Structural identifiability analysis of linear reaction–advection–diffusion processes in mathematical biology

Effective application of mathematical models to interpret biological data and make accurate predictions often requires that model parameters are identifiable. Approaches to assess the so-called structural identifiability of models are well established for ordinary differential equation models, yet there are no commonly adopted approaches that can be applied to assess the structural identifiability of the partial differential equation (PDE) models that are requisite to capture spatial features inherent to many phenomena. The differential algebra approach to structural identifiability has recently been demonstrated to be applicable to several specific PDE models. In this brief article, we present general methodology for performing structural identifiability analysis on partially observed reaction–advection–diffusion PDE models that are linear in the unobserved quantities. We show that the differential algebra approach can always, in theory, be applied to such models. Moreover, despite the perceived complexity introduced by the addition of advection and diffusion terms, consideration of spatial analogues of non-spatial models cannot exacerbate structural identifiability. We conclude by discussing future possibilities and the computational cost of performing structural identifiability analysis on more general PDE models

Uso de leitos hospitalares privados por sistemas públicos de saúde na resposta à COVID-19

In this study we examined strategies adopted by countries with public health systems that expanded the supply of beds through the use of private hospitals in response to COVID-19. We used selected case studies to explore the institutional context in which measures were implemented, the management instruments used and how to characterize government action in eight countries: Australia, Spain, Ireland, Italy, Chile, Mexico and Peru, in addition to Brazil. This analysis can help to identify mechanisms of health system management that can control actions to respond to ESP situations, as well as improve the governance of health systems in the relationship between public and private sectors.Nesse estudo examinamos estratégias adotadas por países com sistemas públicos de saúde que expandiram a oferta de leitos por meio da utilização de hospitais privados na resposta à COVID-19. Utilizamos estudo de casos selecionados para explorar o contexto institucional em que as medidas foram implementadas, os instrumentos de gestão utilizados e como se caracterizou a ação governamental em oito países: Austrália, Espanha, Irlanda, Itália, Chile, México e Peru, além do Brasil. Essa análise pode auxiliar a identificar mecanismos de gestão de sistema de saúde necessários para a coordenação de ações governamentais para resposta a situações de ESP, bem como para aperfeiçoar a governança dos sistemas de saúde na relação entre setores público e privado

Pharmaceutical consultation as a tool to improve health outcomes for patients with type 2 diabetes

Neste estudo, desenvolvemos e avaliamos um programa de consulta farmacêutica (PCF) visando melhorar o tratamento de pacientes diabéticos tipo 2 (PDT2) e reduzir os fatores de risco de complicações diabéticas com possibilidade de aplicação em outras doenças crônicas. Para alcançar este propósito, PDT2 recebendo tratamento médico convencional, apresentando glicemia de jejum &gt; 140 mg/dl e/ou hemoglobina glicada &gt;7% foram selecionados. O PCF inclui estratégias obtidas a partir do método de Dader, do modelo de cuidados farmacêuticos PWDT (Pharmacist's Workup of Drug Therapy method), do método SOAP (Subjective data, Objective data, Assessment, and Plan of care) e conceitos baseados em um modelo de cuidados em enfermagem. O PCF avaliou o estilo de vida, farmacoterapia e seu monitoramento através de exames laboratoriais, sinais vitais e antropometria. Estes procedimentos foram repetidos a cada 4 meses durante 1 ano. Os dados obtidos em cada consulta possibilitaram oferecer educação focada no estilo de vida e uso de medicamentos. Para os 50 pacientes que concluiram o PCF houve redução da glicemia (P < 0.0001), hemoglobina glicada (P = 0.0022), colesterolemia (P = 0.0072), triacilgliceridemia (P= 0.0204) e pressão arterial (P < 0.0001). O aumento da concordância e a correção dos problemas relacionados a medicamentos contribuíram para melhoria do tratamento. Assim, podemos concluir que o PCF foi adequado para melhorar a saúde de PDT2 ao reduzir fatores de risco de complicações diabéticas.This study develops and evaluates a pharmaceutical consultation program (PCP) to improve treatment for Type 2 diabetes patients (T2DP) and reduce risk factors for diabetic complications with possible application in other chronic diseases. We recruited T2DP receiving conventional medical treatment but with fasting glycemia &gt;140mg/dl and/or glycated hemoglobin &gt;7%. The PCP includes strategies obtained from Dader's method, the PWDT (Pharmacist's Workup of Drug Therapy method) model of pharmaceutical care, the SOAP (Subjective data, Objective data, Assessment, and Plan of care) method, and concepts based on a nursing care model. The PCP evaluated lifestyle, pharmacotherapy and monitoring it using laboratory tests, vital signs, and anthropometry. These procedures were repeated every 4 months for 1 year. Data obtained in each consultation were used to provide patient education focusing on healthy lifestyles and medications. Fifty patients completed the PCP. There were reductions in glycemia (

Neuromyopathy with congenital cataracts and glaucoma: A distinct syndrome caused by POLG variants

We identified three non-related patients manifesting a childhood-onset progressive neuromyopathy with congenital cataracts, delayed walking, distal weakness and wasting, glaucoma and swallowing difficulties. Electrophysiology and nerve biopsies showed a mixed axonal and demyelinating neuropathy, while muscle biopsy disclosed both neurogenic and myopathic changes with ragged red fibers, and muscle MRI showed consistent features across patients, with a peculiar concentric disto-proximal gradient of fatty replacement. We used targeted next generation sequencing and candidate gene approach to study these families. Compound biallelic heterozygous variants, p.[(Pro648Arg)]; [(His932Tyr)] and p.[(Thr251Ile),(Pro587Leu)]; [(Arg943Cys)], were found in the three patients causing this homogeneous phenotype. Our report on a subset of unrelated patients, that showed a distinct autosomal recessive childhood-onset neuromyopathy with congenital cataracts and glaucoma, expands the clinical spectrum of POLG-related disorders. It also confirms the association between cataracts and neuropathy with variants in POLG. Early onset cataract is otherwise rare in POLG-related disorders and so far reported only in a few patients with the clinical pattern of distal myopathy or neuromyopathy

Citron Kinase Deficiency Leads to Chromosomal Instability and TP53-Sensitive Microcephaly

Mutations in citron (CIT), leading to loss or inactivation of the citron kinase protein (CITK), cause primary microcephaly in humans and rodents, associated with cytokinesis failure and apoptosis in neural progenitors. We show that CITK loss induces DNA damage accumulation and chromosomal instability in both mammals and Drosophila. CITK-deficient cells display "spontaneous" DNA damage, increased sensitivity to ionizing radiation, and defective recovery from radiation-induced DNA lesions. In CITK-deficient cells, DNA double-strand breaks increase independently of cytokinesis failure. Recruitment of RAD51 to DNA damage foci is compromised by CITK loss, and CITK physically interacts with RAD51, suggesting an involvement of CITK in homologous recombination. Consistent with this scenario, in doubly CitK and Trp53 mutant mice, neural progenitor cell death is dramatically reduced; moreover, clinical and neuroanatomical phenotypes are remarkably improved. Our results underscore a crucial role of CIT in the maintenance of genomic integrity during brain development

Muscle MRI in neutral lipid storage disease (NLSD)

Altres ajuts: This work has been supported by Telethon Grant: GGP14066A.Neutral lipid storage disease (NLSD) is a rare inherited disorder of lipid metabolism resulting in lipid droplets accumulation in different tissues. Skeletal muscle could be affected in both two different form of disease: NLSD with myopathy (NLSD-M) and NLSD with ichthyosis (NLSD-I). We present the muscle imaging data of 12 patients from the Italian Network for NLSD: ten patients presenting NLSD-M and two patients with NLSD-I. In NLSD-M gluteus minimus, semimembranosus, soleus and gastrocnemius medialis in the lower limbs and infraspinatus in the upper limbs were the most affected muscles. Gracilis, sartorius, subscapularis, pectoralis, triceps brachii and sternocleidomastoid were spared. Muscle involvement was not homogenous and characteristic "patchy" replacement was observed in at least one muscle in all the patients. Half of the patients showed one or more STIR positive muscles. In both NLSD-I cases muscle involvement was not observed by T1-TSE sequences, but one of them showed positive STIR images in more than one muscle in the leg. Our data provides evidence that muscle imaging can identify characteristic alterations in NLSD-M, characterized by a specific pattern of muscle involvement with "patchy" areas of fatty replacement. Larger cohorts are needed to assess if a distinct pattern of muscle involvement exists also for NLSD-I

Integration of tumour infiltrating lymphocytes, programmed cell-death ligand-1, CD8 and FOXP3 in prognostic models for triple-negative breast cancer: Analysis of 244 stage I-III patients treated with standard therapy.

Tumour infiltrating lymphocytes (TILs) are an established prognostic biomarker for triple-negative breast cancer (TNBC). We evaluated the role of programmed cell-death ligand-1 (PD-L1), CD8 and FOXP3 expression in refining a prognostic model for non-metastatic TNBC beyond classic factors and TILs.Primary tumour samples from 244 early patients with TNBC, all treated with surgery and chemotherapy, were collected. Stromal TILs were evaluated on haematoxylin-eosin slides according to guidelines. PD-L1, CD8 and FOXP3 were assessed by immunohistochemistry and evaluated by digital pathology.TILs, PD-L1, CD8 and FOXP3 were positively correlated with each other (P 0.001). TILs were confirmed as an independent prognostic factor. When PD-L1, CD8 and FOXP3 were added to multivariable models including classic factors (age, stage, histologic grade) and TILs, PD-L1 provided the largest amount of additional prognostic information: likelihood ratio χBeyond clinicopathological factors and TILs, other immune biomarkers may add prognostic information for early TNBC. The increased PD-L1 expression on residual disease after neoadjuvant chemotherapy strengthens the rationale of testing immune checkpoint inhibitors in the post-neoadjuvant setting

Diagnóstico da necessidade de informação do setor moveleiro do Rio Grande do Sul: estudo do usuário

Esta pesquisa teve como objetivo identificar as necessidades de informação técnica e tecnológica da indústria moveleira gaúcha. Para tanto, foram entrevistadas 80 empresas caracterizando o panorama do setor. Este cenário possibilitará ao Centro Tecnológico do Mobiliário Senai, em especial ao Núcleo Setorial de Informação Tecnológica em Mobiliário e Madeira a adequação dos serviços prestados, garantindo maior qualidade ao atendimento de seu usuário Palavras-chave Diagnóstico de necessidades de informação.Setor mobiliário. Estudo de usuário. Informação tecnológica. Informação industrial. Relatório de pesquisa. Diagnosis of Information needs of the furniture sector of the State of Rio Grande do Sul: a user study Abstract The purpose of this research was to identify the technical and technological Information needs of the gaucho furniture industries. For this goal to be reachead, interviews were conducted with personnel who deal with 80 enterprises characterizing the furniture panorama in the state of Rio Grande do Sul, Brazil. The research will optimize the services of the Senai Furniture Technological Center in general and of the Technological Information Nucleus in particular, thus bringing better services to all their clients. Keywords Diagnosis of information needs/Furniture sector/Brazil. User study. Technological information. Industrial information. Research report

A CONSULTA DE ENFERMAGEM EM PUERICULTURA NA ESTRATÉGIA SAÚDE DA FAMÍLIA

Objetivo: Descrever a consulta de enfermagem em puericultura, identificando as características de seu processo de desenvolvimento. Metodologia: Pesquisa descritiva, exploratória e transversal, cujos dados foram colhidos entre julho e agosto de 2017, em oito unidades de saúde da família, por observação não participante, com instrumento previamente validado, durante as consultas de enfermagem em puericultura. A análise foi estatística descritiva. Resultados: O acolhimento da criança e seu cuidador ocorreu em consonância com as premissas da saúde da família. A anamnese esteve restrita à questionamentos sobre intercorrências e alimentação. A avaliação do crescimento ocorreu conforme o preconizado, contudo, medidas como os perímetros torácico e abdominal não foram verificados. O exame físico se mostrou incompleto. A avaliação da situação vacinal ocorreu sempre. As orientações fornecidas se mostraram insuficientes. Os dados foram registrados na caderneta de saúde da criança e no prontuário, com exceção dos marcos do desenvolvimento. Conclusão: A consulta de puericultura por enfermeiros de saúde da família privilegia aspectos como presença de intercorrências e alimentação da criança, avalia o crescimento e a imunização. A avaliação do desenvolvimento e orientações próprias a cada faixa etária são incompletas

Anticancer and anti-inflammatory activities of a standardized dichloromethane extract from piper umbellatum l. leaves

Despite the advances in anticancer drug discovery field, the worldwide cancer incidence is remarkable, highlighting the need for new therapies focusing on both cancer cell and its microenvironment. The tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nowadays, almost 75% of the anticancer agents used in chemotherapy are derived from natural products, and plants are an important source of new promising therapies. Continuing our research on Piper umbellatum species, here we describe the anticancer (in vitro antiproliferative activity and in vivo Ehrlich solid tumor model) and anti-inflammatory (carrageenan-induced paw edema and peritonitis models) activities of a standardized dichloromethane extract (SDE) from P. umbellatum leaves, containing 23.9% of 4-nerolidylcatechol. SDE showed in vitro and in vivo antiproliferative activity, reducing Ehrlich solid tumor growth by 38.7 and 52.2% when doses of 200 and 400 mg/kg, respectively, were administered daily by oral route. Daily treatments did not produce signals of toxicity. SDE also reduced paw edema and leukocyte migration on carrageenan-induced inflammation models, suggesting that the anticancer activity of SDE from Piper umbellatum leaves could involve antiproliferative and anti-inflammatory effects. These findings highlight P. umbellatum as a source of compounds against cancer and inflammation2015CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPES133897/2012-5sem informaçã