O-linked sialic acid residues on platelet membrane glycoprotein IIb mask the human HPA-9b alloepitope.

Sialic acids occupy the terminal position of glycan chains and have the potential to influence the antigenicity of glycoproteins (GP). The polymorphisms of human platelet alloantigens (HPA)-3 and HPA-9, located near the C-terminus of the extracellular domain of platelet membrane GPIIb, are adjacent to sialyl-core 1 O-glycans emanating from serines 845 and 847. Whether the nearby O-glycans affect the antigenicity of HPA-9b or influence the binding of anti-HPA-9b alloantibodies in clinically significant cases of neonatal alloimmune thrombocytopenia is unknown. To address this issue, we generated a series of O-glycan mutant HPA-9 allele-specific induced pluripotent stem cell lines, differentiated them to megakaryocytes (MKs), and examined their ability to bind HPA-9b-specific alloantibodies. We found that both wild-type MKs treated with neuraminidase and those genetically modified to lack the sialidases ST3GAL1 and ST3GAL2 dramatically increased anti-HPA-9b alloantibody binding, indicating that the HPA-9b epitope is partially masked by terminal sialic acids on nearby O-glycans of GPIIb. Interestingly, mutating the serine residues that carry these glycan chains to alanine actually reduced the binding of anti-HPA-9b alloantibodies, indicating that these 2 O-glycan chains contribute to the presentation of the HPA-9b epitope-perhaps by stabilizing the conformation of the GP in this region. Collectively, our data suggest that detection of anti-HPA-9b alloantibodies may be enhanced through the use of HPA-9b-specific MKs that have been genetically altered to lack nearby terminal sialic acid residues but retain the glycan chains to which they are attached.

Mechanoimmunology in the solid tumor microenvironment.

The tumor microenvironment (TME) is a complex and dynamic ecosystem that adjoins the cancer cells within solid tumors and comprises distinct components such as extracellular matrix, stromal and immune cells, blood vessels, and an abundance of signaling molecules. In recent years, the mechanical properties of the TME have emerged as critical determinants of tumor progression and therapeutic response. Aberrant mechanical cues, including altered tissue architecture and stiffness, contribute to tumor progression, metastasis, and resistance to treatment. Moreover, burgeoning immunotherapies hold great promise for harnessing the immune system to target and eliminate solid malignancies; however, their success is hindered by the hostile mechanical landscape of the TME, which can impede immune cell infiltration, function, and persistence. Consequently, understanding TME mechanoimmunology - the interplay between mechanical forces and immune cell behavior - is essential for developing effective solid cancer therapies. Here, we review the role of TME mechanics in tumor immunology, focusing on recent therapeutic interventions aimed at modulating the mechanical properties of the TME to potentiate T cell immunotherapies, and innovative assays tailored to evaluate their clinical efficacy.

Prophylactic administration of HPA-1a-specific antibodies prevents fetal/neonatal alloimmune thrombocytopenia in mice.

Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal alloantibodies directed against paternally inherited human platelet alloantigens (HPAs) present on the surface of fetal and neonatal platelets. There are currently no approved therapies for the prevention of FNAIT. We report herein the ability of 2 human HPA-1a-specific therapeutic candidates, one a polyclonal, and the other a monoclonal antibody, to prevent alloimmunization in a novel preclinical mouse model of FNAIT. Both antibody preparations effected the rapid and complete elimination of HPA-1a+ platelets from circulation and prevented the development of HPA-1a alloantibodies. HPA-1a- female mice treated prophylactically with anti-HPA-1a antibody prior to exposure to HPA-1a+ platelets gave birth to HPA-1a+/- pups with significantly improved platelet counts and no bleeding symptoms. These preclinical data establish both the potential and threshold exposure targets for prophylactic treatment with HPA-1a-specific antibodies for the prevention of FNAIT in humans.

Pharmacological management of heart failure in adults with congenital heart disease.

Congenital heart disease (CHD) is the most common global congenital defect affecting over 2.4 million individuals in the United States. Ongoing medical and surgical advancements have improved the survival of children with CHD leading to a shift where, as of 2010, adults constitute two-thirds of the CHD patient population. The increasing number and aging of adult congenital heart disease (ACHD) patients present a clinical challenge due to heightened complexity, morbidity, and mortality. Studies indicate that 1 in 13 ACHD patients will develop heart failure (HF) in their lifetime. ACHD-HF patients experience more frequent emergency department visits, higher hospitalization rates, longer hospital stays, and higher mortality compared to non-ACHD patients with heart failure (non-ACHD-HF). Despite HF being the leading cause of death in ACHD patients, there is a notable gap in evidence regarding treatment. While guideline-directed medical therapy (GDMT) has been extensively studied in non-ACHD-HF, research specific to ACHD-HF individuals is limited. This article aims to comprehensively review available literature addressing the pharmacological treatment of ACHD-HF.

Intersecting Stigma and the HIV Care Cascade: Qualitative Insights from Sex Workers, Men who have Sex with Men, and Transgender Women Living with HIV in Jamaica.

In Jamaica, stigma experiences of sex workers (SW), gay men and other men who have sex with men (MSM), and transgender women living with HIV remain understudied. To address this gap, we explored experiences of stigma and linkages with the HIV care cascade among key populations living with HIV in Jamaica, including cisgender women SW, MSM, and transgender women. This qualitative study involved n = 9 focus groups (FG), n = 1 FG per population living with HIV (SW, MSM, transgender women) in each of three sites (Kingston, St. Ann, Montego Bay). We also conducted key informant (KI) interviews. We applied thematic analysis informed by the Health Stigma and Discrimination (HSD) Framework. FG participants (n = 67) included SW (n = 18), MSM (n = 28), and trans women (n = 21); we interviewed n = 10 KI (n = 5 cisgender women, n = 5 cisgender men). Participant discussions revealed that stigma drivers included low HIV treatment literacy, notably misinformation about antiretroviral therapy (ART) benefits and HIV acquisition risks, and a lack of legal protection from discrimination. Stigma targets health (HIV) and intersecting social identities (sex work, LGBTQ identities, gender non-conformity, low socio-economic status). Stigma manifestations included enacted stigma in communities and families, and internalized stigma-including lateral violence. HIV care cascade impacts included reduced and/or delayed HIV care engagement and ART adherence challenges/disruptions. Participants discussed strategies to live positively with HIV, including ART adherence as stigma resistance; social support and solidarity; and accessing affirming institutional support. In addition to addressing intersecting stigma, future research and programing should bolster multi-level stigma-resistance strategies to live positively with HIV.

Atomic Level Dissection of the Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) Homophilic Binding Interface: Implications for Endothelial Cell Barrier Function.

OBJECTIVE: PECAM-1 (platelet endothelial cell adhesion molecule 1) is a 130 kDa member of the immunoglobulin (Ig) gene superfamily that is expressed on the surfaces of platelets and leukocytes and concentrated at the intercellular junctions of confluent endothelial cell monolayers. PECAM-1 Ig domains 1 and 2 (IgD1 and IgD2) engage in homophilic interactions that support a host of vascular functions, including support of leukocyte transendothelial migration and the maintenance of endothelial junctional integrity. The recently solved crystal structure of PECAM-1 IgD1 and IgD2 revealed a number of intermolecular interfaces predicted to play important roles in stabilizing PECAM-1/PECAM-1 homophilic interactions and in formation and maintenance of endothelial cell-cell contacts. We sought to determine whether the protein interfaces implicated in the crystal structure reflect physiologically important interactions. Approach and Results: We assessed the impact of single amino acid substitutions at the interfaces between opposing PECAM-1 molecules on homophilic binding and endothelial cell function. Substitution of key residues within the IgD1-IgD1 and IgD1-IgD2 interfaces but not those within the smaller IgD2-IgD2 interface, markedly disrupted PECAM-1 homophilic binding and its downstream effector functions, including the ability of PECAM-1 to localize at endothelial cell-cell borders, mediate the formation of endothelial tubes, and restore endothelial barrier integrity. CONCLUSIONS: Taken together, these results validate the recently described PECAM-1 IgD1/IgD2 crystal structure by demonstrating that specific residues visualized within the IgD1-IgD1 and IgD1-IgD2 interfaces of opposing molecules in the crystal are required for functionally important homophilic interactions. This information can now be exploited to modulate functions of PECAM-1 in vivo.

Exploring the Protective Value of Using Sexting for Condom Negotiation on Condom use Determinants and Practices Among Forcibly Displaced Adolescents in the Slums of Kampala, Uganda.

Given the global growth of adolescent texting, we evaluate texting-based sexual communication as a potential site for interventions encouraging condom use cascades, particularly among displaced adolescents-a population with disproportionate levels of sexually transmitted infections, including HIV. With data from 242 forcibly displaced adolescents in the slums of Kampala, Uganda, we used path analysis to examine pathways from gender/dating relationship to condom determinant (knowledge of where to access condoms) and practices (access/use of condoms), through sexting-based condom negotiation, controlling for sexting practices. We found direct pathways from gender (boys vs. girls) and from dating relationship (dating vs. not) to condom determinant. Sexting-based condom negotiation partially mediated the pathway from gender/dating relationship to condom determinant, and fully mediated the pathways from gender/dating relationship to condom practices. Future digital sexual health interventions should consider the utility of texting-based applications in promoting knowledge and use of condoms among adolescents.

RESUMEN: Dado el crecimiento global de los mensajes de texto de los adolescentes, evaluamos la comunicación sexual basada en mensajes de texto como un sitio potencial para intervenciones que fomenten el uso de condones en cascada, particularmente entre los adolescentes desplazados, una población con niveles desproporcionados de infecciones de transmisión sexual, incluido el VIH. Con datos de 242 adolescentes desplazados por la fuerza en los barrios marginales de Kampala, Uganda, utilizamos el análisis de caminos para examinar los caminos desde la relación de género/citas hasta el determinante del condón (conocimiento de dónde acceder a los condones) y las prácticas (acceso/uso de condones), a través del sexteo. -negociación basada en condones, controlando las prácticas de sexting. Encontramos caminos directos desde el género (niños vs. niñas) y desde la relación de noviazgo (citas vs. no) al determinante del condón. La negociación de condones basada en sexting medió parcialmente el camino de la relación de género/citas al determinante del condón, y medió completamente las vías de la relación de género/citas a las prácticas del condón. Las futuras intervenciones de salud sexual digital deben considerar la utilidad de las aplicaciones basadas en mensajes de texto para promover el conocimiento y el uso de condones entre los adolescentes.

PrEP eligibility, HIV risk perception, and willingness to use PrEP among high-risk men who have sex with men in India: A cross-sectional survey.

HIV pre-exposure prophylaxis (PrEP) is not yet included in India's national AIDS program, with demonstration projects for MSM in planning stages. In order to support PrEP roll-out for MSM, we assessed: (1) associations between guideline-informed PrEP eligibility, HIV risk perception, and perceived PrEP benefits and costs, with willingness to use PrEP (WTUP); and (2) correlates of non-WTUP among PrEP-eligible MSM. Data were collected from MSM (n = 197) sampled from cruising sites in Mumbai and Chennai. More than half (58.4%) reported inconsistent condom use with male partners, 88.3% >1 male partner, and 48.6% engaging in sex work (all past month). Overall, 76.6% reported they would "definitely use" PrEP. Among 92.9% deemed PrEP-eligible, 79.2% reported WTUP. In adjusted analyses, PrEP eligibility (aOR = 5.31, 95% CI 1.11, 25.45), medium (aOR = 2.41, 95% CI 1.03, 5.63) or high (aOR = 13.08, 95% CI 1.29, 132.27) perceived HIV risk, and greater perceived benefits (aOR = 1.13, 95% CI 1.03, 1.24) were associated with higher odds of WTUP. Among PrEP-eligible MSM, non-WTUP was associated with low HIV risk perception and lower perceived benefits. Facilitating accurate risk assessment and promoting awareness of PrEP benefits and eligibility criteria may increase PrEP uptake among MSM in India.

A stochastic simulation model for assessing the masking effects of road noise for wildlife, outdoor recreation, and bioacoustic monitoring.

Traffic noise is one of the leading causes of reductions in animal abundances near roads. Acoustic masking of conspecific signals and adventitious cues is one mechanism that likely causes animals to abandon loud areas. However, masking effects can be difficult to document in situ and the effects of infrequent noise events may be impractical to study. Here, we present the Soundscapes model, a stochastic individual-based model that dynamically models the listening areas of animals searching for acoustic resources ("searchers"). The model also studies the masking effects of noise for human detections of the searchers. The model is set in a landscape adjacent to a road. Noise produced by vehicles traveling on that road is represented by calibrated spectra that vary with speed. Noise propagation is implemented using ISO-9613 procedures. We present demonstration simulations that quantify declines in searcher efficiency and human detection of searchers at relatively low traffic volumes, fewer than 50 vehicles per hour. Traffic noise is pervasive, and the Soundscapes model offers an extensible tool to study the effects of noise on bioacoustics monitoring, point-count surveys, the restorative value of natural soundscapes, and auditory performance in an ecological context.

'No test, no disease': Multilevel barriers to HIV testing among young men who have sex with men and transgender women in three semi-urban areas in Thailand.

Young gay and other men who have sex with men and young transgender women in Thailand continue to be at high risk for HIV infection. We explored multilevel influences on HIV testing in order to inform the design of tailored interventions. We conducted four focus group discussions with 16-20-year-old gay men and transgender persons (n = 25) and 17 key informant interviews with healthcare providers, NGO leaders, and youth advocates. Focus groups and interviews were transcribed and reviewed using thematic analysis in Thai and English language by a bilingual team. We identified intersecting, culturally situated barriers at individual (lack of HIV knowledge, low HIV risk perception, denial), social (intersectional sexual- and HIV-related stigma, lack of family communication), institutional (inadequate and non-LGBT-inclusive sexual health education in schools, lack of youth-friendly clinics) and policy levels (parental consent requirements for HIV testing by minors). Multilevel and multisystem factors coalesce to form extensive barriers to HIV testing access and utilisation and promote disengagement from HIV prevention more broadly. Multicomponent, youth-engaged interventions informed by Thai sociocultural history and practices are needed in renewed approaches to HIV prevention and testing to end the epidemic among young gay and transgender people in Thailand.

Affirming and negotiating gender in family and social spaces: Stigma, mental health and resilience among transmasculine people in India.

Research on transmasculine people's health is scant globally, including in India. We explored transmasculine people's experiences in affirming their gender in family and social spaces, and how those experiences impact mental health. In 2019, we conducted four focus groups (n = 17 participants) and 10 in-depth interviews with transmasculine people in Mumbai and Chennai. Data analyses were guided by minority stress theory and the gender affirmation model. Within family, the pressure to conform to assigned gender roles and gender policing usually began in adolescence and increased over time. Some participants left parental homes due to violence. In educational settings, participants described the enforcement of gender-normative dress codes, lack of faculty support, and bullying victimisation, which led some to quit schooling. In the workplace, experiences varied depending on whether participants were visibly trans or had an incongruence between their identity documents and gender identity. Everyday discrimination experiences in diverse settings contributed to psychological distress. Amidst these challenges, participants reported resilience strategies, including self-acceptance, connecting with peers, strategic (non)disclosure, and circumventing gendered restrictions on dress and behaviour. Interventions at social-structural, institutional, family and individual levels are needed to reduce stigma and discrimination faced by transmasculine people in India and to promote their mental health.

Public and manager perceptions about prescribed fire in the Mid-Atlantic, United States.

Firescapes of the Mid-Atlantic are understudied compared to other ecosystems in the United States, and little is known about the acceptance of prescribed fire as a forest management tool. Yet, this region harbors high levels of wildland-urban interface (WUI), has a close intermingling of land ownerships, and reflects substantial regional heterogeneity in burning histories and fire hazards. As prescribed fire is increasingly applied in the Mid-Atlantic as a critical tool to meet various land management objectives, research is needed to help managers understand community perceptions of prescribed fire implementation. Through intercept surveys of forest recreationists and online surveys of fire managers, this study investigates perceptions about prescribed fire use in the Mid-Atlantic, in addition to the critical contributing factors of public support toward prescribed fires. Two states, Pennsylvania and New Jersey, were selected as case studies to explore regional differences in social perception due to their contrasts in fire history, policy, management objectives, and social exposure. Our results show moderate social awareness of local prescribed fires, moderate to high familiarity with prescribed burning, high agency trust, and strong community support toward prescribed fires. However, the perceived concerns and benefits differed between managers and forest recreationists and between recreationists from Pennsylvania and New Jersey. The factors influencing the support of prescribed burning practices included forest management beliefs, concern about prescribed fire effects, familiarity with prescribed fires as a forest management tool, and awareness of local prescribed fires. Collectively, these results highlighted needs in public outreach to strengthen education, build broader community awareness, engage critical stakeholder groups such as forest recreationists, and re-align public outreach messages based on community-level concerns and perceived benefits. Additionally, it will be vital for the scientific community to help monitor critical shifts in forest value orientations and fill in significant research gaps regarding prescribed fire benefits.

Generation of 'designer erythroblasts' lacking one or more blood group systems from CRISPR/Cas9 gene-edited human-induced pluripotent stem cells.

Despite the recent advancements in transfusion medicine, red blood cell (RBC) alloimmunization remains a challenge for multiparous women and chronically transfused patients. At times, diagnostic laboratories depend on difficult-to-procure rare reagent RBCs for the identification of different alloantibodies in such subjects. We have addressed this issue by developing erythroblasts with custom phenotypes (Rh null, GPB null and Kx null/Kell low) using CRISPR/Cas9 gene-editing of a human induced pluripotent stem cell (hiPSC) parent line (OT1-1) for the blood group system genes: RHAG, GYPB and XK. Guide RNAs were cloned into Cas9-puromycin expression vector and transfected into OT1-1. Genotyping was performed to select puromycin-resistant hiPSC KOs. CRISPR/Cas9 gene-editing resulted in the successful generation of three KO lines, RHAG KO, GYPB KO and XK KO. The OT1-1 cell line, as well as the three KO hiPSC lines, were differentiated into CD34+ CD41+ CD235ab+ hematopoietic progenitor cells (HPCs) and subsequently to erythroblasts. Native OT1-1 erythroblasts were positive for the expression of Rh, MNS, Kell and H blood group systems. Differentiation of RHAG KO, GYPB KO and XK KO resulted in the formation of Rh null, GPB null and Kx null/Kell low erythroblasts, respectively. OT1-1 as well as the three KO erythroblasts remained positive for RBC markers-CD71 and BAND3. Erythroblasts were mostly at the polychromatic/ orthochromatic stage of differentiation. Up to ~400-fold increase in erythroblasts derived from HPCs was observed. The availability of custom erythroblasts generated from CRISPR/Cas9 gene-edited hiPSC should be a useful addition to the tools currently used for the detection of clinically important red cell alloantibodies.

Bioengineered iPSC-derived megakaryocytes for the detection of platelet-specific patient alloantibodies.

Human platelet membrane glycoprotein polymorphisms can be immunogenic in man and are frequently the cause of clinically important immune reactions responsible for disorders such as neonatal alloimmune thrombocytopenia. Platelets from individuals carrying rare polymorphisms are often difficult to obtain, making diagnostic testing and transfusion of matched platelets challenging. In addition, class I HLA antibodies frequently present in maternal sera interfere with the detection of platelet-reactive alloantibodies. Detection of alloantibodies to human platelet antigen 3 (HPA-3) and HPA-9 is especially challenging, in part because of the presence of cell type-specific glycans situated near the polymorphic amino acid that together form the alloepitope. To overcome these limitations, we generated a series of HLA class I-negative blood group O induced pluripotent stem cell (iPSC) lines that were gene edited to sequentially convert their endogenous HPA-3a alloantigenic epitope to HPA-3b, and HPA-9a to HPA-9b. Subjecting these cell lines, upon differentiation into CD41+/CD42b+ human megakaryocytes (MKs), to flow cytometric detection of suspected anti-HPA-3 and HPA-9 alloantisera revealed that the HPA-3a-positive MKs specifically reacted with HPA-3a patient sera, whereas the HPA-3b MKs lost reactivity with HPA-3a patient sera while acquiring reactivity to HPA-3b patient sera. Importantly, HPA-9b-expressing MKs specifically reacted with anti-HPA-9b-suspected patient samples that had been undetectable using conventional techniques. The provision of specialized iPSC-derived human MKs expressing intact homozygous glycoprotein alloantigens on the cell surface that carry the appropriate endogenous carbohydrate moieties should greatly enhance detection of clinically important and rare HPA-specific alloantibodies that, to date, have resisted detection using current methods.

Syndemic Conditions, Sexual Risk Behavior, and HIV Infection Among Men Who Have Sex with Men in Taiwan.

Men who have sex with men (MSM) continue to constitute the majority of HIV incidence in Taiwan. This study examined the associations between five co-occurring psychosocial health conditions (PHCs)-childhood physical abuse (CPA), childhood sexual abuse (CSA), intimate partner violence (IPV), internalized homophobia (IH), and methamphetamine use (MU), and two outcomes (HIV infection and condomless anal sex) among a community sample of 1,000 Taiwanese MSM (mean age 28.5 years). Compared to MSM who had never experienced any PHC, MSM with one or more PHCs had greater than twofold higher odds of being HIV-positive, and those with three or more PHCs had twofold higher odds of having condomless anal sex. Interactive effects on HIV infection were identified from CPA + CSA + MU and CPA + IPV + MU. An interactive effect on condomless anal sex was detected between IH and MU. In order to control the escalating HIV epidemic among MSM in Taiwan, interventions are needed to address syndemic psychosocial health conditions.

RESUMEN: Los hombres que tienen sexo con hombres (HSH por sus siglas en inglés) continúan constituyendo la mayor parte de la incidencia del VIH en Taiwán. Este estudio examinó las asociaciones existentes entre cinco condiciones de salud psicosocial habituales en la sociedad (APS por sus siglas en inglés) -abuso fisico infantil (CPA), abuso sexual infantil (CSA), violencia en pareja (IPV), homofobia internalizada (IH), y el uso de metanfetamina (MU); y dos resultados de una muestra de 1.000 HSH de origen taiwanés (con una media de edad de 28,5 años) sobre infección por VIH y sexo anal sin condón. En comparación con aquellos HSH que nunca habían experimentado las APS anteriores, los HSH con una o más APS tenían más del doble de probabilidades de ser VIH positivos, y aquellos otros con tres o más APS tenían el doble de probabilidades de tener sexo anal sin condón. Se identificaron efectos interactivos de la infección por VIH a partir de CPA + CSA + MU y CPA + IPV + MU. Se detectó otro efecto interactivo cuyo origen es el sexo anal sin condón entre IH y MU. Con el fin de controlar la escalada de la epidemia del VIH entre los HSH en Taiwán se necesita realizar intervenciones para abordar las condiciones de salud psicosocial en sindemias.

Willingness to Use Pre-exposure Prophylaxis (PrEP) and Preferences Among Men Who have Sex with Men in Mumbai and Chennai, India: A Discrete Choice Experiment.

Pre-exposure prophylaxis (PrEP) programs are planned for key populations in India. We examined PrEP awareness and willingness to use PrEP in order to support products and services for MSM. From December 2016 to March 2017, we conducted a survey and discrete choice experiment (DCE)-a technique to quantify the strength of participants' trade-off preferences among various product attributes-to assess willingness to use PrEP and related preferences. MSM were recruited from cruising sites and HIV prevention services in Mumbai and Chennai. DCE data were analyzed using mixed logit regression models and estimated marginal willingness-to-pay, the relative value participants' place on different PrEP attributes. Overall, 76.6% indicated willingness to use PrEP. Efficacy had the greatest effect on choice (high vs. moderate, aOR = 19.9; 95% CI 13.0-30.4), followed by dosing frequency (intermittent vs. daily regimen, aOR = 2.02; 95% CI 1.8-2.2). Participants preferred no (vs. minor) side-effects, subsidized (vs. market) price, and government (vs. private) hospitals. Findings suggest that educational and social marketing interventions should emphasize PrEP's high efficacy and minimal side effects, and programs should provide government-subsidized PrEP with choices of intermittent or daily dosing delivered by government and private hospitals/clinics in order to optimize PrEP uptake among MSM in India.

LGBT+ inclusion and human rights in Thailand: a scoping review of the literature.

BACKGROUND: Globally, LGBT+ people continue to struggle to achieve full realization of their human rights. Amid reported health and mental health disparities, and economic insecurity, we conducted a scoping review to explore the breadth of the literature, map and summarize the evidence, and identify knowledge gaps on LGBT+ inclusion and human rights in Thailand. METHODS: We conducted a scoping review in accordance with the methodology developed by the Joanna Briggs Institute and PRISMA-ScR guidelines. We systematically searched 16 databases for peer-reviewed literature, and government and nongovernmental organization websites for grey literature, published in English or Thai from January 1, 2000-August 21, 2020. Two reviewers independently screened studies according to pre-set criteria. We abstracted and analyzed data on publication characteristics and focal populations, and synthesized findings in six domains of LGBT+ inclusion: political and civic participation, education, family, personal security and violence, economic well-being, and health. RESULTS: The review captured 3327 results in total, which was scoped to 76 peer-reviewed articles and 39 grey literature sources, the majority published after 2010. Gay men and transgender women were the primary focal populations in the peer-reviewed literature, LGBT+ people as a whole in the grey literature. Health was the predominant domain across publications. Key findings include the absence of generalized antidiscrimination legislation for LGBT+ individuals and lack of recourse for transgender individuals to change their legal gender; multifaceted stigma and discrimination in the educational system; social isolation and exclusion in families; disproportionate prevalence of sexual violence and reluctance to report to police; discrimination and marginalization in employment; and LGBT+ disparities in health and mental health. CONCLUSIONS: Future research and programmatic initiatives on LGBT+ inclusion in Thailand should aim to address: 1) understudied populations-lesbian and bisexual women, transmasculine persons; 2) underrepresented topics, including constraints to LGBT+ advocacy; 3) strategic policy initiatives around anti-discrimination laws and legal recognition of same-sex marriage and families; and 4) the need for consistent collection of disaggregated data on LGBT+ persons in education, family, economic, personal security/violence, and health domains in order to assess indicators of inclusion and progress in advancing human rights for LGBT+ people in Thailand.

Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration.

There is a growing appreciation for the contribution of platelets to immunity; however, our knowledge mostly relies on platelet functions associated with vascular injury and the prevention of bleeding. Circulating immune complexes (ICs) contribute to both chronic and acute inflammation in a multitude of clinical conditions. Herein, we scrutinized platelet responses to systemic ICs in the absence of tissue and endothelial wall injury. Platelet activation by circulating ICs through a mechanism requiring expression of platelet Fcγ receptor IIA resulted in the induction of systemic shock. IC-driven shock was dependent on release of serotonin from platelet-dense granules secondary to platelet outside-in signaling by αIIbß3 and its ligand fibrinogen. While activated platelets sequestered in the lungs and leaky vasculature of the blood-brain barrier, platelets also sequestered in the absence of shock in mice lacking peripheral serotonin. Unexpectedly, platelets returned to the blood circulation with emptied granules and were thereby ineffective at promoting subsequent systemic shock, although they still underwent sequestration. We propose that in response to circulating ICs, platelets are a crucial mediator of the inflammatory response highly relevant to sepsis, viremia, and anaphylaxis. In addition, platelets recirculate after degranulation and sequestration, demonstrating that in adaptive immunity implicating antibody responses, activated platelets are longer lived than anticipated and may explain platelet count fluctuations in IC-driven diseases.

Virality, desire and health assemblages: mapping (dis)continuities in the response to and management of HIV and COVID-19.

In this paper, we explore the relationship between "viral load" as a virological, immunological, epidemiological and social category and how it links the four decades-long global HIV pandemic to the ongoing response to COVID-19. We argue, metaphorically, that the response to SARS-CoV-2 contains 'genetic' material from HIV, which has (as a result of the digital age which reproduces error-filled data at incredible speed) mutated and is being transmitted into the social and political body. Using sexual health and substance use as focal points, we turn to Deleuzoguattarian theoretical insights about the assemblage of desire, affect and material factors that produce epidemics. Contrasting historical and contemporary scenes and issues, we explore the complex assemblage created by viral loads, medical and public health protocols, conceptions of risk, responsibility and fear that connect both pandemics. Finally, we consider the goal of viral eradication and related militaristic metaphors, alongside the increasing convergence of medicine, public health, the law and corporate interests, and contrast this with community responses that engage with what it means to be living and dying in viral times.