Impact of cervical pain, neck mobility, and body mass index on teachers' postural control / Impacto da dor cervical, da mobilidade e do índice de massa corporal no controle postural de professores

ABSTRACT Purpose: to analyze the impact of neck pain, neck mobility, and body mass index on teachers' postural control. Methods: a cross-sectional study with 54 state public school teachers, 68.5% (n = 37) being females, with a mean age of 46.5 ± 9.3 years. Data were collected with the following instruments: Craniocervical Dysfunction Index (Brazilian version), force platform in bipedal and semi-tandem stance, visual analog scale, cervical mobility index, and body mass index. Data were analyzed with nonparametric statistics and multiple linear regression; the significance level was set at p<0.05, with 95% confidence intervals. Results: teachers with neck pain and severely impaired neck mobility had greater postural control changes in the semi-tandem stance. In the bipedal stance, those with mild mobility changes and neck pain had a smaller total displacement. Obese teachers had a smaller movement amplitude in the anteroposterior and mediolateral directions. Conclusion: teachers presented with neck pain and severely impaired neck mobility had a worse postural control. Obese teachers had a smaller total amplitude in both movement directions.

RESUMO Objetivo: analisar o impacto da cervicalgia, mobilidade cervical e índice de massa corporal no controle postural de professores. Métodos: estudo transversal com 54 professores da rede estadual de ensino, com média de idade de 46,5 ± 9,3 anos, dos quais: 68,5% (n = 37) eram do sexo feminino. A coleta de dados teve como base os seguintes instrumentos: Craniocervical Dysfunction Index (versão brasileira), plataforma de força na posição bipodal e semitandem, escala visual analógica, índice de mobilidade cervical e índice de massa corporal. Para análise dos dados, foi utilizada estatística não paramétrica e análise de regressão linear múltipla, com nível de significância p<0,05 e intervalo de confiança de 95%. Resultados: os professores com cervicalgia e comprometimento severo da mobilidade cervical tiveram maior alteração do controle postural na posição semitandem. Na posição bipodal, aqueles com leve alteração da mobilidade e dor cervical apresentaram menor deslocamento total, assim como professores obesos demostraram menor amplitude de movimento nas direções anteroposterior e médio-lateral. Conclusão: os professores com cervicalgia e comprometimento severo da mobilidade cervical tiveram pior controle postural. Já os obesos apresentaram menor amplitude total em ambas as direções do movimento.

4-Dimethylaminoantipyrine as a Broad Electrochemical Indicator for Immunosensors Platform.

Here, we describe 4-dimethylaminoantipyrine (4-DMAA)-mediated interfacing as a broad biochemical indicator to stabilize and promote the higher response of electrodes for immunological detection. We hypothesized that the improved biological interactions of 4-DMAA with electrodes and biological samples may be due to the interaction properties of the benzene and pyrazole chemical groups with graphite and proteins, respectively. In order to demonstrate that 4-DMAA could be used as a general indicator in electrochemical immunoassays, we used peptides as probes for the diagnosis of four neglected tropical infectious diseases Tegumentary leishmaniasis, Visceral leishmaniasis, Strongyloidiasis, and Leprosy on commercial graphite screen-printed electrodes. 4-DMAA oxidation was used to indicate specific biological recognition between the epitope-based peptide and serum immunoglobulin G (IgG) from infected patients. We demonstrated that 4-DMAA should be incorporated into the electrodes prior to serum application, which avoids interference with its sensitivity and specificity. In addition, 4-DMAA oxidizes at a low anodic potential, and the oxidation peak is useful for detecting proteins in biological fluids. In summary, we have successfully demonstrated the broad application of 4-DMAA as a general indicator for the specific diagnosis of four infectious diseases in electrochemical immunosensors. Such a strategy is quite advantageous for indirect detection of proteins that lack electrochemical activities or are spatially inaccessible on the electrode surface. This new indicator opens a new avenue for monitoring biological recognition, especially for immunosensors.

Cytogenotoxic evaluation of the acetonitrile extract, citrinin and dicitrinin-A from Penicillium citrinum.

Endophytic fungi are promising sources of bioactive substances; however, their secondary metabolites are toxic to plants, animals, and humans. This study aimed toevaluate the toxic, cytotoxic, mutagenic and oxidant/antioxidant activities of acetonitrile extract (AEPc), citrinin (CIT) and dicitrinin-A (DIC-A) of Penicillium citrinum. For this, the test substances at 0.5; 1.0; 1.5 and 2 µg/mLwere exposed for 24 and 48 h in Artemia salina, and 48 h in Allium cepa test systems. The oxidant/antioxidant test was evaluated in pre-, co- and post-treatment with the stressor hydrogen peroxide (H2O2) in Saccharomyces cerevisiae. The results suggest that the AEPc, CIT and DIC-A at 0.5; 1.0; 1.5 and 2 µg/mL showed toxicity in A. saline, with LC50 (24 h) of 2.03 µg/mL, 1.71 µg/mL and 2.29 µg/mL, and LC50 (48 h) of 0.51 µg/mL, 0.54 µg/mL and 0.54 µg/mL, respectively.In A. cepa, the test substances also exerted cytotoxic and mutagenic effects. The AEPc, CIT and DIC-A at lower concentrations modulated the damage induced by H2O2 in the proficient and mutant strains of S. cerevisiae for cytoplasmic and mitochondrial superoxide dismutase. Moreover, the AEPc at 2 µg/mL and CIT at the two highest concentrations did not affect the H2O2-induced DNA damage in the test strains. In conclusion, AEPc, CIT and DIC-A of P. citrinum may exert their toxic, cytotoxic and mutagenic effects in the test systems possibly through oxidative stress induction pathway.

Intra-host evolution during SARS-CoV-2 prolonged infection.

Long-term infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a challenge to virus dispersion and the control of coronavirus disease 2019 (COVID-19) pandemic. The reason why some people have prolonged infection and how the virus persists for so long are still not fully understood. Recent studies suggested that the accumulation of intra-host single nucleotide variants (iSNVs) over the course of the infection might play an important role in persistence as well as emergence of mutations of concern. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during prolonged infection. Thirty-three patients who remained reverse transcription polymerase chain reaction (RT-PCR) positive in the nasopharynx for on average 18 days from the symptoms onset were included in this study. Whole-genome sequences were obtained for each patient at two different time points. Phylogenetic, populational, and computational analyses of viral sequences were consistent with prolonged infection without evidence of coinfection in our cohort. We observed an elevated within-host genomic diversity at the second time point samples positively correlated with cycle threshold (Ct) values (lower viral load). Direct transmission was also confirmed in a small cluster of healthcare professionals that shared the same workplace by the presence of common iSNVs. A differential accumulation of missense variants between the time points was detected targeting crucial structural and non-structural proteins such as Spike and helicase. Interestingly, longitudinal acquisition of iSNVs in Spike protein coincided in many cases with SARS-CoV-2 reactive and predicted T cell epitopes. We observed a distinguishing pattern of mutations over the course of the infection mainly driven by increasing A→U and decreasing G→A signatures. G→A mutations may be associated with RNA-editing enzyme activities; therefore, the mutational profiles observed in our analysis were suggestive of innate immune mechanisms of the host cell defense. Therefore, we unveiled a dynamic and complex landscape of host and pathogen interaction during prolonged infection of SARS-CoV-2, suggesting that the host's innate immunity shapes the increase of intra-host diversity. Our findings may also shed light on possible mechanisms underlying the emergence and spread of new variants resistant to the host immune response as recently observed in COVID-19 pandemic.

Lacrimal Gland as a Target Organ for Adenovirus Gene Therapy Encoding Erythropoietin for Dry Eye Induced by Benzalkonium Chloride.

Purpose: The aims of this work were a) to describe the histology of the lacrimal gland (LG) and cornea induced by an adenovirus (Ad) vector encoding the human erythropoietin (Epo) gene delivered to the LG and b) to evaluate the therapeutic potential of this strategy to prevent benzalkonium chloride (BAK) corneal toxicity.Methods: Structure and function of male Wistar rats LG were compared in the groups: 1) naïve control and 2) Ad-hEpo in the right LG (RLG). The protective response against BAK eye drops was compared among the groups 1) naïve control, 2) BAK in the right eye, 3) Ad-hEpo RLG + BAK and 4) Ad-hEpo in the right salivary gland (RSG)+BAK. Ad-hEpo groups received an injection of AdLTR2EF1a-hEPO (25 ul, 1010 particles/ml) in the right LG or SG (positive control). The BAK groups received 0.2% BAK in the right cornea twice a day. The tests applied after 7 days, included tear secretion, hEPO mRNA detection by qRT-PCR, LG and cornea histology, LG ELISA for cytokines and hematocrit.Results: hEPO mRNA was present in the Ad-hEpo RLG and RSG, but not kidney or liver samples (negative controls). TNF-α and IL-1ß increased in the LG exposed to Ad-hEpo compared to naïve control (p = .0115 and p = .0397, respectively). BAK reduced tear secretion, but this reduction was prevented by Ad-hEpo RLG+BAK and Ad-hEpo RSG+BAK (p = .017). The corneal epithelia were thinner in the BAK-treated groups independent of Ad-hEpo (p = .0009). Hematocrit increased only in the Ad-hEpo RSG group (p = .01).Conclusions: Ad-hEpo infection of rat LG and SG induces local, but only the SG infection induced systemic changes in rats. Importantly, Ad-hEpo attenuated the BAK-mediated toxic reduction in tear flow. Future studies must consider viral vector tissue tropism, biodistribution and effective therapeutic gene products for ocular surface diseases.

Citrinin against breast cancer: A cytogenotoxicological study.

Breast cancer is one of the most lethal types of cancer and a leading cause of mortality among Women worldwide. Citrinin (CIT), a polyketide extracted from the fungus Penicillium citrinum, exhibits a wide range of biological activities such as antibacterial, antifungal, and cytotoxic effects. The aim of the current study was to evaluate the antitumoral effects of CIT against 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Swiss mice For this, CIT, DMBA and the standard cyclophosphamide (CPA) induced behavioral changes in experimental animals, and these changes were screened by using the rota rod and open field tests. Additionally, hematological, biochemical, immuno-histochemical, and histopathological analyses were carried out. Results suggest that CIT did not alter behavioral, hematological, and biochemical parameters in mice. DMBA induced invasive mammary carcinoma and showed genotoxic effects in the breasts, bone marrow, lymphocytes, and hepatic cells. It also caused mutagenic effects in the formation of micronuclei, bridges, shoots, and binucleate cells in bone marrow and liver. CIT and CPA genotoxic effects were observed after 3 weeks of therapy, where CIT exhibited a repair capacity and induced significant apoptotic damage in mouse lymphocytes. In conclusion, CIT showed antitumoral effects in Swiss mice, possibly through induction of apoptosis.

Dysphonia, arterial hypertension, diabetes mellitus, thyroid diseases, and noise complaints as probable factors associated with hearing loss among teachers / Disfonia, hipertensão arterial, diabetes mellitus, doenças da tireoide e queixas de ruído como prováveis fatores associados a perda auditiva em professores

ABSTRACT Objective: to verify a possible association between hearing loss and dysphonia, arterial hypertension, diabetes mellitus, thyroid diseases, and noise complaints. Methods: a cross-sectional study involving 60 teachers, mean age 47.05 years. Pure-tone threshold audiometry was used to assess hearing, the voice questionnaire and voice acoustic evaluation were used for voice perception and quality, and the standardized questionnaire verified noise complaint and comorbidities. The statistical analysis was conducted with Mann-Whitney and Fisher's exact tests and multivariate linear regression. Results: there was a significant association between hearing loss and diabetes mellitus, hypertension, and thyroid disease (both p <0.0001), but there was no association between noise complaints and hearing loss in this population. The regression showed that dysphonia (p = 0.0311) and diabetes mellitus (p = 0.0302) are independent risk factors for hearing loss. A correlation was found between hearing loss and voice characteristics: roughness, breathiness, tension, and resonance. Conclusion: this study showed that hypertension and thyroid diseases are factors associated with hearing loss. In addition, dysphonia and diabetes mellitus are independent factors associated with hearing loss in teachers. These results show the need for policies aimed at promoting teachers' health.

RESUMO Objetivo: verificar possível associação da perda auditiva com disfonia, hipertensão arterial (HA), diabetes mellitus (DM), doenças da tireoide e queixas de ruído. Métodos: estudo transversal envolvendo 60 professores, média de idade de 47,05 anos. Foi avaliada a audição por meio da Audiometria tonal limiar, a percepção e qualidade vocal com o questionário vocal e a avaliação vocal acústica, enquanto a queixa de ruído e as comorbidades envolvidas foram investigadas com o questionário padronizado. A análise estatística utilizou os testes Ex-act de Mann Whitney, Fisher e regressão linear multivariada. Resultados: houve associação significante entre perda auditiva e DM, HA e doenças da tireoide (ambas p <0,0001), mas não foi encontrada associação entre queixa de ruído e perda auditiva nesta população. A regressão mostrou que as variáveis disfonia (p = 0,0311) e DM (p = 0,0302) são fatores de risco independentes para perda auditiva. Houve correlação entre perda auditiva e as características vocais rugosidade, soprosidade, tensão e ressonância. Conclusão: este estudo demostrou que HA e doenças da tireoide são fatores associados a perda auditiva, além disso a disfonia e DM se constituem em fatores associados independentes para a perda auditiva em professores. Estes resultados mostram a necessidade de políticas direcionadas a promoção da saúde do professor.

Antitumor effects of citrinin in an animal model of Sarcoma 180 via cytogenetic mechanisms.

Citrinin (CIT) is a cytotoxic, hepatotoxic, nephrotoxic and cardiotoxic metabolite obtained from Penicillium citrinum, that has been increasingly searched as an anticancer drug candidate. In this study, we assessed the antitumor effects of citrinin, using cytogenetic biomarkers for genotoxicity in Sarcoma 180 (S-180) ascitic fluid cells of mice. Citrinin, extracted from P. citrinum acetonitrile extract, was characterized by LC-MS. Cytotoxic assessment was done through using comet (alkaline version) and micronucleus assays. In S-180 cells, CI50 of CIT was 3.77 µg/mL, while at 12.5 and 100 µg/mL, CIT was as cytotoxic as doxorubicin (2 µg/mL). At 0.5, 1.0 and 2.0 µg/mL, it induced genotoxicity and mutagenicity in S-180 cells, especially at 2 µg/mL, triggering oxidative damage similar to hydrogen peroxide (10 mM). The antitumor effects were evidenced by a marked increase in S-180 cells apoptosis and necrosis due to clastogenic and/or aneugenic cytogenetic effects (micronucleus formation), as well as by induction of nucleoplasm bridges and nuclear buds, culminating in S-180 apoptosis and necrosis. CIT has potential as drug candidate for antitumor purposesbyinvolving cytogenetic mechanisms.

Colonization by Enterobacteriaceae is crucial for acute inflammatory responses in murine small intestine via regulation of corticosterone production.

Although dysbiosis in the gut microbiota is known to be involved in several inflammatory diseases, whether any specific bacterial taxa control host response to inflammatory stimuli is still elusive. Here, we hypothesized that dysbiotic indigenous taxa could be involved in modulating host response to inflammatory triggers. To test this hypothesis, we conducted experiments in germ-free (GF) mice and in mice colonized with dysbiotic taxa identified in conventional (CV) mice subjected to chemotherapy-induced mucositis. First, we report that the absence of microbiota decreased inflammation and damage in the small intestine after administration of the chemotherapeutic agent 5-fluorouracil (5-FU). Also, 5-FU induced a shift in CV microbiota resulting in higher amounts of Enterobacteriaceae, including E. coli, in feces and small intestine and tissue damage. Prevention of Enterobacteriaceae outgrowth by treating mice with ciprofloxacin resulted in diminished 5-FU-induced tissue damage, indicating that this bacterial group is necessary for 5-FU-induced inflammatory response. In addition, monocolonization of germ-free (GF) mice with E. coli led to reversal of the protective phenotype during 5-FU chemotherapy. E. coli monocolonization decreased the basal plasma corticosterone levels and blockade of glucocorticoid receptor in GF mice restored inflammation upon 5-FU treatment. In contrast, treatment of CV mice with ciprofloxacin, that presented reduction of Enterobacteriaceae and E. coli content, induced an increase in corticosterone levels. Altogether, these findings demonstrate that Enterobacteriaceae outgrowth during dysbiosis impacts inflammation and tissue injury in the small intestine. Importantly, indigenous Enterobacteriaceae modulates host production of the anti-inflammatory steroid corticosterone and, consequently, controls inflammatory responsiveness in mice.

Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer.

Omeprazole (OME) is commonly used to treat gastrointestinal disorders. However, long-term use of OME can increase the risk of gastric cancer. We aimed to characterize the pharmacological effects of OME and to correlate its adverse effects and toxicogenetic risks to the genomic instability mechanisms and cancer-based on database reports. Thus, a search (till Aug 2019) was made in the PubMed, Scopus, and ScienceDirect with relevant keywords. Based on the study objective, we included 80 clinical reports, forty-six in vitro, and 76 in vivo studies. While controversial, the findings suggest that long-term use of OME (5 to 40 mg/kg) can induce genomic instability. On the other hand, OME-mediated protective effects are well reported and related to proton pump blockade and anti-inflammatory activity through an increase in gastric flow, anti-inflammatory markers (COX-2 and interleukins) and antiapoptotic markers (caspases and BCL-2), glycoprotein expression, and neutrophil infiltration reduction. The reported adverse and toxic effects, especially in clinical studies, were atrophic gastritis, cobalamin deficiencies, homeostasis disorders, polyp development, hepatotoxicity, cytotoxicity, and genotoxicity. This study highlights that OME may induce genomic instability and increase the risk of certain types of cancer. Therefore, adequate precautions should be taken, especially in its long-term therapeutic strategies and self-medication practices.

Antitumoral effects of [6]-gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] in sarcoma 180 cells through cytogenetic mechanisms.

BACKGROUND: [6]-Gingerol [(S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone] is a phenolic substance reported for several ethnopharmacological usage by virtue of its antioxidant, antiemetic, anti-inflammatory and anticancer properties. This study assessed the antitumoral effects of [6]-Gingerol in primary cells of Sarcoma 180 as well as in peripheral blood lymphocytes of mice. METHODS: The effect of [6]-Gingerol was assessed by applying cytogenetic biomarkers as indicative of genotoxicity, mutagenicity and apoptosis. Ascitic liquid cells were treated with [6]-Gingerol at concentrations of 21.33, 42.66 and 85.33 µM and subjected to the cytotoxicity assays using Trypan blue test and the comet assay, as well as the cytokinesis-block micronucleus assay. Doxorubicin (6 µM) and hydrogen peroxide (85.33 µM) were used as positive controls. RESULTS: [6]-Gingerol, especially at concentrations of 42.66 and 85.33 µM, showed notable cytotoxicity in Sarcoma 180 cells by reducing cell viability and cell division rates via induction of apoptosis. Genotoxicity at the concentrations used was punctuated by the increase in the index and frequency of DNA damage in tested groups. [6]-Gingerol, at all concentrations tested, did not induce significant aneugenic and/or clastogenic effects. It did, however, induced other nuclear abnormalities, such as nucleoplasmic bridges, nuclear buds and apoptosis. The genotoxic effects observed in the cotreatment with H2O2 (challenge assay) employing neoplastic and healthy cells, indicated that [6]-Gingerol may induce oxidative stress. CONCLUSIONS: Observations suggest that [6]-Gingerol may be a candidate for pharmaceutical antitumoral formulations due to its cytotoxicity and to mechanisms associated with genetic instability generated by nuclear alterations especially by apoptosis.

SSR and ISSR markers in assessing genetic diversity in Gallus gallus domesticus: a quantitative analysis of scientific production / Marcadores SSR e ISSR na avaliação da diversidade genética em Gallus gallus domesticus: uma análise quantitativa da produção científica

ABSTRACT: Poultry meat is a major source of animal protein in the world. Research indicates a high inbreeding rate derived from a relative absence of heterozygous subpopulations of chicken from different suppliers. Molecular markers can provide information for the genetic basis of chicken consumed in rural areas and help establishing a chicken database for product quality and warranty. The bibliometric research, comprises between 1994 and 2018, from five previously selected databases: Google Scholar, PubMed, ScienceDirect, Scopus and Web of Science, using the following descriptors: 'microsatellites', 'SSR', 'ISSR', 'genetic variability' and 'genetic diversity', all of them coupled to 'chicken' and/or 'birds' results in 66 scientific publications. The publications were then categorized according to their titles to the use of ISSR or SSR markers. They were also addressed by countries according first author cited. The publications data appointed that countries with the height production of poultry meat and hens are the most interested in the genetic diversity study of these species. The SSR markers, due to its more specific characteristic, are more frequently applied to genetic diversity assignment, compared to ISSR.

RESUMO: A carne de frango é uma das principais fontes de proteína animal do mundo. Pesquisas indicam uma alta taxa de endogamia derivada de uma relativa ausência de subpopulações heterozigotas de frango de diferentes fornecedores. Marcadores moleculares podem fornecer informações para a base genética de frango consumido em áreas rurais, e ajudar a estabelecer um banco de dados de frango para qualidade e garantia do produto. A pesquisa bibliométrica compreende entre 1994 e 2018, a partir de cinco bancos de dados selecionados anteriormente: Google Scholar, PubMed, ScienceDirect, Scopus e Web of Science, usando os seguintes descritores: 'microssatélites', 'SSR', 'ISSR', 'variabilidade genética' e 'diversidade genética', todos eles associados a resultados de 'galinha' e / ou 'aves' o que resultou em 66 publicações científicas. As publicações foram então categorizadas de acordo com seus títulos para o uso de marcadores ISSR ou SSR. Eles também foram abordados pelos países, segundo o primeiro autor citado. Os dados das publicações obtidas apontam que os países com grande produção de carnes de frangos são os mais interessados no estudo da diversidade genética dessas espécies. Os marcadores SSR, devido à sua característica mais específica, são frequentemente aplicados à atribuição de diversidade genética, em comparação com o ISSR.

Possible Association between the Lack of Regular Physical Activity with Tinnitus and Headache: Cross-sectional Study

Introduction: Physical inactivity is an important risk factor for many aging-related symptoms. Studies suggest that physical activity may help to relieve tinnitus and headache. Objective: To investigate the presence of tinnitus and headache in elderly individuals by associating it with the lack of regular physical activity. Methods: A cross-sectional study including elderly individuals who live independently. The practice of physical activity and the complaints of headache and of tinnitus were checked by means of a questionnaire with objective questions. The statistical analysis was performed using the chi-squared test and relative risk, and a multiple logistic regression model was used to determine how well each factor predicted headache while controlling for each of the other factors. Results: Based on a sample of 494 subjects, it was found that 213 (43.11%) complained of tinnitus. Among the complainants, 97 (45.53%) practiced physical activity regularly. We have confirmed associations between headache with lack of physical activity among elderly individuals with tinnitus (p = 0.0440). It was also observed that certain factors, such as male gender and tinnitus, are independent factors for the complaint of headache. Conclusion: We have found that headache could be a symptom related to the lack of regular physical activity among elderly individuals with tinnitus. (AU)

Possible Association between the Lack of Regular Physical Activity with Tinnitus and Headache: Cross-sectional Study.

Introduction Physical inactivity is an important risk factor for many aging-related symptoms. Studies suggest that physical activity may help to relieve tinnitus and headache. Objective To investigate the presence of tinnitus and headache in elderly individuals by associating it with the lack of regular physical activity. Methods A cross-sectional study including elderly individuals who live independently. The practice of physical activity and the complaints of headache and of tinnitus were checked by means of a questionnaire with objective questions. The statistical analysis was performed using the chi-squared test and relative risk, and a multiple logistic regression model was used to determine how well each factor predicted headache while controlling for each of the other factors. Results Based on a sample of 494 subjects, it was found that 213 (43.11%) complained of tinnitus. Among the complainants, 97 (45.53%) practiced physical activity regularly. We have confirmed associations between headache with lack of physical activity among elderly individuals with tinnitus ( p = 0.0440). It was also observed that certain factors, such as male gender and tinnitus, are independent factors for the complaint of headache. Conclusion We have found that headache could be a symptom related to the lack of regular physical activity among elderly individuals with tinnitus.

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children.

INTRODUCTION: Zika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes. METHODS AND ANALYSIS: We will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty. ETHICS AND DISSEMINATION: The IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: PROSPERO International prospective register of systematic reviews (CRD42017068915).

In-depth characterization of congenital Zika syndrome in immunocompetent mice: Antibody-dependent enhancement and an antiviral peptide therapy.

BACKGROUND: Zika virus (ZIKV) infection during pregnancy may cause major congenital defects, including microcephaly, ocular, articular and muscle abnormalities, which are collectively defined as Congenital Zika Syndrome. Here, we performed an in-depth characterization of the effects of congenital ZIKV infection (CZI) in immunocompetent mice. METHODS: Pregnant dams were inoculated with ZIKV on embryonic day 5.5 in the presence or absence of a sub-neutralizing dose of a pan-flavivirus monoclonal antibody (4G2) to evaluate the potential role of antibody-dependent enhancement phenomenon (ADE) during short and long outcomes of CZI. FINDINGS: ZIKV infection induced maternal immune activation (MIA), which was associated with occurrence of foetal abnormalities and death. Therapeutic administration of AH-D antiviral peptide during the early stages of pregnancy prevented ZIKV replication and death of offspring. In the post-natal period, CZI was associated with a decrease in whole brain volume, ophthalmologic abnormalities, changes in testicular morphology, and disruption in bone microarchitecture. Some alterations were enhanced in the presence of 4G2 antibody. INTERPRETATION: Our results reveal that early maternal ZIKV infection causes several birth defects in immunocompetent mice, which can be potentiated by ADE phenomenon and are associated with MIA. Additionally, antiviral treatment with AH-D peptide may be beneficial during early maternal ZIKV infection. FUND: This work was supported by the Brazilian National Science Council (CNPq, Brazil), Minas Gerais Foundation for Science (FAPEMIG), Funding Authority for Studies and Projects (FINEP), Coordination of Superior Level Staff Improvement (CAPES), National Research Foundation of Singapore and Centre for Precision Biology at Nanyang Technological University.

Antioxidant, anti-inflammatory and cytotoxic/antitumoral bioactives from the phylum Basidiomycota and their possible mechanisms of action.

Biologically active compounds from species of the phylum Basidiomycota have been shown a wide range of pharmacological activities and provide a vast reservoir of potential innovational drugs. The aim of this review is to discuss some mechanisms of action involved in antioxidant, anti-inflammatory and cytotoxic/antitumoral activities attributed to the bioactive compounds from species of the phylum Basidiomycota. We show that isolated compounds from extracts, secondary metabolites and polysaccharides that presented antioxidant properties have mechanisms of action involved in the elimination/capture of free radicals and reduction of lipid peroxidation. Also, some bioactives with anti-inflammatory activity were reported to enhance innate and cell-mediated immune responses. Finally, compounds that presented cytotoxic/antitumoral activity induces increased free radical production, collapse of the mitochondrial membrane potential and increased expression of proteins responsible for cell cycle arrest and apoptosis. Investigating the mechanisms of action of biologically active compounds will facilitate further efforts to accelerate the discovery of novel therapeutic strategies.

Prevention of Corneal Neovascularization by Adenovirus Encoding Human Vascular Endothelial Growth Factor Soluble Receptor (s-VEGFR1) in Lacrimal Gland.

Purpose: The aims of this study were (1) to determine the efficacy of adenovirus vector serotype 5 (Ad) encoding human soluble VEGF receptor 1 (s-VEGFR1) gene transfer to the lacrimal gland (LG); (2) to investigate whether expression of s-VEGFR1 prevents corneal neovascularization (CNV) induced by alkali burns; and (3) to evaluate the safety of the procedure. Methods: AdVEGFR1 vectors (25 µL, 1 × 1010 pfu/mL) were injected in the right LGs of rats and were compared with AdNull vector (25 µL, 1 × 1010 pfu/mL) or 25 µL of saline (Control) before cornea alkali burns with 1 M NaOH. After 7 days, CNV was documented at the slit lamp. Tear secretion was measured with phenol red threads. The animals were tested for s-VEGFR1 mRNA and protein in the LG by quantitative (q)PCR and immunohistochemistry staining, respectively. qPCR was used to compare the mRNA levels of IL-1ß, IL-6, and TNF-α in the LG and ipsilateral trigeminal ganglion (TG). Results: Ad-VEGFR1 transfected 83% (10/12) of the rats. VEGFR1 was present in LG acinar cells. CNV was prevented in 9 of 12 animals in the Ad-VEGFR1 group, compared with the Ad-Null (3:10) and Control groups (1:10) (P = 0.0317). The tear secretion and cytokine mRNA levels in the LG and TG were similar in all three groups (P > 0.05). Conclusions: Adenoviral vector gene transfer was safe for LG structure and function. The LG as the target tissue showed local expression of human s-VEGFR1, and CNV was prevented in most of the eyes exposed to alkali burns.

Evidence of natural Zika virus infection in neotropical non-human primates in Brazil.

In Africa, Old World Primates are involved in the maintenance of sylvatic circulation of ZIKV. However, in Brazil, the hosts for the sylvatic cycle remain unknown. We hypothesized that free-living NHPs might play a role in urban/periurban ZIKV dynamics, thus we undertook an NHP ZIKV investigation in two cities in Brazil. We identified ZIKV-positive NHPs and sequences obtained were phylogenetically related to the American lineage of ZIKV. Additionally, we inoculated four C. penicillata with ZIKV and our results demonstrated that marmosets had a sustained viremia. The natural and experimental infection of NHPs with ZIKV, support the hypothesis that NHPs may be a vertebrate host in the maintainance of ZIKV transmission/circulation in urban tropical settings. Further studies are needed to understand the role they may play in maintaining the urban cycle of the ZIKV and how they may be a conduit in establishing an enzootic transmission cycle in tropical Latin America.

Translation to Brazilian Portuguese and Cultural Adaptation of the Craniocervical Dysfunction Index.

Introduction Functional disorders of the craniocervical region affect 77.78% of Brazilian teachers. Among the most common instruments used to assess craniocervical disorders in a detailed and objective way, none had been translated to Brazilian Portuguese and adapted to Brazilian culture. Objectives To translate to Brazilian Portuguese and to culturally adapt the Craniocervical Dysfunction Index (CDI). Method The first phase of the study consisted of the translation, synthesis, back-translation, and review of the contents by a committee of experts, who developed a trial version and sent all the steps to the original author. The trial version was applied to 50 teachers of an institution. The reliability and internal consistency were evaluated by Cronbach α. For the validation, the Brazilian Portuguese version of the CDI was correlated with the Visual Analogue Scale (VAS) domains for cervicalgia and evaluated by Spearman ρ. Result Some expressions were adapted to the Brazilian culture. Among the participants who did not report neck pain in the VAS, 84.21% suffered from craniocervical dysfunction acording to the CDI. Among the participants who reported neck pain in the VAS, 100% suffered from craniocervical dysfunction according to the CDI. The CDI showed good internal consistency and satisfactory reliability measured by Cronbrach α (α = 0.717). There was a strong correlation between the CDI and the VAS score (ρ = 0.735). Conclusion No difficulties were encountered in the translation and back-translation of the CDI, and no problems were observed regarding the trial version developed; therefore, the Brazilian Portuguese version of the CDI is a valid and reliable instrument to evaluate the functional alteration of the craniocervical region.