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Zika virus is an arthropod-borne virus that is a member of the family Flaviviridae transmitted mainly by mosquitoes of the genus Aedes. Although usually asymptomatic, infection can result in a mild and self-limiting illness characterised by fever, rash, arthralgia, and conjunctivitis. An increase in the number of children born with microcephaly was noted in 2015 in regions of Brazil with high transmission of Zika virus. More recently, evidence has been accumulating supporting a link between Zika virus and microcephaly. Here, we describe findings from three fatal cases and two spontaneous abortions associated with Zika virus infection. In this case series, formalin-fixed paraffin-embedded tissue samples from five cases, including two newborn babies with microcephaly and severe arthrogryposis who died shortly after birth, one 2-month-old baby, and two placentas from spontaneous abortions, from Brazil were submitted to the Infectious Diseases Pathology Branch at the US Centers for Disease Control and Prevention (Atlanta, GA, USA) between December, 2015, and March, 2016. Specimens were assessed by histopathological examination, immunohistochemical assays using a mouse anti-Zika virus antibody, and RT-PCR assays targeting the NS5 and envelope genes. Amplicons of RT-PCR positive cases were sequenced for characterisation of strains. Viral antigens were localised to glial cells and neurons and associated with microcalcifications in all three fatal cases with microcephaly. Antigens were also seen in chorionic villi of one of the first trimester placentas. Tissues from all five cases were positive for Zika virus RNA by RT-PCR, and sequence analyses showed highest identities with Zika virus strains isolated from Brazil during 2015. These findings provide strong evidence of a link between Zika virus infection and different congenital central nervous system malformations, including microcephaly as well as arthrogryposis and spontaneous abortions. None.

Background Reliable mortality data are essential for the development of public health policies. In Brazil, although there is a well-consolidated universal system for mortality data, the quality of information on causes of death (CoD) is not even among Brazilian regions, with a high proportion of ill-defined CoD. Verbal autopsy (VA) is an alternative to improve mortality data. This study aimed to evaluate the performance of an adapted and reduced version of VA in identifying the underlying causes of non-forensic deaths, in São Paulo, Brazil. This is the first time that a version of the questionnaire has been validated considering the autopsy as the gold standard. Methods The performance of a physician-certified verbal autopsy (PCVA) was evaluated considering conventional autopsy (macroscopy plus microscopy) as gold standard, based on a sample of 2060 decedents that were sent to the Post-Mortem Verification Service (SVOC-USP). All CoD, from the underlying to the immediate, were listed by both parties, and ICD-10 attributed by a senior coder. For each cause, sensitivity and chance corrected concordance (CCC) were computed considering first the underlying causes attributed by the pathologist and PCVA, and then any CoD listed in the death certificate given by PCVA. Cause specific mortality fraction accuracy (CSMF-accuracy) and chance corrected CSMF-accuracy were computed to evaluate the PCVA performance at the populational level. Results There was substantial variability of the sensitivities and CCC across the causes. Well-known chronic diseases with accurate diagnoses that had been informed by physicians to family members, such as various cancers, had sensitivities above 40% or 50%. However, PCVA was not effective in attributing Pneumonia, Cardiomyopathy and Leukemia/Lymphoma as underlying CoD. At populational level, the PCVA estimated cause specific mortality fractions (CSMF) may be considered close to the fractions pointed by the gold standard. The CSMF-accuracy was 0.81 and the chance corrected CSMF-accuracy was 0.49. Conclusions The PCVA was efficient in attributing some causes individually and proved effective in estimating the CSMF, which indicates that the method is useful to establish public health priorities.

http://dx.doi.org/10.4025/actascihealthsci.v36i1.14668This study investigated and compared the effects of low-level laser therapy (LLLT) and microcurrent in the burn healing process in Wistar rats. We conducted a randomized controlled study with 30 rats divided into 3 groups (n = 10); control group (CG), laser group (LG) and microcurrent group (MG). After thermal damage, 10 applications of 660 nm diode laser were performed in GL and 10 applications of 60 Hz microcurrent (160 μA) in MG. The semi-quantitative histological analysis was done using scores (0–3), in sections stained by hematoxylin and eosin and Masson’s trichrome. The results indicated a significant improvement in the fibroblasts proliferation, collagen fibers deposition, neoangiogenesis, and cutaneous appendages regeneration in MG and LG. When microcurrent and LLLT were compared, no difference was detected, except the regeneration and formation of new cutaneous appendages, observed in MG. Despite the similar effects, GM showed faster tissue repair with the formation of skin appendages.

Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015. Here, Martines et al describe evidence of a link between Zika virus infection and microcephaly and fetal demise through detection of viral RNA and antigens in brain tissues from two congenitally infected newborns and two fetal losses reported in the country in 2015.

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria. INTRODUÇÃO: Leishmaniose visceral (LV) é uma doença tropical negligenciada com uma resposta imune complexa em diferentes órgãos. Este padrão de resposta imune órgão-específica nunca foi avaliada no trato gastrointestinal. O objetivo deste estudo foi determinar a resposta imune in situ em biópsias duodenais de pacientes com LV. MÉTODOS: Um estudo de caso controle com 13 pacientes com LV foi comparado com 9 controles. A resposta imune foi avaliada por imunohistoquímica para CD4, CD8, CD68, IL-4, IFN-γ, TNF-α e IL-10. Achados histológicos nos vilos, criptas e processo inflamatório foram analisados. RESULTADOS: Todos os casos de LV apresentaram antígenos de Leishmania. Nenhum antígeno foi encontrado no grupo controle. O tamanho do vilo foi maior em pacientes com LV (p < 0,05). CD68 (macrófagos) e CD4 estavam aumentados em pacientes com LV (p < 0,05). Nenhuma diferença foi demonstrada na expressão de CD8, TNF-α, IL-10 e IL-4. O número de células expressando IFN-γ foi mais baixo que no grupo controle (p < 0,05). CONCLUSÕES: Baixos níveis de citocinas foram encontrados no trato gastrointestinal de pacientes com LV. Este padrão não foi encontrado em outros órgãos acometidos pela doença. Uma imunotolerância do tecido contra Leishmania poderia explicar estes achados, como ocorre com as bactérias entéricas.

Um caso de leishmaniose visceral em associação com a síndrome da imunodeficiência adquirida em paciente do sexo masculino, com 32 anos de idade é relatado, tendo a protozoonose sido responsável pelo óbito do paciente. À necropsia, a leishmaniose visceral manifestou-se de uma forma atípica, com intenso parasitismo visceral, comprometendo órgãos não comumente atingidos pela doença, tais como adrenais, rins, pulmão e cérebro. Os órgãos do sistema fagocítico mononuclear foram intensamente afetados e macrófagos parasitados foram observados na luz de pequenos vasos em vários tecidos. Foi realizado estudo imuno- histoquímico de amostras tissulares de baço, linfonodo e cérebro, comprovando-se a presença de material antigênico relacionado com a leishmânia. A case of fatal visceral leishmaniasis associated with immunodeficiency syndrome in a 32 year-old male patient is reported. The protozoonosis was responsible for the patient's death. Visceral leishmaniasis showed itself in an atypical form, at necropsy, with an intense parasitation of the mononuclear phagocitic system and damaging organs not usually affected by the disease, such as the adrenals, the kidneys, the lungs and the brain. Parasitised cells were observed within small vessels in several tissues. An immunohistochemical study was done on samples from the spleen, tymphonodes and brain, showing strong reactivity with antibody directed against leishmania.

Chronic weight loss in marmosets is often associated with wasting marmoset syndrome (WMS), an important disease that occurs in callitrichid colonies around the world. Even though its etiology is very difficult to determine, particular variables, such as weight loss, diarrhea and alopecia, associated or not with infestation in the pancreatic ducts with Trichospirura leptossoma (Nematoda: Thelazioidea), seem to be linked with the syndrome. This study investigated the histopathology of the lungs, duodenum, liver, gallbladder, extrahepatic bile ducts and pancreatic ducts of six common marmosets ( Callithrix jacchus ) suffering from severe non-diarrheic weight loss. Three individuals died naturally and the other three were euthanized. Microscopic findings showed the presence of adult flukes ( Platynosomum ) in the liver. These flukes, which provoke common infection in cats, were also observed inside the gallbladder as well as in the intra and extrahepatic bile ducts in common marmosets. Portal fibrosis was observed in two animals, which developed chronic fibrosing hepatopathy (biliary pattern, grade 3). The disease progresses without diarrhea and without pancreatic lesions or infestation. With the progression, the animals presented with ascending cholangitis, cholestasis and portal fibrosis, sometimes culminating in secondary biliary cirrhosis. Therefore, this infirmity, associated with chronic weight loss in common marmosets, could be another etiological factor linked with WMS.

This study investigated and compared the effects of low-level laser therapy (LLLT) and microcurrent in the burn healing process in Wistar rats. We conducted a randomized controlled study with 30 rats divided into 3 groups (n = 10); control group (CG), laser group (LG) and microcurrent group (MG). After thermal damage, 10 applications of 660 nm diode laser were performed in GL and 10 applications of 60 Hz microcurrent (160 [micro]A) in MG. The semi-quantitative histological analysis was done using scores (0-3), in sections stained by hematoxylin and eosin and Masson's trichrome. The results indicated a significant improvement in the fibroblasts proliferation, collagen fibers deposition, neoangiogenesis, and cutaneous appendages regeneration in MG and LG. When microcurrent and LLLT were compared, no difference was detected, except the regeneration and formation of new cutaneous appendages, observed in MG. Despite the similar effects, GM showed faster tissue repair with the formation of skin appendages. Keywords: low-level laser therapy, electric stimulation therapy, wound healing. RESUMO. Este trabalho teve por objetivo investigar e comparar os efeitos da laserterapia de baixa intensidade (LTBI) e microcorrente no processo de reparo de queimadura em ratos Wistar. Foi realizado um estudo randomizado controlado com 30 ratos divididos em 3 grupos (n = 10); grupo controle (GC), grupo laser (GL) e grupo microcorrente (GM). Apos lesao termica, 10 aplicacoes de laser InGaAlP de 660 nm foram submetidas ao GL e 10 aplicacoes de microcorrente de 60 Hz (160 [micro]A) ao GM. Foi realizada analise semi-quantificativa dos dados histologicos atraves de escores (0-3), em cortes corados por hematoxilina e eosina e tricromico de Masson. Os resultados indicaram que houve melhora significativa na proliferacao de fibroblastos, deposicao de fibras colagenas, neoangiogenese e regeneracao de apendices cutaneos no GM e GL. Quando a microcorrente e a LTBI foram comparados, nao houve diferenca, exceto na regeneracao e formacao de apendices cutaneos, observada no GM. O laser e a microcorrente produziram melhora no reparo tecidual de queimaduras em ratos. Embora possua efeitos semelhantes, o GM apresentou reparacao tecidual mais rapida com o aparecimento de apendices cutaneos. Palavras-chave: terapia a laser de baixa intensidade, terapia por estimulacao eletrica, cicatrizacao.

Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson's trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism.

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.INTRODUÇÃO: Leishmaniose visceral (LV) é uma doença tropical negligenciada com uma resposta imune complexa em diferentes órgãos. Este padrão de resposta imune órgão-específica nunca foi avaliada no trato gastrointestinal. O objetivo deste estudo foi determinar a resposta imune in situ em biópsias duodenais de pacientes com LV. MÉTODOS: Um estudo de caso controle com 13 pacientes com LV foi comparado com 9 controles. A resposta imune foi avaliada por imunohistoquímica para CD4, CD8, CD68, IL-4, IFN-γ, TNF-α e IL-10. Achados histológicos nos vilos, criptas e processo inflamatório foram analisados. RESULTADOS: Todos os casos de LV apresentaram antígenos de Leishmania. Nenhum antígeno foi encontrado no grupo controle. O tamanho do vilo foi maior em pacientes com LV (p < 0,05). CD68 (macrófagos) e CD4 estavam aumentados em pacientes com LV (p < 0,05). Nenhuma diferença foi demonstrada na expressão de CD8, TNF-α, IL-10 e IL-4. O número de células expressando IFN-γ foi mais baixo que no grupo controle (p < 0,05). CONCLUSÕES: Baixos níveis de citocinas foram encontrados no trato gastrointestinal de pacientes com LV. Este padrão não foi encontrado em outros órgãos acometidos pela doença. Uma imunotolerância do tecido contra Leishmania poderia explicar estes achados, como ocorre com as bactérias entéricas.