Sexo sem tabu: relato de um caso de ação comunitária, com foco na promoção de saúde de adolescentes, em uma escola técnica na cidade de São Paulo

A sexualidade, apesar de sua relevância no âmbito da promoção da saúde, é pouco abordada durante os cursos de graduação e por profissionais da saúde na prática clínica. O objetivo deste trabalho é descrever o projeto “Sexo sem Tabu”, realizado por alunos do primeiro ano do curso de Medicina da Universidade de São Paulo, dentro da proposta da disciplina “Atenção Primária à Saúde I”. Após delineamento do tema e revisão literária, foram executados dois dias de intervenção. Baseados em dinâmicas propostas pelo Ministério da Saúde, discutimos sexualidade e temas correlatos em saúde, com pequenos grupos de alunos de uma escola técnica na cidade de São Paulo. Dentre os alunos participantes, 115/117 (98,3%) disseram ter dúvidas solucionadas durante a discussão e 114/117 (97,4%) consideraram que as informações que foram trazidas eram relevantes para suas vidas. Os alunos da Faculdade de Medicina relataram a oportunidade de treinar várias habilidades afetivas e cognitivas como habilidades de comunicação, desenvoltura, capacidade de lidar com o imprevisto, além de reconhecer que a abordagem da sexualidade não se restringe aos aspectos relacionados às doenças sexualmente transmissíveis, mas também a questões emocionais, morais e fisiológicas. Em conclusão, esta ação comunitária, com foco em promoção da saúde dos adolescentes e abordando o tema da sexualidade, trouxe resultados positivos para os alunos do ensino médio e para a formação profissional dos estudantes de medicina.Although sexuality has an evident importance in health promotion, it is rarely discussed during undergraduate courses or assessed by health professionals during clinical practice. The aim of this article is to describe the “Sexo sem Tabu” project, a community action realized by first year medical students from the Faculdade de Medicina da Universidade de São Paulo, during the course “Primary Care I” (“Atenção Primária à Saúde I”). After establishing project design and adequate literature review, we realized two days of community action. Based on dynamics proposed by the Brazilian Ministry of Health, we discussed sexuality and other related health topics within small groups of students from a technical high school in the city of São Paulo. Among high school participants, 115/117 (98.3%) considered that they had their doubts solved during the discussion and 114/117(97.4%) found the information was relevant for their lives. First year medical students documented the opportunity to train several cognitive and affective abilities such as communication, resourcefulness, and how to interact in uncontrolled situations. Furthermore, they recognized that sexuality was not restricted to sexually transmitted diseases, but included emotional, ethical and physiological issues. Concluding, this community action, focused on health promotion for teenagers assessing themes on sexuality, brought positive results for high school students and for the training of medical students

EBOVAC-Salone: lessons learned from implementing an Ebola vaccine trial in an Ebola-affected country.

Background/aims During the 2014-2016 West African Ebola epidemic, clinical trials were fast-tracked in order to identify prophylactic vaccines and experimental treatments that might be useful in preventing or treating Ebola. These trials included the ongoing EBOVAC-Salone study, which was established and implemented in Sierra Leone to assess the safety and immunogenicity of the Ad26.ZEBOV/MVA-BN-Filo prime-boost Ebola vaccine regimen. Methods This article describes the experiences of the EBOVAC-Salone research team in setting up and implementing the trial, and provides recommendations for research teams aiming to conduct clinical trials in future outbreak situations. Results Establishing a clinical trial during an outbreak brought some unique challenges, including those related to trial design and the regulatory environment, operational issues, and community engagement. The situation was further complicated by the weak infrastructure and limited experience of clinical trials in Sierra Leone. However, operating in an outbreak context also brought some benefits to the research team, including strong stakeholder support. The EBOVAC-Salone study recruited participants both during and after the outbreak, leading to additional challenges to trial implementation during the post-outbreak transition. Conclusion Many lessons have been learned about setting up and implementing a clinical trial during a devastating Ebola epidemic, and some of the experiences of the EBOVAC-Salone team were mirrored by those of other researchers operating in the region. Common to several of these research groups is a recommendation that research should be more closely incorporated into outbreak response planning, which could expedite the establishment of timely and appropriate research projects. We recommend that the lessons learned by researchers during the West African Ebola epidemic are built into programmes and strategies to improve the responses to future epidemics, wherever they occur

Long-term clinical safety of the Ad26.ZEBOV and MVA-BN-Filo Ebola vaccines: a prospective, multi-country, observational study

In this prospective, observational study (ClinicalTrials.gov Identifier: NCT02661464), long-term safety information was collected from participants previously exposed to the Ebola vaccines Ad26.ZEBOV and/or MVA-BN-Filo while enrolled in phase 1, 2, or 3 clinical studies. The study was conducted at 15 sites in seven countries (Burkina Faso, France, Kenya, Tanzania, Uganda, the United Kingdom, and the United States). Adult participants and offspring from vaccinated female participants who became pregnant (estimated conception ≤28 days after vaccination with MVA-BN-Filo or ≤3 months after vaccination with Ad26.ZEBOV) were enrolled. Adults were followed for 60 months after their first vaccination, and children born to female participants were followed for 60 months after birth. In the full analysis set (n = 614 adults; median age [range]: 32.0 [18–65] years), 49 (8.0%) had ≥1 serious adverse event (SAE); the incidence rate of any SAE was 27.4 per 1000 person-years (95% confidence interval: 21.0, 35.2). The unrelated SAEs of malaria were reported in the two infants in the full analysis set, aged 11 and 18 months; both episodes were resolved. No deaths or life-threatening SAEs occurred during the study. Overall, no major safety issues were identified; one related SAE was reported. These findings support the long-term clinical safety of the Ad26.ZEBOV and MVA-BN-Filo vaccines

Safety and Immunogenicity of a 2-Dose Heterologous Vaccination Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Uganda and Tanzania.

BACKGROUND: Ebola vaccine development was accelerated in response to the 2014 Ebola virus infection outbreak. This phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malaria-endemic settings. METHODS: Healthy volunteers aged 18-50 years from Tanzania (n = 25) and Uganda (n = 47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (first vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV (second vaccination) dose 2, respectively, with intervals of 28 or 56 days. RESULTS: Seventy-two adults were randomized to receive vaccine (n = 60) or placebo (n = 12). No vaccine-related serious adverse events were reported. The most frequent solicited local and systemic adverse events were injection site pain (frequency, 70%, 66%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively) and headache (57%, 56%, and 46%, respectively). Adverse event patterns were similar among regimens. Twenty-one days after dose 2, 100% of volunteers demonstrated binding antibody responses against Ebola virus glycoprotein, and 87%-100% demonstrated neutralizing antibody responses. Ad26.ZEBOV dose 1 vaccination induced more-robust initial binding antibody and cellular responses than MVA-BN-Filo dose 1 vaccination. CONCLUSIONS: Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola virus is well tolerated and immunogenic in healthy volunteers. CLINICAL TRIALS REGISTRATION: NCT02376400

Heterologous hyperimmune polyclonal antibodies against SARS-COV-2: A broad coverage, affordable, and scalable potential immunotherapy for Covid-19

The emergence and dissemination of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting COVID-19 pandemic triggered a global public health crisis. Although several SARS-CoV-2 vaccines have been developed, demand far exceeds supply, access to them is inequitable, and thus, populations in low- and middle-income countries are unlikely to be protected soon (1). Furthermore, there are no specific therapies available, which is a challenge for COVID-19 patient care (2). Thus, the appearance of SARS-CoV-2 variants and reports of reinfections associated with immune escape (3, 4) highlight the urgent need for effective and broad coverage COVID-19 therapeutics. Intravenous administration of human or heterologous antibodies is a therapy successfully used in patients with viral respiratory diseases (5). Accordingly, formulations containing SARS-CoV-2 specific antibodies are an attractive therapeutic option for COVID-19 patients (6). SARS-CoV-2 specific antibodies could limit infection by direct virion neutralization and/or by targeting infected cells for elimination via complement or antibody-mediated cytotoxicity (6). Specific SARS-CoV-2 antibody-based therapeutics include convalescent plasma (CP), monoclonal antibodies (mAbs), human polyclonal IgG formulations purified from CP or transgenic animals, and heterologous hyperimmune polyclonal antibodies (pAbs) (6). Although the window for using antibody-based therapeutics varies, clinical data show that they are mainly effective if administered early after symptoms onset (6).Universidad de Costa Rica/[741-C0-198]/UCR/Costa RicaCaja Costarricense del Seguro Social/[]/CCSS/Costa RicaBanco Centroamericano de Integración Económica/[]/BCIE/Costa RicaGerman academic exchange services/[57592642]/DAAD/AlemaniaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de MedicinaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Enfermedades Tropicales (CIET

Long-Term Clinical Safety of the Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: A Prospective, Multi-Country, Observational Study.

In this prospective, observational study (ClinicalTrials.gov Identifier: NCT02661464), long-term safety information was collected from participants previously exposed to the Ebola vaccines Ad26.ZEBOV and/or MVA-BN-Filo while enrolled in phase 1, 2, or 3 clinical studies. The study was conducted at 15 sites in seven countries (Burkina Faso, France, Kenya, Tanzania, Uganda, the United Kingdom, and the United States). Adult participants and offspring from vaccinated female participants who became pregnant (estimated conception ≤28 days after vaccination with MVA-BN-Filo or ≤3 months after vaccination with Ad26.ZEBOV) were enrolled. Adults were followed for 60 months after their first vaccination, and children born to female participants were followed for 60 months after birth. In the full analysis set (n = 614 adults; median age [range]: 32.0 [18-65] years), 49 (8.0%) had ≥1 serious adverse event (SAE); the incidence rate of any SAE was 27.4 per 1000 person-years (95% confidence interval: 21.0, 35.2). The unrelated SAEs of malaria were reported in the two infants in the full analysis set, aged 11 and 18 months; both episodes were resolved. No deaths or life-threatening SAEs occurred during the study. Overall, no major safety issues were identified; one related SAE was reported. These findings support the long-term clinical safety of the Ad26.ZEBOV and MVA-BN-Filo vaccines

Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment

VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved residues within the C terminus of the VAMP2 SNARE motif. Affected individuals carrying de novo non-synonymous variants involving the C-terminal region presented a more severe phenotype with additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. Reconstituted fusion involving a lipid-mixing assay indicated impairment in vesicle fusion as one of the possible associated disease mechanisms. The genetic synaptopathy caused by VAMP2 de novo mutations highlights the key roles of this gene in human brain development and function

Ebola Virus Glycoprotein IgG Seroprevalence in Community Previously Affected by Ebola, Sierra Leone.

We explored the association of Ebola virus antibody seropositivity and concentration with potential risk factors for infection. Among 1,282 adults and children from a community affected by the 2014-2016 Ebola outbreak in Sierra Leone, 8% were seropositive for virus antibodies but never experienced disease symptoms. Antibody concentration increased with age

Inhibition of G-protein signalling in cardiac dysfunction of intellectual developmental disorder with cardiac arrhythmia (IDDCA) syndrome

Background: Pathogenic variants of GNB5 encoding the β5 subunit of the guanine nucleotide-binding protein cause IDDCA syndrome, an autosomal recessive neurodevelopmental disorder associated with cognitive disability and cardiac arrhythmia, particularly severe bradycardia. Methods: We used echocardiography and telemetric ECG recordings to investigate consequences of Gnb5 loss in mouse. Results: We delineated a key role of Gnb5 in heart sinus conduction and showed that Gnb5-inhibitory signalling is essential for parasympathetic control of heart rate (HR) and maintenance of the sympathovagal balance. Gnb5-/- mice were smaller and had a smaller heart than Gnb5+/+ and Gnb5+/-, but exhibited better cardiac function. Lower autonomic nervous system modulation through diminished parasympathetic control and greater sympathetic regulation resulted in a higher baseline HR in Gnb5-/- mice. In contrast, Gnb5-/- mice exhibited profound bradycardia on treatment with carbachol, while sympathetic modulation of the cardiac stimulation was not altered. Concordantly, transcriptome study pinpointed altered expression of genes involved in cardiac muscle contractility in atria and ventricles of knocked-out mice. Homozygous Gnb5 loss resulted in significantly higher frequencies of sinus arrhythmias. Moreover, we described 13 affected individuals, increasing the IDDCA cohort to 44 patients. Conclusions: Our data demonstrate that loss of negative regulation of the inhibitory G-protein signalling causes HR perturbations in Gnb5-/- mice, an effect mainly driven by impaired parasympathetic activity. We anticipate that unravelling the mechanism of Gnb5 signalling in the autonomic control of the heart will pave the way for future drug screening

Underlying heart diseases and acute COVID-19 outcomes

Background: The presence of any underlying heart condition could influence outcomes during the coronavirus disease 2019 (COVID-19). Methods: The registry HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19, NCT04334291) is an international ambispective study, enrolling COVID-19 patients discharged from hospital, dead or alive. Results: HOPE enrolled 2798 patients from 35 centers in 7 countries. Median age was 67 years (IQR: 53.0–78.0), and most were male (59.5%). A relevant heart disease was present in 682 (24%) cases. These were older, more frequently male, with higher overall burden of cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking habit, obesity) and other comorbidities such renal failure, lung, cerebrovascular disease and oncologic antecedents (p < 0.01, for all). The heart cohort received more corticoids (28.9% vs. 20.4%, p < 0.001), antibiotics, but less hydroxychloroquine, antivirals or tocilizumab. Considering the epidemiologic profile, a previous heart condition was independently related with shortterm mortality in the Cox multivariate analysis (1.62; 95% CI 1.29–2.03; p < 0.001). Moreover, heart patients needed more respiratory, circulatory support, and presented more in-hospital events, such heart failure, renal failure, respiratory insufficiency, sepsis, systemic infammatory response syndrome and clinically relevant bleedings (all, p < 0.001), and mortality (39.7% vs. 15.5%; p < 0.001).Conclusions: An underlying heart disease is an adverse prognostic factor for patients suffering COVID-19. Its presence could be related with different clinical drug management and would benefit from maintaining treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers during in-hospital stay