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Dermoscopy has been used for the non-invasive diagnosis of demodicosis. Several studies have evaluated the usefulness of this tool in the diagnosis, however, there are differences in the gold standard (SSSB or KOH test) and criteria of positivity used between studies. Added to this, is the lack of controls and objective quantification of the usefulness of dermoscopic signs in clinically observable and relevant ranges. To validate the usefulness of dermoscopy for the diagnosis of demodicosis by calculating the performance indicators for the different dermoscopic signs. Retrospective intrapatient case-control study, which included adults with suspicion of demodicosis. Dermoscopic photographs and scraping of healthy and lesional skin were obtained. Samples were analyzed microscopically by trained personnel. Photographs were evaluated by determining the presence of Demodex tails (DT), dilated follicular openings (DFO) and dilated blood vessels (DBV) in pre-defined ranges. 64 patients were included (total = 256 samples); the presence of demodex on skin scraping was seen in 69%. Under dermoscopy, the presence of DT in range 11-20/field had a positive likelihood ratio (LR) of 12.10 (95%CI 6.52-22.45) and negative LR 0.32 (95%CI 0.23-0.45). Combined and dichotomized performance for at least one positive sign under dermoscopy (DT > 10/field, DFO > 10/field or DBV > 50% of the field): positive LR 7.14 (95%CI 4.80-10.62) and negative LR 0.11 (95%CI 0.06-0.22). The presence of DT, DFO or DBV has a high correlation with a positive mite test, so the diagnosis of demodicosis could be made only through dermoscopy.
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Dermoscopia , Infestações por Ácaros , Ácaros , Humanos , Infestações por Ácaros/diagnóstico , Estudos Retrospectivos , Feminino , Adulto , Estudos de Casos e Controles , Masculino , Pessoa de Meia-Idade , Animais , Idoso , Pele/patologia , Pele/parasitologia , Pele/diagnóstico por imagem , Adulto JovemRESUMO
INTRODUCTION: Peruvian young transgender women (YTW) ages 16-24 years are a critical but understudied group for primary HIV prevention efforts, due to sharp increases in HIV prevalence among TW ages 25 years and older. METHODS: Between February and July 2022, a cross-sectional quantitative study with YTW ages 16-24 years in Peru (N = 211) was conducted consisting of a bio-behavioural survey accompanied by laboratory-based testing for HIV and sexually transmitted infections (STIs). Bivariate and multivariable Poisson regression models were used to estimate prevalence ratios between socio-demographic and behavioural characteristics and HIV status. RESULTS: HIV prevalence was 41.5% (95% CI: 33.9-49.4%), recent syphilis acquisition 19.4% (95% CI: 12.7-28.4), chlamydia 6.3% (95% CI: 3.1-11.1) and gonorrhoea 12.3% (95% CI: 7.9-18.7). Almost half (47.9%) reported condomless anal sex in the past 6 months, 50.7% reported sex work in the past 30 days and 13.7% reported accepting more money for condomless sex. There were no significant differences in reported sexual behaviours by HIV status. Only 60.8% of participants reported ever having been tested for HIV, and 25.6% reported a past 6-month STI test. More than two-thirds (67.8%) had not heard of antiretroviral pre-exposure prophylaxis (PrEP) and only 4.7% had taken PrEP in the past month. Current moderate-to-severe psychological distress was endorsed by 20.3%, 10.0% reported attempting suicide in the past 6 months and 85.4% reported alcohol misuse. CONCLUSIONS: Findings show that the HIV epidemic for YTW in Lima, Peru is situated in the context of widespread social exclusion, including economic vulnerabilities, violence victimization and the mental health sequelae of transphobic stigma that starts early in life. Future research should aim to further understand the intersection of these vulnerabilities. Moreover, there is an urgent necessity to design and evaluate HIV prevention programmes that address the root systems driving HIV vulnerabilities in YTW and that focus on developmentally specific clusters of stigma-related conditions.
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Infecções por HIV , Pessoas Transgênero , Humanos , Peru/epidemiologia , Pessoas Transgênero/psicologia , Pessoas Transgênero/estatística & dados numéricos , Adolescente , Feminino , Adulto Jovem , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Infecções por HIV/prevenção & controle , Estudos Transversais , Masculino , Prevalência , Comportamento Sexual/estatística & dados numéricos , Comportamento Sexual/psicologia , Infecções Sexualmente Transmissíveis/epidemiologia , Inquéritos e QuestionáriosRESUMO
Lineage plasticity is a recognized hallmark of cancer progression that can shape therapy outcomes. The underlying cellular and molecular mechanisms mediating lineage plasticity remain poorly understood. Here, we describe a versatile in vivo platform to identify and interrogate the molecular determinants of neuroendocrine lineage transformation at different stages of prostate cancer progression. Adenocarcinomas reliably develop following orthotopic transplantation of primary mouse prostate organoids acutely engineered with human-relevant driver alterations (e.g., Rb1-/-; Trp53-/-; cMyc+ or Pten-/-; Trp53-/-; cMyc+), but only those with Rb1 deletion progress to ASCL1+ neuroendocrine prostate cancer (NEPC), a highly aggressive, androgen receptor signaling inhibitor (ARSI)-resistant tumor. Importantly, we show this lineage transition requires a native in vivo microenvironment not replicated by conventional organoid culture. By integrating multiplexed immunofluorescence, spatial transcriptomics and PrismSpot to identify cell type-specific spatial gene modules, we reveal that ASCL1+ cells arise from KRT8+ luminal epithelial cells that progressively acquire transcriptional heterogeneity, producing large ASCL1+;KRT8- NEPC clusters. Ascl1 loss in established NEPC results in transient tumor regression followed by recurrence; however, Ascl1 deletion prior to transplantation completely abrogates lineage plasticity, yielding adenocarcinomas with elevated AR expression and marked sensitivity to castration. The dynamic feature of this model reveals the importance of timing of therapies focused on lineage plasticity and offers a platform for identification of additional lineage plasticity drivers.
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Insects are the largest group of animals when it comes to the number and diversity of species. Yet, with the exception of Drosophila, no information is currently available on the primary structure of their sperm nuclear basic proteins (SNBPs). This paper represents the first attempt in this regard and provides information about six species of Neoptera: Poecillimon thessalicus, Graptosaltria nigrofuscata, Apis mellifera, Nasonia vitripennis, Parachauliodes continentalis, and Tribolium castaneum. The SNBPs of these species were characterized by acetic acid urea gel electrophoresis (AU-PAGE) and high-performance liquid chromatography fractionated. Protein sequencing was obtained using a combination of mass spectrometry sequencing, Edman N-terminal degradation sequencing and genome mining. While the SNBPs of several of these species exhibit a canonical arginine-rich protamine nature, a few of them exhibit a protamine-like composition. They appear to be the products of extensive cleavage processing from a precursor protein which are sometimes further processed by other post-translational modifications that are likely involved in the chromatin transitions observed during spermiogenesis in these organisms.
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Sequência de Aminoácidos , Protaminas , Animais , Masculino , Protaminas/metabolismo , Protaminas/química , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/genética , Insetos/metabolismo , Dados de Sequência Molecular , Espermatozoides/metabolismoRESUMO
INTRODUCTION: Transgender women in the United States experience high HIV incidence and suboptimal Pre-exposure prophylaxis (PrEP) engagement. We sought to estimate PrEP initiation and discontinuation rates and characterize PrEP discontinuation experiences among a prospective cohort of transgender women. METHODS: Using a sequential, explanatory, mixed-methods design, 1312 transgender women at risk for HIV acquisition were enrolled from March 2018 to August 2020 and followed through July 2022 (median follow-up 24 months; interquartile range 15-36). Cox regression models assessed predictors of initiation and discontinuation. In-depth interviews were conducted among 18 participants, including life history calendars to explore key events and experiences surrounding discontinuations. Qualitative and quantitative data were integrated to generate typologies of discontinuation, inform meta-inferences and facilitate the interpretation of findings. RESULTS: 21.8% (n = 286) of participants reported taking PrEP at one or more study visits while under observation. We observed 139 PrEP initiations over 2127 person-years (6.5 initiations/100 person-years, 95% CI: 5.5-7.7). Predictors of initiation included identifying as Black and PrEP indication. The rate of initiation among those who were PrEP-indicated was 9.6 initiations/100 person-years (132/1372 person-years; 95% CI: 8.1-11.4). We observed 138 PrEP discontinuations over 368 person-years (37.5 discontinuations/100 person-years, 95% CI: 31.7-44.3). Predictors of discontinuation included high school education or less and initiating PrEP for the first time while under observation. Four discontinuation typologies emerged: (1) seroconversion following discontinuation; (2) ongoing HIV acquisition risk following discontinuation; (3) reassessment of HIV/STI prevention strategy following discontinuation; and (4) dynamic PrEP use coinciding with changes in HIV acquisition risk. CONCLUSIONS: PrEP initiation rates were low and discontinuation rates were high. Complex motivations to stop using PrEP did not consistently correspond with HIV acquisition risk reduction. Evidence-based interventions to increase PrEP persistence among transgender women with ongoing acquisition risk and provide HIV prevention support for those who discontinue PrEP are necessary to reduce HIV incidence in this population.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Infecções Sexualmente Transmissíveis , Pessoas Transgênero , Masculino , Humanos , Feminino , Estados Unidos/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Estudos de Coortes , Homossexualidade Masculina , Infecções Sexualmente Transmissíveis/epidemiologia , Estudos Prospectivos , Fármacos Anti-HIV/uso terapêutico , Profilaxia Pré-Exposição/métodosRESUMO
Transgender and gender diverse (TGD) people are affected by mental health inequities. Gender euphoria-positive emotions or joy in gender-may be associated with positive mental health. Between February 2019-July 2021, we surveyed 2,165 adult TGD patients (median age = 28 years; 29.2 % people of color; 29.6 % nonbinary; 81.0 % taking hormones) evaluating gender euphoria and mental health. Overall, 35.0 % self-reported gender euphoria, 50.9 % gender dysphoria, 23.5 % alcohol misuse, and 44.5 % resilience. Gender euphoria differed by race, gender, insurance, and hormone use, and was associated with reduced gender dysphoria (adjusted Odds Ratio[aOR] = 0.58; 95 % confidence interval [95 %CI] = 0.47-0.72) and alcohol misuse (aOR = 0.75; 95 %CI = 0.60-0.95), and increased resilience (aOR = 1.31; 95 %CI = 1.07-1.61). The construct of gender euphoria may be a promising mental health target.
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Alcoolismo , Pessoas Transgênero , Adulto , Humanos , Pessoas Transgênero/psicologia , Euforia , Identidade de Gênero , Saúde MentalRESUMO
BACKGROUND: Globally transgender women (TW) are at heightened vulnerability for HIV infection. In Lima Peru, sharp increases in HIV prevalence are seen among TW ages 25 years and older highlighting the need for early HIV prevention efforts for young TW. This study conducted in-depth qualitative interviews to elucidate the social and developmental contexts of HIV vulnerability for young TW in Lima Peru. METHODS: Between November 2019 and February 2020, young TW ages 16-24 years (n = 21) in Lima Peru were purposively sampled using in-person (e.g., face-to-face outreach) and online (e.g., social media, networking websites) social network-based methods. Interviews were conducted in Spanish and a rapid qualitative analysis was conducted using a modified immersion crystallization methodology to identify themes. RESULTS: Five themes emerged, informing the conceptualization of a Life Course Health Development Model of HIV Vulnerabilities and Resiliencies: (1) interpersonal contexts (family, school, partners, sexual debut, trans mothers); (2) structural vulnerabilities (poverty, educational constraints, migration, hostile environments, sex work, police violence); (3) concomitant mental health and psychosocial factors (discrimination, violence, depression, suicidality, substance use, life hopes/dreams/future expectations); (4) gender affirmation processes (gender identity development, hormones, surgery, legal name/gender marker change); (5) HIV prevention and treatment barriers (PrEP uptake, HIV care, condom use, risk reduction). CONCLUSIONS: Young TW experience formidable developmental challenges associated with transphobia, violence, and pre-maturely facing accelerated milestones. Developmentally and culturally appropriate interventions to mitigate HIV vulnerability in Peru are needed, including those that consider co-occurring stigma-related conditions in adolescence and young adulthood.
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Infecções por HIV , Pessoas Transgênero , Masculino , Adolescente , Humanos , Feminino , Adulto Jovem , Adulto , Infecções por HIV/epidemiologia , Identidade de Gênero , Acontecimentos que Mudam a Vida , Peru/epidemiologiaRESUMO
Ammonium (NH4+) is an essential nitrogen source for plants, but excessive exposure can trigger stress responses that vary among and within different plant species. This study investigated the phenotypic variations in response to ammonium nutrition in five oil palm genotypes seedlings. Nitrate nutrition was used as a reference for a non-stressful condition, and three different nitrogen concentrations (5, 10, and 15 mM) were examined. Control groups without external nitrogen application were included for each genotype. Several parameters were analyzed, including plant growth, root length, gas exchange, fluorescence, chlorophyll, reducing sugars, amino acids, proteins, and nitrogen uptake. The results revealed a significant genotype effect, particularly between the interspecific OxG hybrid and the Elaeis guinensis genotypes. Ammonium nutrition increased shoot growth in all genotypes compared to nitrate nutrition. Additionally, there was a trend towards increased primary root length, amino acids, proteins, and nitrogen uptake under ammonium supply. These findings are promising, particularly considering the recommendation to use ammonium with inhibitors for environmental sustainability.
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BACKGROUND: Migration is recognized as a key determinant of health. Yet, limited research addresses the arc of intranational migration and, even less, the experiences of transgender (trans) adolescents and women migrants and the associated health vulnerabilities. Using intersectional stigma as a theoretical frame, this study seeks to better understand the sexual health vulnerabilities and needs of trans women migrants in Peru. METHODS: Between October and November 2016, in-depth interviews (n = 14) and two focus groups (n = 20) were conducted in Spanish with trans women in three Peruvian cities. To explore pre- and during migration experiences, focus groups were conducted in Pucallpa and Iquitos, key cities in the Amazon where trajectories often originate. To assess during migration and post-migration experiences, we conducted interviews in Pucallpa, Iquitos, and Lima to better understand processes of relocation. Audio files were transcribed verbatim and analysed via an immersion crystallization approach, an inductive and iterative process, using Dedoose (v.6.1.18). RESULTS: Participants described migration as an arc and, thus, results are presented in three phases: pre-migration; during migration; and post-migration. Intersectional stigma was identified as a transversal theme throughout the three stages of migration. The pre-migration stage was characterized by poverty, transphobia, and violence frequently motivating the decision to migrate to a larger city. Exploitation was also described as pervasive during migration and in relocation. Many participants spoke of their introduction to sex work during migration, as key to economic earning and associated violence (police, clients). CONCLUSION: Findings advance understandings of intranational migration and forced displacement as key determinants of trans women's health. Dimensions of violence at the intersection of classism and cisgenderism render trans women highly vulnerable at every step of their migratory journeys. Experiences of intranational mobility and relocation were described as uniquely tied to age, intersectional transphobic stigma, engagement in sex work, and multiple forms of violence, which impact and can magnify sexual health vulnerabilities for transgender women in Peru who migrated intranationally.
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Infecções por HIV , Pessoas Transgênero , Humanos , Feminino , Adolescente , Peru , Estigma Social , Trabalho Sexual , ViolênciaRESUMO
BACKGROUND: Young adults who are transgender and/or nonbinary (TNB) experience discrimination, violence, and other social stressors as a result of cissexism, the system of power relations that marginalizes people whose genders diverge from sociocultural expectations for the sex they were assigned at birth. However, variation in TNB young adults' exposure to social stressors across gender groups, particularly specific nonbinary gender groups (e.g., agender, genderqueer), has not been well characterized. METHODS: We analyzed data from an online cross-sectional survey of U.S. TNB young adults (N = 667; ages 18-30 years; 44% White, 24% multiracial, 14% Black, 10% Latinx, 7% Asian, 1% another race/ethnicity), assessing gender non-affirmation; cissexist discrimination, rejection, and victimization; general discrimination; sexual assault victimization; and psychological, physical, and sexual abuse in childhood/adolescence. We used generalized linear models to test for variation in stressors across six gender groups (transgender woman [n = 259], transgender man [n = 141], agender [n = 36], gender fluid [n = 30], genderqueer [n = 51], nonbinary [n = 150]) and compare each group to the full sample. We performed similar analyses among nonbinary gender groups. RESULTS: Exposure to stressors was considerable in all groups. Several stressors (e.g., past-year cissexist discrimination) did not vary significantly by gender group. Compared to the full sample, transgender women reported greater lifetime cissexist rejection and lifetime and past-year cissexist victimization. Compared to the full sample, transgender men and women reported greater lifetime cissexist discrimination and lower past-year gender non-affirmation. No stressors varied significantly across nonbinary gender groups. CONCLUSION: Among TNB young adults, women, men, and nonbinary people experience distinct patterns of some (though not all) stigma-related stressors. Decisions about (dis)aggregating research participants by gender group, or providing gender-tailored services for TNB people, should account for patterning of pertinent stressors. Efforts to eliminate structural cissexism should address intersections with other systems of power relations, including sexism and binary normativity.
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Vítimas de Crime , Pessoas Transgênero , Adolescente , Recém-Nascido , Humanos , Feminino , Masculino , Adulto Jovem , Pessoas Transgênero/psicologia , Estudos Transversais , Identidade de Gênero , ViolênciaRESUMO
INTRODUCTION: Transgender women (TW) experience an increased risk of human immunodeficiency virus (HIV) acquisition. This study identified patterns of HIV awareness and prevention strategies used by TW who were not living with HIV. METHODS: Data were drawn from a baseline survey of the LITE Study, a multi-site cohort of TW in Eastern and Southern United States (March 2018-August 2020). We conducted a latent class analysis to identify classes of HIV awareness and prevention strategies among TW who reported past 12-month sexual activity (N = 958) using 10 variables spanning HIV knowledge, receipt and use of HIV prevention strategies, and sexual practices. Due to differences across the cohort arms, classes were estimated separately for TW enrolled in site-based versus online study arms. We identified demographic characteristics, gender-affirming indicators and HIV vulnerabilities associated with class membership. RESULTS: Four parallel classes emerged: class 1 "limited strategies-less sexually active" (15% and 9%, site-based and online, respectively), class 2 "limited strategies-insertive sex" (16%/36%), class 3 "limited strategies-receptive sex" (33%/37%) and class 4 "multiple strategies-insertive and receptive sex" (36%/18%). Across all classes, condomless sex, pre-exposure prophylaxis (PrEP)/post-exposure prophylaxis (PEP) prevention knowledge and awareness were high but reported PrEP/PEP use was low. Compared with class 1, membership in class 4 was associated with being a person of colour (site-based OR = 2.15, 95% CI = 1.15-4.00, online OR = 4.54, 95% CI = 1.09-18.81) increased odds of self-perceived medium-to-high HIV risk (site-based OR = 4.12, 95% CI = 2.17-7.80, online OR = 11.73, 95% CI = 2.98-46.13), sexually transmitted infections (STI) diagnosis (site-based OR = 6.69, 95% CI = 3.42-13.10, online OR = 8.46, 95% CI = 1.71-41.78), current sex work (site-based OR = 6.49, 95% CI = 2.61-16.11, online OR = 10.25, 95% CI = 1.16-90.60) and 2-4 sexual partners in the last 3 months (site-based OR = 2.61, 95% CI = 1.33-5.13). Class 3, compared with class 1, had increased odds of current sex work partners (site-based OR = 3.09, 95% CI = 1.19-8.07) and of having 2-4 sexual partners in the last 3 months (site-based OR = 3.69, 95% CI = 1.85-7.39). CONCLUSIONS: TW have varied HIV awareness and prevention strategy utilization, with clear gaps in the uptake of prevention strategies. Algorithms derived from latent class membership may be used to tailor HIV prevention interventions for different subgroups and those reached through facility-based or digital methods.
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Infecções por HIV , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Pessoas Transgênero , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Estados Unidos/epidemiologia , Sexo sem ProteçãoRESUMO
PURPOSE: Victimization contributes to mental and behavioral health inequities among transgender and gender diverse (TGD) people, but few studies have simultaneously examined health-promoting resiliencies. We sought to identify classes of risk and resilience among TGD adults, assess characteristics associated with these classes, and examine their relationship with mental health and substance use outcomes. METHODS: Cross-sectional data were from the 2015 US Transgender Survey, a non-probability study including 26,957 TGD adults. Using latent class analysis, we classified patterns of vulnerability and resilience based on risk (past-year denial of equal treatment, verbal harassment, physical attack, bathroom-related discrimination; lifetime sexual assault, intimate partner violence) and protective (activism; family, work, classmate support) factors. Regression models were fit to (1) determine the association between sociodemographic and gender affirmation characteristics and latent classes; (2) model associations between latent classes and mental health (current serious psychological distress, past-year and lifetime suicidal thoughts and attempts, and lifetime gender identity/transition-related counseling) and substance use (current binge alcohol use, smoking, illicit drug use; past-year drug/alcohol treatment) outcomes. RESULTS: Three latent classes were identified: high risks, with activism involvement ("risk-activism," 35%); low risks, with not being out about one's TGD identity ("not-out," 25%); and low risks, with high family support ("family-support," 40%). Gender affirmation and sociodemographic characteristics, such as race/ethnicity and sexual orientation, were associated with latent classes. Risk-activism class membership was associated with higher odds of negative mental health and substance use outcomes, while the family-support class had lower odds of these outcomes. CONCLUSIONS: Interventions leveraging family support, and policy protections from discrimination and victimization, may promote TGD mental and behavioral health.
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Transtornos Relacionados ao Uso de Substâncias , Pessoas Transgênero , Adulto , Feminino , Humanos , Masculino , Pessoas Transgênero/psicologia , Identidade de Gênero , Saúde Mental , Estudos Transversais , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Lung cancer is the leading cause of cancer-related death worldwide. Lung adenocarcinoma (LUAD), the most common histological subtype, accounts for 40% of all cases. While existing genetically engineered mouse models (GEMMs) recapitulate the histological progression and transcriptional evolution of human LUAD, they are time-consuming and technically demanding. In contrast, cell line transplant models are fast and flexible, but these models fail to capture the full spectrum of disease progression. Organoid technologies provide a means to create next-generation cancer models that integrate the most advantageous features of autochthonous and transplant-based systems. However, robust and faithful LUAD organoid platforms are currently lacking. Here, we describe optimized conditions to continuously expand murine alveolar type 2 (AT2) cells, a prominent cell of origin for LUAD, in organoid culture. These organoids display canonical features of AT2 cells, including marker gene expression, the presence of lamellar bodies, and an ability to differentiate into the AT1 lineage. We used this system to develop flexible and versatile immunocompetent organoid-based models of KRAS, BRAF, and ALK mutant LUAD. Notably, organoid-based tumors display extensive burden and complete penetrance and are histopathologically indistinguishable from their autochthonous counterparts. Altogether, this organoid platform is a powerful, versatile new model system to study LUAD.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Animais , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Organoides , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Receptores Proteína Tirosina Quinases/metabolismoRESUMO
Centers for the research of patients with pulmonary hypertension (PH) usually perform right cardiac catheterization (RHC) to document this hemodynamic condition; traditionally, the procedure is performed by the interventional cardiologist, while the interventional radiologist generally conducts the study of hepatic hemodynamics. In our center, where the leading cause of catheterization of the hepatic veins is orthotopic liver transplantation, the cardio-pulmonologist performs the procedure to diagnose the possibility of porto-pulmonary hypertension and its implications. Routine measurement of the hepatic venous pressure gradient (HVPG) during RHC is not recommended but is performed to confirm the diagnosis of portal hypertension (PoH). Our objective in this review was to graphically describe the technique of hemodynamic recording of suprahepatic veins in patients with chronic liver disease and PoH who are in liver transplant protocol. The concepts included in this manuscript are measuring portal pressure, the definition of the hepatic venous pressure gradient (HVPG), procedures for a correct measurement of the HVPG, techniques associated with a suprahepatic vein catheterization, contraindications, and complications of HVPG, and clinical applications of HVPG. Clinically significant PoH is defined as an increase in GPVH ≥10 mmHg. HVPG measurement is currently the best available method for assessing the presence and severity of PoH. The RHC is the standard gold method for diagnosing PoPH that confirms its existence and provides additional data to exclude other causes of PAH in liver transplant candidates.
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Hipertensão Portal , Hipertensão Pulmonar , Cateterismo Cardíaco/efeitos adversos , Hemodinâmica , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/etiologia , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Pressão na Veia PortaRESUMO
The GATA4 transcription factor acts as a master regulator of development of multiple tissues. GATA4 also acts in a distinct capacity to control a stress-inducible pro-inflammatory secretory program that is associated with senescence, a potent tumor suppression mechanism, but also operates in non-senescent contexts such as tumorigenesis. This secretory pathway is composed of chemokines, cytokines, growth factors, and proteases. Since GATA4 is deleted or epigenetically silenced in cancer, here we examine the role of GATA4 in tumorigenesis in mouse models through both loss-of-function and overexpression experiments. We find that GATA4 promotes non-cell autonomous tumor suppression in multiple model systems. Mechanistically, we show that Gata4-dependent tumor suppression requires cytotoxic CD8 T cells and partially requires the secreted chemokine CCL2. Analysis of transcriptome data in human tumors reveals reduced lymphocyte infiltration in GATA4-deficient tumors, consistent with our murine data. Notably, activation of the GATA4-dependent secretory program combined with an anti-PD-1 antibody robustly abrogates tumor growth in vivo.
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Transporte Biológico/fisiologia , Fator de Transcrição GATA4/metabolismo , Neoplasias/metabolismo , Linfócitos T Citotóxicos/metabolismo , Animais , Anticorpos Monoclonais Humanizados , Quimiocina CCL2/metabolismo , Fator de Transcrição GATA4/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio , Humanos , Evasão da Resposta Imune , Pulmão/patologia , Melanoma , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Neoplasias/imunologia , Neoplasias/patologia , TranscriptomaRESUMO
This study aimed to identify Top, Bottom, and Versatile sexual role identities and anal sex behavior profiles using latent class analysis in a sample of 942 sexual minority men living in Bogotá. A Versatile-insertive and receptive class (52.2%) was the most prevalent of the four resulting classes, whereas the least common was a class (1.7%) that did not use labels and had a low probability of anal sex. We examined whether identity and relational factors (i.e., sexual orientation, LGBT collective identity, and partner type) were associated with profiles. Gay identity was associated with versatile and receptive classes and bisexual identity was associated with insertive and versatile classes. LGBT collective identity was associated with the class characterized by Bottom identity and receptive positioning. Partner type was not associated with class membership, but versatile behaviors were more common among encounters with a main partner. Models using data at different timescales offered consistent patterns of behavior between the last encounter and the past three months, though the versatile class in the three-month model split into two classes based on frequency of versatile positioning. Findings highlight the relationship between sexual identity and positioning and can inform interventions for sexual health education and identity development.
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Infecções por HIV , Minorias Sexuais e de Gênero , Bissexualidade , Colômbia , Feminino , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual , Parceiros SexuaisRESUMO
Sexual role identities for anal sex and anal sex positionings are often conflated in research. This study aimed to identify profiles of sexual minority men based on sexual role identity and anal sex positioning and determine correlates of these profiles, including individual (i.e., HIV-status identity, condom use, partner type, sexual orientation) and cultural (i.e., same-race partnering, country of birth, acculturation) factors. A sample of Brazilian, Colombian, and Dominican immigrant sexual minority men (n = 480) living in New York City were surveyed about identity and positioning at the two most recent encounters. Individual and cultural factors were examined as correlates of profiles identified through latent class analysis. Four latent classes were identified: No Labels (12%), Receptive Bottoms (16%), Insertive Tops (23%), Insertive and Receptive Versatiles (49%). We found a concordance rate of ~70% between identity and behavior. A proportion (12%) of behaviorally versatile men chose not to use sexual role labels. Living with HIV was associated with receptive and versatile classes, sex with main partners was associated with versatility, and sexual orientation differed across classes. Identity and behavior should not be used interchangeably in research or applied domains, particularly given the complexities of versatility and men who prefer to not use labels.
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Emigrantes e Imigrantes , Infecções por HIV , Minorias Sexuais e de Gênero , Brasil , Colômbia , Preservativos , República Dominicana , Feminino , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual , Parceiros SexuaisRESUMO
Adipose tissue total amount, distribution, and phenotype influence metabolic health. This may be partially mediated by the metabolic effects that these adipose tissue characteristics exert on the nearby and distant tissues. Thus, adipose tissue may influence the capacity of cells, tissues, and the organism to adapt fuel oxidation to fuel availability, i.e., their metabolic flexibility (MetF). Our aim was to systematically review the evidence for an association between adipose tissue characteristics and MetF in response to metabolic challenges in human adults. We searched in PubMed (last search on September 4, 2021) for reports that measured adipose tissue characteristics (total amount, distribution, and phenotype) and MetF in response to metabolic challenges (as a change in respiratory quotient) in humans aged 18 to <65 years. Any study design was considered, and the risk of bias was assessed with a checklist for randomized and non-randomized studies. From 880 records identified, 22 remained for the analysis, 10 of them measured MetF in response to glucose plus insulin stimulation, nine in response to dietary challenges, and four in response to other challenges. Our main findings were that: (a) MetF to glucose plus insulin stimulation seems inversely associated with adipose tissue total amount, waist circumference, and visceral adipose tissue; and (b) MetF to dietary challenges does not seem associated with adipose tissue total amount or distribution. In conclusion, evidence suggests that adipose tissue may directly or indirectly influence MetF to glucose plus insulin stimulation, an effect probably explained by skeletal muscle insulin sensitivity. Systematic Review Registration: PROSPERO [CRD42020167810].
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Monoclonal gammopathies of uncertain significance (MGUS) correspond to pre-malignant hematological disorders characterized by the production of a monoclonal protein and infiltration of less than 10% of the bone marrow by plasma cells. Its importance lies in the risk of progression to malignant disorders and in the association with different renal, neurological and skin manifestations. There are pathophysiological mechanisms that support a causal relationship between monoclonal gammopathies (MGs) and different skin diseases, such as type I cryoglobulinemia (CG), primary systemic amyloidosis (PSA) or necrobiotic xanthogranuloma (NXG). However, there is a group of skin diseases associated with MGs whose pathogenesis has not been elucidated. In this context, the role of the dermatologist is crucial in the suspicion of different haematological disorders based on skin manifestations and in the multidisciplinary treatment of these patients. In this article, we carry out an exhaustive review of the literature published in this area and propose a screening algorithm for MGs in patients with specific skin diseases.