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2.
J Med Virol ; 96(5): e29621, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38654686

RESUMO

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.


Assuntos
Surtos de Doenças , Humanos , Brasil/epidemiologia , Masculino , Feminino , Adulto , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Animais , Zoonoses/epidemiologia , Zoonoses/virologia , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/isolamento & purificação , Criança , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Anticorpos Antivirais/sangue , Idoso , Imunoglobulina G/sangue
3.
Cardiovasc Res ; 120(7): 769-781, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38501595

RESUMO

AIMS: Prevention of human hypertension is an important challenge and has been achieved in experimental models. Brief treatment with renin-angiotensin system (RAS) inhibitors permanently reduces the genetic hypertension of the spontaneously hypertensive rat (SHR). The kidney is involved in this fascinating phenomenon, but relevant changes in gene expression are unknown. METHODS AND RESULTS: In SHR, we studied the effect of treatment between 10 and 14 weeks of age with the angiotensin receptor blocker, losartan, or the angiotensin-converting enzyme inhibitor, perindopril [with controls for non-specific effects of lowering blood pressure (BP)], on differential RNA expression, DNA methylation, and renin immunolabelling in the kidney at 20 weeks of age. RNA sequencing revealed a six-fold increase in renin gene (Ren) expression during losartan treatment (P < 0.0001). Six weeks after losartan, arterial pressure remained lower (P = 0.006), yet kidney Ren showed reduced expression by 23% after losartan (P = 0.03) and by 43% after perindopril (P = 1.4 × 10-6) associated with increased DNA methylation (P = 0.04). Immunolabelling confirmed reduced cortical renin after earlier RAS blockade (P = 0.002). RNA sequencing identified differential expression of mRNAs, miRNAs, and lncRNAs with evidence of networking and co-regulation. These included 13 candidate genes (Grhl1, Ammecr1l, Hs6st1, Nfil3, Fam221a, Lmo4, Adamts1, Cish, Hif3a, Bcl6, Rad54l2, Adap1, Dok4), the miRNA miR-145-3p, and the lncRNA AC115371. Gene ontogeny analyses revealed that these networks were enriched with genes relevant to BP, RAS, and the kidneys. CONCLUSION: Early RAS inhibition in SHR resets genetic pathways and networks resulting in a legacy of reduced Ren expression and BP persisting for a minimum of 6 weeks.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Metilação de DNA , Modelos Animais de Doenças , Redes Reguladoras de Genes , Hipertensão , Rim , Losartan , Perindopril , Ratos Endogâmicos SHR , Sistema Renina-Angiotensina , Renina , Animais , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/genética , Rim/metabolismo , Rim/efeitos dos fármacos , Losartan/farmacologia , Hipertensão/fisiopatologia , Hipertensão/genética , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Metilação de DNA/efeitos dos fármacos , Masculino , Anti-Hipertensivos/farmacologia , Renina/genética , Renina/metabolismo , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Perindopril/farmacologia , Fatores de Tempo , Epigênese Genética/efeitos dos fármacos , Regulação da Expressão Gênica , Pressão Arterial/efeitos dos fármacos , Transcriptoma , Ratos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética
4.
J Clin Sleep Med ; 20(6): 983-990, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427322

RESUMO

STUDY OBJECTIVES: The aim of this study was to develop a sleep staging classification model capable of accurately performing on different wearable devices. METHODS: Twenty-three healthy participants underwent a full-night type I polysomnography and used two device combinations: (A) flexible single-channel electroencephalogram (EEG) headband + actigraphy (n = 12) and (B) rigid single-channel EEG headband + actigraphy (n = 11). The signals were segmented into 30-second epochs according to polysomnographic stages (scored by a board-certified sleep technologist; model ground truth) and 18 frequency and time features were extracted. The model consisted of an ensemble of bagged decision trees. Bagging refers to bootstrap aggregation to reduce overfitting and improve generalization. To evaluate the model, a training dataset under 5-fold cross-validation and an 80-20% dataset split was used. The headbands were also evaluated without the actigraphy feature. Participants also completed a usability evaluation (comfort, pain while sleeping, and sleep disturbance). RESULTS: Combination A had an F1-score of 98.4% and the flexible headband alone of 97.7% (error rate for N1: combination A = 9.8%; flexible headband alone = 15.7%). Combination B had an F1-score of 96.9% and the rigid headband alone of 95.3% (error rate for N1: combination B = 17.0%; rigid headband alone = 27.7%); in both, N1 was more confounded with N2. CONCLUSIONS: We developed an accurate sleep classification model based on a single-channel EEG device, and actigraphy was not an important feature of the model. Both headbands were found to be useful, with the rigid one being more disruptive to sleep. Future research can improve our results by applying the developed model in a population with sleep disorders. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Actigraphy, Wearable EEG Band and Smartphone for Sleep Staging; URL: https://clinicaltrials.gov/study/NCT04943562; Identifier: NCT04943562. CITATION: Melo MC, Vallim JRS, Garbuio S, et al. Validation of a sleep staging classification model for healthy adults based on 2 combinations of a single-channel EEG headband and wrist actigraphy. J Clin Sleep Med. 2024;20(6):983-990.


Assuntos
Actigrafia , Eletroencefalografia , Polissonografia , Fases do Sono , Adulto , Feminino , Humanos , Masculino , Actigrafia/instrumentação , Actigrafia/métodos , Actigrafia/estatística & dados numéricos , Eletroencefalografia/instrumentação , Eletroencefalografia/métodos , Voluntários Saudáveis , Polissonografia/instrumentação , Polissonografia/métodos , Reprodutibilidade dos Testes , Fases do Sono/fisiologia , Dispositivos Eletrônicos Vestíveis , Punho/fisiologia
5.
Microorganisms ; 12(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38543527

RESUMO

This study aimed to evaluate the antibacterial, leishmanicidal, and cytotoxic potential of metabolites produced by bacteria isolated from rhizosphere soil samples. The bacterium was identified by genome sequencing as Streptomyces kronopolitis. A preliminary screening was carried out for the antimicrobial activity of S. kronopolitis, demonstrating activity against Staphylococcus aureus ATCC 6538, Corynebacterium diphtheriae ATCC 27010, C. diphtheriae ATCC 27012, and Mycobacterium abscessus, with inhibition halos of sizes 25, 36, 29, and 33 mm, respectively. To obtain secondary metabolites, the bacteria were subjected to submerged fermentation, and the metabolites were extracted using the liquid-liquid method with ethyl acetate. There was a similar MIC for M. abscessus and the two strains of C. diphtherium, reaching a concentration of 12.5 µg/mL, while that of S. aureus was 0.048 µg/mL. Assays for leishmanicidal activity and cytotoxicity against HEp-2 cells and red blood cells were performed. The metabolite showed an IC50 of 9.0 ± 0.9 µg/mL and CC50 of 221.2 ± 7.0 µg/mL. This metabolite does not have hemolytic activity and is more selective for parasites than for mammalian cells, with a selectivity index of 24.6. Thus, the studied metabolite may be a strong candidate for the development of less toxic drugs to treat diseases caused by pathogens.

6.
J Appl Microbiol ; 135(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38323496

RESUMO

AIM: The objective of this study was to investigate the antimicrobial resistance genes (ARGs) in plasmids of Enterobacteriaceae from soil, sewage, and feces of food-producing animals and humans. METHODS AND RESULTS: The plasmid sequences were obtained from the NCBI database. For the identification of ARG, comprehensive antibiotic resistance database (CARD), and ResFinder were used. Gene conservation and evolution were investigated using DnaSP v.6. The transfer potential of the plasmids was evaluated using oriTfinder and a MOB-based phylogenetic tree was reconstructed using Fastree. We identified a total of 1064 ARGs in all plasmids analyzed, conferring resistance to 15 groups of antibiotics, mostly aminoglycosides, beta-lactams, and sulfonamides. The greatest number of ARGs per plasmid was found in enterobacteria from chicken feces. Plasmids from Escherichia coli carrying multiple ARGs were found in all ecosystems. Some of the most abundant genes were shared among all ecosystems, including aph(6)-Id, aph(3'')-Ib, tet(A), and sul2. A high level of sequence conservation was found among these genes, and tet(A) and sul2 are under positive selective pressure. Approximately 62% of the plasmids carrying at least one ARG were potentially transferable. Phylogenetic analysis indicated a potential co-evolution of Enterobacteriaceae plasmids in nature. CONCLUSION: The high abundance of Enterobacteriaceae plasmids from diverse ecosystems carrying ARGs reveals their widespread distribution and importance.


Assuntos
Antibacterianos , Enterobacteriaceae , Animais , Humanos , Enterobacteriaceae/genética , Antibacterianos/farmacologia , Filogenia , Ecossistema , Farmacorresistência Bacteriana/genética , Plasmídeos/genética , Escherichia coli/genética
7.
J Med Virol, v. 96, n. 5, e29621, mai. 2024
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5317

RESUMO

Mpox is a zoonotic disease historically reported in Africa. Since 2003, limited outbreaks have occurred outside Africa. In 2022, the global spread of cases with sustained interhuman transmission and unusual disease features raised public health concerns. We explore the mpox outbreak in Rio de Janeiro (RJ) state, Brazil, in an observational study of mpox-suspected cases from June to December 2022. Data collection relied on a public healthcare notification form. Diagnosis was determined by MPXV-PCR. In 46 confirmed cases, anti-OPXV IgG was determined by ELISA, and seven MPXV genomes were sequenced. A total of 3095 cases were included, 816 (26.3%) with positive MPXV-PCR results. Most positive cases were men in their 30 s and MSM. A total of 285 (34.9%) MPXV-PCR+ patients live with HIV. Eight were coinfected with varicella-zoster virus. Anogenital lesions and adenomegaly were associated with the diagnosis of mpox. Females and individuals under 18 represented 9.4% and 5.4% of all confirmed cases, respectively, showing higher PCR cycle threshold (Ct) values and fewer anogenital lesions compared to adult men. Anti-OPXV IgG was detected in 29/46 (63.0%) patients. All analyzed sequences belonged to clade IIb. In RJ state, mpox presented a diverse clinical picture, represented mainly by mild cases with low complication rates and prominent genital involvement. The incidence in females and children was higher than usually reported. The observation of a bimodal distribution of Ct values, with few positive results, may suggest the need to review the diagnostic criteria in these groups.

8.
Artigo em Inglês | LILACS-Express | LILACS, Index Psicologia - Periódicos | ID: biblio-1564846

RESUMO

Abstract The Psychology of Working Theory has achieved notable prominence in career studies for its focus on how various - both individual and contextual - influence careers and job outcomes. "Volition" stands out as one of the key elements of this theory, representing the individuals' ability to make career choices despite obstacles. This study aimed to adapt and validate both internal and external structures of the Work Volition Scale - Student Version (WVS-SV) to Brazil. A total of 590 university students from public and private institutions of varied courses and semesters, mostly women (59%), took part in the study. Exploratory and confirmatory factor analyses indicated that the scale effectively measured two dimensions: volition and constraints. External evidence, including satisfaction with life and career, supported the theoretical aspects of this construct. The results indicated good psychometric properties of the scale to the Brazilian setting, contributing to a better understanding of career choices among university students.


Resumo O modelo da Psicologia do Trabalhar tem se destacado nos estudos de carreira, abordando como variáveis contextuais e individuais influenciam a trajetória profissional. Um conceito-chave é a volição, que representa a capacidade de fazer escolhas de carreira diante de obstáculos. O objetivo desse estudo é adaptar e apresentar evidências de validade de estrutura interna e externa para o Brasil da Work Volition Scale - Student Version. Participaram 590 estudantes universitários de diferentes cursos e semestres, de instituições públicas e privadas, com uma predominância de mulheres (59%). As análises fatoriais exploratórias e confirmatórias mostraram uma estrutura adequada, composta por duas dimensões: restrições e volição. Além disso, identificaram-se evidências externas ao relacionar com a satisfação com a vida e a carreira. Os resultados indicam boas qualidades psicométricas da Work Volition Scale - Student Version no contexto brasileiro, contribuindo para melhorar a compreensão das escolhas de carreira entre os estudantes universitários.


Resumen El modelo de Psicología del Trabajo se ha destacado en estudios de carrera, explorando cómo las variables contextuales e individuales influyen en la trayectoria profesional. Un concepto clave es la volición, que representa la capacidad de la toma de decisiones de carrera frente a obstáculos. Este estudio buscó adaptar y presentar evidencias de validez de la estructura interna y externa para Brasil de la Work Volition Scale - Student Version. Participaron 590 estudiantes universitarios de diversos cursos y semestres, tanto de instituciones públicas como privadas, con predominio de mujeres (59%). Los análisis factoriales exploratorios y confirmatorios demostraron una estructura adecuada con dos dimensiones: restricciones y volición. Además, se identificaron evidencias externas al relacionarlas con la satisfacción en la vida y la carrera. Los resultados indican buenas cualidades psicométricas de la Work Volition Scale - Student Version en el contexto brasileño, contribuyendo a una mejor comprensión de las elecciones de carrera entre los estudiantes universitarios.

9.
Elife ; 122023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37772793

RESUMO

The pre-Bötzinger complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetized and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviors. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviors have been associated with the development and progression of diseases.


While breathing seems to come easy, it is a complex process in which many muscles coordinate to allow air to flow into the lungs. These muscles also control the flow of air we breathe out to allow us to talk, sing, eat, or drink. The brain circuits that control these muscles, can also influence other parts of the brain. The preBötzinger Complex, which is a key region of brainstem circuits that generate and control breathing, contains neurons that also project widely, connecting to other regions of the brain. This helps to modulate the sense of smell, emotional state, heart rate, and even blood pressure. Understanding how the preBötzinger Complex is organized can untangle how breathing can influence these other processes. Melo et al. wanted to learn whether they could manipulate the activity of a subgroup of preBötzinger Complex neurons that project into the facial nucleus ­ a region of the brain that controls the muscles of the face when we breathe ­ without affecting breathing. If this can be done, it might also be possible to affect blood pressure by manipulating selective preBötzinger neurons, and thus the development of hypertension, without having any impact on breathing. To test this hypothesis, Melo et al. used rats in which the activation of preBötzinger Complex neurons that project into the facial nucleus was blocked. This decreased the activity of the muscles around the nose with hardly any effect on breathing. Melo et al. also found that the state of consciousness of the rat (anesthetized or conscious) could affect how preBötzinger Complex neurons control these muscles. Melo et al. also observed that preBötzinger Complex neurons projecting into the facial nucleus had projections into many other regions in the brainstem. This might help to the coordinate respiratory, cardiovascular, orofacial, and potentially other physiological functions. The findings of Melo et al. set a technical foundation for exploring the influence of specific subgroups of preBötzinger Complex neurons on respiratory modulation of other physiological activities, including blood pressure and heart rate and in conditions, such as hypertension and heart failure. More broadly, most brain regions contain complex and heterogeneous groups of neurons and the strategy validated by Melo et. al. could be applied to unravel other brain-function relationships.


Assuntos
Núcleo do Nervo Facial , Ratos , Animais , Centro Respiratório , Respiração , Neurônios Motores , Tronco Encefálico
10.
J Hypertens ; 41(10): 1634-1644, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37466439

RESUMO

BACKGROUND: A growing body of evidence suggests that oxidative stress plays a role in the pathophysiology of hypertension. However, the involvement of the reactive oxygen species (ROS) in the commissural nucleus of the solitary tract (commNTS) in development the of hypertension remains unclear. METHOD: We evaluated the hemodynamic and sympathetic responses to acute inhibition of NADPH oxidase in the commNTS in renovascular hypertensive rats. Under anesthesia, male Holtzman rats were implanted with a silver clip around the left renal artery to induce 2-kidney 1-clip (2K1C) hypertension. After six weeks, these rats were anesthetized and instrumented for recording mean arterial pressure (MAP), renal blood flow (RBF), renal vascular resistance (RVR), and renal sympathetic nerve activity (RSNA) during baseline and after injection of apocynin (nicotinamide adenine dinucleotide phosphate oxidase inhibitor), NSC 23766 (RAC inhibitor) or saline into the commNTS. RESULTS: Apocynin into the commNTS decreased MAP, RSNA, and RVR in 2K1C rats. NSC 23766 into the commNTS decreased MAP and RSNA, without changing RVR in 2K1C rats. CONCLUSION: These results demonstrate that the formation of ROS in the commNTS is important to maintain sympathoexcitation and hypertension in 2K1C rats and suggest that NADPH oxidase in the commNTS could be a potential target for therapeutics in renovascular hypertension.


Assuntos
Hipertensão Renovascular , Hipertensão , Ratos , Masculino , Animais , Pressão Arterial , Núcleo Solitário/metabolismo , NADP , Espécies Reativas de Oxigênio , Pressão Sanguínea/fisiologia , Rim , Sistema Nervoso Simpático , Ratos Sprague-Dawley , NADPH Oxidases/metabolismo
11.
Front Immunol ; 14: 1220600, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37520570

RESUMO

Introduction: The pandemic caused by SARS-CoV-2 has had a major impact on health systems. Vaccines have been shown to be effective in improving the clinical outcome of COVID-19, but they are not able to fully prevent infection and reinfection, especially that caused by new variants. Methods: Here, we tracked for 450 days the humoral immune response and reinfection in 52 healthcare workers from Brazil. Infection and reinfection were confirmed by RT-qPCR, while IgM and IgG antibody levels were monitored by rapid test. Results: Of the 52 participants, 19 (36%) got reinfected during the follow-up period, all presenting mild symptoms. For all participants, IgM levels dropped sharply, with over 47% of them becoming seronegative by the 60th day. For IgG, 90% of the participants became seropositive within the first 30 days of follow-up. IgG antibodies also dropped after this period reaching the lowest level on day 270 (68.5 ± 72.3, p<0.0001). Booster dose and reinfection increased the levels of both antibodies, with the interaction between them resulting in an increase in IgG levels of 130.3 arbitrary units. Conclusions: Overall, our data indicate that acquired humoral immunity declines over time and suggests that IgM and IgG antibody levels are not associated with the prevention of reinfection.


Assuntos
COVID-19 , Imunidade Humoral , Humanos , SARS-CoV-2 , Brasil/epidemiologia , Estudos Longitudinais , Reinfecção , Imunoglobulina G , Pessoal de Saúde , Imunoglobulina M
12.
J Infect Public Health ; 16(7): 1081-1088, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37210925

RESUMO

BACKGROUND: COVID-19 has become a major public health problem after the outbreak caused by SARS-CoV-2 virus. Great efforts to contain COVID-19 transmission have been applied worldwide. In this context, accurate and fast diagnosis is essential. METHODS: In this prospective study, we evaluated the clinical performance of three different RNA-based molecular tests - RT-qPCR (Charité protocol), RT-qPCR (CDC (USA) protocol) and RT-LAMP - and one rapid test for detecting anti-SARS-CoV-2 IgM and IgG antibodies. RESULTS: Our results demonstrate that RT-qPCR using the CDC (USA) protocol is the most accurate diagnostic test among those evaluated, while oro-nasopharyngeal swabs are the most appropriate biological sample. RT-LAMP was the RNA-based molecular test with lowest sensitivity while the serological test presented the lowest sensitivity among all evaluated tests, indicating that the latter test is not a good predictor of disease in the first days after symptoms onset. Additionally, we observed higher viral load in individuals who reported more than 3 symptoms at the baseline. Nevertheless, viral load had not impacted the probability of testing positive for SARS-CoV-2. CONCLUSION: Our data indicates that RT-qPCR using the CDC (USA) protocol in oro-nasopharyngeal swabs samples should be the method of choice to diagnosis COVID-19.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Teste para COVID-19 , Estudos Prospectivos , Brasil/epidemiologia , Técnicas de Laboratório Clínico/métodos , Pessoal de Saúde , RNA , Imunoglobulina G , Imunoglobulina M , Sensibilidade e Especificidade
14.
Sci Adv ; 9(11): eade6675, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36921041

RESUMO

Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Here, we investigated the impact of the BAF complex inhibitor pyrimethamine on the reservoir of people living with HIV-1 (PLWH). Twenty-eight PLWH on suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLWH, substantiating its potential advancement in clinical studies.


Assuntos
Infecções por HIV , HIV-1 , Humanos , Linfócitos T CD4-Positivos , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Pirimetamina/farmacologia , Pirimetamina/uso terapêutico , RNA , Ácido Valproico/farmacologia , Ativação Viral , Latência Viral
15.
Saúde Soc ; 32(1): e210307pt, 2023.
Artigo em Português | LILACS | ID: biblio-1424477

RESUMO

Resumo Neste artigo, aprofunda-se a discussão crítica às políticas adotadas pelo governo Bolsonaro em relação à saúde pública, particularmente no que tange ao financiamento em geral, ao enfrentamento da pandemia e ao primeiro ano de implantação do novo modelo de "financiamento" para a Atenção Primária à Saúde (APS). A análise evidencia o acirramento da legitimidade restrita do regime político, assumida por políticas ultraneoliberais e pelo neofascismo do governo Bolsonaro. Estas formas de dominação - política e econômica - engendram uma conjuntura interna que visa remodelar a acumulação de capital na saúde pública via APS por meio de mecanismos "operacionais" burocráticos sutis de desconstrução da universidade do "financiamento". Na primeira parte, discute-se a abrangência da crise tripla do capital - sanitária, econômica e ecológica - e sua relação orgânica com o Estado no capitalismo dependente brasileiro, abrindo espaço para o crescimento da restrição do regime político endossado pela ascensão do neofascismo. Na segunda parte, aborda-se a escalada do desfinanciamento do Sistema Único de Saúde (SUS) em plena crise de covid-19 e os efeitos da implementação do modelo de financiamento da APS, evidenciando a continuidade do processo de valorização de um "SUS operacional" em detrimento do seu princípio de universalidade como dimensão neofascista do governo Bolsonaro.


Abstract This article deepens the critical discussion about the policies of the Bolsonaro government regarding public health, particularly regarding the general financing, the confrontation of the pandemic, and the first year of implementation of the new financing model for Primary Health Care (PHC). The analysis evidences the aggravation of the restrict legitimacy of the political regime, assumed by ultra-neoliberal policies and by the neofascism of the Bolsonaro government. These forms of domination - political and economic - produce an internal conjuncture that seeks to remodel the capital accumulation in public health by PHC by subtle bureaucratic "operational" mechanisms of deconstruction of financing universality. In the first part, the coverage of the triple crisis of the capital - sanitary, economic and ecological - and its organic relationship to the State in the Brazilian dependent capitalism is discussed, opening space to the increase of the restriction of the political regime endorsed by the ascension of the neofascism. In the second part, the increase of the de-financing of the Unified Health System (SUS) right in the middle of the covid-19 crisis and the effects of the implementation of the financing model of the PHC, evidencing the continuity of the process of valuing an "operational SUS" in detriment of its universality principle as a neofascist dimension of Bolsonaro's government.


Assuntos
Humanos , Masculino , Feminino , Política , Atenção Primária à Saúde , Estado , Financiamento da Assistência à Saúde , COVID-19 , Sistema Único de Saúde , Adaptação Psicológica , Fascismo
16.
Med Sci Educ ; 33(6): 1371-1378, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38188394

RESUMO

Understanding veterinary anatomy is an essential skill for the study of veterinary medicine as well as for diagnostic imaging and therapy. Dissection facilities are increasingly limited in some schools and its alternatives have often focussed on using two-dimensional images. However, the study of veterinary anatomy is mainly concerned with identifying structures and spatial relationships between them within a 3D space, and the use of 2D teaching approaches does not provide accurate information. We tested whether PlayDoh® student-built models could be an inexpensive potential tool beneficial to veterinary students learning anatomy in three distinct scenarios: (1) during a lecture, introducing a new concept; (2) during a flipped classroom approach where a video-podcast lecture was to be watched by the students prior to the lecture and (3) as a revision session where students brought their own questions and created, under supervision, their own models to respond to them. PlayDoh® sessions benefitted 172 first-year Veterinary Medicine and Animal Science students. The most accurate visualisation of anatomical structures in 3D was the principal benefit mentioned by the learners (35%). In addition, the learners noted that the technique would help with 'retention' (18%). According to the students' preferences, it was possible to create four groups: A, B, C and D. Group A encompassed the methodologies most liked by students and consisted of lectures, dissection and demonstrations. Group B included demonstrations and 3D modelling using PlayDoh®. Group C consisted of 3D modelling using PlayDoh®, books and online and, finally, group D included the methodologies least preferred by students, i.e. online and PBL. Our findings suggest that using 3D PlayDoh® modelling has potential as a method to enhance the learning of veterinary anatomy and may be most valuable to those students learning more complex subject areas that require a 3D teaching approach in practice. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01892-y.

17.
Rev. baiana enferm ; 37: e43919, 2023. tab
Artigo em Português | LILACS, BDENF - Enfermagem | ID: biblio-1529660

RESUMO

Objetivo: analisar a qualidade de vida de pessoas com úlceras do pé diabético em tratamento ambulatorial. Método: estudo descritivo e transversal, realizado entre fevereiro e abril de 2019, com 50 pessoas com Diabetes Mellitus, acompanhados em ambulatório especializado. Foram aplicados o questionário sociodemográfico e clínico, o instrumento Freiburg Life Quality Assessment Wound Versão Feridas (FLQA-WK), estatística descritiva e os testes de Comparação t de Student e Anova. Resultados: observou-se menor escore no domínio sintomas físicos (1.84) e maior no domínio vida diária (3.52). O escore total de qualidade de vida foi de 2.61, numa escala que varia de um a cinco, com correlação significativa entre as variáveis clínicas, como tempo de diagnóstico de diabetes >10 anos (p-valor=0,005), internações hospitalares (p-valor=0,019) e nefropatia (p-valor=0,001). Conclusão: a qualidade de vida foi considerada regular, com alteração no domínio vida diária, sendo influenciada negativamente por variáveis clínicas.


Objetivo: analizar la calidad de vida de personas con úlceras diabéticas en tratamiento ambulatorio. Método: estudio descriptivo y transversal, realizado entre febrero y abril de 2019, con 50 personas con Diabetes Mellitus, acompañados en ambulatorio especializado. Fueron aplicados el cuestionario sociodemográfico y clínico, el instrumento Freiburg Life Quality Assessment Wound Versión Heridas (FLQA-WK), estadística descriptiva y los test de Comparación t de Student y Anova. Resultados: se observó menor escore en el dominio síntomas físicos (1.84) y mayor en el dominio vida diaria (3.52). El puntaje total de calidad de vida fue de 2.61, en una escala que varía de uno a cinco, con correlación significativa entre las variables clínicas, como tiempo de diagnóstico de diabetes >10 años (p-valor=0,005), internaciones hospitalarias (p-valor=0,019) y nefropatía (p-valor=0,001). Conclusión: la calidad de vida fue considerada regular, con alteración en el dominio vida diaria, siendo influenciada negativamente por variables clínicas.


Objective: to analyze the quality of life of people with diabetic foot ulcers in outpatient treatment. Method: descriptive and cross-sectional study, conducted between February and April 2019, with 50 people with Diabetes Mellitus, followed in a specialized outpatient clinic. The sociodemographic and clinical questionnaire, the Freiburg Life Quality Assessment Wound Version (FLQA-WK), descriptive statistics and the Student's t-comparison and Anova tests were applied. Results: a lower score was observed in the physical symptoms domain (1.84) and a higher score in the daily life domain (3.52). The total quality of life score was 2.61, on a scale ranging from one to five, with significant correlation between clinical variables, such as time of diagnosis of diabetes >10 years (p-value=0.005), hospital admissions (p-value=0.019) and nephropathy (p-value=0.001). Conclusion: quality of life was considered regular, with changes in the daily life domain, being negatively influenced by clinical variables.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Qualidade de Vida , Pé Diabético , Diabetes Mellitus , Assistência Ambulatorial , Estudos Transversais
18.
Eur J Cancer Care (Engl) ; 31(6): e13758, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36285424

RESUMO

OBJECTIVE: This study aims to analyse patients' clinical profiles seen at an emergency unit of a public oncology reference hospital in Belo Horizonte, Brazil. METHODS: This is a cross-sectional, observational, retrospective study, with data collection through patients' medical records seen between 2016 and 2018. The identification of patients was carried out through research on hospital admission authorization guides. RESULTS: A total of 2932 medical records were evaluated, of which only 21.5% were cancer patients. A cancer diagnosis was made for 21.5% of patients during hospitalisation. In this group, pain and weight loss are frequent symptoms, and haematological diseases (15.2%) were the most frequent tumour type. Patients with a previous cancer diagnosis presented the most prevalent tumour breast (18.3%) and altered consciousness level as a leading symptom. Analgesics were the most prescribed drugs in both groups. CONCLUSION: This study showed two distinct groups of cancer patients: with or without a previous cancer diagnosis. However, these two groups are comparable in almost all the variables analysed. Therefore, we believe that the factors that could guide the care in an emergency are related to education on cancer symptoms for the population to contribute to an early diagnosis and cancer training for emergency department (ED) professionals' to better monitor advanced-stage patients for symptom management.


Assuntos
Serviço Hospitalar de Emergência , Neoplasias , Humanos , Estudos Retrospectivos , Estudos Transversais , Hospitalização , Neoplasias/terapia
19.
J Comp Neurol ; 530(17): 3072-3103, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35988033

RESUMO

Anatomical tracing studies examining the vagal system can conflate details of sensory afferent and motor efferent neurons. Here, we used a serotype of adeno-associated virus that transports retrogradely and exhibits selective tropism for vagal afferents, to map their soma location and central termination sites within the nucleus of the solitary tract (NTS). We examined the vagal sensory afferents innervating the trachea, duodenum, stomach, or heart, and in some animals, from two organs concurrently. We observed no obvious somatotopy in the somata distribution within the nodose ganglion. The central termination patterns of afferents from different organs within the NTS overlap substantially. Convergence of vagal afferent inputs from different organs onto single NTS neurons is observed. Abdominal and thoracic afferents terminate throughout the NTS, including in the rostral NTS, where the 7th cranial nerve inputs are known to synapse. To address whether the axonal labeling produced by viral transduction is so widespread because it fills axons traveling to their targets, and not just terminal fields, we labeled pre and postsynaptic elements of vagal afferents in the NTS . Vagal afferents form multiple putative synapses as they course through the NTS, with each vagal afferent neuron distributing sensory signals to multiple second-order NTS neurons. We observe little selectivity between vagal afferents from different visceral targets and NTS neurons with common neurochemical phenotypes, with afferents from different organs making close appositions with the same NTS neuron. We conclude that specific viscerosensory information is distributed widely within the NTS and that the coding of this input is probably determined by the intrinsic properties and projections of the second-order neuron.


Assuntos
Núcleo Solitário , Nervo Vago , Animais , Neurônios Motores , Neurônios Aferentes/fisiologia , Gânglio Nodoso , Ratos , Núcleo Solitário/fisiologia , Nervo Vago/fisiologia
20.
Neurosci Lett ; 787: 136817, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-35905886

RESUMO

Interruption of the activity of neurons in the commissural portion of the nucleus of the solitary tract (cNTS) decreases blood pressure (BP) in experimental models of hypertension, such as the spontaneously hypertensive (SH) rat. To examine whether PHOX2B expressing cNTS neurons are involved in maintaining the elevated BP, we used replication-deficient viruses with a modified Phox2 binding site promoter to express the inhibitory chemogenetic allatostatin receptor or green fluorescent protein in the cNTS. Following administration of allatostatin, we observed a depressor and bradycardic response in anesthetized SH rats that expressed the allatostatin receptor. Injection of allatostatin did not affect BP or heart rate (HR) in control SH rats expressing green fluorescent protein in the cNTS. Immunohistochemistry showed that the majority of transduced cNTS neurons were PHOX2B-immunoreactive and some also expressed tyrosine hydroxylase. We conclude that in anesthetized SH rat, the Phox2B expressing cNTS neurons maintain elevated BP.


Assuntos
Neurônios , Núcleo Solitário , Animais , Pressão Sanguínea , Proteínas de Fluorescência Verde/metabolismo , Frequência Cardíaca , Neurônios/metabolismo , Ratos , Ratos Endogâmicos SHR , Núcleo Solitário/metabolismo , Fatores de Transcrição/metabolismo
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