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ABSTRACT: Long-acting injectable cabotegravir (CAB-LA) was US Food and Drug Administration-approved in 2021. However, little is known about providers' CAB-LA knowledge, attitudes, challenges, and prescribing preferences for transgender women patients. Understanding this is critical to developing new pre-exposure prophylaxis (PrEP) interventions tailored to transgender women. We conducted 45-min, in-depth Zoom interviews (IDIs) with United States-based health care providers who prescribe PrEP to transgender women. IDIs focused on providers' CAB-LA knowledge/acceptability, willingness to prescribe CAB-LA to transgender women, potential challenges, and solutions to mitigate challenges. Providers ( N = 17) had a mean age of 43 years, and 35.4% ( n = 6) identified as people of color. Most ( n = 12) had basic knowledge of CAB-LA but wanted additional training. All participants found CAB-LA acceptable and were willing to prescribe. Most ( n = 11) anticipated minimal challenges to implementation. Others ( n = 4) reported potential issues, including logistical/scheduling concerns that impede CAB-LA integration and staffing concerns. Many providers expressed support for self-injection ( n = 13) and injections at "drop-in" clinics ( n = 8) to overcome challenges.
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Fármacos Anti-VIH , Infecciones por VIH , Personal de Salud , Profilaxis Pre-Exposición , Piridonas , Investigación Cualitativa , Personas Transgénero , Humanos , Personas Transgénero/psicología , Personas Transgénero/estadística & datos numéricos , Femenino , Adulto , Estados Unidos , Masculino , Profilaxis Pre-Exposición/métodos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Personal de Salud/psicología , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Piridonas/administración & dosificación , Piridonas/uso terapéutico , Persona de Mediana Edad , Conocimientos, Actitudes y Práctica en Salud , Inyecciones , Accesibilidad a los Servicios de Salud , Preparaciones de Acción Retardada , Actitud del Personal de Salud , Entrevistas como Asunto , DicetopiperazinasRESUMEN
Transgender women are disproportionately burdened by HIV. Though there is a substantial body of research exploring barriers and facilitators of HIV prevention among transgender women, many barriers remain unaddressed. This study identifies strategies to make HIV prevention trials more congruent with transgender women's preferences and needs to boost trial participation and ultimately enhance initiation and uptake of pre-exposure prophylaxis (PrEP). We conducted in-depth interviews with 15 sexually active, HIV-negative transgender women in New York City to understand: (1) preferences concerning long-acting injectable cabotegravir for PrEP and (2) ideas on how to make HIV prevention trial environments more comfortable. We identified five themes related to increasing transgender women's appeal to trials: (1) creating a more inclusive/welcoming environment, (2) providing compensation that is responsive to transgender women and community needs, (3) centering transgender women in recruitment and informational materials, (4) training study staff on gender-affirming practices, and (5) hiring transgender people as study staff. Participants wanted to see more gender diversity, representation, correct pronouns, gender-affirming practices, and compensation or reimbursements. Together, these practices may improve recruitment and retention of transgender women in HIV prevention trials.
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Human immunodeficiency virus (HIV) is a public health concern among young sexual minority men (YSMM), ages 17 to 24, in the United States. Biomedical prevention methods, such as pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (nPEP), can help reduce the risk of HIV transmission among this population. However, there is limited awareness and use of nPEP by YSMM. This study aims to explore the perceptions of YSMM regarding the nPEP care continuum, which consists of three areas of focus: awareness, uptake, and linkage to other HIV prevention services. This study draws on synchronous online focus groups with a sample of 41 YSMM in the United States. Transcripts from the focus groups were analyzed using reflexive thematic analysis. Participants reported limited nPEP awareness and prior use, a process of personal appraisal of nPEP need based on HIV risk and costs, and a preference for PrEP over PEP for long-term HIV prevention. Interventions should be tailored to increase awareness of nPEP among YSMM and reduce addressable barriers to nPEP use for YSMM, including cost and confidentiality concerns, in situations where nPEP is warranted. Finally, more research is needed on how nPEP use can act as a bridge to PrEP initiation for this population.
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Fármacos Anti-VIH , Continuidad de la Atención al Paciente , Grupos Focales , Infecciones por VIH , Conocimientos, Actitudes y Práctica en Salud , Profilaxis Posexposición , Minorías Sexuales y de Género , Humanos , Masculino , Infecciones por VIH/prevención & control , Infecciones por VIH/psicología , Adolescente , Adulto Joven , Estados Unidos , Minorías Sexuales y de Género/psicología , Fármacos Anti-VIH/uso terapéutico , Investigación Cualitativa , Accesibilidad a los Servicios de Salud , Profilaxis Pre-Exposición , Homosexualidad Masculina/psicología , Homosexualidad Masculina/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , PercepciónRESUMEN
While most mammalian enhancers regulate their cognate promoters over moderate distances of tens of kilobases (kb), some enhancers act over distances in the megabase range. The sequence features enabling such extreme-distance enhancer-promoter interactions remain elusive. Here, we used in vivo enhancer replacement experiments in mice to show that short- and medium-range enhancers cannot initiate gene expression at extreme-distance range. We uncover a novel conserved cis-acting element, Range EXtender (REX), that confers extreme-distance regulatory activity and is located next to a long-range enhancer of Sall1. The REX element itself has no endogenous enhancer activity. However, addition of the REX to other short- and mid-range enhancers substantially increases their genomic interaction range. In the most extreme example observed, addition of the REX increased the range of an enhancer by an order of magnitude, from its native 71kb to 840kb. The REX element contains highly conserved [C/T]AATTA homeodomain motifs. These motifs are enriched around long-range limb enhancers genome-wide, including the ZRS, a benchmark long-range limb enhancer of Shh. Mutating the [C/T]AATTA motifs within the ZRS does not affect its limb-specific enhancer activity at short range, but selectively abolishes its long-range activity, resulting in severe limb reduction in knock-in mice. In summary, we identify a sequence signature globally associated with long-range enhancer-promoter interactions and describe a prototypical REX element that is necessary and sufficient to confer extreme-distance gene activation by remote enhancers.
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Remote enhancers are thought to interact with their target promoters via physical proximity, yet the importance of this proximity for enhancer function remains unclear. Here we investigate the three-dimensional (3D) conformation of enhancers during mammalian development by generating high-resolution tissue-resolved contact maps for nearly a thousand enhancers with characterized in vivo activities in ten murine embryonic tissues. Sixty-one percent of developmental enhancers bypass their neighboring genes, which are often marked by promoter CpG methylation. The majority of enhancers display tissue-specific 3D conformations, and both enhancer-promoter and enhancer-enhancer interactions are moderately but consistently increased upon enhancer activation in vivo. Less than 14% of enhancer-promoter interactions form stably across tissues; however, these invariant interactions form in the absence of the enhancer and are likely mediated by adjacent CTCF binding. Our results highlight the general importance of enhancer-promoter physical proximity for developmental gene activation in mammals.
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Elementos de Facilitación Genéticos , Mamíferos , Animales , Ratones , Elementos de Facilitación Genéticos/genética , Regiones Promotoras Genéticas/genética , Activación Transcripcional/genética , Mamíferos/genética , Cromatina/genéticaRESUMEN
The cellular complexity of the endochondral bone underlies its essential and pleiotropic roles during organismal life. While the adult bone has received significant attention, we still lack a deep understanding of the perinatal bone cellulome. Here, we have profiled the full composition of the murine endochondral bone at the single-cell level during the transition from fetal to newborn life and in comparison with the adult tissue, with particular emphasis on the mesenchymal compartment. The perinatal bone contains different fibroblastic clusters with blastema-like characteristics in organizing and supporting skeletogenesis, angiogenesis and hematopoiesis. Our data also suggest dynamic inter- and intra-compartment interactions, as well as a bone marrow milieu that seems prone to anti-inflammation, which we hypothesize is necessary to ensure the proper program of lymphopoiesis and the establishment of central and peripheral tolerance in early life. Our study provides an integrative roadmap for the future design of genetic and cellular functional assays to validate cellular interactions and lineage relationships within the perinatal bone.
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Células Madre Mesenquimatosas , Osteogénesis , Ratones , Animales , Osteogénesis/genética , Huesos , Médula Ósea , HematopoyesisRESUMEN
Parkinson disease (PD) is characterized by the loss of dopaminergic neurons because of oxidative stress and neuroinflammation. Polyphenols in vegetables, known for their high antioxidant capacity, may prevent the onset, or delay the progression of the disease; among these, flavonoids are the most abundant class of polyphenols in foods. Clinical and cohort studies have evaluated the effect of polyphenol consumption on the risk of developing PD or of attenuating the symptoms after diagnosis; therefore, it is necessary to integrate the scientific evidence into making dietary recommendations. The objective of this study was to perform a systematic review of randomized controlled trials and cohort studies that have investigated the use of polyphenols in PD. The studies were identified through the PubMed, Science Direct, Scielo, and Web of Science databases. A total of 1100 studies were found; these were analyzed and filtered by 2 independent reviewers. After completion, 5 studies were included (3 randomized controlled trials and 2 cohort studies). The consumption of flavonoids, anthocyanins, or 2-5 servings/week of specific foods (apples, red wine, blueberries, and strawberries) reduces the risk of PD and associated mortality. Treatment with licorice, curcumin, or cocoa, which are rich in flavonoids and other polyphenols, improves motor function in PD patients. No statistically significant differences were found in quality of life, disease progression or nonmotor symptoms such as cognitive ability and mood. Although cohort studies suggest a neuroprotective effect, further clinical studies are urgently needed to evaluate the effect of specific flavonoids and other polyphenols in PD.
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Enfermedad de Parkinson , Humanos , Antocianinas/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Polifenoles/farmacología , Polifenoles/uso terapéutico , Calidad de VidaRESUMEN
Presenilin-1 (PSEN1) is the catalytic subunit of the intramembrane protease γ-secretase and undergoes endoproteolysis during its maturation. Heterozygous mutations in the PSEN1 gene cause early-onset familial Alzheimer's disease (eFAD) and increase the proportion of longer aggregation-prone amyloid-ß peptides (Aß42 and/or Aß43). Previous studies had suggested that PSEN1 mutants might act in a dominant-negative fashion by functional impediment of wild-type PSEN1, but the exact mechanism by which PSEN1 mutants promote pathogenic Aß production remains controversial. Using dual recombinase-mediated cassette exchange (dRMCE), here we generated a panel of isogenic embryonic and neural stem cell lines with heterozygous, endogenous expression of PSEN1 mutations. When catalytically inactive PSEN1 was expressed alongside the wild-type protein, we found the mutant accumulated as a full-length protein, indicating that endoproteolytic cleavage occurred strictly as an intramolecular event. Heterozygous expression of eFAD-causing PSEN1 mutants increased the Aß42/Aß40 ratio. In contrast, catalytically inactive PSEN1 mutants were still incorporated into the γ-secretase complex but failed to change the Aß42/Aß40 ratio. Finally, interaction and enzyme activity assays demonstrated the binding of mutant PSEN1 to other γ-secretase subunits, but no interaction between mutant and wild-type PSEN1 was observed. These results establish that pathogenic Aß production is an intrinsic property of PSEN1 mutants and strongly argue against a dominant-negative effect in which PSEN1 mutants would compromise the catalytic activity of wild-type PSEN1 through conformational effects.
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Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Proteínas Mutantes/genética , Mutación , Fragmentos de Péptidos/metabolismo , Presenilina-1/metabolismo , Animales , RatonesRESUMEN
Background: Methicillin-resistant S. aureus (MRSA) especially ST398, is a zoonotic agent. This study aimed to determine the prevalence of methicillin-susceptible S. aureus (MSSA) and MRSA among workers in the pork production chain. Methods: 659 workers associated with 123 pig farms, livestock transporters, one pig slaughterhouse, pork transporters and 23 pork butcheries were studied for S. aureus recovery, and all isolates were characterized (antibiotic resistance, MLST and spa-typing). Results: The prevalence of S. aureus was 35.5%, 75.6% of isolates being MRSA. The prevalence of MRSA was 68.7% (149/217) among pig farm, 33.9% (19/56) livestock transporters, 2.9% (9/306) slaughterhouse, 0% in pork transporters (0/36) and butchery workers (0/44). Of the 234 S. aureus-positive workers, 100% (149/149) of pig farm workers, 82.6% (19/23) of livestock transporters, and 16.4% (9/55) of slaughterhouse workers carried MRSA isolates (p < 0.001). Of the workers who had contact with live swine, 61.8% (178/288) were S. aureus-positive, MRSA being detected in 96.1% of cases (p < 0.001). The most frequent lineage among MRSA were: ST398 (97.7%; 173/177) and ST1 (1.7%; 3/177); and among MSSA were ST30 (19.2%; 11/57) and ST5 (10.5%; 6/57). The most frequent spa-types among MRSA were t011 (93.8%, 166/177) and t1451 (2.25%, 4/177), and among MSSA: t084 (10.5%, 6/57) and t021 (7.0%, 4/57). All MRSA isolates showed resistance to tetracycline, 92.7% to clindamycin, 81.9% to erythromycin and 40.1% to cotrimoxazole. Conclusions: Pig industry workers having occupational contact with live animals present a high risk of colonization of MRSA, especially by MRSA-ST398. Prevention measures should be intensified in any employment sector involving live animals.
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BACKGROUND: We aimed to describe infective endocarditis cases from noncardiac surgery centers, as current knowledge on infective endocarditis is derived mostly from cardiac surgery hospitals. METHODS: An observational retrospective study (2009-2018) was conducted in 9 noncardiac surgery hospitals in Central Catalonia. All adult patients diagnosed with definitive infective endocarditis were included. Transferred and nontransferred cohorts were compared, and a logistic regression model was used to ascertain the prognostic factors. RESULTS: Overall, 502 infective endocarditis episodes were included: 183 (36.5%) were transferred to the cardiac surgery center, whereas 319 were not, with (18.7%) and without (45%) surgical indications. Cardiac surgery was performed in 83% of transferred patients. In-hospital (14% vs 23%) and 1-year (20% vs 35%) mortality rates were significantly lower in transferred patients (P < .001). Among the patients not undergoing cardiac surgery despite an indication, 55 (54%) died within 1 year. The multivariate analysis identified the following independent predictive factors for in-hospital mortality: Staphylococcus aureus infective endocarditis (odds ratio: 1.93 [1.08, 3.47]), heart failure (odds ratio: 3.87 [2.28, 6.57]), central nervous system embolism (odds ratio: 2.95 [1.41, 5.14]), and Charlson score (odds ratio: 1.19 [1.09, 1.30]), whereas community acquisition (odds ratio: 0.52 [0.29, 0.93]), cardiac surgery (odds ratio: 0.42 [0.20, 0.87]), but not transfer (odds ratio: 1.23 [0.84, 3.95]) were identified as protective factors. One-year mortality was associated with S. aureus infective endocarditis (odds ratio: 1.82 [1.04, 3.18]), heart failure (odds ratio: 3.74 [2.27, 6.16]), and Charlson score (odds ratio: 1.23 [1.13, 1.33]), whereas cardiac surgery (odds ratio: 0.41 [0.21, 0.79]) was identified as a protective factor. CONCLUSION: Patients not transferred to a referral cardiac surgery center have a worse prognosis compared to those ultimately transferred, as cardiac surgery is associated with lower mortality rates.
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Endocarditis Bacteriana , Endocarditis , Insuficiencia Cardíaca , Adulto , Humanos , Estudios Retrospectivos , Staphylococcus aureus , Endocarditis Bacteriana/diagnóstico , Endocarditis Bacteriana/cirugía , Endocarditis/diagnóstico , Endocarditis/cirugía , Endocarditis/complicaciones , Mortalidad Hospitalaria , Factores de RiesgoRESUMEN
We present experiences of transgender women (TW) who have sex with men with SMARTtest, a smartphone app to accompany the INSTI Multiplex®, a one-minute, dual blood-based HIV/syphilis rapid test. TW participants (N = 11) received 10 INSTI Multiplex® tests to take home for self- and/or partner-testing and installed the SMARTtest app on their phones. The SMARTtest app aimed to support INSTI Multiplex users in correctly performing the test, interpreting the results, and connecting with care following a positive HIV or syphilis screening. After 3 months, users completed in-depth interviews on their experiences. A total of 9 TW used SMARTtest with partners. App feedback was positive, but refining is necessary. Specifically, TW reported that SMARTtest is easy to use and convenient; instructions on how to use the INSTI Multiplex presented on the app were helpful to complete procedures correctly; the most frequently used feature on SMARTtest was the information on clinics that offered confirmatory testing; and participants and their partners were not concerned about app privacy but reported that this could change if INSTI Multiplex detected an HIV-positive result. Further, participants provided recommendations on how to improve SMARTtest, and changes were mostly related to features, content, functionality, navigation, and overall "look" of the app. SMARTtest is promising to facilitate INSTI Multiplex® use in TW. User feedback should be integrated in future versions.
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Infecciones por VIH , Aplicaciones Móviles , Sífilis , Personas Transgénero , Masculino , Humanos , Femenino , Sífilis/diagnóstico , Teléfono Inteligente , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & control , Homosexualidad MasculinaRESUMEN
Skates are cartilaginous fish whose body plan features enlarged wing-like pectoral fins, enabling them to thrive in benthic environments1,2. However, the molecular underpinnings of this unique trait remain unclear. Here we investigate the origin of this phenotypic innovation by developing the little skate Leucoraja erinacea as a genomically enabled model. Analysis of a high-quality chromosome-scale genome sequence for the little skate shows that it preserves many ancestral jawed vertebrate features compared with other sequenced genomes, including numerous ancient microchromosomes. Combining genome comparisons with extensive regulatory datasets in developing fins-including gene expression, chromatin occupancy and three-dimensional conformation-we find skate-specific genomic rearrangements that alter the three-dimensional regulatory landscape of genes that are involved in the planar cell polarity pathway. Functional inhibition of planar cell polarity signalling resulted in a reduction in anterior fin size, confirming that this pathway is a major contributor to batoid fin morphology. We also identified a fin-specific enhancer that interacts with several hoxa genes, consistent with the redeployment of hox gene expression in anterior pectoral fins, and confirmed its potential to activate transcription in the anterior fin using zebrafish reporter assays. Our findings underscore the central role of genome reorganization and regulatory variation in the evolution of phenotypes, shedding light on the molecular origin of an enigmatic trait.
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Aletas de Animales , Evolución Biológica , Genoma , Genómica , Rajidae , Animales , Aletas de Animales/anatomía & histología , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Rajidae/anatomía & histología , Rajidae/genética , Pez Cebra/genética , Genes Reporteros/genéticaRESUMEN
Rapid or immediate antiretroviral therapy (iART) after HIV diagnosis improves linkage to care and time to viral suppression. However, iART may affect or be affected by HIV-related stigma and medical mistrust. In this mixed-methods pilot study, we examined the bi-directional role of HIV stigma, medical mistrust, and visit adherence (VA) in the context of iART in a diverse, newly diagnosed patient population. Participants were recruited from an HIV clinic in New York City and we utilized a convergent parallel design integrating quantitative data from demographic surveys, the HIV Stigma Survey (HIVSS), the Medical Mistrust Index (MMI) and electronic medical records, and qualitative data from in-depth interviews. Among the sample (N = 30), 26% (N = 8) initiated ART same-day or within 3 days, while the majority (N = 17) initiated between 4 and 30 days, and 17% (N = 5) initiated ART > 30 days. The median (range) age was 35, and most were English-speaking, Black or Hispanic men and identified as gay. Time to ART initiation was associated with time to linkage to care and time to viral suppression. Day 0-3 group's major theme was iART as stigma prevention, and they had the highest mean HIVSS, lowest MMI score, and a visit adherence of 0.86. Day 4-30 group's major theme was alleviation of internalized stigma, and they had the lowest mean HIVSS score, and highest visit adherence of 0.91. Day > 30 group's major theme was exacerbation of perceived or anticipated stigma, had the highest MMI score and a visit adherence of 0.85. iART implementation requires equitable strategies that address HIV-stigma and mistrust.
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Infecciones por VIH , Retención en el Cuidado , Masculino , Humanos , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Proyectos Piloto , ConfianzaRESUMEN
Topologically associating domain (TAD) boundaries partition the genome into distinct regulatory territories. Anecdotal evidence suggests that their disruption may interfere with normal gene expression and cause disease phenotypes1-3, but the overall extent to which this occurs remains unknown. Here we demonstrate that targeted deletions of TAD boundaries cause a range of disruptions to normal in vivo genome function and organismal development. We used CRISPR genome editing in mice to individually delete eight TAD boundaries (11-80 kb in size) from the genome. All deletions examined resulted in detectable molecular or organismal phenotypes, which included altered chromatin interactions or gene expression, reduced viability, and anatomical phenotypes. We observed changes in local 3D chromatin architecture in 7 of 8 (88%) cases, including the merging of TADs and altered contact frequencies within TADs adjacent to the deleted boundary. For 5 of 8 (63%) loci examined, boundary deletions were associated with increased embryonic lethality or other developmental phenotypes. For example, a TAD boundary deletion near Smad3/Smad6 caused complete embryonic lethality, while a deletion near Tbx5/Lhx5 resulted in a severe lung malformation. Our findings demonstrate the importance of TAD boundary sequences for in vivo genome function and reinforce the critical need to carefully consider the potential pathogenicity of noncoding deletions affecting TAD boundaries in clinical genetics screening.
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Cromatina , Genoma , Animales , Ratones , Cromatina/genética , FenotipoRESUMEN
BACKGROUND: Spectra™ VRE agar (Remel, Lenexa, KS) is a chromogenic agar that is FDA approved for screening patients for VRE colonization. The package insert recommends confirming isolates with identification and susceptibility testing, but confirming every culture delays time to result. Given the agar's historic high specificity for E. faecium isolates, we theorized the agar could be utilized as a stand-alone screening to minimize reagents and time. AIM: Our laboratory sought to develop a workflow to optimize the use of the medium. METHODS: We plated 3,815 rectal swabs to the Spectra VRE agar and compared results to traditional identification and susceptibility testing. RESULTS: Dark blue or purple colonies on the agar demonstrated a sensitivity of 98% and specificity of 85% for detection of VRE faecium, but light blue colonies were significantly less specific for E. faecalis. CONCLUSIONS: We streamlined our workflow to accept dark blue or purple colonies as VRE faecium and plan to perform additional testing only on light blue colonies. Interestingly, higher quantity of growth increased the accuracy of the agar. In the future, growth quantity may be used to further streamline the workflow once more data is obtained.
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Enterococcus faecium , Infecciones por Bacterias Grampositivas , Enterococos Resistentes a la Vancomicina , Humanos , Enterococcus faecalis , Agar , Vancomicina , Flujo de Trabajo , Resistencia a la Vancomicina , Infecciones por Bacterias Grampositivas/diagnóstico , Antibacterianos/farmacologíaRESUMEN
One-quarter of gay, bisexual, and other men who have sex with men (GBMSM) with diagnosed HIV are not engaged in HIV care. Between 2018 and 2019, 50 GBMSM completed qualitative interviews 3 months after receiving an HIV-positive result. Interviews explored barriers to and facilitators of engagement and retention in HIV testing and care. Thematic analysis revealed five major themes: (1) reason for HIV testing (e.g., self-testing), (2) linkage to care (e.g., appointment/logistic issues and social support as encouragement), (3) barriers to engagement in care (e.g., financial burden, competing priorities, and fear/stigma), (4) facilitators of engagement (e.g., financial assistance, patient-provider relationships, auxiliary support services, and health agency), and (5) PrEP as a missed prevention opportunity. Addressing individual-, social-, and policy-level barriers could improve GBMSM's engagement in HIV care. Further, capitalizing on GBMSM's health agency through partnerships with local agencies and fostering better patient-provider relationships could optimize HIV care continuity.
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Infecciones por VIH , Minorías Sexuales y de Género , Bisexualidad , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , Conducta Sexual , Estados UnidosRESUMEN
Cisgender men who have sex with men (cMSM) and transgender women (TGW) are disproportionally burdened by HIV. Among these populations, HIV partner-testing is a highly acceptable harm reduction tool. Particularly, cMSM and TGW report a stronger preference for blood-based tests that include assays for multiple STIs. However, no existing research has explored how these populations negotiate blood-based testing with sexual partners. In the SMARTtest study, 48 sexually active cMSM and TGW took home dual, blood-based HIV/Syphilis kits for self- and partner-testing. After 3 months, they completed a follow-up assessment and in-depth interviews about their experiences initiating testing. Of the 42 responding participants, 27 (64%) reported that it had been "fairly" or "very easy" to raise the idea of testing with partners. Participants predominantly employed partner-conscious communication strategies, including framing the testing proposal as a mandatory, non-personal component of their participation in a research study, gradually incorporating testing mentions into discussions about sexual health, and using the kits to facilitate joint testing. Yet, 21 (44%) participants reported having sex with at least one partner they did not ask to test. Concern regarding partner reactions emerged as a significant barrier to discussing test use; similarly, many partners were averse to taking a blood-based test in the context of a casual sexual encounter. Nonetheless, these findings suggest that dual, blood-based HIV/STI rapid tests may represent acceptable harm reduction tools among similar populations of cMSM and TGW, particularly if future partner-testing research is broadened to consider key couples' dynamics that may impact test usage.
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Infecciones por VIH , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Sífilis , Personas Transgénero , Femenino , Infecciones por VIH/diagnóstico , Homosexualidad Masculina , Humanos , Masculino , Negociación , Ciudad de Nueva York , Conducta Sexual , Parejas Sexuales , Sífilis/diagnósticoRESUMEN
BACKGROUND: Autoimmune autonomic ganglionopathy is a rare, immune-mediated disorder associated with anti-ganglionic α3-subunit nicotinic acetylcholine receptor (anti-α3gAChR) antibodies, which bind to acetylcholine receptor in autonomic ganglia (parasympathetic and sympathetic) leading to autonomic failure. This disorder is mostly associated with viral infections, but it can also be associated with systemic malignancies. Here, we report the case of a paraneoplastic autonomic ganglionopathy as the first symptom of bladder cancer. METHOD: Case report. RESULTS: A 47-year-old man, without medical history of interest, stated to the emergency department for progressive blurry vision with eye and mouth dryness, constipation, and dizziness upon standing for the last 2 weeks. Orthostatic hypotension was demonstrated by a drop in 13.3 mmHg mean blood pressure (BP) from supine (100/60 mmHg) to 45° reclining sitting position (80/50 mmHg). Blood tests, chest X-ray, brain MRI, and electroneuronography were unremarkable. Electrochemical skin conductance was reduced. Serological examination was positive for anti-α3gAChR antibodies. A full-body CT scan revealed a bladder tumor, which was treated by transurethral bladder resection. The pathologic study demonstrated a low-grade non-muscle-invasive bladder urothelial carcinoma. After tumor resection, and treatment with intravenous immunoglobulins and corticoids, a gradually improvement was observed. Today, the patient remains asymptomatic. CONCLUSION: Subacute panautonomic failure can be the first symptom for systemic malignancies. This case reports a paraneoplastic autonomic ganglionopathy as the first symptom of bladder cancer. This case highlights the importance of a systemic study to rule out the presence of cancer when autoimmune autonomic ganglionopathy is present.