Systematic review and evidence gap mapping of biomarkers associated with neurological manifestations in patients with COVID-19.

OBJECTIVE: This study aimed to synthesize the existing evidence on biomarkers related to coronavirus disease 2019 (COVID-19) patients who presented neurological events. METHODS: A systematic review of observational studies (any design) following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the Cochrane Collaboration recommendations was performed (PROSPERO: CRD42021266995). Searches were conducted in PubMed and Scopus (updated April 2023). The methodological quality of nonrandomized studies was assessed using the Newcastle‒Ottawa Scale (NOS). An evidence gap map was built considering the reported biomarkers and NOS results. RESULTS: Nine specific markers of glial activation and neuronal injury were mapped from 35 studies published between 2020 and 2023. A total of 2,237 adult patients were evaluated in the included studies, especially during the acute phase of COVID-19. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) biomarkers were the most frequently assessed (n = 27 studies, 77%, and n = 14 studies, 40%, respectively). Although these biomarkers were found to be correlated with disease severity and worse outcomes in the acute phase in several studies (p < 0.05), they were not necessarily associated with neurological events. Overall, 12 studies (34%) were judged as having low methodological quality, 9 (26%) had moderate quality, and 9 (26%) had high quality. CONCLUSIONS: Different neurological biomarkers in neurosymptomatic COVID-19 patients were identified in observational studies. Although the evidence is still scarce and conflicting for some biomarkers, well-designed longitudinal studies should further explore the pathophysiological role of NfL, GFAP, and tau protein and their potential use for COVID-19 diagnosis and management.

Antidiabetic activity of Musa x paradisiaca extracts in streptozotocin-induced diabetic rats and chemical characterization by HPLC-DAD-MS.

ETHNOPHARMACOLOGICAL RELEVANCE: The Musa x paradisiaca L. inflorescence, known as banana blossom or banana heart, is used in traditional medicine for the treatment of diabetes mellitus. AIM OF THE STUDY: The aim of the study was to investigate the antidiabetic activity of aqueous extracts and fractions prepared from the bracts and flowers of Musa x paradisiaca in streptozotocin (STZ)-induced diabetic rats and to chemically characterize the extracts. MATERIALS AND METHODS: Standard aqueous extracts of the flowers, bracts, and their fractions were prepared and their chemical composition was determined tentatively by high-performance liquid chromatography coupled to diode-array detection and mass spectrometry (HPLC-DAD-MS). Changes in fasting glycemia and oral glucose tolerance were evaluated in STZ-induced diabetic rats (n = 8) treated with aqueous extracts of Musa x paradisiaca (200 mg/kg) for 20 days. RESULTS: Chemical analyses detected 21 compounds and 17 metabolites were identified, among which were glycosylated and acetylated phenylpropanoids of p-coumaric acid and caffeic acid, as well as a glycosylated flavonol and anthocyanins. Following 15 days of treatment, the bract aqueous extracts and the methanolic fraction of the flower had significant effects on the glycemic profile after glucose load in diabetic rats as compared with the untreated diabetic group. CONCLUSIONS: The results of the present study show the antidiabetic potential of extracts of the flowers and bracts of M. x paradisiaca.

A network meta-analysis of primary prophylaxis for invasive fungal infection in haematological patients.

WHAT IS KNOWN AND OBJECTIVE: Antifungal prophylaxis is an option to reduce the incidence of invasive fungal infection (IFI) in haematological patients. To date, no network meta-analysis (NMA) of high-quality evidence (double-blind randomized controlled trials) has been performed on this subject. This systematic review and NMA aimed to evaluate the safety and efficacy of different antifungal agents used for prophylaxis of IFI in patients with haematological disorders. METHODS: A systematic review was performed according to PRISMA and Cochrane recommendations. The search for articles was conducted on PubMed, Scopus and the Web of Science. We searched for double-blind randomized clinical trials comparing antifungal agents for IFI prophylaxis head-to-head vs placebo in patients with any blood cancer. Network meta-analyses were conducted using Addis version 1.16.6. Evaluation of the quality of included RCTs was also performed. RESULTS: Twenty-five trials were included in the qualitative and quantitative analyses. Posaconazole stood out as the best IFI prophylaxis option and for avoiding IFI-related mortality. For the incidence of candidiasis outcome, the azoles were superior to placebo. Voriconazole and posaconazole were, respectively, the first and second best options. For the incidence of aspergillosis outcome, the probability rank suggested that voriconazole followed by liposomal amphotericin B is, possibly, the best choice. The quality of studies was considered good, with a mean Jadad score of 4.0. WHAT IS NEW AND CONCLUSION: The results of our work support prophylaxis with antifungal agents as reducing the risk of IFI in haematological patients. Overall, the second-generation azoles were found to be the best option for preventing IFI in this population.

Safety of interferon-free therapies for chronic hepatitis C: a network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Interferon-free (IFN-free) therapies for hepatitis C virus (HCV) have been developed to provide more effective, tolerable and safer therapeutic strategies. To date, no network meta-analysis (NMA) evaluating the safety profile of these regimens has been performed. This systematic review and NMA aimed to evaluate safety outcomes of IFN-free treatment options for chronic hepatitis C. METHODS: A systematic review was performed according to PRISMA and Cochrane recommendations. A literature search was conducted in PubMed/Medline, Scopus, Cochrane Library, International Pharmaceutical Abstracts and Web of Science electronic databases and included only randomized clinical trials that provided safety outcomes of interest of evaluated second-generation direct-acting antivirals: incidence of any adverse events (AEs) and serious AE. NMA allowed estimating probability for the relative safety of the interventions. A consistency model was used to draw conclusions about relative safety of treatments, presented as odds ratio (OR) and corresponding 95% credible interval (CrI). RESULTS: Fifty-one clinical trials were included (13 089 participants). Most participants had hepatitis C genotype 1 virus (76%) and were treated for 12 weeks. Two NMAs were built to investigate the incidence of AEs and serious AEs, comparing 13 and 10 IFN-free treatment options, respectively. For the outcome incidence of AEs, few significant differences were observed, which were explained by the presence of RBV. Elbasvir with grazoprevir and placebo were both safer than ombitasvir in combination with paritaprevir, ritonavir, daclatasvir plus RBV [ORs with 95% Crl of 4·09 (1·17-14·09) and 2·40 (1·19-4·77), respectively] and sofosbuvir with RBV [ORs with 95% Crl of 0·22 (0·07-0·72) and 2·69 (1·53-4·80), respectively]. Furthermore, elbasvir with grazoprevir was safer than sofosbuvir used with velpatasvir and RBV [OR 0·19 (95% CrI 0·03-0·98)]; ombitasvir in combination with paritaprevir, ritonavir, daclatasvir was safer than the same therapy but combined with RBV [OR 2·14 (95% CrI 1·09-4·44)]; and sofosbuvir used with velpatasvir was safer than sofosbuvir with RBV [OR 2·07 (95% CrI 1·13-3·79)]. Elbasvir with grazoprevir (50%) followed by placebo (28%) had the highest probabilities of less AEs. No significant differences were observed for serious AE outcomes. WHAT IS NEW AND CONCLUSION: This meta-analysis included a large number of therapies. Small differences were observed in any AEs, but not in serious AEs.

Profile of bioactive compounds from grape pomace (Vitis vinifera and Vitis labrusca) by spectrophotometric, chromatographic and spectral analyses.

The aim of this study was to characterize grape pomace (GP) from winemaking byproducts of different grape samples (Cabernet Sauvignon-CS; Merlot-ME; Mix composed of 65% Bordeaux, 25% Isabel and 10% BRS Violet-MI and Terci-TE) with a view to exploiting its potential as a source of bioactive compounds and an alternative to the reuse of waste. Bioactive compounds such as individual phenolic compounds and polyunsaturated fatty acids (PUFA) were identified and quantified by spectrophotometric, chromatographic and spectral analyses. The sample of MI had the highest concentrations for total phenolic compounds and total flavonoids, while TE had the highest content for total monomeric anthocyanins. For all samples it was possible to identify 13 different anthocyanins by high performance liquid chromatography (HPLC) and mass spectrometry (MS). Moreover, the GP samples showed phenolic acids; flavan-3-ols such as catechin; flavonols such as quercetin, rutin and kaempferol; and stilbenes such as trans-resveratrol. Therefore, grape pomace can be considered a source for the recovery of phenolic compounds having antioxidant activity as well as a rich source of PUFA. Thus it can be used as an ingredient in the development of new food products, since it is suitable for human consumption, and a viable alternative both to adding nutritional value to food and to reduce environmental contamination.

Qualidade de vida em adultos com diabetes tipo 1 e validade do DQOL-Brasil / Quality of life in adults with type 1 diabetes and validity of DQOL-Brazil

O objetivo deste estudo foi estabelecer validade de critério e construto, e também, avaliar qualitativamente a versão brasileira do Questionário de Medida da Qualidade de Vida em Diabetes (DQOL-Brasil), quando utilizado em pacientes adultos com diabete melito (DM) tipo 1. O DQOL-Brasil foi autoadministrado a 150 indivíduos (63,3% mulheres) com tempo diagnóstico médio de DM tipo 1 de 14,17 anos e na faixa etária de 18 a 56 anos. O escore médio obtido foi de 2,46 (IC 95% 2,35 - 2,56). Entre os itens, os melhores e piores escores foram obtidos nos domínios de impacto da doença e preocupações com o DM, respectivamente. O instrumento como um todo apresentou elevada consistência interna, alfa de Cronbach = 0,94. Constatou-se validade convergente ao se co-administrar o questionário genérico de avaliação da qualidade de vida: Perfil de Saúde de Nottingham. O DQOL-Brasil foi readministrado a 52 pacientes em um intervalo médio de 98,25 dias, e constatou-se reprodutibilidade aceitável, através de coeficientes de correlação intraclasse superiores a 0,7. Entretanto, a análise fatorial comprovou deficiências. Deste modo, o DQOL-Brasil é válido para medida da qualidade de vida em pacientes adultos com DM tipo 1 e útil para aplicação em pesquisas e comparações com dados internacionais. Porém, para a prática clínica, recomenda-se seleção criteriosa dos itens do instrumento que sejam mais relacionados às características específicas da enfermidade em brasileiros; uma seleção ponderada de itens provavelmente seria útil às versões do DQOL traduzidas e validadas em outras nações...

The aim of this study was both to determine the criterion and construct validity and to make a qualitative assessment of the Brazilian version of the Diabetes Quality of Life questionnaire (DQoL-Brazil), when applied to adult patients with type 1 diabetes mellitus (DM1). The DQoL-Brazil was self-administered to 150 subjects (63.3% women) with DM1 diagnosed for an average of 14.17 years and aged 18 to 56 years. The mean score obtained was 2.46 (95% CI 2.35 to 2.56). Among the items in the questionnaire, the best and worst scores were obtained in the responses on disease impact and concerns about diabetes, respectively. The instrument as a whole had high internal consistency, with a Cronbach's alpha of 0.94. Convergent validity was observed when the Nottingham Health Profile, a general questionnaire used to measure patients' quality of life, was administered along side DQoL. DQoL-Brazil was readministered to 52 patients after a mean interval of 98.25 days and acceptable reproducibility was verified by intraclass correlation coefficients exceeding 0.7. Nevertheless, the factor analysis demonstrated shortcomings. We concluded that DQoL-Brazil is valid for measuring the quality of life of adult patients with type 1 DM and useful for application in research and comparisons with international data. However, for clinical practice, a careful selection of the items that are more related to the specific characteristics of the illnessin Brazilians is recommended. A weighted selection of items would probably be useful for versions of DQOL translated and validated in other societies...

Avaliação da sensibilidade e especificidade da metodologia de enzimaimunoensaio com micropartículas para dosagem de ferritinas / Sensibility and specificity evaluation of microparticle enzyme immunoassay method for ferritin measurement

A ferritina é a principal preteína envolvida no armazenamento de ferro, sendo encontrada no meio intracelular e também como um constituinte normal do plasma, fluídos corporais e das hemácias circulantes. Ferritinas derivadas de diferentes tecidos apresentam distintas propriedades como: estrutura primária, teor de fosfato no núcleo mineral, mobilidade eletroforética e proporção relativa de subunidades H e L, determinando diferenças estruturais, imunológicas, em ponto isoelétrico e capacidade oxidativa. estudos demonstram a relação direta entre a concentração de ferritina no soro e os estoques de ferro nos tecidos. Os sistemas comerciais disponíveis para a dosagem de ferritina plasmática nos laboratórios clínicos, estão baseados em ensaios imunoenzimáticos utilizando anticorpos antiferritina específicos ligados à enzimas. neste trabalho, avaliamos se a metodologia de enzimaimunoensaio com micropartículas (MEIA), do sistema ASXYM - Abbott Laboratories, quantifica adequadamente ferritinas em função do tecido de origem (baço, fígado e coração), e se alguns medicamentos, especialemente de uso prolongado, podem influenciar na metodologia. Os resultados das dosagens de ferritinas teciduais indicaram especificadade e sensibilidade para ferritina de baço (93 a 100%), porém não quantificando adequadamente as ferritinas de fígado (10%) e coração (0%). No estudo de interferência causada por medicamentos (nitrofurantoína, metronidazol, paracetamol, aciclovir e ciprofloxacina), observou-se que em concentrãções específicas de fármaco e proteína ocorre interferência significativa da ciprofloxacina na metodologia e, como consequência, nos resultados.

Qualidade microbiológica das plantas medicinais produzidas no Estado do Paraná / Microbiological quality of medicinal plants produced by the State of Paraná (Brazil)

Foram analisadas 72 amostras de plantas medicinais, enviadas por produtores de sete regiões do Estado do Paraná, segundo metodologia preconizada pela Organização Mundial da Saúde (OMS). Os resultados das análises microbiológicas realizadas (contagem de microrganismos aeróbios viáveis, contagem de bolores e leveduras, pesquisa de enterobactérias, Escherichia coli, Salmonella sp., Staphylococcus aureus e Pseudomonas aeruginosa indicaram que a maioria das amostras (79 por cento) não atendia os parâmetros estabelecidos pela OMS, tanto para utilização da planta medicinal na forma de chá ou para uso tópico quanto para uso interno. A maioria das amostras foi reprovada pelo fato de apresentar contagens de microrganismos aeróbios e de bolores e leveduras elevadas. Tal reprovação evidencia a necessidade de um programa de treinamento dos produtores, envolvendo as diversas etapas de produção e o posterior processamento.

72 samples of medicinal plants produced at seven different regions of Paraná State, Brazil, were analysed according to the World Health Organization methodology. The results of the microbiological analysis (total viable aerobic count, yeasts and moulds count, detection of Enterobacteriaceae and other Gram-negative bacteria: Escherichia coli, Salmonella sp., Pseudomonas aeruginosa and Staphylococcus aureus indicated that the majority of the samples (79 percent) is not in accord to World Health Organization parameters for medicinal plants to be used for herbal tea or topic and internal uses. The main reason of this poor microbiological quality was due to aerobic microrganisms and yeasts and moulds counting. It is an evidence that producers must be orientated by capable professionals in every stage of production in order to provide the necessary quality of the raw material to further medicinal usage.

Some structural studies on the galactose-containing polysaccharide from bovine placenta.

Polysaccharides were extracted from 8-month-old placenta with aqueous HgCl2. The protein-free material was purified by selective precipitation with Cetavlon in the presence of sodium borate at pH 8.5 and was homogeneous on molecular-sieve chromatography, electrophoresis, and on treatment with Concanavalin A. The preparation contained galactose and glucose as principal monosaccharides with 5 per cent of hexosamines. Methylation studies suggested that D-gluco and D-galactopyranosyl units may be constituents of glucan and galactan respectively which form a molecular aggregate that does not dissociate during the fractionation procedures. After treatment of the fraction with beta-amylase, the proportion of glucose in the polysaccharide diminished, indicating the presence of (1-->4)-linked alpha-D-glucopyranosyl residues. Also, when the fraction was treated with a crude protease having glucosidase activity a residual alpha-D-galactopyranan was isolated and found to contain non-reducing end-groups (30.0 per cent), 3-O-(39.5 per cent) and 3,6-di-O-substituted (30.5 per cent) units. The structure of the galactan was not modified according to methylation data, on removal of the glucosyl component. The polysaccharide fraction (pH 8.5 Cetavlon), isolated from bovine placenta, thus contains a glycogen-like material associated with a galactan as molecular aggregate. This galactan has not been previously recognized in bovine placenta and its occurrence in this organ supports the hypothesis that galactose-containing polysaccharides are involved in foetal development.

Estudos de polissacarídeos da placenta bovina em diferentes estágios de gestaçäo / Studies on the polisaccharides from bovine placenta at different stages of pregnancy

Polysaccharides were extracted from bovine placenta at different stages of pregnancy, namely terms of 3, 6, 8, and 9 months, with aqueous HgCl2. Tjhe protein-free material was then purified by selective precipitation with Cetavlon in the presence of sodium borate at pH 8,5. The fractions obtained from 3, 6, 8, and 9 month-old placentas wera designated PL-3, PL-8, and PL-9 respectively and wereeach homobeneous on electrophoresis, molecular-sieve chromatography, and on treatment with Concanavalin A. Polysaccharide contents of the fractions were uniform and acyd hydrolisis provided, in each case, galactose and glucose as principal monosaccharides. G.l.c. analysis of derived alditol acetates showed no variation between the D-glucose: D-galactose ratio obtanined from PL-3 and PL-6, being 68:32, but there was a gradual decreasein the D-glucose content of the PL-8 (58:42) and PL-9 (45:55) fractions