Modulation of Contact System Proteases by Glycosaminoglycans SELECTIVE ENHANCEMENT OF THE INHIBITION OF FACTOR XIa

Abstract We investigated the influence of dextran sulfate, heparin, heparan sulfate, and dermatan sulfate on the inhibition of FXIa (where FXIa is activated factor XI, for example), FXIIa, and kallikrein by C1 inhibitor, α1-antitrypsin, α2-antiplasmin, and antithrombin III. The second-order rate constants for the inhibition of FXIa by C1 inhibitor, α1-antitrypsin, α2-antiplasmin, and antithrombin III, in the absence of glycosaminoglycans, were 1.8, 0.1, 0.43, and 0.32 × 103 M−1 s−1, respectively. The rate constants of the inactivation of FXIa by C1 inhibitor and by antithrombin III increased up to 117-fold in the presence of glycosaminoglycans. These data predicted that considering the plasma concentration of the inhibitors, C1 inhibitor would be the main inhibitor of FXIa in plasma in the presence of glycosaminoglycans. Results of experiments in which the formation of complexes between serine protease inhibitors and FXIa was studied in plasma agreed with this prediction. Glycosaminoglycans did not enhance the inhibition of α-FXIIa, β-FXIIa, or kallikrein by C1 inhibitor. Thus, physiological glycosaminoglycans selectively enhance inhibition of FXIa without affecting the activity of FXIIa and kallikrein, suggesting that glycosaminoglycans may modulate the biological effects of contact activation, by inhibiting intrinsic coagulation without affecting the fibrinolytic potential of FXIIa/kallikrein

Negative Effects of “Predatory” Journals on Global Health Research

Se analiza el efecto perjudicial que ocasionan en la investigación en salud las revistas conocidas como "Depredadoras".Predatory journals (PJ) exploit the open-access model promising high acceptance rate and fast track publishing without proper peer review. At minimum, PJ are eroding the credibility of the scientific literature in the health sciences as they actually boost the propagation of errors. In this article, we identify issues with PJ and provide several responses, from international and interdisciplinary perspectives in health sciences. Authors, particularly researchers with limited previous experience with international publications, need to be careful when considering potential journals for submission, due to the current existence of large numbers of PJ. Universities around the world, particularly in developing countries, might develop strategies to discourage their researchers from submitting manuscripts to PJ or serving as members of their editorial committees

A IMPORTÂNCIA DA SALIVA PARA A MANUTENÇÃO DA SAÚDE BUCAL: UMA REVISÃO DA LITERATURA

Introdução: A cavidade oral é considerada um ecossistema complexo e extremamente influenciável pelas alterações ambientais internas e externas. Dentro deste microambiente, a saliva é um componente de grande importância, uma vez que seus componentes (pH, fluxo, capacidade de tamponamento) podem atuar de forma que impede ou auxilia o desenvolvimento de problemas bucais, podendo até provocar patologias na cavidade oral. Além disso, possui diversos componentes orgânicos e inorgânicos que colaboram para a manutenção da saúde dos tecidos orais e do indivíduo como um todo. O pH da cavidade oral é regulado pela saliva e este pode sofrer alterações em virtude do consumo de alimentos ou bebidas, bem como pela própria capacidade de tamponamento. Sobre o nível do pH salivar, existe um consenso na literatura de que o valor de referência considerado normal varia entre 6,8 e 7,2 nas diferentes populações do mundo. É importante ressaltar que o pH bucal também serve como indicativo da presença ou não de ácidos na cavidade oral A elevação ou queda do mesmo pode desencadear o início e/ou a evolução de doenças na cavidade oral, portanto, é extremamente importante realizar a manutenção dos seus níveis. Objetivo: Este trabalho tem como objetivo criar uma abordagem a respeito do tema em questão, o qual serviu como ponto de referência para acadêmicos de odontologia e para profissionais da área. Metodologia: Foi realizada uma revisão da literatura narrativa descritiva de artigos científicos disponíveis em bancos de dados como BVSalud, Scielo, PUBMed e Google Acadêmico. Os artigos estão apresentados nas línguas portuguesa e inglesa. Não foi utilizado nenhum meio de restrição quanto ao ano de publicação. Considerações: Apesar de seu papel fundamental para a saúde bucal, a saliva não recebe a devida atenção por parte dos profissionais da área e pelos próprios pacientes. Contudo, é extremamente importante que seja enfatizado o cuidado desta para a qualidade da saúde bucal e sistêmica, tendo em mente o quão crucial é este componente para o ecossistema oral

miRIAD-integrating microRNA inter- and intragenic data

MicroRNAs (miRNAs) are a class of small (similar to 22 nucleotides) non-coding RNAs that post-transcriptionally regulate gene expression by interacting with target mRNAs. A majority of miRNAs is located within intronic or exonic regions of protein-coding genes (host genes), and increasing evidence suggests a functional relationship between these miRNAs and their host genes. Here, we introduce miRIAD, a web-service to facilitate the analysis of genomic and structural features of intragenic miRNAs and their host genes for five species (human, rhesus monkey, mouse, chicken and opossum). miRIAD contains the genomic classification of all miRNAs (inter-and intragenic), as well as classification of all protein-coding genes into host or non-host genes (depending on whether they contain an intragenic miRNA or not). We collected and processed public data from several sources to provide a clear visualization of relevant knowledge related to intragenic miRNAs, such as host gene function, genomic context, names of and references to intragenic miRNAs, miRNA binding sites, clusters of intragenic miRNAs, miRNA and host gene expression across different tissues and expression correlation for intragenic miRNAs and their host genes. Protein-protein interaction data are also presented for functional network analysis of host genes. In summary, miRIAD was designed to help the research community to explore, in a user-friendly environment, intragenic miRNAs, their host genes and functional annotations with minimal effort, facilitating hypothesis generation and in-silico validations

miRIAD-integrating microRNA inter- and intragenic data

MicroRNAs (miRNAs) are a class of small (similar to 22 nucleotides) non-coding RNAs that post-transcriptionally regulate gene expression by interacting with target mRNAs. A majority of miRNAs is located within intronic or exonic regions of protein-coding genes (host genes), and increasing evidence suggests a functional relationship between these miRNAs and their host genes. Here, we introduce miRIAD, a web-service to facilitate the analysis of genomic and structural features of intragenic miRNAs and their host genes for five species (human, rhesus monkey, mouse, chicken and opossum). miRIAD contains the genomic classification of all miRNAs (inter-and intragenic), as well as classification of all protein-coding genes into host or non-host genes (depending on whether they contain an intragenic miRNA or not). We collected and processed public data from several sources to provide a clear visualization of relevant knowledge related to intragenic miRNAs, such as host gene function, genomic context, names of and references to intragenic miRNAs, miRNA binding sites, clusters of intragenic miRNAs, miRNA and host gene expression across different tissues and expression correlation for intragenic miRNAs and their host genes. Protein-protein interaction data are also presented for functional network analysis of host genes. In summary, miRIAD was designed to help the research community to explore, in a user-friendly environment, intragenic miRNAs, their host genes and functional annotations with minimal effort, facilitating hypothesis generation and in-silico validations

The ultra-processed foods hypothesis: a product processed well beyond the basic ingredients in the package

The NOVA classification of food items has become increasingly popular and is being used in several observational studies as well as in nutritional guidelines and recommendations. We propose that there is a need for this classification and its use in the formulation of public health policies to be critically discussed and re-appraised. The terms "processing" and "ultra-processing," which are crucial to the NOVA classification, are ill-defined, as no scientific, measurable, or precise reference parameters exist for them. Likewise, the theoretical grounds of the NOVA classification are unclear and inaccurate. Overall, the NOVA classification conflicts with the classic, evidence-based evaluation of foods based on composition and portion size because NOVA postulates that the food itself (or how much of it is eaten) are unimportant, but rather that dietary effects are due to how the food is produced. We contend that the NOVA system suffers from a lack of biological plausibility so the assertion that ultra-processed foods are intrinsically unhealthful is largely unproven, and needs further examination and elaboration

Negative Effects of “Predatory” Journals on Global Health Research

Predatory journals (PJ) exploit the open-access model promising high acceptance rate and fast track publishing without proper peer review. At minimum, PJ are eroding the credibility of the scientific literature in the health sciences as they actually boost the propagation of errors. In this article, we identify issues with PJ and provide several responses, from international and interdisciplinary perspectives in health sciences. Authors, particularly researchers with limited previous experience with international publications, need to be careful when considering potential journals for submission, due to the current existence of large numbers of PJ. Universities around the world, particularly in developing countries, might develop strategies to discourage their researchers from submitting manuscripts to PJ or serving as members of their editorial committees

PERFIL DA MORBIMORTALIDADE POR DOENÇA PULMONAR OBSTRUTIVA CRÔNICA NO BRASIL ENTRE 2011 E 2021

The aim of the present study was to investigate the profile of hospital morbidity and mortality due to COPD in Brazil between 2011 and 2021, in order to understand the evolution of related health indicators and identify the need for improvement in public policies for prevention and treatment strategies. for the disease. From the processed information, a significant decrease in the prevalence of hospitalizations for COPD was evidenced. The age groups that represented the highest numbers of hospitalizations were “50 years or older” and “under 5 years”. Proportional mortality declined, while COPD-specific mortality did not change statistically significantly over the entire decade. Mortality showed an increasing pattern according to age group, with more than 40% of deaths occurring in individuals aged 80 years or older. The highest numbers of hospitalizations and deaths occurred in the Southeast, South and Northeast regions, with a predominance of males. COPD is a problem that requires greater attention from health services, because despite the decrease in hospitalizations due to exacerbations, severe forms of the disease are still frequent, which highlights weaknesses in the primary and secondary prevention of the disease. Thus, new studies that extensively investigate the factors that determine the epidemiological behavior of the disease are fundamental, because only in this way can strategies and interventions be developed to improve trends in hospitalization and mortality due to COPD in Brazil.O objetivo do presente estudo foi investigar o perfil da morbidade hospitalar e mortalidade por DPOC no Brasil entre os anos de 2011 e 2021, para compreender a evolução dos indicadores em saúde relacionados e identificar a necessidade de aprimoramento em políticas públicas de prevenção e estratégias de tratamento para a doença. A partir das informações processadas, foi evidenciada diminuição importante da prevalência de internações hospitalares por DPOC. As faixas etárias que representaram os maiores números de hospitalizações foram “50 anos ou mais” e “menores de 5 anos”. A mortalidade proporcional diminuiu, enquanto a mortalidade específica por DPOC não sofreu alterações estatisticamente significativas ao longo de toda a década. A mortalidade apresentou padrão crescente de acordo com a faixa etária, com mais de 40% dos óbitos ocorrendo em indivíduos com 80 anos ou mais. Os maiores números de hospitalizações e óbitos ocorreram nas regiões Sudeste, Sul e Nordeste, com predomínio em indivíduos do sexo masculino. A DPOC é um problema que exige maior atenção dos serviços de saúde, porque apesar de as hospitalizações por exacerbações diminuírem, formas graves da doença ainda são frequentes, o que evidencia fragilidades na prevenção primária e secundária da doença. Dessa forma, novos estudos que investiguem extensivamente os fatores que determinam o comportamento epidemiológico da doença são fundamentais, porque somente assim estratégias e intervenções podem ser elaboradas para melhorar as tendências de hospitalização e mortalidade por DPOC no Brasil

TENDÊNCIAS DA MORBIMORTALIDADE POR DIABETES MELLITUS NO BRASIL ENTRE 2010 E 2020

Diabetes mellitus (DM) é a doença que cursa com estados de hiperglicemia e distúrbios do metabolismo de carboidratos, lipídios e proteínas. Estudos epidemiológicos estimam que 1 em cada 11 adultos (20 a 79 anos) eram portadores de DM em 2015 e espera-se que a prevalência de DM aumente em 50% nos próximos 20 anos, especialmente nos países em desenvolvimento. Conhecer as taxas de mortalidade de uma doença e sua distribuição demográfica, além do perfil da morbidade hospitalar, permite a elaboração de políticas públicas e estratégias para intervenção mais eficientes a partir de novos estudos. Considerando a ausência de artigos sobre tal tema, justifica-se a importância do presente estudo, cujo objetivo foi conduzir uma análise longitudinal da morbidade hospitalar e mortalidade por diabetes e suas complicações no Brasil entre os anos 2000 e 2020, a partir de sistemas de informação do SUS. Apesar dos números de internações hospitalares diminuírem, os de óbitos aumentaram sucessivamente, o que revela um manejo deficiente de complicações e casos graves. Dessa forma, conclui-se que o Brasil precisa investir em estratégias para tratamento precoce e eficaz de quadros graves, assim como em medidas de prevenção para diminuir o número de casos por diabetes e, consequentemente, o número de óbitos também

Whole exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association

Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum-stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle’s loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or CAKUT in VACTERL association