic studies in patients with TB are scarce. The aim was to develop a population model for INH in Colombian patients with TB suitable for predicting drug exposure and assessing the probability of target attainment of pharmacodynamic goals. METHODS: Ten hospitalized adult patients with TB undergoing INH treatment were recruited. After an 8-hour fasting, subjects took 300 mg of INH, and 10 samples were taken from 0 to 12 hours. INH was quantified by high-performance liquid chromatography-UV, and data were analyzed with the Pmetrics R package software. A Monte Carlo simulation with the model parameters was run to determine the probability of target attainment for optimal efficacy. RESULTS: The best model included 2 compartments, first-order absorption (Ka), delayed absorption (Tlag), and linear clearance (CL). Median Tlag was 0.25 hours, 5.54 hour for Ka, (Equation is included in full-text article.)for CL, (Equation is included in full-text article.)for the volume of the central compartment (Vc), 1.04 L/h for intercompartmental clearance (Q), and 788 L for the volume of the peripheral compartment (Vp). CL and Vc were allometrically scaled on basis of the normalized body weight. CONCLUSIONS: The Monte Carlo simulation indicated that 300 mg of INH per day is appropriate for Mycobacterium tuberculosis strains with minimal inhibitory concentration (MIC) up to 0.03 mg/L (target: area under the concentration-time curve/MIC >597); however, to cover strains with MIC up to 0.125 mg/L (80% of clinical isolates), a dose of 900 mg per day would be required.

Selenium impedes cadmium and arsenic toxicity in potato by modulating carbohydrate and nitrogen metabolism.

Past studies have already determined that selenium (Se) is very effective in alleviating cell oxidative damage caused by various abiotic stresses in plants. Past studies have also indicated other physiological pathways by which Se may benefit plants. In order to better understand the full array of potential applications for Se in agriculture, this study investigated the influence of Se on carbohydrate and nitrogen (N) metabolism in potato plants (Solanum tuberosum L. cv. Sante) grown under cadmium (Cd) and/or arsenic (As) toxicity. Potato plants were grown in a growth chamber and fertigated with Hoagland nutrient solution with or without Se (9 µM). After 48-d of growth under Cd (40 µM) and/or As (40 µM) stress, carbohydrate and N metabolism in leaves, roots and stolons were measured. For carbohydrate metabolism, various sugars-i.e., sucrose, starch, glucose, fructose, and total soluble sugar contents (TSSC)-and the activities of enzymes associated with sucrose metabolism and glycolysis-i.e., acid invertase (AI), neutral invertase (NI), sucrose-synthetase (SS), sucrose phosphatesynthetase (SPS), fructokinase (FK), hexokinase (HK), phosphofructokinase (PFK), and pyruvatekinase (PK)-were measured. For N metabolism, NO3-, NO2- and NH4+ contents along with the enzymatic activities of nitrate reductase (NRA), nitrite reductase (NiRA), glutamine-synthetase (GS), and glutamate-synthetase (GOGAT) were measured. Overall, Cd and/or As treatments had reduced plant growth relative to those plants grown without heavy metal toxicity, due to hindered photosynthesis and alterations in N metabolism and glycolysis. Regarding N metabolism, heavy metal toxicity caused a reduction in NO3- and NO2- content and NRA and NiRA enzymatic activity and enhanced NH4+ content and GDH activity in leaves, roots and stolons. Regarding glycolysis, the activity of enzymes of glycolysis-i.e., FK, HK, PFK, and PK-were also reduced. In the C metabolism study, plants combatted Cd and As toxicity naturally by an adaptation mechanism which caused an increase in soluble sugars (fructose, glucose, sucrose) by increasing NI, SS and SSP enzymatic activity. Supplementation with Se in the Cd and/or As treatments in the carbohydrate and N metabolism studies improved plant growth. Selenium supplementation in the Cd and As treatments decreased Cd and/or As content in the plant tissue and alleviating the Cd- and/or As-induced toxicity by enhancing the C-metabolism adaptation mechanism. Applying Se to Cd and As treatments also decreased nitrogen losses by hindering Cd- and As-induced changes in the N-metabolism. Se also limited Cd and As accumulation in the plant tissue by the antagonistic effect between Cd/Se and As/Se in the roots. The results of this study indicate that in the presence of Cd and/or As. soil toxicity, Se may be a powerful tool for promoting plant growth.

Arbuscular mycorrhizal symbiosis improves tolerance of Carrizo citrange to excess boron supply by reducing leaf B concentration and toxicity in the leaves and roots.

This study explores the possibility of using mycorrhization as a novel technique for diminishing the negative effects of boron (B) in the nutrient solution on seedlings of Carrizo citrange rootstock plants. For this, an experiment was planned for studying the physiological (gas exchange and chlorophyll fluorescence parameters), morphological (vegetative growth parameters), nutritional (organic solutes, carbohydrates) and oxidative stress responses of seedlings that were either mycorrhized (+AM, Rhizophagus irregularis; previously known as Glomus intraradices) or not mycorrhized (-AM), and irrigated with water containing different concentrations of B (0.5, 5 and 10 mg L-1). It was observed that an excess of B in the nutrient solution decreased the vegetative growth in both +AM and -AM plants, but this decrease was greater in -AM plants. Mycorrhized plants (+AM) under high B concentration accumulated less B in the leaves, and had a smaller reduction of net assimilation rate of CO2 and lower MDA concentration than non-mycorrhized plants. Thus, it can be concluded that mycorrhization increased the tolerance to high boron concentration in the irrigation water of citrange Carrizo seedlings by reducing both the B concentration in the plant tissue and the B toxicity in the physiological processes. The study of organic solutes and carbohydrates also pointed to a different response model between +AM and -AM plants that could be related to the different tolerance observed between these plants.

Impact of an educational initiative targeting non-radiologist staff on overall notification times of critical findings in radiology.

INTRODUCTION: The timely reporting of critical findings is considered by the Joint Commission as one of the main patient safety goals. Delays in critical radiological findings communication are directly related to delayed treatment initiation and death, constituting a major cause of medical malpractice suits. The aim of this study was to evaluate the impact of an educational initiative performed to reduce the notification times of critical radiological findings. MATERIALS AND METHODS: All records of critical findings reported in the Radiology Department were evaluated. The notification times before and after performing the educational intervention taking into account the patient type, study, and critical diagnosis were calculated, evaluated, and compared. T test and chi-square test were used for statistical analysis, considering a p value less than 0.05 to indicate statistically significant differences. RESULTS: We included 1949 reports, 805 before (41.3%) and 1144 (58.7%) after the intervention. Before the intervention, the mean time of critical finding report was 2.85 h for emergency patients and 3.07 h for hospitalized patients. After the intervention, a statistically significant decrease in the notification time was observed with a mean of 1.37 h for emergency patients and 2.43 h in the hospitalization patients. A statistically significant increase was observed in the proportion of reported findings in less than 15 min (7.08%, p < 0.01), 45 min (45.55%, p < 0.01), 60 min (55.86%, p < 0.01), and 120 min (80.68%, p < 0.01). CONCLUSION: The healthcare process in the Department of Radiology involves multiple actors who must be sensitized in the identification and reporting of critical radiological findings in order to reduce the notification times. Ensuring effective communication of critical findings is indispensable to ensure timely medical treatment.