Engineered Microenvironments for Maturation of Stem Cell Derived Cardiac Myocytes

Through the use of stem cell-derived cardiac myocytes, tissue-engineered human myocardial constructs are poised for modeling normal and diseased physiology of the heart, as well as discovery of novel drugs and therapeutic targets in a human relevant manner. This review highlights the recent bioengineering efforts to recapitulate microenvironmental cues to further the maturation state of newly differentiated cardiac myocytes. These techniques include long-term culture, co-culture, exposure to mechanical stimuli, 3D culture, cell-matrix interactions, and electrical stimulation. Each of these methods has produced various degrees of maturation; however, a standardized measure for cardiomyocyte maturation is not yet widely accepted by the scientific community

Revisão de literatura da classificação histológica do carcinoma nasofaríngeo / Literature review of the histological classification of nasopharyngeal carcinoma

INTRODUÇÃO: O carcinoma nasofaríngeo é uma neoplasia epitelial maligna de cabeça e pescoço, que se origina na porção superior da faringe e se estende do palato mole até a base do crânio. Esta neoplasia possui um conjunto único de características geográficas e étnicas, com a maior incidência concentrada no sudeste asiático, sul da China, Hong Kong, norte da África e na população esquimó do Alasca. A classificação histopatológica do tumor é atualmente representada, em ordem de frequência, pelo carcinoma tipo não queratinizado (subdividido em tipo diferenciado e não diferenciado), carcinoma tipo queratinizado e carcinoma tipo basalóide. Já sua etiologia, é multifatorial e inclui fatores genéticos, ambientais e virais, com destaque para a infecção do vírus Epstein Barr-Vírus (EBV), que está presente em aproximadamente 90% dos casos observados em regiões endêmicas. OBJETIVOS: Demonstrar, através de uma revisão bibliográfica atualizada, os aspectos histológicos, fatores genéticos, ambientais e dados de prognóstico do carcinoma nasofaríngeo. METODOLOGIA: Foi realizada uma revisão e análise de literatura sobre histologia e histopatologia do carcinoma nasofaríngeo, entre os anos de 2005 a 2021, nas bases de dados CAPES (assinantes) e PubMed (gratuito), utilizando-se os seguintes descritores, em português e inglês: carcinoma nasofaríngeo, classificação histopatológica do carcinoma nasofaríngeo e incidência do carcinoma nasofaríngeo. Dos quarenta e dois artigos selecionados, doze foram excluídos por não usarem a classificação histológica da OMS.RESULTADOS: Carcinoma nasofaríngeo é um tumor epitelial que acomete as células escamosas na região da nasofaringe, representando 0.78% dos casos totais mundiais. O tipo não queratinizado, constitui a maior parte dos casos (80-90%), com praticamente todos os casos relacionados ao vírus EBV e a maior taxa de sobrevivência (65%) entre os três tipos do carcinoma. Já o tipo queratinizado, é o segundo mais comum sendo composto por células tumorais poligonais estratificadas, que podem formar pedras de queratina ao redor do tumor. O tipo basalóide, com incidência menor que 1%, apresenta a pior taxa de sobrevivência, 10%, e com um melhor prognóstico em homens e mulheres com idade inferior a 40 anos. Além disso, o índice de prognóstico do carcinoma nasofaríngeo está diretamente relacionado com metástases à distância, a qual atinge aproximadamente 30%  dos pacientes diagnosticados. Enquanto o tipo queratinizado é mais propenso a formar metástase local, o tipo não queratinizado possui maior propensão a metástase nos linfonodos cervicais. CONCLUSÃO: A escassez de estudos e artigos a respeito desse câncer mostra-se muito preocupante. Apesar do carcinoma nasofaríngeo ser uma neoplasia rara, apresenta alto índice de mortalidade. Dessa forma, é de suma importância a sua análise histopatológica, para que haja um correto diagnóstico e um maior conhecimento acerca de seu prognóstico, assim impactando na taxa de sobrevida do paciente. Ademais, a identificação de fatores genéticos, ambientais e virais são essenciais para um melhor prognóstico.         

Enzymatically crosslinked gelatin–laminin hydrogels for applications in neuromuscular tissue engineering

We report a water-soluble and non-toxic method to incorporate additional extracellular matrix proteins into gelatin hydrogels, while obviating the use of chemical crosslinkers such as glutaraldehyde. Gelatin hydrogels were fabricated using a range of gelatin concentrations (4%–10%) that corresponded to elastic moduli of approximately 1 kPa–25 kPa, respectively, a substrate stiffness relevant for multiple cell types. Microbial transglutaminase was then used to enzymatically crosslink a layer of laminin on top of gelatin hydrogels, resulting in 2-component gelatin–laminin hydrogels. Human induced pluripotent stem cell derived spinal spheroids readily adhered and rapidly extended axons on GEL-LN hydrogels. Axons displayed a more mature morphology and superior electrophysiological properties on GEL-LN hydrogels compared to the controls. Schwann cells on GEL-LN hydrogels adhered and proliferated normally, displayed a healthy morphology, and maintained the expression of Schwann cell specific markers. Lastly, skeletal muscle cells on GEL-LN hydrogels achieved long-term culture for up to 28 days without delamination, while expressing higher levels of terminal genes including myosin heavy chain, MyoD, MuSK, and M-cadherin suggesting enhanced maturation potential and myotube formation compared to the controls. Future studies will employ the superior culture outcomes of this hybrid substrate for engineering functional neuromuscular junctions and related organ on a chip applications

The value of open-source clinical science in pandemic response: lessons from ISARIC

International audienc

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4 % presented with RS, while 13.6 % had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7 % vs RS: 37.5 %). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1 % vs. RS 32.0 %), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use