Evidence for Host Epigenetic Signatures Arising From Arbovirus Infections: A Systematic Review.

Background: Arbovirus infections have steadily become a major pandemic threat. This study aimed at investigating the existence of host epigenetic markers arising from the principal arboviruses infections impacting on human health. We set to systematically review all published evidence describing any epigenetic modifications associated with infections from arboviruses, including, but not limited to, microRNAs, DNA methylation, and histone modifications. Methods: A comprehensive search was conducted using the electronic databases PubMed, Science Direct and Cochrane Library from inception to January 4th, 2018. We included reports describing original in vivo or in vitro studies investigating epigenetic changes related to arbovirus infections in either clinical subjects or human cell lines. Studies investigating epigenetic modifications related to the virus or the arthropod vector were excluded. A narrative synthesis of the findings was conducted, contextualizing comparative evidence from in vitro and in vivo studies. Results: A total of 853 unique references were identified and screened by two independent researchers. Thirty-two studies met the inclusion criteria and were reviewed. The evidence was centered mainly on microRNA and DNA methylation signatures implicated with secondary Dengue fever. Evidence for recent epidemic threats, such as the infections by Zika or Chikungunya viruses is still scant. Conclusions: Major epigenetic alterations found on arboviruses infections were miR-146, miR-30e and the Dicer complex. However, existing studies frequently tested distinct hypotheses resulting in a heterogeneity of methodological approaches. Whilst epigenetic signatures associated with arbovirus infections have been reported, existing studies have largely focused on a small number of diseases, particularly dengue. Validation of epigenetic signatures have an untapped potential, but concerted investigations are certainly required to deliver robust candidates of clinical utility for diagnosis, staging and prognosis of specific arboviral diseases.

Role of preoperative retrograde enema on inflammatory and healing parameters in colonic anastomosis: experimental study in dogs / Papel do enema pré-operatório em parâmetro de inflamação e cicatrização em anastomose cólica: estudo experimental em cães

Objective: The purpose of this experimental study was to compare the inflammatory and wound healing response of dogs submitted to colonic anastomosis with and without preoperative retrograde enema. Methods: The study included two groups of 31 female dogs (Canis familiaris). G-I (control): no preoperative bowel preparation; G-II (study): preoperative retrograde enema using a 10% glycerin solution. All the animals were submitted to laparotomy and colotomy at 20 cm from the anal verge, followed by closure with a running extramucosal single-layer suture (Prolene® 000). The animals were then anesthetized and euthanized on the 7th (n = 10) or 21st (n = 20) postoperative day (POD) to remove the anastomosed colon segment for histological and immunohistochemical analysis evaluating the parameters: anastomotic edema, vasoproliferation, abdominal adhesions, type I and III collagen, nitric oxide and myeloperoxidase. The observed differences were analyzed with the Mann-Whitney test for nonparametric data and Student's t test for unpaired samples and parametric data. Results: One animal from G-I and one from G-II died on POD 7 and POD 10 due to anastomotic complications and sepsis, respectively The groups did not differ significantly with regard to inflammatory and healing parameters, although the levels of mature collagen were significantly lower in the animals submitted to preoperative bowel preparation. Conclusion: It has been shown that both procedures are safe to be used, however, the group with bowel preparation showed a lower amount of mature collagen in the immediate postoperative period and may be constituted a preventive factor for surgical complications for this type of surgical procedure, although no evidence in this study could be determined. (AU)

Objetivo: O objetivo deste estudo experimental foi comparar a resposta inflamatória e cicatrização de feridas em cães submetidos a anastomose cólica com e sem enema retrógrada pré-operatório. Métodos: O estudo incluiu dois grupos de 31 cães fêmeas (Canis familiaris). G-I (controle): sem preparo intestinal pré-operatório; G-II (estudo): Enema retrógrada pré-operatória com uma solução de glicerina a 10%. Todos os animais foram submetidos à laparotomia e colotomia a 20 cm da borda anal, seguido de fechamento em sutura extramucosa contínua (Prolene ® 000). Os animais foram anestesiados e, em seguida, submetidos à eutanásia no 7° (n = 10) ou 21 (n = 20) pós-operatório (DPO) para remover o segmento de cólon anastomosado para análise histológica e imunohistoquímica avaliando os parâmetros: edema da anastomose, vasoproliferação, aderências abdominais, colagénio tipo I e III, o óxido nítrico e a mieloperoxidase. As diferenças observadas foram analisadas com o teste de Mann-Whitney para os dados não paramétricos e teste t de Student para amostras não pareadas e dados paramétricos. Resultados: Um animal do GI e um do G-II morreu no dia 7 e 10° DPO devido a complições de anastomose e sepse, respectivamente. Os grupos não diferiram significativamente em relação aos parâmetros inflamatórios e de cura, embora os níveis de colágeno maduro foram significativamente menores nos animais submetidos ao preparo intestinal pré-operatório. Conclusão: Demonstrou-se que ambos os procedimentos são seguros para serem usados, no entanto, o grupo com a preparação do intestino mostrou uma menor quantidade de colágeno maduro no período pós-operatório imediato, podendo ser constituído um fator preventivo para compliçães cirúrgicas para este tipo de procedimento cirúrgico, embora nenhuma evidência neste estudo. (AU)