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1.
bioRxiv ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38895230

RESUMO

Identifying cell types and states remains a time-consuming and error-prone challenge for spatial biology. While deep learning is increasingly used, it is difficult to generalize due to variability at the level of cells, neighborhoods, and niches in health and disease. To address this, we developed TACIT, an unsupervised algorithm for cell annotation using predefined signatures that operates without training data, using unbiased thresholding to distinguish positive cells from background, focusing on relevant markers to identify ambiguous cells in multiomic assays. Using five datasets (5,000,000-cells; 51-cell types) from three niches (brain, intestine, gland), TACIT outperformed existing unsupervised methods in accuracy and scalability. Integration of TACIT-identified cell with a novel Shiny app revealed new phenotypes in two inflammatory gland diseases. Finally, using combined spatial transcriptomics and proteomics, we discover under- and overrepresented immune cell types and states in regions of interest, suggesting multimodality is essential for translating spatial biology to clinical applications.

2.
Arch Dermatol Res ; 316(5): 156, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734816

RESUMO

Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus, and chronic skin colonization by Staphylococcus aureus. To understand the inflammatory status in AD, we investigated the inflammasome complex, that activates ASC (Apoptosis-associated speck-like protein containing a CARD), caspase-1 and GSDMD (gasdermin-D), and production of IL-1ß and IL-18. We aimed to evaluate the expression of the inflammasome pathway in the skin of adults with AD. Thirty patients with moderate to severe AD and 20 healthy controls were enrolled in the study. We performed the analysis of the inflammasome components NLRP1, NLRP3, AIM-2, IL-1ß, IL-18, Caspase-1, ASC, GSDMD, and CD68 expression (macrophage marker) by immunohistochemistry and immunofluorescence. The main findings included increased expression of NLRP3, NLRP1 and AIM-2 at dermal level of severe AD; augmented IL-18 and IL-1ß expression at epidermis of moderate and severe patients, and in the dermis of severe AD; augmented expression of ASC, caspase-1 and GSDMD in both epidermis and dermis of moderate and severe AD. We detected positive correlation between caspase-1, GSDMD and IL-1ß (epidermis) and caspase-1 (dermis) and AD severity; NLRP3, AIM-2 and IL-1ß, and NLRP3 with IL-18 in the epidermis; ASC, GSDMD and IL-1ß, and NLRP3, AIM-2, caspase-1, and IL-18 in the dermis. We also evidenced the presence of CD68+ macrophages secreting GSDMD, ASC and IL-1ß in moderate and severe AD. Cutaneous macrophages, early detected in moderate AD, have its role in the disease inflammatory mechanisms. Our study indicates a canonical activation pathway of inflammasomes, reinforced by the chronic status of inflammation in AD. The analysis of the inflammasome complex evidenced an imbalance in its regulation, with increased expression of the evaluated components, which is remarkably in severe AD, emphasizing its relevance as potential disease biomarkers and targets for immunomodulatory interventions.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Caspase 1 , Dermatite Atópica , Inflamassomos , Macrófagos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Estudos de Casos e Controles , Caspase 1/metabolismo , Molécula CD68 , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Proteínas de Ligação a DNA , Epiderme/imunologia , Epiderme/metabolismo , Epiderme/patologia , Gasderminas , Inflamassomos/metabolismo , Inflamassomos/imunologia , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Índice de Gravidade de Doença , Pele/patologia , Pele/imunologia , Pele/metabolismo
3.
Curr HIV Res ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38752644

RESUMO

BACKGROUND: The time elapsed since HIV infection diagnosis (TdiagHIV) affects the quality of life (QoL) and can get worse when chronic illnesses start. OBJECTIVE: The aim of this study was to analyze the impact of metabolic syndrome (MetS) and cardiovascular risk (CVR) on the QoL of people living with HIV (PLHIV). METHODS: Cross-sectional study, with 60 PLHIV followed at a Reference Center in the city of Jataí, Goiás, Brazil. Data collection involved sociodemographic, clinical, CVR, MetS, and QoL information. The data were analyzed using descriptive and inferential statistics, with the BioEstat 5.3 program adopting p0.05. RESULTS: There was a predominance of men (61.7%), aged ≥38 years (53.3%), with a TdiagHIV of 97.88Añ85.65 months and use of antiretroviral therapy (ART) of 80.13Añ69.37 months. The worst domain of QoL was concern about confidentiality (40 points), and the best was medication concerns (95 points). MetS predominated at 18.3% and a moderate CVR at 11.7%. MetS was positively associated with age 38 years, the female sex, with the lowest score in QoL for general function, and the highest for TdiagHIV and the use of ART (p0.05). A moderate CRV was positively related to higher TdiagHIV and ART use, and low HDL-c, and the lowest score for QoL was found for trust in a professional (p0.05). CONCLUSION: PLHIV who are older, have a higher TdiagHIV, and use ART are more likely to develop MetS and moderate CVR. The presence of these diseases in PLHIV causes impairment in areas of QoL.

4.
Respir Res ; 25(1): 129, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500106

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity. METHODS: We compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis. RESULTS: We observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO2/FiO2 ratio, and positively correlated with bronchopneumonia percentage and hyaline membrane score. RAGE tissue expression was negatively correlated with mechanical ventilation duration in both ARDS and septic groups. In septic patients, elafin was positively correlated with ICU admission length, SP-D was positively correlated with serum lactate and RAGE was correlated with C-reactive protein. CONCLUSIONS: Lung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients.


Assuntos
Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Sepse , Humanos , Elafina , Proteína D Associada a Surfactante Pulmonar , Pulmão , Síndrome do Desconforto Respiratório/diagnóstico , Sepse/diagnóstico , Sepse/complicações
5.
Sci Rep ; 14(1): 2688, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302568

RESUMO

An ideal blood biomarker for stroke should provide reliable results, enable fast diagnosis, and be readily accessible for practical use. Neuron-specific enolase (NSE), an enzyme released after neuronal damage, has been studied as a marker for brain injury, including cerebral infarction. However, different methodologies and limited sample sizes have restricted the applicability of any potential findings. This work aims to determine whether NSE levels at Emergency Department (ED) admission correlate with stroke severity, infarcted brain volume, functional outcome, and/or death rates. A systematic literature review was performed using PubMed, Embase, and Scopus databases. Each reviewer independently assessed all published studies identified as potentially relevant. All relevant original observational studies (cohort, case-control, and cross-sectional studies) were included. Eleven studies (1398 patients) met the inclusion criteria. Among these, six studies reported a significant correlation between NSE levels and stroke severity, while only one found no association. Four studies indicated a positive relationship between infarcted brain volume assessed by imaging and NSE levels, in contrast to the findings of only one study. Four studies identified an association related to functional outcome and death rates, while three others did not reach statistical significance in their findings. These data highlight that NSE levels at ED admissions proved to be a promising tool for predicting the outcome of ischemic stroke patients in most studies. However, they presented high discrepancies and low robustness. Therefore, further research is necessary to establish and define the role of NSE in clinical practice.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Biomarcadores , Estudos Transversais , Infarto , AVC Isquêmico/diagnóstico por imagem , Fosfopiruvato Hidratase , Prognóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Volume Sistólico
6.
An. bras. dermatol ; 99(1): 72-79, Jan.-Feb. 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1527691

RESUMO

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.

7.
Eur J Radiol Open ; 12: 100546, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38293283

RESUMO

Objectives: Performing autopsies in a pandemic scenario is challenging, as the need to understand pathophysiology must be balanced with the contamination risk. A minimally invasive autopsy might be a solution. We present a model that combines radiology and pathology to evaluate postmortem CT lung findings and their correlation with histopathology. Methods: Twenty-nine patients with fatal COVID-19 underwent postmortem chest CT, and multiple lung tissue samples were collected. The chest CT scans were analyzed and quantified according to lung involvement in five categories: normal, ground-glass opacities, crazy-paving, small consolidations, and large or lobar consolidations. The lung tissue samples were examined and quantified in three categories: normal lung, exudative diffuse alveolar damage (DAD), and fibroproliferative DAD. A linear index was used to estimate the global severity of involvement by CT and histopathological analysis. Results: There was a positive correlation between patient mean CT and histopathological severity score indexes - Pearson correlation coefficient (R) = 0.66 (p = 0.0078). When analyzing the mean lung involvement percentage of each finding, positive correlations were found between the normal lung percentage between postmortem CT and histopathology (R=0.65, p = 0.0082), as well as between ground-glass opacities in postmortem CT and normal lungs in histopathology (R=0.65, p = 0.0086), but negative correlations were observed between ground-glass opacities extension and exudative diffuse alveolar damage in histological slides (R=-0.68, p = 0.005). Additionally, it was found is a trend toward a decrease in the percentage of normal lung tissue on the histological slides as the percentage of consolidations in postmortem CT scans increased (R =-0.51, p = 0.055). The analysis of the other correlations between the percentage of each finding did not show any significant correlation or correlation trends (p ≥ 0.10). Conclusions: A minimally invasive autopsy is valid. As the severity of involvement is increased in CT, more advanced disease is seen on histopathology. However, we cannot state that one specific radiological category represents a specific pathological correspondent. Ground-glass opacities, in the postmortem stage, must be interpreted with caution, as expiratory lungs may overestimate disease.

8.
An Bras Dermatol ; 99(1): 72-79, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37730501

RESUMO

BACKGROUND: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). OBJECTIVE: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. METHODS: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. RESULTS: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. STUDY LIMITATIONS: Small sample size and limited length of follow-up. CONCLUSIONS: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03327116.


Assuntos
Dermatite Atópica , Adulto , Humanos , Dermatite Atópica/tratamento farmacológico , Metotrexato/uso terapêutico , Estudos de Coortes , Estudos Prospectivos , Citocinas
9.
Int J Parasitol Parasites Wildl ; 22: 243-248, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38059178

RESUMO

During a helminthological survey of snakes in the Cerrado Biome in Maranhão State, Brazil, we found intestinal nematodes in Leptodeira annulata (Linnaeus), belonging to the genus Oxyascaris Travassos, 1920. We observed that the specimens found are distinct from their congeners by the combination of presented characters, mainly the cuticular expansion at the anterior region of the body, presence of a single papilla at the anterior cloacal lip, number, and arrangement of caudal papillae, presence of somatic papillae along body cuticle, as well as some morphometric characters. Thus, we describe the new species using light and scanning electron microscopy and, revise the morphological characters used to identify Oxyascaris spp. and propose a key to the species of the genus. Therefore, we describe the seventh species in the genus, the second reported to parasitize snakes, the sixth species recorded in Brazil, and the first described in the Cerrado Biome.

10.
Medicina (Ribeirao Preto, Online) ; 56(4)dez. 2023. tab, ilus
Artigo em Inglês | LILACS | ID: biblio-1538285

RESUMO

Introduction: The change in handgrip strength (HGS) is an indicator of the emergence of some chronic diseases, such as diabetes mellitus (DM) and systemic arterial hypertension (SAH). Objective: Analyze the relationship between HGS and body composition and laboratory indicators of diabetic and hypertensive patients assisted in Primary Health Care. Methods: The sample consisted of 185 users of a Basic Health Unit in the city of Santarém, Pará, distributed into two groups: control (CTL) ­ users without a diagnosis of DM and/or SAH (n=66); and DM/SAH (n=119) ­ users with DM or SAH or both diseases. Data collection involved sociodemographic, clinical, anthropometric, biochemical, and HGS information. Data were analyzed using descriptive and inferential statistics, adopting p<0.05. Results: It was noted that low HGS in the DM/SAH group was associated with high values of body mass index, abdominal circumference, fat percentage, fat mass, total cholesterol, and triglycerides and with more factors for metabolic syndrome (p<0.05). The CTL group, in relation to DM/SAH for the same HGS classification, demonstrated significance for lower blood pressure values, body mass index, abdominal circumference, fat percentage, and fat mass, as well as a lower chance of developing metabolic syndrome (p<0.05). Conclusion: According to the study proposal, it is concluded that the evaluation and follow-up of HGS in individuals with chronic diseases, especially DM and SAH, is relevant to monitor body adiposity and dyslipidemia and avoid the aggravation of existing diseases or the emergence of new ones (AU).


Introdução: A alteração na força de preensão (FP) manual é indicador para surgimento de algumas doenças crônicas, como a diabetes mellitus (DM) e hipertensão arterial sistêmica (HAS). Objetivo: Analisar a relação da FP com a composição corporal e indicadores laboratoriais de diabéticos e hipertensos assistidos na Atenção Primária à Saúde. Métodos: A amostra foi composta por 185 usuários de uma Unidade Básica de Saúde na cidade de Santarém, Pará, sendo distribuídos em dois grupos: controle (CTL) ­ usuários sem o diagnóstico para DM e/ou HAS (n=66); e DM/HAS (n=119) ­ usuários com DM ou HAS ou as duas doenças. A coleta de dados envolveu informações sócio-demográficas, clínicas, antropométricas, bioquímicas e FP. Os dados foram analisados por estatística descritiva e inferencial, adotando-se p<0,05. Resultados: Notou-se que a FP baixa no grupo DM/HAS apresentou associação com valores elevados do índice de massa corporal, circunferência abdominal, percentual de gordura, massa gorda, colesterol total, triglicerídeos e com mais fatores para a síndrome metabólica (p<0,05). Já o grupo CTL, em rela-ção do DM/HAS para uma mesma classificação de FP, demonstrou significância para menores valores pressóricos, do índice de massa corporal, da circunferência abdominal, percentual de gordura, massa gorda, bem como menor chance para o desenvolvimento da síndrome metabólica (p<0,05). Conclusão: Conclui-se, conforme a proposta do estudo, que é relevante a avaliação e acompanhamento da FP em indivíduos com doenças crônicas, em especial a DM e a HAS, a fim de monitorar a adiposidade corporal e a dislipidemia, evitando o agravo das doenças instaladas ou o surgimento de novas (AU).


Assuntos
Humanos , Força da Mão , Diabetes Mellitus , Hipertensão
11.
Respir Res ; 24(1): 281, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964271

RESUMO

BACKGROUND: Lung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS. METHODS: We have quantified different ECM elements and TGF-ß expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile. RESULTS: We observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-ß, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-ß was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course. CONCLUSIONS: Fatal COVID-19 is associated with an early TGF-ß expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.


Assuntos
COVID-19 , Fibrose Pulmonar , Síndrome do Desconforto Respiratório , Humanos , Feminino , Fibrose Pulmonar/metabolismo , COVID-19/metabolismo , Matriz Extracelular/metabolismo , Colágeno/metabolismo , Pulmão/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Síndrome do Desconforto Respiratório/metabolismo
12.
Clinics (Sao Paulo) ; 78: 100311, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38008037

RESUMO

OBJECTIVE: Gastroschisis (GS) is a congenital anomaly in the abdominal wall with the intestinal loops exiting laterally to the umbilicus. The contact of the loops with Amniotic Fluid (AF) causes an inflammatory process in the exposed part, leading to an extended hospital stay and an increased risk of morbidity due to alterations related to intestinal motility. The authors aimed to evaluate the time of exposure to the AF in the experimental GS and to search for potential biomarkers of intestinal inflammation by measuring microRNAs. METHODS: Rat fetuses were divided into three groups: a) CONTROL, b) GS reared on day 18 (GS = 18), and c) GS reared on day 19.5 (GS = 19) (term = 22 days). On day 21.5, the fetuses were removed for biometric parameters and biochemical analyses: 1) Biometrics: Body and Intestinal Weight (BW, IW), and intestinal-body weight ratio (IW/BW); 2) Descriptive histopathology and 3) miR-143 quantification by real-time Polymerase Chain Reaction (PCR). RESULTS: BW was higher in CONTROL than GS 18 and G19 (p < 0.05). IW, IW/BW, intestinal water, and mRNA-143 were higher in GS 18 and GS 19 than in CONTROL, and GS 18 was higher than GS 19 (p < 0.05). The average of the inflammation score from the intestinal wall with mucosal inflammation and intra-epithelial lymphocytes shows worst in GS 18 and GS 19 vs. CONTROL (p < 0.05). CONCLUSIONS: The tissue expression of mRNA-143 and the morphological changes in the intestine of GS worsened according to the time of exposure to AF, which could be a possible marker of fetal intestinal damage.


Assuntos
Gastrosquise , MicroRNAs , Animais , Ratos , Líquido Amniótico/metabolismo , Gastrosquise/genética , Gastrosquise/complicações , Gastrosquise/metabolismo , Inflamação , Intestinos/patologia
15.
J Appl Physiol (1985) ; 135(4): 950-955, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37675474

RESUMO

Endothelial dysfunction is a key phenomenon in COVID-19, induced by direct viral endothelial infection and secondary inflammation, mainly affecting the microvascular circulation. However, few studies described the subcellular aspects of the lung microvasculature and the associated thrombotic phenomena, which are widely present in severe COVID-19 cases. To that end, in this transversal observational study we performed transmission and scanning electron microscopy in nine lung samples of patients who died due to COVID-19, obtained via minimally invasive autopsies in Sao Paulo, Brazil, in 2020. All patients died due to acute respiratory failure and had microvascular thrombosis at histology. Electron microscopy revealed areas of endothelial damage with basal lamina disruption and virus infection in endothelial cells. In the capillary lumens, the ultrastructure of the thrombi is depicted, with red blood cells stacking, dysmorphism and hemolysis, fibrin meshworks, and extracellular traps. Our description illustrates the complex pathophysiology of microvascular thrombosis at the cellular level, which leads to some of the peculiar characteristics of severe COVID-19.NEW & NOTEWORTHY In this study, electron microscopy was used to explain the pathophysiology of respiratory failure in severe COVID-19. Before the advent of vaccination, as the virus entered the respiratory system, it rapidly progressed to the alveolar capillary network and, before causing exudative alveolar edema, it caused mainly thrombosis of the pulmonary microcirculation with preserved lung compliance explaining "happy hypoxia." Timing of anticoagulation is of pivotal importance in this disease.


Assuntos
COVID-19 , Insuficiência Respiratória , Trombose , Humanos , COVID-19/complicações , SARS-CoV-2 , Células Endoteliais/patologia , Brasil , Pulmão/patologia , Insuficiência Respiratória/etiologia
16.
EBioMedicine ; 96: 104810, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37757571

RESUMO

BACKGROUND: Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF. METHODS: This retrospective autopsy study included cases from the São Paulo (Brazil) epidemic of 2017-2019. We reviewed medical records and performed cardiac tissue histopathological evaluation, electron microscopy, immunohistochemical assays, RT-qPCR for YF virus (YFV)-RNA, and proteomics analysis on inflammatory and endothelial biomarkers. FINDINGS: Seventy-three confirmed YF cases with a median age of 48 (34-60) years were included. We observed myocardial fibrosis in 68 (93.2%) patients; cardiomyocyte hypertrophy in 68 (93.2%); endothelial alterations in 67 (91.8%); fiber necrosis in 50 (68.5%); viral myocarditis in 9 (12.3%); and secondary myocarditis in 5 (6.8%). Four out of five patients with 17DD vaccine-associated viscerotropic disease presented with myocarditis. The cardiac conduction system showed edema, hemorrhages and endothelial fibrinoid necrosis. Immunohistochemistry detected CD68-positive inflammatory interstitial cells and YFV antigens in endothelial and inflammatory cells. YFV-RNA was detected positive in 95.7% of the cardiac samples. The proteomics analysis demonstrated that YF patients had higher levels of multiple inflammatory and endothelial biomarkers in comparison to cardiovascular controls, and higher levels of interferon gamma-induced protein 10 (IP-10) in comparison to sepsis (p = 0.01) and cardiovascular controls (p < 0.001) in Dunn test. INTERPRETATION: Myocardial injury is frequent in severe YF, due to multifactorial mechanisms, including direct YFV-mediated damage, endothelial cell injury, and inflammatory response, with a possible prominent role for IP-10. FUNDING: This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo, Bill and Melinda Gates Foundation, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.


Assuntos
Traumatismos Cardíacos , Miocardite , Febre Amarela , Humanos , Pessoa de Meia-Idade , Febre Amarela/epidemiologia , Miocardite/etiologia , Quimiocina CXCL10 , Estudos Retrospectivos , Brasil/epidemiologia , RNA , Autopsia , Biomarcadores , Necrose
17.
Int J STD AIDS ; 34(13): 932-939, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37436258

RESUMO

BACKGROUND: Handgrip strength (HGS) is an important health indicator that can be influenced by body composition and biochemical markers of people living with HIV, contributing to better understanding of health-related outcomes. OBJECTIVE: To analyze the relationship between HGS and health indicators in people living with HIV. METHODS: Cross-sectional study, with 207 people living with HIV, attending a reference center, located in Santarém, Pará, Brazil. Data collection covered sociodemographic, clinical, laboratory, physical activity level, body composition, and HGS information. Data were analyzed using descriptive and inferential statistics, adopting p < .05. RESULTS: There was a predominance of men (60%), aged 33-47 years (42%). A relationship was observed between adequate HGS and the male sex (p < .001), and adequate values for body mass index (p = .003), abdominal circumference (p < .001), and total cholesterol (p = .012). In addition, higher values of fat mass (p < .001), and lower lean mass (p = .006) were observed for people living with HIV with low HGS. CONCLUSION: People living with HIV present an association between lean body mass and high HGS. On the other hand, low HGS favored obesity and hypercholesterolemia. Thus, monitoring HGS is an important indicator of body, laboratory, and functional capacity changes, with HGS being an additional element in the clinical evaluation.


Assuntos
Infecções por HIV , Força da Mão , Humanos , Masculino , Feminino , Brasil/epidemiologia , Estudos Transversais , Índice de Massa Corporal , Infecções por HIV/epidemiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-37283411

RESUMO

Visceral leishmaniasis (VL) is a chronic vector-borne zoonotic disease caused by trypanosomatids, considered endemic in 98 countries, mainly associated with poverty. About 50,000-90,000 cases of VL occur annually worldwide, and Brazil has the second largest number of cases in the world. The clinical picture of VL is fever, hepatosplenomegaly, and pancytopenia, progressing to death in 90% of cases due to secondary infections and multi-organ failure, if left untreated. We describe the case of a 25-year-old female who lived in the metropolitan area of Sao Paulo, who had recently taken touristic trips to several rural areas in Southeastern Brazil and was diagnosed post-mortem. During the hospitalization in a hospital reference for the treatment of COVID-19, the patient developed acute respiratory failure, with chest radiographic changes, and died due to refractory shock. The ultrasound-guided minimally invasive autopsy diagnosed VL (macrophages containing amastigote forms of Leishmania in the spleen, liver and bone marrow), as well as pneumonia and bloodstream infection by gram-negative bacilli.


Assuntos
COVID-19 , Leishmaniose Visceral , Insuficiência Respiratória , Feminino , Humanos , Adulto , Leishmaniose Visceral/complicações , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , Diagnóstico Diferencial , Autopsia , COVID-19/diagnóstico , Brasil , Insuficiência Respiratória/diagnóstico , Teste para COVID-19
19.
Sci Rep ; 13(1): 7693, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37169804

RESUMO

This study aimed to observe the relationships between the maturity status on the network-based centrality measures of young athletes in small-sided soccer games (SSG). The study included 81 male players (14.4 ± 1.1 years). Measurements included height, sitting height, body mass, and bone age (TW3 method). The applied protocols were the following: Countermovement Jump (CMJ), Yo-Yo Intermittent Recovery Test Level 1 (YYIRT1), Repeated Sprints Ability (RSA), observational analysis of techniques, and interactions performed by players in SSG. The relationship between the set of evaluated variables within each maturity status was obtained from the correlational analysis of networks (P < 0.05). The maturity status explained a significant portion of the variance in body mass (η2 = 0.37), height (η2 = 0.30), sitting height (η2 = 0.30), and performance on the YYIRT1 (η2 = 0.08), CMJ (η2 = 0.14), and RSA (η2 = 0.13). No effect of maturity status on network-based centrality measures of young athletes was identified (P > 0.05). For the late maturity group, there was a correlation between the degree of centrality and physical growth indicators (rmean = 0.88). For players with maturation "on time", physical growth indicators relate to the degree of prestige (rmean = 0.36). It is concluded that body size and bone age impact how late and on-time maturity groups interact within the match.


Assuntos
Desempenho Atlético , Corrida , Futebol , Humanos , Masculino , Teste de Esforço/métodos , Aptidão Física , Tamanho Corporal
20.
Artigo em Português | LILACS | ID: biblio-1442381

RESUMO

Introdução: O diabete mellitus (DM) e a hipertensão arterial sistêmica (HAS) são doenças crônicas não-transmissíveis que se associam a alto risco de mortalidade. Objetivo: Analisar o perfil laboratorial de pessoas com DM e HAS acompanhados na atenção primária à saúde. Método: Estudo descritivo e transversal, com a amostra de 345 pessoas em acompanhamento pelas estratégias de saúde da família pertencentes a duas Unidades Básicas de Saúde da zona urbana do município de Santarém, Pará, Brasil. Os participantes foram divididos em quatro grupos conforme diagnóstico: HAS; DM; ambas (DM-HAS); ou nenhuma (SEM). Foram coletadas informações socioeconômicas e clínicas dos participantes, com posterior coleta de sangue para as variáveis bioquímicas. Para a análise de dados foi realizada a estatística descritiva e inferencial, adotando-se significância de p<0,05. Resultados: Em todos os grupos predominaram participantes do sexo feminino, casados, pardos, com renda até dois salários, com 4-7 anos de estudo, não tabagistas e não estilistas. Em relação ao SEM, o DM se associou com valores alterados para glicose (p<0,0001), HDL-c (p=0,0481), ureia (p=0,0252), creatinina (p=0,0006) e hemoglobina (p=0,0024). Já o DM-HAS se associou com a presença de alteração para glicose (p<0,0001), ureia (p=0,0009), creatinina (p=0,0059) e taxa de filtração glomerular (p=0,0048). Conclusão: Conclui-se, conforme o método proposto, que a presença da DM e/ou HAS são capazes de modificar o perfil bioquímico de maneira negativa, bem como se ressalta a importância do acompanhamento desta pessoa pela atenção primária à saúde, visto que algumas pessoas apresentaram alterações bioquímicas que chamam atenção e não estão em acompanhamento (AU).


Introduction:Diabetes mellitus (DM) and systemic arterial hypertension (SAH) are chronic non-communicable diseases that are associated with a high risk of mortality. Objective: To analyze the laboratory profile of people with DM and SAH followed up in primary health care. Methods: Descriptive and cross-sectional study, with a sample of 345 people being monitored by family health strategies belonging to two Basic Health Units in the urban area of the city of Santarém, Pará, Brazil. Participants were divided into four groups according to their diagnosis: SAH; DM; both (DM-SAH); or neither (NO). Socioeconomic and clinical information was collected from the participants, with subsequent blood collection for biochemical variables. Descriptive and inferential statistics were used for data analysis, adopting a significance of p<0.05. Results: In all groups, female participants, married, brown, with an income of up to two salaries, 4-7 years of schooling, non-smokers, and non-alcoholics predominated. Compared to NO, DM was associated with altered values for glucose (p<0.001), HDL-c (p=0.048), urea (p=0.025), creatinine (p<0.001), and hemoglobin (p=0.002). DM-SAH was associated with the presence of alterations in glucose (p<0.001), urea (p<0.001), creatinine (p=0.005), and glomerular filtration rate (p=0.004). Conclusion: In conclusion, the results using the proposed method indicate that the presence of DM and/or SAH is able to negatively modify the biochemical profile. In addition, the importance of monitoring this population in primary health care was demonstrated, since some people presented potentially worrying biochemical alterations that are not being followed up (AU).


Assuntos
Humanos , Atenção Primária à Saúde , Fenômenos Bioquímicos , Indicadores Básicos de Saúde , Diabetes Mellitus/diagnóstico , Hipertensão/diagnóstico
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