Tissue-resident macrophages are the most abundant immune cell population in healthy adipose tissue. Adipose tissue macrophages (ATMs) change during metabolic stress and are thought to contribute to ...metabolic syndrome. Here, we studied ATM subpopulations in steady state and in response to nutritional and infectious challenges. We found that tissue-resident macrophages from healthy epididymal white adipose tissue (eWAT) tightly associate with blood vessels, displaying very high endocytic capacity. We refer to these cells as vasculature-associated ATMs (VAMs). Chronic high-fat diet (HFD) results in the accumulation of a monocyte-derived CD11c
CD64
double-positive (DP) macrophage eWAT population with a predominant anti-inflammatory/detoxifying gene profile, but reduced endocytic function. In contrast, fasting rapidly and reversibly leads to VAM depletion, while acute inflammatory stress induced by pathogens transiently depletes VAMs and simultaneously boosts DP macrophage accumulation. Our results indicate that ATM populations dynamically adapt to metabolic stress and inflammation, suggesting an important role for these cells in maintaining tissue homeostasis.
Sound sensitive dogs have exaggerated responses to sound stimuli that can negatively impact the welfare of the dog. Behavioural reactions combined with the response to sound involve a marked ...autonomic imbalance towards sympathetic predominance and release of cortisol. The purpose of the present study was to evaluate, in the laboratory, the cardiac autonomic modulation using heart rate variability (HRV) analysis, serum cortisol levels and behavioural parameters in response to sounds of fireworks in dogs with a history of sensitivity to fireworks. Based on these data, and combining qualitative measures and categorical measures, we propose one short and one full index of sound sensitivity in dogs. Six privately owned dogs with no history and another twelve dogs with a history of sound sensitivity to fireworks were used. The sound stimulus consisted of a standardised recording of fireworks (180-seconds long) with a peak intensity of 103-104 dB. The cardiac intervals were recorded using a frequency meter (Polar® RS800CX model) to evaluate the HRV, and the acquired data were processed using CardioSeries 2.4.1 software. Twenty-one behavioural parameters were analysed quantitatively by time, frequency or categorically by scores and were grouped in behavioural categories of arousal, fear, relaxation and "other". Sound sensitive dogs had exacerbated autonomic responses to the sound stimulus in the laboratory compared to non-sensitive dogs, with higher LF/HF ratios suggesting autonomic imbalance towards sympathetic predominance, but the cortisol levels were similar between the sensitive and non-sensitive dogs. Sound sensitive dogs showed pronounced responses for the parameters: alert and attention, search sound, startle, trembling, hiding, run away and less intense responses for the parameters rest and wink/sleep. Furthermore, the behavioural categories of arousal, fear, relaxation (lack of) and LF/HF were correlated to the caregiver's perception of the sound sensitivity of the dogs. Not only the short index for sound sensitivity (behavioural categories arousal, fear and relaxation, and LF/HF ratio) but also the full index for sound sensitivity (all behavioural categories, LF/HF and cortisol levels) was highly correlated to sound fear response at home. These indexes can contribute to the development of strategies to treat sound sensitive dogs.
Currently known risk factors explain only a small fraction of preterm birth (PTB). Previous PTB is one of the most important predictors. However, this information is not available in primiparous ...women. Few studies have looked at associations between regulatory cytokine expression (RCE) and PTB and the results are conflicting.
To investigate the association of RCE-Interleukin 10 (IL-10) and Transforming Growth Factor β (TGF-β)-with PTB, and to assess whether bacterial vaginosis (BV) is involved in this relationship.
This was a case-control study nested in a prospective cohort-called BRISA. Women with singleton pregnancies were interviewed from 22 to 25 weeks of gestational age (GA). Women were recruited from health services in São Luís, Brazil. A blood sample was collected and gynecological examination was performed. Serum IL-10 and TGF-β were determined using cytometric bead array. Nugent score >7 and/or the presence of clue cells were used for BV diagnosis. All PTB estimated by ultrasound dating performed before 20 weeks of gestational age were considered cases. Controls were selected by simple random sampling from the rest of the cohort, at a 2:1 ratio. Different models were tested, according to the main independent variable. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated by regression analyses.
The study included 327 pregnant women, 109 cases and 218 controls. No associations were found between BV and PTB (P = 1.44; 95%CI: 0.51-3.77). Low levels of IL-10 (OR = 2.92 95%CI: 1.38-6.16) or TGF-β (OR = 16.90 95%CI: 6.42-44.51) or both simultaneously (OR = 77.16 95%CI: 7.99-744.88) were associated with increasing odds of PTB, even after adjustment for confounding.
Decreased RCE is a risk factor for PTB. This relationship, however, is not triggered by the presence of BV. Low IL-10/TGF-β levels from 22 to 25 weeks of GA could be used as early predictors of PTB. We suggest monitoring of these RCE, especially among primiparous women, for whom history of previous PTB is not available.
Since angiotensin-converting enzyme 2, ACE2, was identified as the receptor for SARS-CoV-2 and considering the intense physiological interplay between the two angitensinases isoforms, ACE and ACE2, ...as counter-regulatory axis of the renin-angiotensin system, we proposed the evaluation of polymorphisms in these two key regulators in relation to COVID-19 severity. A genetic association study involving 621 COVID-19 hospitalized patients from Brazil was performed. All subjects had a confirmed diagnosis of COVID-19 via RT-PCR. Patients were categorized into two groups: the "mild" group (N = 296), composed of individuals hospitalized in ward beds who progressed to cure, and the "severe" group (N = 325), composed of individuals who required hospitalization in an intensive care unit (ICU), or who died. Blood samples were genotyped for ACE I/D polymorphism and ACE2 G8790A polymorphism by real-time PCR via TaqMan assay. The analysis of combined polymorphisms revealed a protective role for genotypic profile II/A_ (OR.sup.A = 0,26; p = 0,037) against the worsening of COVID-19 in women. The results indicate a protection profile to COVID-19 progression, in which the II/A_ carriers have almost four times less chance of a severe outcome. It is proposed that a decreased activity of ACE (deleterious effects) in conjunction with an increased ACE2 activity (protective effects), should be the underlying mechanism. The findings are unprecedented once other studies have not explored the genotypic combination analysis for ACE and ACE2 polymorphisms and bring perspectives and expectations for dealing with the COVID-19 pandemic based on definitions of genetically-based risk groups within the context of personalized medicine.
Auranofin is a thioredoxin reductase-1 inhibitor originally approved for the treatment of rheumatoid arthritis. Recently, auranofin has been repurposed as an anticancer drug, with pharmacological ...activity reported in multiple cancer types. In this study, we characterized transcriptional and genetic alterations associated with auranofin response in cancer. By integrating data from an auranofin cytotoxicity screen with transcriptome profiling of lung cancer cell lines, we identified an auranofin resistance signature comprising 29 genes, most of which are classical targets of the transcription factor NRF2, such as genes involved in glutathione metabolism (GCLC, GSR, SLC7A11) and thioredoxin system (TXN, TXNRD1). Pan-cancer analysis revealed that mutations in NRF2 pathway genes, namely KEAP1 and NFE2L2, are strongly associated with overexpression of the auranofin resistance gene set. By clustering cancer types based on auranofin resistance signature expression, hepatocellular carcinoma, and a subset of non-small cell lung cancer, head-neck squamous cell carcinoma, and esophageal cancer carrying NFE2L2/KEAP1 mutations were predicted resistant, whereas leukemia, lymphoma, and multiple myeloma were predicted sensitive to auranofin. Cell viability assays in a panel of 20 cancer cell lines confirmed the augmented sensitivity of hematological cancers to auranofin; an effect associated with dependence upon glutathione and decreased expression of NRF2 target genes involved in GSH synthesis and recycling (GCLC, GCLM and GSR) in these cancer types. In summary, the omics-based identification of sensitive/resistant cancers and genetic alterations associated with these phenotypes may guide an appropriate repurposing of auranofin in cancer therapy.
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•A 29-gene auranofin resistance signature was obtained from lung cancer datasets.•Auranofin signature is enriched with classical NRF2 target genes.•KEAP1/NRF2 mutations are key features associated with signature upregulation.•Hematological cancers express low levels of auranofin resistance gene set.•Hematological cancers are more sensitive to auranofin than solid cancer cell lines.
Internações de pacientes com HIV permanecem elevadas apesar da terapia antirretroviral(TARV) disponível. O atraso diagnóstico ou a falha de adesão propiciam infecções oportunistas com necessidade de ...internação. O estudo foi realizado para conhecer o perfil clínico/epidemiológico dessas internações em uma enfermaria especializada.
Estudo retrospectivo descritivo dos pacientes com infecção pelo HIV internados na enfermaria de Infectologia do Hospital de Base de janeiro/2017 a janeiro/2020. Dados pesquisados em prontuários: momento do diagnóstico, sexo, idade, contagem de linfócitos TCD4(CD4), carga viral do HIV (CVHIV), doenças oportunistas, comorbidades, coinfecções, TARV, mortalidade e indetecção da CVHIV em 6 meses. Informações transcritas em formulário GoogleForms obtendo-se resultados em percentuais e gráficos.
201 pacientes, 65,2% diagnóstico prévio; 73,6% sexo masculino; 59,3% de de 18-40 anos, 22,9% de 41-50 anos,13,4% de 51-65 anos. 37,2% CD4 menor que 50 células/mm3, 38,2% 50 a 200 células/mm3 e 24,6% acima de 200 células/mm3. Quanto à CVHIV, 8,2% apresentavam maior que 1.000.000 de cópias/ml, 29,6% entre 100.000 a 1.000.000 cópias/ml, 32,1% 1.000 a 100.000 cópias/ml, 28,1% menor que 1.000 cópias/ml. Diagnosticou-se neurotoxoplasmose em 28,1%, pneumocistose em 19,9%, citomegalovirose em 13,5%, neurocriptococose em 9,4%, candidíase esofágica em 8,2%, leucoencefalopatia multifocal progressiva em 7,6%. Coinfecção com hepatite B em 5,2%, hepatite C 7% e sífilis 33%. 41,7% apresentaram hipertensão arterial sistêmica, 17,4% doença renal crônica e 16,5%. 87,8% usaram tenofovir, 95,9% lamivudina, 53,3% dolutegravir, 18,8% raltegravir e 13,7% darunavir. Mortalidade de 15,9%, 56,3% em até 2 semanas da internação. 54,2% apresentaram sequelas, 22% motoras. Na avaliação em 6 meses, 66,5% tinham CVHIV indetectável.
A maioria dos pacientes era do sexo masculino, entre 18 e 40 anos, com diagnóstico prévio, CD4 entre 50 e 200 células/mm3 e CVHIV entre 1.000 e 100.000 cópias/ml. Neurotoxoplasmose foi a infecção oportunista mais prevalente, seguida de pneumocistose, citomegalovirose, candidíase esofágica e neurocriptococose. Coinfecção com sífilis foi encontrada em um terço dos pacientes. A TARV mais utilizada continha tenofovir, lamivudina e dolutegravir. Mais da metade dos óbitos ocorreram em até 2 semanas da internação. Mais de dois terços dos pacientes reavaliados após 6 meses apresentaram CVHIV indetectável.
MELIOIDOSE: RELATO DE CASO NO DISTRITO FEDERAL Vale, Eveline Fernandes Nascimento; Matias, Raquel Nascimento
The Brazilian journal of infectious diseases,
January 2022, 2022-01-01, Letnik:
26
Journal Article
Recenzirano
Odprti dostop
A meliodose é causada pela bactéria Burkholderia pseudomallei, um bacilo gram negativo encontrado principalmente no solo do Sudeste Asiático e norte da Austrália. No Brasil, foram identificados casos ...nos estados do Ceará, Alagoas e Mato Grosso. A doença possui um amplo espectro clínico, variando de infecção de partes moles, formação de abscessos, pneumonia e sepse com evolução fulminante.
OVL, 56 anos, sexo masculino, portador de diabetes mellitus II, morador de Brasília há 30 anos. Iniciou quadro de astenia, febre, vômitos e hiporexia. Referia perda de peso progressiva há quatro meses da admissão e apresentava artrite em joelho direito, abscessos esplênicos e plaquetopenia. Foi iniciada antibioticoterapia empírica com ceftriaxona e oxacilina, porém paciente persistia com febre diária de até 39°C. No 12° dia de internação, evoluiu com tosse produtiva e dispneia importante com dessaturação e necessidade de intubação orotraqueal e ventilação mecânica. Progrediu com hipotensão, leucocitose com desvio à esquerda e insuficiência renal aguda. Em duas amostras de hemocultura e na urocultura houve crescimento da bactéria Burkholderia pseudomallei. Paciente evoluiu para o óbito a despeito da terapia antimicrobiana adequada instituída após o diagnóstico de melioidose.
A melioidose é doença sistêmica com manifestações clínicas variadas, desde a forma assintomática à sepse fulminante, podendo causar pneumonia e abscessos pulmonares, hepáticos e esplênicos. É uma doença emergente na América Latina, considerando o aumento de relato de casos ocorridos. A suspeita diagnóstica e a investigação precoce são primordiais para o início da terapia adequada na tentativa de modificar o prognóstico do paciente.
The immune microenvironment of tumors can play a critical role in promoting or inhibiting tumor progression depending on the context. We present evidence that tumor-associated macrophages/microglia ...(TAMs) can promote tumor progression in the sonic hedgehog subgroup of medulloblastoma (SHH-MB). By combining longitudinal manganese-enhanced magnetic resonance imaging (MEMRI) and immune profiling of a sporadic mouse model of SHH-MB, we found the density of TAMs is higher in the ~50% of tumors that progress to lethal disease. Furthermore, reducing regulatory T cells or eliminating B and T cells in Rag1 mutants does not alter SHH-MB tumor progression. As TAMs are a dominant immune component in tumors and are normally dependent on colony-stimulating factor 1 receptor (CSF1R), we treated mice with a CSF1R inhibitor, PLX5622. Significantly, PLX5622 reduces a subset of TAMs, prolongs mouse survival, and reduces the volume of most tumors within 4 weeks of treatment. Moreover, concomitant with a reduction in TAMs the percentage of infiltrating cytotoxic T cells is increased, indicating a change in the tumor environment. Our studies in an immunocompetent preclinical mouse model demonstrate TAMs can have a functional role in promoting SHH-MB progression. Thus, CSF1R inhibition could have therapeutic potential for a subset of SHH-MB patients.
As infecções relacionadas à assistência em saúde (IRAS) são consideradas hoje, um problema de grande impacto na morbi-mortalidade de pacientes, principalmente em áreas críticas. No entanto, algumas ...medidas de prevenção quando realizadas em conjunto, são fundamentais para que tais infecções não ocorram. Associado a isto, alta prevalência de germes multidroga resistentes, tendo como seu catalisador o uso irracional de antimicrobianos, também aponta como grande problema de saúde pública em âmbito mundial. Considerando a residência médica como um momento de formação, no qual é imprescindível avaliar o paciente de forma global, independentemente da especialidade a qual se destina, iniciou-se no mês de maio de 2023,promovido pelo Núcleo de controle de Infecção hospitalar (NCIH), o primeiro workshop de prevenção de IRAS e uso racional de antimicrobianos para Programas de Residência Médica do Hospital de Base do Distrito Federal, com duração de seis semanas, o qual tinha como objetivos, orientar o residente a cerca das principais medidas de prevenção das Infecções relacionadas à assistência (IRAS); reconhecimento e diagnóstico das principais IRAS, tratamento empírico adequado com base nos protocolos institucionais, considerando o uso racional de antimicrobianos e perfil de resistência dos microorganismos da instituição, reconhecimento e o uso adequado dos antimicrobianos no contexto da sepse. O curso foi dividido em seis módulos, e cada módulo é composto por treinamentos teóricos, feitos por vídeo aula gravados pela equipe de enfermeiros e médicos do NCIH, com realização de pós teste e também treinamentos práticos em centro de simulação realística disponível na instituição. No treinamento prático, os médicos residentes foram expostos a situações clínicas, as quais eram interligadas com medidas de biosegurança, indicação, inserção e manejo de dispositivos, dentro das condutas seguras preconizadas.
Geopropolis is a mixture of plant resins, waxes, and soil produced by the stingless bee Melipona fasciculata Smith. This paper describes the antioxidant activity and chemical composition of ...geopropolis produced by M. fasciculata. The total phenolic content determined with the Folin–Ciocalteu reagent was highest in the ethyl acetate fraction and hydroalcoholic extract. Antioxidant activity was assayed by the in vitro DPPH, ABTS, and FRAP assays. The hydroalcoholic extract and fractions of geopropolis, except for the hexane fraction, exhibited antioxidant activity against DPPH, ABTS, and FRAP. The phenolic compounds were identified by HPLC-DAD-MS on the basis of the evaluation of their UV–vis absorption maxima (λmax) and mass spectral analysis. Eleven compounds belonging to the classes of phenolic acids and hydrolyzable tannins (gallotannins and ellagitannins) were tentatively identified. These compounds are responsible for the antioxidant activity and high phenolic content of geopropolis produced by M. fasciculata.
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