BLOOD VESSELS IN GANGLIA IN HUMAN ESOPHAGUS MIGHT EXPLAIN THE HIGHER FREQUENCY OF MEGAESOPHAGUS COMPARED WITH MEGACOLON

This study aimed to determine the existence of blood vessels within ganglia of the myenteric plexus of the human esophagus and colon. At necropsy, 15 stillborns, newborns and children up to two years of age, with no gastrointestinal disorders, were examined. Rings of the esophagus and colon were analyzed and then fixed in formalin and processed for paraffin. Histological sections were stained by hematoxylin-eosin, Giemsa and immunohistochemistry for the characterization of endothelial cells, using antibodies for anti-factor VIII and CD31. Blood vessels were identified within the ganglia of the myenteric plexus of the esophagus, and no blood vessels were found in any ganglia of the colon. It was concluded that the ganglia of the myenteric plexus of the esophagus are vascularized, while the ganglia of the colon are avascular. Vascularization within the esophageal ganglia could facilitate the entrance of infectious agents, as well as the development of inflammatory responses (ganglionitis) and denervation, as found in Chagas disease and idiopathic achalasia. This could explain the higher frequency of megaesophagus compared with megacolon

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Habilidade de localização e lateralização sonora em deficientes visuais Sound localization and lateralization in individuals with visual deficiency

OBJETIVO: Verificar o desempenho de ouvintes, cegos ou com visão subnormal, nos testes de localização sonora em cinco direções e de lateralização, comparando-o com indivíduos videntes, com sensibilidade auditiva normal, nas mesmas tarefas. MÉTODOS: Foram selecionados 21 indivíduos com sensibilidade auditiva normal, faixa etária média de 30 anos, de ambos os gêneros, reunidos pela presença cegueira e/ou visão subnormal congênita ou adquirida. Foram realizados os testes que compõem a avaliação audiológica básica, o Teste de Localização Sonora e o Teste de Lateralização com Som Verbal, nas técnicas ascendente e descendente. Os resultados obtidos com os testes realizados pelo grupo de 21 indivíduos com deficiência visual foram comparados com os de 40 adultos videntes e ouvintes normais. RESULTADOS: No grupo estudo (deficientes visuais), tanto na técnica ascendente quanto na descendente, existem diferenças estatisticamente significantes entre os limiares de lateralização sonora para as orelhas direita e esquerda. O maior limiar de lateralização foi observado na orelha esquerda em cada grupo. Em cada técnica, ascendente e descendente, não existiram diferenças estatisticamente significantes para o limiar de lateralização por orelha, em cada grupo. Comparando os dados do teste de lateralização sonora do grupo de deficientes visuais por técnica e orelha, com os dados do grupo de comparação de videntes, verificamos que existiram diferenças estatisticamente significantes em ambas as técnicas e orelhas, com exceção da orelha esquerda, na técnica ascendente. CONCLUSÃO: Os deficientes visuais avaliados têm um excelente desempenho em lateralização de sons, muito melhor do que sujeitos videntes e ouvintes típicos ou normais.<br>PURPOSE: To verify the auditory performance of blind or subnormal sight individuals in tests for sound localization in five directions and lateralization, compared to individuals with normal sight and normal auditory sensibility. METHODS: Twenty-one individuals with normal auditory sensibility were selected, mean age of 30 years, both genders, grouped according to presence of blindness and/or acquired or congenital subnormal sight. Audiological evaluation tests, Sound Localization Test and Lateralization Test with verbal sound, using both ascending and descending techniques, were carried out. Results obtained on the tests by the 21 subjects with visual deficiency were compared to those of 40 adults with normal sight and hearing. RESULTS: The visually impaired group, both in ascending and descending techniques, presented statistically significant differences between sound lateralization limits for right and left ears. The higher lateralization threshold was observed on the left ear in each group. In each technique, ascending and descending, there were no statistically significant differences in the lateralization threshold per ear in each group. Comparing data from the sound lateralization test of the visually impaired per technique and ear, with data from the comparison group with normal sight, it was verified that there were statistically significant differences for both techniques and ears, except for the left ear in the ascending technique. CONCLUSION: The visually impaired evaluated showed an excellent performance in sound lateralization, much better than individuals with normal sight and hearing