Exploring the immunomodulatory properties of glucan particles in human primary cells.

The immunomodulatory properties of ß-glucans have sparked interest among various medical fields. As vaccine adjuvants, glucan particles offer additional advantages as antigen delivery systems. This study reported the immunomodulatory properties of glucan particles with different size and chemical composition. The effect of glucan microparticles (GPs) and glucan nanoparticles (Glu 130 and 355 NPs) was evaluated on human immune cells. While GPs and Glu 355 NPs demonstrated substantial interaction with Dectin-1 receptor on monocytes, Glu 130 NPs exhibited reduced activation of this receptor. This observation was substantiated by blocking Dectin-1, resulting in inhibition of reactive oxygen species production induced by GPs and Glu 355 NPs. Notably, monocyte-derived dendritic cells (moDCs) stimulated by Glu 355 NPs exhibited phenotypic and functional maturation, essential for antigen cross-presentation. The immunomodulatory efficacy was investigated using an autologous mixed lymphocyte reaction (AMLR), resulting in considerable rates of lymphocyte proliferation and an intriguing profile of cytokine and chemokine release. Our findings highlight the importance of meticulously characterizing the size and chemical composition of ß-glucan particles to draw accurate conclusions regarding their immunomodulatory activity. This in vitro model mimics the human cellular immune response, and the results obtained endorse the use of ß-glucan-based delivery systems as future vaccine adjuvants.

Artificial Dendritic Cells: A New Era of Promising Antitumor Immunotherapy.

The accelerated development of antitumor immunotherapies in recent years has brought immunomodulation into the spotlight. These include immunotherapeutic treatments with dendritic cell (DC)-based vaccines which can elicit tumor-specific immune responses and prolong survival. However, this personalized treatment has several drawbacks, including being costly, labor-intensive, and time consuming. This has sparked interest in producing artificial dendritic cells (aDCs) to open up the possibility of standardized "off-the-shelf" protocols and circumvent the cumbersome and expensive personalized medicine. aDCs take advantage of materials that can be designed and tailored for specific clinical applications. Here, an overview of the immunobiology underlying antigen presentation by DCs is provided in an attempt to select the key features to be mimicked and/or improved through the development of aDCs. The inherent properties of aDCs that greatly impact their performance in vivo and, consequently, the fate of the triggered immune response are also outlined.

From Chronic Alcohol Consumption to Coma: Report of an Uncommon Cause.

Marchiafava-Bignami disease is a rare condition characterized by demyelination of the corpus callosum that can evolve into necrosis. It is associated with thiamine deficiency, chronic alcohol consumption, and less frequently, severe malnutrition. The diagnosis is based on clinical presentation - altered mental state and changes in a neurological examination - and on neuroimaging studies, especially magnetic resonance imaging. Treatment with parenteral thiamine is recommended. The authors present a case of a 50-year-old male, with chronic alcohol abuse and malnutrition, admitted to the hospital with an acute form of the Marchiafava-Bignami disease. An early diagnosis and treatment facilitated neurological and cognitive recovery.

CuMV VLPs Containing the RBM from SARS-CoV-2 Spike Protein Drive Dendritic Cell Activation and Th1 Polarization.

Dendritic cells (DCs) are the most specialized and proficient antigen-presenting cells. They bridge innate and adaptive immunity and display a powerful capacity to prime antigen-specific T cells. The interaction of DCs with the receptor-binding domain of the spike (S) protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pivotal step to induce effective immunity against the S protein-based vaccination protocols, as well as the SARS-CoV-2 virus. Herein, we describe the cellular and molecular events triggered by virus-like particles (VLPs) containing the receptor-binding motif from the SARS-CoV-2 spike protein in human monocyte-derived dendritic cells, or, as controls, in the presence of the Toll-like receptors (TLR)3 and TLR7/8 agonists, comprehending the events of dendritic cell maturation and their crosstalk with T cells. The results demonstrated that VLPs boosted the expression of major histocompatibility complex molecules and co-stimulatory receptors of DCs, indicating their maturation. Furthermore, DCs' interaction with VLPs promoted the activation of the NF-kB pathway, a very important intracellular signalling pathway responsible for triggering the expression and secretion of proinflammatory cytokines. Additionally, co-culture of DCs with T cells triggered CD4+ (mainly CD4+Tbet+) and CD8+ T cell proliferation. Our results suggested that VLPs increase cellular immunity, involving DC maturation and T cell polarization towards a type 1 T cells profile. By providing deeper insight into the mechanisms of activation and regulation of the immune system by DCs, these findings will enable the design of effective vaccines against SARS-CoV-2.

Development of colorimetric cellulose-based test-strip for the rapid detection of antibodies against SARS-CoV2 virus.

Given the pandemic situation, there is an urgent need for an accurate test to monitor antibodies anti-SARS-CoV-2, providing crucial epidemiological and clinical information to monitor the evolution of coronavirus disease in 2019 (COVID-19) and to stratify the immunized and asymptomatic population. Therefore, this paper describes a new cellulose-based test strip for rapid and cost-effective quantitative detection of antibodies to SARS-CoV2 virus by colorimetric transduction. For this purpose, Whatman paper was chemically modified with sodium metaperiodate to introduce aldehyde groups on its surface. Subsequently, the spike protein of the virus is covalently bound by forming an imine group. The chemical control of cellulose paper modification was evaluated by Fourier transform infrared spectroscopy, thermogravimetry and contact angle analysis. Colorimetric detection of the antibodies was performed by a conventional staining method using Ponceau S solution as the dye. Color analysis was performed after image acquisition with a smartphone using Image J software. The color intensity varied linearly with the logarithm of the anti-S concentration (from 10 ng/mL to 1 µg/mL) in 500-fold diluted serum samples when plotted against the green coordinate extracted from digital images. The test strip was selective in the presence of nucleocapsid antibodies, urea, glucose, and bovine serum albumin with less than 15% interference, and detection of antibodies in human serum was successfully performed. Overall, this is a simple and affordable design that can be readily used for mass population screening and does not require sophisticated equipment or qualified personnel. Supplementary Information: The online version contains supplementary material available at 10.1007/s10570-022-04808-y.

An ultra-sensitive electrochemical biosensor using the Spike protein for capturing antibodies against SARS-CoV-2 in point-of-care.

This work presents an innovative ultra-sensitive biosensor having the Spike protein on carbon-based screen-printed electrodes (SPEs), for monitoring in point-of-care antibodies against SARS-CoV-2, a very important tool for epidemiological monitoring of COVID-19 infection and establishing vaccination schemes. In an innovative and simple approach, a highly conductive support is combined with the direct adsorption of Spike protein to enable an extensive antibody capture. The high conductivity was ensured by using carboxylated carbon nanotubes on the carbon electrode, by means of a simple and quick approach, which also increased the surface area. These were then modified with EDC/NHS chemistry to produce an amine layer and undergo Spike protein adsorption, to generate a stable layer capable of capturing the antibodies against SARS-CoV-2 in serum with great sensitivity. Electrochemical impedance spectroscopy was used to evaluate the analytical performance of this biosensor in serum. It displayed a linear response between 1.0 â€‹pg/mL and 10 â€‹ng/mL, with a detection limit of ∼0.7 â€‹pg/mL. The analysis of human positive sera containing antibody in a wide range of concentrations yielded accurate data, correlating well with the reference method. It also offered the unique ability of discriminating antibody concentrations in sera below 2.3 â€‹µg/mL, the lowest value detected by the commercial method. In addition, a proof-of-concept study was performed by labelling anti-IgG antibodies with quantum dots to explore a new electrochemical readout based on the signal generated upon binding to the anti-S protein antibodies recognised on the surface of the biosensor. Overall, the alternative serologic assay presented is a promising tool for assessing protective immunity to SARS-CoV-2 and a potential guide for revaccination.

Crosstalk between estrogen, dendritic cells, and SARS-CoV-2 infection.

The novel coronavirus disease 2019 (Covid-19) first appeared in Wuhan and has so far killed more than four million people worldwide. Men are more affected than women by Covid-19, but the cellular and molecular mechanisms behind these differences are largely unknown. One plausible explanation is that differences in sex hormones could partially account for this distinct prevalence in both sexes. Accordingly, several papers have reported a protective role of 17ß-estradiol during Covid-19, which might help explain why women appear less likely to die from Covid-19 than men. 17ß-estradiol is the predominant and most biologically active endogenous estrogen, which signals through estrogen receptor α, estrogen receptor ß, and G protein-coupled estrogen receptor 1. These receptors are expressed in mature cells from the innate and the adaptive immune system, particularly on dendritic cells (DCs), suggesting that estrogens could modulate their effector functions. DCs are the most specialized and proficient antigen-presenting cells, acting at the interface of innate and adaptive immunity with a powerful capacity to prime antigen-specific naive CD8+ T cells. DCs are richly abundant in the lung where they respond to viral infection. A relative increase of mature DCs in broncho-alveolar lavage fluids from Covid-19 patients has already been reported. Here we will describe how SARS-CoV-2 acts on DCs, the role of estrogen on DC immunobiology, summarise the impact of sex hormones on the immune response against Covid-19, and explore clinical trials regarding Covid-19.

Avaliação do ruído em Unidades de Terapia Intensiva / Noise Assessment in Intensive Care Units

As Unidades de Terapia Intensiva são ambientes em que existem inúmeras fontes geradoras de ruído. Recomenda-se, em diferentes ambientes hospitalares, níveis de pressão sonora entre 35 e 45db(A). OBJETIVO: Realizar mensuração dos níveis de pressão sonora de três Unidades de Terapia Intensiva de um hospital em Jundiaí, Estado de São Paulo, Brasil. FORMA DE ESTUDO: Observacional. MATERIAL E MÉTODOS: Foi utilizado decibelímetro Minipa modelo MSL1532C (USA) de acordo com as normas da Associação Brasileira de Normas Técnicas (NBR 10151), para medir os níveis sonoros nas Unidades de Terapia Intensiva em períodos variados, isto é, manhã, tarde e noite em horários de pico de atividade. RESULTADOS: Os valores encontrados durante as aferições dos níveis de pressão sonora foram de 64.1dB(A) na Primeira Unidade de Terapia Intensiva, 58.9 dB(A) na Unidade Coronariana e 64dB(A) na Segunda Unidade de Terapia Intensiva. CONCLUSÃO: Níveis elevados de pressão sonora em Unidades de Terapia Intensiva ainda significam um problema importante na morbidade dos pacientes de tais unidades de atendimento à saúde. Nenhuma das três UTI apresentaram níveis maiores que 85dB, demonstrando que não há risco ocupacional para as equipes de saúde nos ambientes pesquisados.

Intensive Care Units are environments with numerous noise sources. In different hospital environments it is recommended to have a sound pressure level between 35 and 45db(A). AIM: To measure the sound pressure levels in three ICU at a hospital in Jundiaí, State of São Paulo, Brazil. STUDY DESIGN: Observational. MATERIALS AND METHODS: we used a Minipa model MSL1532C (USA) sound meter, according to the Brazilian Technical Standards (NBR 10151), in order to measure sound levels in the ICUs at different moments, that is, the morning, afternoon and night at peak times of activity. RESULTS: The values found during the checking of the sound pressure levels were 64.1dB (A) in the First ICU, 58.9 dB (A) in the Coronary Unit and 64dB (A) in the second ICU. CONCLUSION: High sound pressure levels in ICU still mean an important health-related problem for patients in these units. None of the three ICU pad levels above 85dB, showing that there is no occupational risk for the health care teams in the environments studied.

Noise assessment in intensive care units.

UNLABELLED: Intensive Care Units are environments with numerous noise sources. In different hospital environments it is recommended to have a sound pressure level between 35 and 45db(A). AIM: To measure the sound pressure levels in three ICU at a hospital in Jundiaí, State of São Paulo, Brazil. STUDY DESIGN: Observational. MATERIALS AND METHODS: we used a Minipa model MSL1532C (USA) sound meter, according to the Brazilian Technical Standards (NBR 10151), in order to measure sound levels in the ICUs at different moments, that is, the morning, afternoon and night at peak times of activity. RESULTS: The values found during the checking of the sound pressure levels were 64.1dB (A) in the First ICU, 58.9 dB (A) in the Coronary Unit and 64dB (A) in the second ICU. CONCLUSION: High sound pressure levels in ICU still mean an important health-related problem for patients in these units. None of the three ICU pad levels above 85dB, showing that there is no occupational risk for the health care teams in the environments studied.