Efficacy and Safety of BCG Revaccination With M. bovis BCG Moscow to Prevent COVID-19 Infection in Health Care Workers: A Randomized Phase II Clinical Trial.

The Bacillus Calmette-Guérin (BCG) vaccine, which is widely used to protect children against tuberculosis, can also improve immune response against viral infections. This unicentric, randomized-controlled clinical trial assessed the efficacy and safety of revaccination with BCG Moscow in reducing the positivity and symptoms of COVID-19 in health care workers (HCWs) during the COVID-19 pandemic. HCWs who had negative COVID-19 IgM and IgG and who dedicated at least eight hours per week in facilities that attended to individuals suspected of having COVID-19 were included in the study and were followed for 7, 15, 30, 60, and 180 days by telemedicine. The HCWs were randomly allocated to a revaccinated with BCG group, which received the BCG vaccine, or an unvaccinated group. Revaccination with BCG Moscow was found to be safe, and its efficacy ranged from 30.0% (95.0%CI -78.0 to 72.0%) to 31.0% (95.0%CI -74.0 to 74.0%). Mycobacterium bovis BCG Moscow did not induce NK cell activation at 15-20 days post-revaccination. As hypothesized, revaccination with BCG Moscow was associated with a lower incidence of COVID-19 positivity, though the results did not reach statistical significance. Further studies should be carried out to assess whether revaccination with BCG is able to protect HCWs against COVID-19. The protocol of this clinical trial was registered on August 5th, 2020, at REBEC (Registro Brasileiro de Ensaios Clínicos, RBR-4kjqtg - ensaiosclinicos.gov.br/rg/RBR-4kjqtg/1) and the WHO (# U1111-1256-3892). The clinical trial protocol was approved by the Comissão Nacional de ética de pesquisa- CONEP (CAAE 31783720.0.0000.5078).

Transcutaneous Electrical Nerve Stimulation of PC5 and PC6 Acupoints Increases Sympathovagal Balance but Not Oxidative Stress in Healthy Subjects: A Randomized Clinical Trial.

Background: Transcutaneous electrical acupoint stimulation (TEAS) improves autonomic balance and reduces oxidative stress in subjects with chronic diseases, that decreases the risk of low-grade chronic inflammatory diseases, including cardiovascular diseases. However, these beneficial effects have never been demonstrated in healthy subjects. Objectives: To evaluate the acute effects of TEAS on autonomic balance and oxidative stress of healthy subjects. Methods: A randomized clinical trial was conducted with male healthy subjects (18-30 years old), randomly allocated to control (no intervention; n = 14), placebo (placebo intervention; n = 14) and TEAS group (at PC5 and PC6 acupoints; n = 13). The protocol consisted of accommodation (20 min), intervention (40 min), and recovery (30 min) periods. The acute effects of TEAS on hemodynamics were studied through measurements of heart rate, blood pressure and double product; on the autonomic nervous system by assessing heart rate variability; and on oxidative stress by quantifying reactive oxygen species in saliva samples, collected at the end of each period. Results: TEAS increased heart rate and double-product compared to control and placebo groups (p < 0.01). Moreover, TEAS increased sympathetic and reduced parasympathetic tonus, increasing the sympathovagal balance compared to the control and placebo groups. However, TEAS exerted no effect on oxidative stress in saliva samples. Conclusion: In healthy subjects, TEAS at PC5 and PC6 acupoints acutely improved autonomic balance, increasing sympathetic and reducing parasympathetic tonus, reflecting little improvement on hemodynamic responses. Whether it could be used as a cardioprotective strategy remains uncertain since it exerted no effect on oxidative stress.

In-depth transcriptome reveals the potential biotechnological application of Bothrops jararaca venom gland

Lack of complete genomic data of Bothrops jararaca impedes molecular biology research focusing on biotechnological applications of venom gland components. Identification of full-length coding regions of genes is crucial for the correct molecular cloning design. Methods: RNA was extracted from the venom gland of one adult female specimen of Bothrops jararaca. Deep sequencing of the mRNA library was performed using Illumina NextSeq 500 platform. De novo assembly of B. jararaca transcriptome was done using Trinity. Annotation was performed using Blast2GO. All predicted proteins after clustering step were blasted against non-redundant protein database of NCBI using BLASTP. Metabolic pathways present in the transcriptome were annotated using the KAAS-KEGG Automatic Annotation Server. Toxins were identified in the B. jararaca predicted proteome using BLASTP against all protein sequences obtained from Animal Toxin Annotation Project from Uniprot KB/Swiss-Pro database. Figures and data visualization were performed using ggplot2 package in R language environment. Results: We described the in-depth transcriptome analysis of B. jararaca venom gland, in which 76,765 de novo assembled isoforms, 96,044 transcribed genes and 41,196 unique proteins were identified. The most abundant transcript was the zinc metalloproteinase-disintegrin-like jararhagin. Moreover, we identified 78 distinct functional classes of proteins, including toxins, inhibitors and tumor suppressors. Other venom proteins identified were the hemolytic lethal factors stonustoxin and verrucotoxin. Conclusion: It is believed that the application of deep sequencing to the analysis of snake venom transcriptomes may represent invaluable insight on their biotechnological potential focusing on candidate molecules.(AU)

In-depth transcriptome reveals the potential biotechnological application of Bothrops jararaca venom gland

Background: Lack of complete genomic data of Bothrops jararaca impedes molecular biology research focusing on biotechnological applications of venom gland components. Identification of full-length coding regions of genes is crucial for the correct molecular cloning design. Methods: RNA was extracted from the venom gland of one adult female specimen of Bothrops jararaca. Deep sequencing of the mRNA library was performed using Illumina NextSeq 500 platform. De novo assembly of B. jararaca transcriptome was done using Trinity. Annotation was performed using Blast2GO. All predicted proteins after clustering step were blasted against non-redundant protein database of NCBI using BLASTP. Metabolic pathways present in the transcriptome were annotated using the KAAS-KEGG Automatic Annotation Server. Toxins were identified in the B. jararaca predicted proteome using BLASTP against all protein sequences obtained from Animal Toxin Annotation Project from Uniprot KB/Swiss-Pro database. Figures and data visualization were performed using ggplot2 package in R language environment. Results: We described the in-depth transcriptome analysis of B. jararaca venom gland, in which 76,765 de novo assembled isoforms, 96,044 transcribed genes and 41,196 unique proteins were identified. The most abundant transcript was the zinc metalloproteinase-disintegrin-like jararhagin. Moreover, we identified 78 distinct functional classes of proteins, including toxins, inhibitors and tumor suppressors. Other venom proteins identified were the hemolytic lethal factors stonustoxin and verrucotoxin. Conclusion: It is believed that the application of deep sequencing to the analysis of snake venom transcriptomes may represent invaluable insight on their biotechnological potential focusing on candidate molecules.

Hypermethylation Pattern of COX-2 and Rb1 in Head and Neck Squamous Cell Carcinomas

Head and neck cancer is among the ten most common human cancers worldwide, being 90% of all cases squamous cell carcinoma histological subtype. These tumors are always associated with high rates of mortality and patients with disease presenting in the same site with the same stage that under go the similar treatment, may have different oncologic outcomes. These aspects show the necessity of developing effective molecular markers that may be able to increase survival rates. Epigenetic mechanisms contribute to the carcinogenesis process, especially by the methylation of cytosines in CpG islands. The identification of aberrantly methylated DNA may help carcinogenesis understanding as well as potential clinical targets for studies in cancer. We analyzed genes RB1 and COX-2 methylation status by the quantitative, high-throughput Q-MSP assay in cell lines, 30 tumor samples and 10 normal oral cavity mucosa samples. These two genes evaluation was not informative because the incidence of hypermethylation was completely absent (RB1) or ubiquitous (COX-2), RB1, regardless of tissue type. These results suggest that the hypermethylation pattern of both RB1 and COX-2 might not be a reasonable biomarker for head and neck squamous cell carcinomas.

Hydralazine reduces myocardial tissue damage in rats submitted to chronic inhibition of systemic nitric oxide synthesis during 4, 14 and 28 days

The aim of the present work was to develop a qualitative chronopathological study concerning abnormalities in myocardium, due to nitric oxide (NO) blockage. We used 60 Wistar normotensive young male rats from several breeds. Groups of rats were submitted to L-Name (L) via oral administration dissolved in water (750mg/l) during days 4, 14 and 28. Other groups were submitted concomitantly to L-Name and hydralazine hydrocloride (L + H) (120mg/l). On days 4 and 14 (L group) we have found myocardial abnormalities and lesions while in L + H we could not identify abnormalities. Considering L group on day 28, the myocardium presented characteristic fibrosis (reactive and reparative), vascular damage with increasing wall thickness due mainly to proliferation of the arterial smooth muscle cell. Total obliteration of vessels was noted only in this period. We also observed reactive fibrosis between muscle cells of the vascular wall and proliferation of cells in the intimal layer. In L + H (day 28), similar vascular abnormalities described for L group (less frequent and less apparent) were also observed. In L + H we did not identify total vascular obstructions. In L + H, infarct areas were not observed. Control groups did not present any abnormalities. Our results support the idea that, at least in some cases, hypertrophy vascular abnormalities and myocardial lesions in arterial hypertension can occur because of the reduction in organic nitric oxide production. Our results also suggested that these morbid processes can be postponed by the use of hydralazine which, however, does not avoid abnormalities after long-term experimental blockage of NO

Adenocarcinoma da área pancreaticoduodenal de sítio primário desconhecido / Pancreaticoduodenal area adenocarcinoma of unknow primary site

Os autores relatam um caso de neoplasia maligna, cuja manifestação clínica inicial se fez pela metástase: umadenocarcinoma pouco diferenciado metastático, da área pancreaticoduodenal. No acompanhamento foram empregados métodos radiológicos, cirúrgicos, endoscópicos, anatomopatológicos e imuno-histoquímicos, na tentativa da identificação do sítio primário, sendo tal pesquisa importante no sentido de direcionar o tratamento paliativo da paciente, uma vez que o tratamento cirúrgico definitivo se tornou contra-indicado.