The high numbers of COVID-19 cases and deaths in Brazil have made Latin America an epicentre of the pandemic. SARS-CoV-2 established sustained transmission in Brazil early in the pandemic, but important gaps remain in our understanding of virus transmission dynamics at a national scale. We use 17,135 near-complete genomes sampled from 27 Brazilian states and bordering country Paraguay. From March to November 2020, we detected co-circulation of multiple viral lineages that were linked to multiple importations (predominantly from Europe). After November 2020, we detected large, local transmission clusters within the country. In the absence of effective restriction measures, the epidemic progressed, and in January 2021 there was emergence and onward spread, both within and abroad, of variants of concern and variants under monitoring, including Gamma (P.1) and Zeta (P.2). We also characterized a genomic overview of the epidemic in Paraguay and detected evidence of importation of SARS-CoV-2 ancestor lineages and variants of concern from Brazil. Our findings show that genomic surveillance in Brazil enabled assessment of the real-time spread of emerging SARS-CoV-2 variants.
We examined the activity of neutrophils isolated from sputum and blood of subjects with chronic bronchial sepsis in terms of interleukin-8 (IL-8), IL-1beta, and tumor necrosis factor-alpha (TNF alpha) production. In sputum, the numbers of neutrophils correlated with the concentrations of these cytokines. Sputum neutrophils constitutively secreted large amounts of IL-8, IL-1beta, and TNF alpha. The patterns of secretion, however, differed from those of blood neutrophils stimulated with bacterial lipopolysaccharide (LPS). Cytokine secretion was time-dependent and was inhibited by cycloheximide and dexamethasone. IL-10 inhibition of IL-8 production by sputum neutrophils was significantly less than that noted with activated neutrophils. Antibody to IL-1beta but not to TNF alpha, inhibited IL-8 secretion by sputum neutrophils, contrasting with results found using blood neutrophils. Incubation of blood neutrophils in sputum sol induced a similar cytokine secretion profile to that following exposure to LPS. The inhibitory effects on IL-8 protein production correlated with messenger RNA (mRNA) gene expression. These observations indicate that neutrophils are a significant source of IL-8 in purulent sputum, and that an autocrine loop involving IL-1beta maintains secretion within the bronchus lumen.
Neutrophils are central to the control of infection within the bronchial mucosa. To determine whether the link between bacterial and viral infection in the respiratory tract can be partly explained by acute reduction of neutrophil function, we examined the influence of influenza virus on lysozyme secretion by sputum neutrophils obtained from patients with bronchiectasis. Sputum neutrophils infected with influenza A virus had a significantly reduced capacity to secrete lysozyme but not myeloperoxidase. Influenza virus A strains were more effective in inhibiting lysozyme secretion than were influenza B virus strains. Reduction of bactericidal activity was similarly reduced by different strains of influenza A virus, but an influenza virus B strain had no effect. Our results show that downregulation of sputum neutrophil function characterized by lysozyme secretion and bactericidal activity could contribute to reduction in the capacity to control bacterial colonization in the respiratory tract following influenza virus infection.
Background: Lesbian, gay, bisexual, and transgender (LGBT) seniors are generally a medically underserved population that faces unique healthcare challenges. When compared to younger patients, LGBT seniors are at a greater risk for social isolation and have higher rates of smoking, disability, physical and mental distress, and lack of access to healthcare services. They are often reluctant to discuss their sexual orientations and gender identities with healthcare providers due to fear of discrimination and receiving inferior care based on prior unsatisfactory experiences with untrained or insensitive healthcare providers. Furthermore, recent research has revealed that only about 50% of primary care providers indicated confidence in providing culturally competent LGBT healthcare, highlighting the need for more LGBT proficiency training in medical school curricula. Objectives: The aim of this study was to provide early intervention training to first-year medical students regarding best practices for equitable healthcare for LGBT seniors through integrative, small group, case-based discussions. The impact of this activity on the knowledge and attitudes of medical students regarding LGBT healthcare was also assessed. Methods: First-year medical students participated in a two-hour small group, case-based discussion. Each group consisted of seven to eight students with one of seven facilitators who were invited members of the LGBT community. Students were provided with two clinical case scenarios related to treatment of LGBT senior patients. Students were given a pre/post-session knowledge and attitude survey to assess the impact of the session on their attitudes and understanding of the importance of providing equitable healthcare to LGBT patients. A rubric was also used by facilitators to evaluate level of student engagement and professionalism. Results: A total of 51 first-year medical students attended the session and 38 (74.5%) completed the pre/post surveys. There was diverse representation in our student demographic with 5.2% of respondents identifying as LGBT. Survey results showed a significant increase in knowledge confidence and attitudes following the session. Students’ attitudes regarding determinants of health status changed significantly for nine of the 13 (69%) survey items. In addition, their confidence in knowledge regarding healthcare barriers, health issues, and practices for LGBT culturally competent care significantly increased post-session. Data from our assessment rubrics also show that students were highly professional and engaged with the LGBT facilitators. Conclusion: Our study provides some evidence that case-based training of medical students regarding issues that affect health of LGBT seniors can improve attitudes and sensitize them to the unique needs of this population. Through this activity, the students indicated their desire to learn more about the topics covered and to receive further training in this field of study. While the study wa...
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