Assessing HIV Risk, Syndemics, Resilience and Engagement in Care in a Large National Cohort of Gay, Bisexual and Other Men Who Have Sex With Men in the United States

Background: HIV continues to be a pervasive public health issue in the United States with more than 1.2 million people living with HIV (PLWHIV) across the nation. Gay, bisexual and other men who have sex with men (GBM) account for over two-thirds of all new HIV diagnoses with racial and ethnic minorities shouldering a large proportion of the burden of disease. Although HIV transmission is predominantly driven by sexual behaviors, there are underlying complex individual, behavioral, and structural factors that contribute to high rates of sexual behavior and subsequent HIV acquisition. Moreover, difficulties remain in maximizing linkage to care and viral suppression for PLWHIV. Despite the wealth of research showing the importance of viral suppression as a tool for controlling the HIV epidemic, over one-quarter of HIV-positive GBM are not fully engaged in HIV primary medical care; Sexual minority populations of color experience starkly worse rates of engagement in HIV care. This multi-method dissertation aimed to understand how multi-level factors compound HIV risk in a U.S. national sample of GBM and to describe engagement in HIV care among those newly diagnosed with HIV. The following specific aims were addressed: Aim 1: Measure exposure to syndemic conditions, describe the conditions most likely to co-occur and examine their association to HIV risk. Aim 2: Describe the levels of resilience and identify associations with HIV risk and conduct comparisons by race/ethnicity, region, age and other socio-demographic characteristics. Aim 3: Describe the barriers and facilitators to engagement in prompt HIV care 3-months after the delivery of an HIV-positive result. Methods: Data for this study was collected as part of the Together 5,000 study, a U.S. national, internet-based cohort study of men, transgender men, and transgender women who have sex with men. For Aims 1 and 2, we conducted secondary analysis of quantitative survey data from a cohort of 6,118 GBM ages 16-49 at high risk for HIV transmission. The surveys gathered data on demographics, HIV risk behaviors, HIV and STI testing history, mental health, and interpersonal factors. For Aim 1, we evaluated the prevalence of syndemic conditions and explored their associations with HIV risk. Descriptive statistics were used to describe the sample and the prevalence of syndemic conditions. The associations were determined using adjusted multiple linear regressions. For Aim 2, we measured and described the sociodemographic differences in levels of resilience and explored the association between resilience and HIV risk. The associations were determined using adjusted multiple linear regressions. For aim 3, we conducted secondary analysis of qualitative in-depth interviews from 50 GBM diagnosed HIV-positive during their participation in Together 5,000. The goal of Aim 3 was to described participants experiences getting linked-to-care and identify barriers and facilitators to engagement in HIV care using thematic analysis. Results: In Aim 1 we found a high prevalence of intimate partner violence (IPV), experiences of childhood sexual abuse, homelessness and mental health issues. Further, IPV, depression, polydrug use, incarceration history and homelessness were positively associated with HIV risk. We also demonstrated that increasing cumulative syndemic conditions were associated with higher HIV risk. Those who reported 3 or more co-occurring conditions had the highest risk for HIV. In Aim 2, we found higher mean resilience scores among those identifying as black, with higher education, having full-time employment, higher incomes, and those who have health insurance. Although we found no statistically significant association between resilience and our composite measure of HIV risk, we did find a significant association between higher resilience and lower condomless receptive anal sex acts in the last 3 months. In Aim 3, we found that the majority of participants reported being linked-to-care, while only 74.5% of those reported initiating ART. Thematic analysis identified 4 major themes related to participants’ engagement in care: 1) Reasons for HIV testing (e.g., HIV self-testing and expectation of positivity), 2) Linkage-to-care (e.g., appointment/logistic issues and social support as encouragement), 3) Barriers (e.g., financial burden, competing priorities and fear/stigma) and facilitators (e.g., financial assistance, patient-provider relationships, auxiliary support services and health agency) to engagement in HIV care, and 4) PrEP as a missed prevention opportunity. Conclusion: Overall, the findings from this multi-method dissertation suggest that the HIV epidemic is complex, and therefore an effective response requires an understanding of the diversity and dynamic nature of individuals, communities, and our socio-political environment. We demonstrated that environmental and behavioral factors such as homelessness, incarceration are prevalent among GBM in the U.S. and contribute to HIV acquisition, thus offering compelling evidence for the adoption of these variables in future syndemic models. Further, there needs to be a more comprehensive investigation of the unique risk factors in this population, particularly those that may impact uptake and adoption of preventive HIV health behaviors, such as pre-exposure prophylaxis (PrEP). For instance, larger structural factors like societal racial discrimination, anti-immigration laws, lack of health insurance coverage and unemployment can significantly impact adherence to biomedical tools and use of testing services. Future research should explore these social and structural determinants within the context of HIV prevention. There is a need for targeted interventions for those at the highest risk, particularly racial and ethnic minorities and those from impoverished communities to increase HIV testing frequency and facilitate better engagement in care. Further, as seen in our study findings, HIV prevention is a multi-faceted process. As such, there is a need for a more holistic approach to prevention, wherein HIV prevention is conceptualized as more than just HIV testing and PrEP initiation but that takes into account intrapersonal (e.g,, resilience) and interpersonal factors (e.g., social support). Finally, addressing policy-, social- and individual-level barriers could improve GBM’s engagement in HIV care. Capitalizing on GBM’s health agency through partnerships with local agencies and fostering better patient-provider relationships could optimize continuity of HIV care. We possess the tools needed to end the HIV epidemic in the U.S., particularly by advocating for a new federal policy which streamlines HIV testing, linkage-to-care and ART initiation

(Un)Suitability of Anonymous Communication Systems to WSN

Abstract Anonymous communication systems have been extensively studied by the research community to prevent the disclosure of sensitive information from the analysis of individuals' traffic patterns. Many remarkable solutions have been developed in this area, most of which have proven to be effective in the protection of user privacy against different types of attacks. Recently, the privacy preservation problem has also been considered in the realm of wireless sensor networks (WSNs) due to their imminent adoption in real-world scenarios. A special challenge that arises from the analysis of the flow of sensor nodes' communications is the location privacy problem. In this work we concentrate on analyzing the suitability of traditional anonymous communication systems originally designed for the Internet to the original scenario of sensor networks. The results show that, in most cases, traditional solutions do not provide the adequate protection means for the particular problem of location privacy, while other solutions are too resource-consuming for the restricted capabilities of sensor nodes

The Netrin-related domain of Sfrp1 interacts with Wnt ligands and antagonizes their activity in the anterior neural plate

<p>Abstract</p> <p>Background</p> <p>Secreted frizzled related proteins (SFRPs) are multifunctional modulators of Wnt and BMP (Bone Morphogenetic Protein) signalling necessary for the development of most organs and the homeostasis of different adult tissues. SFRPs fold in two independent domains: the cysteine rich domain (Sfrp_CRD) related to the extracellular portion of Frizzled (Fz, Wnt receptors) and the Netrin module (Sfrp_NTR) defined by homologies with molecules such as Netrin-1, inhibitors of metalloproteinases and complement proteins. Due to its structural relationship with Fz, it is believed that Sfrp_CRDinterferes with Wnt signalling by binding and sequestering the ligand. In contrast, the functional relevance of the Sfrp_NTRhas been barely addressed.</p> <p>Results</p> <p>Here, we combine biochemical studies, mutational analysis and functional assays in cell culture and medaka-fish embryos to show that the Sfrp1_NTRmimics the function of the entire molecule, binds to Wnt8 and antagonizes Wnt canonical signalling. This activity requires intact tertiary structure and is shared by the distantly related Netrin-1_NTR. In contrast, the Sfrp1_CRDcannot mirror the function of the entire molecule <it>in vivo </it>but interacts with Fz receptors and antagonizes Wnt8-mediated β-catenin transcriptional activity.</p> <p>Conclusion</p> <p>On the basis of these results, we propose that SFRP modulation of Wnt signalling may involve multiple and differential interactions among Wnt, Fz and SFRPs.</p

PRoFIT: Modelo forense-IoT con integración de requisitos de privacidad

[ES] La Internet de las cosas (IoT) complica sobremanera la extracción de evidencias electrónicas que pueden servir de base para una investigación forense. En entornos altamente cambiantes y con una densidad de dispositivos tan elevada, es muy difícil entender completamente el contexto de la ofensa. Es por ello que la cooperación de los individuos, aún no estando directamente implicados en la ofensa, puede ser muy relevante para el analista forense. En este artículo se propone un nuevo modelo para la IoT-Forensics, que pretende sentar las bases para la cooperación voluntaria de los individuos en las investigaciones de delitos telemáticos. Para ello, el modelo integra requisitos de privacidad de la norma ISO/IEC 29100:2011 durante todo el ciclo de vida de la investigaciónEste trabajo ha sido financiado por la Junta de Andalucía a través del proyecto FISICCO (TIC-07223), y por el Ministerio de Economía y Competitividad a través de los proyectos SMOG (TIN2016-79095-C2-1-R) e IoTest (TIN2015-72634-EXP).Nieto, A.; Rios, R.; Lopez, J. (2018). PRoFIT: Modelo forense-IoT con integración de requisitos de privacidad. En XIII Jornadas de Ingeniería telemática (JITEL 2018). Libro de actas. Editorial Universitat Politècnica de València. 302-309. https://doi.org/10.4995/JITEL2017.2017.6449OCS30230

Human intronic enhancers control distinct sub-domains of Gli3 expression during mouse CNS and limb development

<p>Abstract</p> <p>Background</p> <p>The zinc-finger transcription factor GLI3 is an important mediator of Sonic hedgehog signaling and crucial for patterning of many aspects of the vertebrate body plan. In vertebrates, the mechanism of SHH signal transduction and its action on target genes by means of activating or repressing forms of GLI3 have been studied most extensively during limb development and the specification of the central nervous system. From these studies it has emerged, that <it>Gli3 </it>expression must be subject to a tight spatiotemporal regulation. However, the genetic mechanisms and the cis-acting elements controlling the expression of <it>Gli3 </it>remained largely unknown.</p> <p>Results</p> <p>Here, we demonstrate in chicken and mouse transgenic embryos that human <it>GLI3</it>-intronic conserved non-coding sequence elements (CNEs) autonomously control individual aspects of <it>Gli3 </it>expression. Their combined action shows many aspects of a <it>Gli3</it>-specific pattern of transcriptional activity. In the mouse limb bud, different CNEs enhance <it>Gli3</it>-specific expression in evolutionary ancient stylopod and zeugopod versus modern skeletal structures of the autopod. Limb bud specificity is also found in chicken but had not been detected in zebrafish embryos. Three of these elements govern central nervous system specific gene expression during mouse embryogenesis, each targeting a subset of endogenous <it>Gli3 </it>transcription sites. Even though fish, birds, and mammals share an ancient repertoire of gene regulatory elements within <it>Gli3</it>, the functions of individual enhancers from this catalog have diverged significantly. During evolution, ancient broad-range regulatory elements within <it>Gli3 </it>attained higher specificity, critical for patterning of more specialized structures, by abolishing the potential for redundant expression control.</p> <p>Conclusion</p> <p>These results not only demonstrate the high level of complexity in the genetic mechanisms controlling <it>Gli3 </it>expression, but also reveal the evolutionary significance of <it>cis</it>-acting regulatory networks of early developmental regulators in vertebrates.</p

The cis-regulatory architecture of a gene desert controlling pleiotropic Shox2 expression and cardiac pacemaker development

Trabajo presentado en Weinstein Meeting, celebrado en Marsella (Francia) del 12 al 14 de mayo de 2022

Spatial regulation by multiple Gremlin1 enhancers provides digit development with cis-regulatory robustness and evolutionary plasticity.

Precise cis-regulatory control of gene expression is essential for normal embryogenesis and tissue development. The BMP antagonist Gremlin1 (Grem1) is a key node in the signalling system that coordinately controls limb bud development. Here, we use mouse reverse genetics to identify the enhancers in the Grem1 genomic landscape and the underlying cis-regulatory logics that orchestrate the spatio-temporal Grem1 expression dynamics during limb bud development. We establish that transcript levels are controlled in an additive manner while spatial regulation requires synergistic interactions among multiple enhancers. Disrupting these interactions shows that altered spatial regulation rather than reduced Grem1 transcript levels prefigures digit fusions and loss. Two of the enhancers are evolutionary ancient and highly conserved from basal fishes to mammals. Analysing these enhancers from different species reveal the substantial spatial plasticity in Grem1 regulation in tetrapods and basal fishes, which provides insights into the fin-to-limb transition and evolutionary diversification of pentadactyl limbs

Methods for epidemiological studies in competitive cycling:an extension of the IOC consensus statement on methods for recording and reporting of epidemiological data on injury and illness in sport 2020

In 2020, the IOC released a consensus statement that provides overall guidelines for the recording and reporting of epidemiological data on injury and illness in sport. Some aspects of this statement need to be further specified on a sport-by-sport basis. To extend the IOC consensus statement on methods for recording and reporting of epidemiological data on injury and illness in sports and to meet the sport-specific requirements of all cycling disciplines regulated by the Union Cycliste Internationale (UCI). A panel of 20 experts, all with experience in cycling or cycling medicine, participated in the drafting of this cycling-specific extension of the IOC consensus statement. In preparation, panel members were sent the IOC consensus statement, the first draft of this manuscript and a list of topics to be discussed. The expert panel met in July 2020 for a 1-day video conference to discuss the manuscript and specific topics. The final manuscript was developed in an iterative process involving all panel members. This paper extends the IOC consensus statement to provide cycling-specific recommendations on health problem definitions, mode of onset, injury mechanisms and circumstances, diagnosis classifications, exposure, study population characteristics and data collection methods. Recommendations apply to all UCI cycling disciplines, for both able-bodied cyclists and para-cyclists. The recommendations presented in this consensus statement will improve the consistency and accuracy of future epidemiological studies of injury and illness in cycling

RET Fusion Testing in Patients With NSCLC: The RETING Study

Introduction: RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identi fication of RET fusions remains a dif ficult challenge. Most guidelines encourage the upfront use of next -generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC. Methods: This situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion -positive NSCLC (n 1 / 4 38) to obtain real -world data. In addition to RNA -based NGS (the criterion standard method), all positive specimens underwent break -apart RET FISH with two different assays and were also tested by an RT-PCR assay. Results: The most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGSpositive but FISH -negative samples contained a KIF5B(15)RET(12) fusion. The three RET fusions not identi fied with RT-PCR were AKAP13(35)-RET(12) , KIF5B(24)-RET(9) and KIF5B(24)-RET(11) . All three false -negative RT-PCR cases were FISH -positive, exhibited a typical break -apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively). Conclusions: In-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false -negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)