Transforming growth factor-β regulates the splicing pattern of fibronectin messenger RNA precursor

AbstractFibronectin (FN) polymorphism is caused by alternative splicing patterns in at least three regions (ED-A, ED-B and IIICS) of the primary transcript of a single gene. Using monoclonal antibodies, we previously demonstrated that transforming growth factor-β (TGF-β) preferentially increases the accumulation of the FN isoforms containing the ED-A sequence in cultured normal human fibroblasts [Balza et al., (1988) FEBS Lett. 228, 42-44]. To determine the basis of this effect, we have examined through S1 nuclease analysis, the levels of ED-A- and ED-B-containing mRNAs in cultured normal human skin flbroblasts before and after TGF-β treatment. These experiments have shown that TGF-β increases the relative amount of m-RNA for ED-A- and ED-B-containing FN isoforms. These data demonstrate that a growth factor may regulate the splicing pattern of a pre-mRNA

Multipotent Mesenchymal Stromal Stem Cell Expansion by Plating Whole Bone Marrow at a Low Cellular Density: A More Advantageous Method for Clinical Use

Mesenchymal stem cells (MSCs) are a promising source for cell therapy due to their pluripotency and immunomodulant proprieties. As the identification of “optimal” conditions is important to identify a standard procedure for clinical use. Percoll, Ficoll and whole bone marrow directly plated were tested from the same sample as separation methods. The cells were seeded at the following densities: 100 000, 10 000, 1000, 100, 10 cells/cm2. After reaching confluence, the cells were detached, pooled and re-plated at 1000, 500, 100, and 10 cells/cm2. Statistical analyses were performed. Cumulative Population Doublings (PD) did not show significant differences for the separation methods and seeding densities but only for the plating density. Some small quantity samples plated in T25 flasks at plating densities of 10 and 100 cells/cm2 did not produce any expansion. However, directly plated whole bone marrow resulted in a more advantageous method in terms of CFU-F number, cellular growth and minimal manipulation. No differences were observed in terms of gross morphology, differentiation potential or immunophenotype. These data suggest that plating whole bone marrow at a low cellular density may represent a good procedure for MSC expansion for clinical use

Adolescentes com Transtorno do Espectro Autista: singularidades do desenvolvimento psicossocial

Psychosocial development presents particular characteristics at each stage of the life cycle and it is linked to the experiences between individual and environment. The present study characterized the psychosocial development of adolescents with Autism Spectrum Disorder, considering relational singularities from the perspective of interaction, inclusion and social integration, in the view of parents and / or guardians. It is a quantitative work made by the application of an authorial form to 26 parents and/or guardians of adolescents attending a specific institution. The results pointed out losses mainly in the personal relationships and social inclusion, negatively affecting the psychosocial development. In this sense, strategies are needed to expand the development of this population, with support to the families, incentive of personal skills and contact with coherent activities with the stage of life. However, the lack of instrumentalisation of health services and socialization in integrated environments fosters the need for new knowledge in this context to guarantee equity.El desarrollo psicosocial presenta características particulares en cada etapa del ciclo de vida y está vinculado con las experiencias entre individuo y ambiente. El presente estudio ha sido caracterizado con el desarrollo psicosocial de adolescentes con Trastorno del Espectro Autista, considerando las singularidades relacionales sobre el prisma interacción, inclusión y integración social, en la perspectiva de los padres y/o los responsables. Se trata de un recorte cuantitativo a partir de la aplicación de formulario de autor con 26 padres y/o responsables de adolescentes institucionalizados en una entidad específica. Los resultados apuntaron perjuicios principalmente en las relaciones personales y de integración social, repercutiendo de modo negativo en el desarrollo psicosocial. En este sentido, son necesarias estrategias para ampliar el desarrollo de esta población, con apoyo a las familias, estímulo de las habilidades personales y contacto con actividades coherentes con la etapa de vida. Sin embargo, la carencia de instrumentalización de los servicios de salud y de socialización en entornos integrados fomenta la necesidad de nuevos saberes en este contexto para la garantía de la equidad.O desenvolvimento psicossocial apresenta características particulares em cada etapa do ciclo de vida e está vinculado com as experiências entre indivíduo e ambiente. O presente estudo caracterizou o desenvolvimento psicossocial de adolescentes com Transtorno do Espectro Autista, considerando singularidades relacionais sobre o prisma interação, inclusão e integração social, na perspectiva de pais e/ou responsáveis. Trata-se de um recorte quantitativo, a partir da aplicação de formulário autoral, com 26 pais e/ou responsáveis de adolescentes institucionalizados em entidade específica. Os resultados apontaram prejuízos principalmente nas relações pessoais e de integração social, repercutindo de modo negativo no desenvolvimento psicossocial. Neste sentido, são necessárias estratégias para ampliar o desenvolvimento desta população, com apoio às famílias, estímulo das habilidades pessoais e contato com atividades coerentes com a etapa de vida. Todavia, a carência de instrumentalização dos serviços de saúde e de socialização em ambientes integrados fomenta a necessidade de novos saberes neste contexto para a garantia da equidade.

Prognostic Role of Serum Cytokeratin-19 Fragment (CYFRA 21-1) in Patients with Hepatocellular Carcinoma

Keratin 19 (K19) is a cancer stem cell marker expressed by a subpopulation of hepatocellular carcinoma (HCC), associated with tumor aggressiveness. We evaluated the prognostic value of serum K19 fragment (CYFRA 21-1), in comparison or in combination with alpha-fetoprotein (AFP) and protein induced by vitamin-K absence or antagonist-II (PIVKA-II), in patients with HCC. A total of 160 patients (28F/132M; median age 62, range 44-86 years) with a new diagnosis of HCC and available serum samples collected at tumor diagnosis were analyzed retrospectively. Median overall survival (OS) after HCC diagnosis was 35.1, 95% CI 27.1-70.5 months. Multivariate Cox regression analysis showed that CYFRA 21-1 > 2.7 ng/mL (hazard ratio (HR) = 3.39, p 20 ng/mL (HR = 2.27, p = 0.007), and PIVKA-II > 200 mAU/mL (HR = 2.17, p = 0.020) were independent predictors of OS. The combination of biomarkers positivity allowed us to stratify patients with HCC into four risk categories associated with a progressively lower survival probability (log-rank test, p < 0.001). CYFRA 21-1 resulted an independent prognostic factor of patients with HCC and its combination with AFP and PIVKA-II might be useful to tailor personalized treatment strategies

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men