Pulmonary inflammation and viral replication define distinct clinical outcomes in fatal cases of COVID-19.

COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and the host determinants that determine the different clinical outcomes are still unclear. In this study, we assessed lung autopsies of 47 COVID-19 patients and examined the inflammatory profiles, viral loads, and inflammasome activation. Additionally, we correlated these factors with the patient's clinical and histopathological conditions. Robust inflammasome activation was detected in the lungs of lethal cases of SARS-CoV-2. Experiments conducted on transgenic mice expressing hACE2 and infected with SARS-CoV-2 showed that Nlrp3-/- mice were protected from disease development and lethality compared to Nlrp3+/+ littermate mice, supporting the involvement of this inflammasome in disease exacerbation. An analysis of gene expression allowed for the classification of COVID-19 patients into two different clusters. Cluster 1 died with higher viral loads and exhibited a reduced inflammatory profile than Cluster 2. Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, thrombosis, viral loads, and inflammasome activation significantly differed between the two clusters. Our data demonstrated two distinct profiles in lethal cases of COVID-19, thus indicating that the balance of viral replication and inflammasome-mediated pulmonary inflammation led to different clinical outcomes. We provide important information to understand clinical variations in severe COVID-19, a process that is critical for decisions between immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19.

Activities of the oral health teams in primary health care: a time-motion study.

BACKGROUND: Efficient planning of the oral health workforce in Primary Health Care (PHC) is paramount to ensure equitable community access to services. This requires a meticulous examination of the population's needs, strategic distribution of oral health professionals, and effective human resource management. In this context, the average time spent on care to meet the needs of users/families/communities is the central variable in healthcare professional workforce planning methods. However, many time measures are solely based on professional judgment or experience. OBJECTIVE: Calculate the average time parameters for the activities carried out by the oral health team in primary health care. METHOD: This is a descriptive observational study using the time-motion method carried out in five Primary Health Care Units in the city of São Paulo, SP, Brazil. Direct and continuous observation of oral health team members occurred for 40 h spread over five days of a typical work week. RESULTS: A total of 696.05 h of observation were conducted with 12 Dentists, three Oral Health Assistants, and five Oral Health Technicians. The Dentists' main activity was consultation with an average duration of 24.39 min, which took up 42.36% of their working time, followed by documentation with 12.15%. Oral Health Assistants spent 31.57% of their time on infection control, while Oral Health Technicians spent 22.37% on documentation. CONCLUSION: The study establishes time standards for the activities performed by the dental care team and provides support for the application of workforce planning methods that allow for review and optimization of the work process and public policies.

CASP4/11 Contributes to NLRP3 Activation and COVID-19 Exacerbation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers activation of the NLRP3 inflammasome, which promotes inflammation and aggravates severe COVID-19. Here, we report that SARS-CoV-2 induces upregulation and activation of human caspase-4/CASP4 (mouse caspase-11/CASP11), and this process contributes to NLRP3 activation. In vivo infections performed in transgenic hACE2 humanized mice, deficient or sufficient for Casp11, indicate that hACE2 Casp11-/- mice were protected from disease development, with the increased pulmonary parenchymal area, reduced clinical score of the disease, and reduced mortality. Assessing human samples from fatal cases of COVID-19, we found that CASP4 was expressed in patient lungs and correlated with the expression of inflammasome components and inflammatory mediators, including CASP1, IL1B, IL18, and IL6. Collectively, our data establish that CASP4/11 promotes NLRP3 activation and disease pathology, revealing a possible target for therapeutic interventions for COVID-19.

Oropouche virus infection induces ROS production and oxidative stress in liver and spleen of mice.

Oropouche virus (OROV) is the aetiological agent of Oropouche fever, the symptoms of which are common to most arboviruses, such as fever, headache, malaise, nausea and vomiting. More than half a million people have been infected with OROV since its isolation in 1955. Although Oropouche fever is classified as a neglected and emerging disease, to date, there are no antiviral drugs or vaccines available against the infection and little is known about its pathogenicity. Therefore, it is essential to elucidate the possible mechanisms involved in its pathogenesis. Since oxidative stress plays a pivotal role in the progression of various viral diseases, in this study, redox homeostasis in the target organs of OROV infection was evaluated using an animal model. Infected BALB/c mice exhibited reduced weight gain, splenomegaly, leukopenia, thrombocytopenia, anaemia, development of anti-OROV neutralizing antibodies, increased liver transaminases, and serum levels of pro-inflammatory cytokines tumour necrosis factor (TNF-α) and interferon-γ (IFN-γ). The OROV genome and infectious particles were detected in the liver and spleen of infected animals, with liver inflammation and an increase in the number and total area of lymphoid nodules in the spleen. In relation to redox homeostasis in the liver and spleen, infection led to an increase in reactive oxygen species (ROS) levels, increased oxidative stress biomarkers malondialdehyde (MDA) and carbonyl protein, and decreased activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Taken together, these results help elucidate some important aspects of OROV infection that may contribute to the pathogenesis of Oropouche.

Challenges and strategies for conducting research in primary health care practice: an integrative review.

BACKGROUND: Providing accessible and high-quality patient-centered healthcare remains a challenge in many countries, despite global efforts to strengthen primary health care (PHC). Research and knowledge management are integral to enhancing PHC, facilitating the implementation of successful strategies, and promoting the use of evidence-based practices. Practice-based research in primary care (PC-PBR) has emerged as a valuable approach, with its external validity to diverse PHC settings, making it an effective means of translating research findings into professional practice. OBJECTIVE: To identify challenges and strategies for conducting practice-based research in primary health care services. METHOD: An integrative literature review was conducted by searching the PubMed, Embase, Scopus, Web of Science, and Lilacs databases. The research question, guided by the PICo framework, directed the execution of study selection and data extraction. Data analysis followed the RAdAR method's three phases: pre-analysis, data analysis, and interpretation of results. RESULTS: Out of 440 initially identified articles, 26 met the inclusion criteria. Most studies were conducted in high-income countries, primarily the United States. The challenges and strategies for PC-PBR were categorized into six themes: research planning, infrastructure, engagement of healthcare professionals, knowledge translation, the relationship between universities and health services, and international collaboration. Notable challenges included research planning complexities, lack of infrastructure, difficulties in engaging healthcare professionals, and barriers to knowledge translation. Strategies underscore the importance of adapting research agendas to local contexts, providing research training, fostering stakeholder engagement, and establishing practice-based research networks. CONCLUSION: The challenges encountered in PC-PBR are consistent across various contexts, highlighting the need for systematic, long-term actions involving health managers, decision-makers, academics, diverse healthcare professionals, and patients. This approach is essential to transform primary care, especially in low- and middle-income countries, into an innovative, comprehensive, patient-centered, and accessible healthcare system. By addressing these challenges and implementing the strategies, PC-PBR can play a pivotal role in bridging the gap between research and practice, ultimately improving patient care and population health.

Mental Health Care in Primary Health Care: An Integrative Review.

In this study, we analyzed recent studies on mental health approaches developed in primary health care to identify the emphasis of such interventions, their technical feasibility for the setting in question, and their levels of evidence. An integrative review was conducted of primary studies from the LILACS, PubMed, Embase, CINAHL, and Web of Science databases using the PRISMA search strategy. Nineteen studies were identified with a high level of evidence that contribute to the advancement of knowledge in the area. However, academic, cultural, and linguistic barriers still need to be overcome to facilitate sharing of such interventions' findings and protocols.

Molecular detection of omicron SARS-CoV-2 variant is achieved by RT-LAMP despite genomic mutations.

BACKGROUND: Severe acute respiratory syndrome coronavirus (SARS-CoV-2) omicron variant was first detected in South Africa in November 2021. Since then, the number of cases due to this variant increases enormously every day in different parts of the world. Mutations within omicron genome may impair the molecular detection resulting in false negative results during Coronavirus disease 19 (COVID-19) diagnosis. OBJECTIVES: To verify if colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) targeting N and E genes would work efficiently to detect omicron SARS-CoV-2 variant and its sub-lineages. METHODS: SARS-CoV-2 reverse transcription quantitative polymerase chain reaction (RT-qPCR) positive samples were sequenced by next generation DNA sequencing. The consensus sequences generated were submitted to Pangolin tool for SARS-CoV-2 lineage identification. RT-LAMP reactions were performed at 65ºC/30 min targeting N and E. FINDINGS: SARS-CoV-2 omicron can be detected by RT-LAMP targeting N and E genes despite the genomic mutation of this more transmissible lineage. Omicron SARS-CoV-2 sub-lineages were tested and efficiently detected by RT-LAMP. We demonstrated that this test is very sensitive in detecting omicron variant, with LoD as low as 0.4 copies/µL. MAIN CONCLUSIONS: Molecular detection of omicron SARS-CoV-2 variant and its sub-lineages can be achieved by RT-LAMP despite the genomic mutations as a very sensitive surveillance tool for COVID-19 molecular diagnosis.

Cartilaginous choristoma on the lateral surface of the tongue: a case report.

A cartilaginous choristoma is a nonneoplastic nodular growth of histologically normal cartilage in an abnormal site. This report describes a case of a cartilaginous choristoma on the lateral surface of the tongue in a 65-year-old woman. The entire lesion was excised, and histologic examination revealed mature cartilaginous tissue surrounded by dense connective tissue. Choristomas are rare findings in the oral cavity, easily confused with proliferative processes or soft tissue neoplasms. Nevertheless, choristomas may be part of the differential diagnosis for lesions similar to the one described in this case report.

Anti-Inflammatory and Antinociceptive Properties of Kielmeyerone A, a Chromenone Isolated from the Roots of Kielmeyera reticulata.

Four new chromenones, kielmeyerones A-D (1-4), were obtained from the roots of Kielmeyera reticulata. Their structures were elucidated based on spectroscopic data (NMR and HRESIMS) interpretation. The pharmacological activity of kielmeyerone A (1), the major compound, was evaluated using in vitro and in vivo inflammation and pain models. During in vitro screening, 1, at noncytotoxic concentrations (0.097-1.56 µM), inhibited NO production by J774 macrophages stimulated with LPS and IFN-γ. In the complete Freund's adjuvant-induced inflammation model in mice, 1 (12.5-50 mg/kg) inhibited paw edema, demonstrating an anti-inflammatory effect. Additionally, 1 (12.5-50 mg/kg) induced a dose-dependent antinociceptive effect in the late phase of the formalin test, a profile similar to those of nonsteroidal anti-inflammatory drugs. Mice treated with 1 (100 mg/kg) did not show motor performance alterations using a rota-rod test. Thus, the present study has characterized new chromenones from Kielmeyera reticulata and has provided evidence of the anti-inflammatory and antinociceptive properties of one of these, kielmeyerone A (1).

Social support networks of users of crack cocaine and the role of a Brazilian health program for people living on the street: A qualitative study.

This cross-sectional qualitative study analyzed characteristics of social support for users of crack cocaine and the role of "Consultório na Rua" (CR), or "Office in the Street," a Brazilian program for people living on the street. Data were collected using 1) ethnographic field observations during the delivery of services from this program, 2) in-depth interviews with 17 users of crack cocaine, and 3) a focus group with professionals from CR. To analyze data, we used content analysis and analytical categories based on Social Network Analysis (SNA) theoretical statements. Results showed that family, peers, community members, and professionals from CR were the main social support providers. Participants mentioned receiving material, informational, and emotional support from CR members. It was observed that CR had a welcoming and inclusive approach, but CR team members identified challenges related to stigma directed toward people who use substances and live on the street. CR assumed a central role in the health and social assistance of users of crack cocaine living on the street, providing an important link to healthcare and social services. However, initiatives related to motivation to receive mental health services, treatment, or social reintegration were not observed in conjunction with this program.

Biogas production in a tropical landfill: Long-term monitoring results and analysis of variables of influence.

The use of landfill gas for power production is a very attractive option in tropical sanitary landfills mainly in developing countries, where the waste composition, water content, and the climate conditions are favorable to a fast depletion of waste organic matter and a robust short term biogas production response. In this paper, the results of long-term monitoring and methane extraction activities in a tropical landfill are presented, and the obtained results are analyzed taking into account the structure of the prokaryotic communities and the fugitive emissions through the temporary covers. It is shown that waste depletion by aerobic processes and fugitive emissions are probable related to the drop in the efficiency of the extraction system verified in the field and that the performance of the temporary covers is of paramount importance when implementing good practices of waste management in sanitary landfills. The fugitive emissions through temporary covers was estimated at about 12% of the methane production in the field, and the distance from drains and sampling depth were confirmed as having an influence on the environmental conditions for waste depletion and on the relative abundance of the bacterial communities.

Violence, drugs, and psychiatric disorders: news from the Brazilian press.

The aim of this study is to describe the way that the Brazilian press reports on episodes of violence involving people with substance-related problems or psychiatric disorders. To develop this documentary study, we analyzed news reports from September 2009 to August 2015 in two major Brazilian newspaper who make their published articles available electronically in the Lexis Nexis Academic® database. The analyses were conducted using descriptive statistics and association tests. We identified 269 news stories related to these themes during the study period. The reported events occurred mainly in São Paulo and Rio de Janeiro, and 68% of the stories suggested a causal relationship between substance use or mental illness and violence. A marked minority (10%) of the stories made reference to prevention or treatment for the conditions studied. We concluded that the Brazilian press issues incomplete reports on episodes of violence involving people with substance-related problems or psychiatric disorders, emphasizing the relationships between these conditions and potential danger, particularly in cases involving drugs.

The Social Support Buffering Effect in the Relationship Between Perceived Stress and Alcohol Use Among Brazilian Women.

This cross-sectional study interviewed Brazilian women regularly attending primary care to investigate whether the relationship between social support and alcohol use is direct or is mediated by stress, in order to support the development of recommendations related to health prevention and mental health promotion actions. The results suggest that social support affects the outcome alcohol use in the women studied by buffering the effect of stress. Based on these results, recommendations are made for amplifying the social support network that prevents stress-induced alcohol use.

The use of benzodiazepines by women cared for at a Family Health Unit.

OBJECTIVE: Estimate the prevalence of benzodiazepine use by adult women at a Family Health Unit and identify the risk factors associated with this usage. METHOD: Quantitative cross-sectional study that employed secondary data developed at a Family Health Unit in the state of São Paulo, Brazil. We collected the data from the following sources: medical charts, registration forms, and the archive of prescriptions from the pharmacy at the referred health unit. We employed the chi-squared, Student's t, and Mann-Whitney tests, as well as logistic regression analysis. RESULTS: We identified 81 benzodiazepine users amongst 1,094 adult women (7.4%). Regarding the risk factors, the comparison between the groups of benzodiazepine users (n = 64) and non-users (n = 70) showed that having a chronic disease and using other psychotropic drugs were significantly associated with the use of benzodiazepines. CONCLUSION: The prevalence found was lower than the described in previous studies performed in Primary Health Units. The group that must receive greater attention regarding the consumption of benzodiazepines is that of middle-aged women or older, with low education levels, and chronic illnesses.

Evaluation of social support and stress in nursing students. / Avaliação do apoio social e estresse em estudantes de enfermagem.

OBJECTIVE: To analyze the perception of stress and social support of nursing students considering the number of supporters and the satisfaction with them. METHOD: Quantitative, cross-sectional study performed with nursing students from a public university in the state of São Paulo, Brazil. We used the Stress Evaluation in Nursing Students scale and the Social Support Questionnaire. We performed the chi-squared test and analyzed the structure of the support network using software Gephi version 0.9.1. RESULTS: 192 students participated. Family and friends were the most mentioned supporters. Despite counting on a low number of supporters, most participants were satisfied with the perceived support. The students presented high intensity of stress in the "professional training" domain. Furthermore, the students who were pleased with the perceived social support presented low intensity of stress in accomplishing the theoretical activities of the undergraduate course. CONCLUSION: The creation of more welcoming spaces in the academic environment, the qualification of the social support, and the employment of strategies to improve the transition from the student stage to the professional stage are important recommendations that will contribute for positive outcomes regarding the coping with student stress.

Implications of oxidative stress on viral pathogenesis.

Reactive species are frequently formed after viral infections. Antioxidant defences, including enzymatic and non-enzymatic components, protect against reactive species, but sometimes these defences are not completely adequate. An imbalance in the production of reactive species and the body's inability to detoxify these reactive species is referred to as oxidative stress. The aim of this review is to analyse the role of oxidative stress in the pathogenesis of viral infections and highlight some major therapeutic approaches that have gained importance, with regards to controlling virus-induced oxidative injury. Attention will be focused on DNA viruses (papillomaviruses, hepadnaviruses), RNA viruses (flaviviruses, orthomyxoviruses, paramyxoviruses, togaviruses) and retroviruses (human immunodeficiency virus). In general, viruses cause an imbalance in the cellular redox environment, which depending on the virus and the cell can result in different responses, e.g. cell signaling, antioxidant defences, reactive species, and other processes. Therefore, the modulation of reactive species production and oxidative stress potentially represents a novel pharmacological approach for reducing the consequences of viral pathogenesis.

Structure of the Social Support Network of Patients with Severe and Persistent Psychiatric Disorders in Follow-Ups to Primary Health Care.

The objective of this study is to analyze the characteristics of social support networks of patients with psychiatric disorders at follow-up to primary care. This is a cross-sectional qualitative research study. Forty-five interviews were held with patients and their supporters. The results showed small and dense networks, with a strong emphasis on the bonds with formal supporters and a scant network of informal supporters. It is recommended to develop strategies to improve social support networks and use this as an outcome indicator related to social integration of these patients and to the quality of services involved with outpatient healthcare.

Synthesis and biological evaluation of novel piperidine-benzodioxole derivatives designed as potential leishmanicidal drug candidates.

A novel series of ester and carbamate derivatives was synthesized and evaluated its activities against Leishmania amazonensis. All compounds exhibited weaker leishmanicidal activity than amphotericin B. However, results indicated that substituents on the aryl-acyl subunit are important for modulation of the leishmanicidal effect. The nitro derivative showed the highest activity of the series with an IC50 = 17.24 µM, and comparable potency to the 3,4-benzodioxole ester and n-hexyl carbamate derivatives. All compounds showed low toxicity against human cells. These results revealed interesting novel piperine-like molecular pattern for exploitation in search and development of effective and low toxic antileishmanial drug candidates.

The 2',4'-dihydroxychalcone could be explored to develop new inhibitors against the glycerol-3-phosphate dehydrogenase from Leishmania species.

The enzyme glycerol-3-phosphate dehydrogenase (G3PDH) from Leishmania species is considered as an attractive target to design new antileishmanial drugs and a previous in silico study reported on the importance of chalcones to achieve its inhibition. Here, we report the identification of a synthetic chalcone in our in vitro assays with promastigote cells from Leishmania amazonensis, its biological activity in animal models, and docking followed by molecular dynamics simulation to investigate the molecular interactions and structural patterns that are crucial to achieve the inhibition complex between this compound and G3PDH. A molecular fragment of this natural product derivative can provide new inhibitors with increased potency and selectivity.

Synthesis and evaluation of novel prenylated chalcone derivatives as anti-leishmanial and anti-trypanosomal compounds.

Chalcones form a class of compounds that belong to the flavonoid family and are widely distributed in plants. Their simple structure and the ease of preparation make chalcones attractive scaffolds for the synthesis of a large number of derivatives enabling the evaluation of the effects of different functional groups on biological activities. In this Letter, we report the successful synthesis of a series of novel prenylated chalcones via Claisen-Schmidt condensation and the evaluation of their effect on the viability of the Trypanosomatidae parasites Leishmania amazonensis, Leishmania infantum and Trypanosoma cruzi.