Real-time and label free determination of ligand binding-kinetics to primary cancer tissue specimens; a novel tool for the assessment of biomarker targeting

In clinical oncology, diagnosis and evaluation of optimal treatment strategies are mostly based on histopathological examination combined with immunohistochemical (IHC) expression analysis of cancer-associated antigens in formalin fixed paraffin-embedded (FFPE) tissue biopsies. However, informative IHC analysis depends on both the specificity and affinity of the binding reagent, which are inherently difficult to quantify in situ. Here we describe a label-free method that allows for the direct and real-time assessment of molecular binding kinetics in situ on FFPE tissue specimens using quartz crystal microbalance (QCM) enabled biosensor technology. We analysed the interaction between the rVAR2 protein and its placental-like chondroitin sulfate (pl-CS) receptor in primary human placenta tissue and in breast and prostate tumour specimens in situ. rVAR2 interacted with FFPE human placenta and cancer tissue with an affinity in the nanomolar range, and showed no detectable interaction with pl-CS negative normal tissue. We further validated the method by including analysis with the androgen receptor N-20 antibody (anti-AR). As the KD value produced by this method is independent of the number of epitopes available, this readout offers a quantitative and unbiased readout for in situ binding-avidity and amount of binding epitopes. In summary, this method adds a new and important dimension to classical IHC-based molecular pathology by adding information about the binding characteristics in biologically relevant conditions. This can potentially be used to select optimal biologics for diagnostic and for therapeutic applications as well as guide the development of novel high affinity binding drugs. Keywords: Quartz crystal microscale, Biomarker, Biosensor, VAR2CSA, Cancer, Malari

Factors associated with frailty in patients with neurodegenerative diseases

Objetivo: Identificar os fatores associados à fragilidade em pacientes com doenças neurodegenerativas. Método: Estudo transversal, cuja amostra foi composta por 150 pacientes com diagnóstico de doenças neurodegenerativas atendidos em um ambulatório de Fonoaudiologia de um hospital de referência no sul do Brasil. Foi realizada análise secundária exploratória dos prontuários dos pacientes atendidos neste ambulatório entre o período de abril de 2016 e maio de 2019. As informações coletadas foram: sexo, idade, escolaridade, tipo de doença neurodegenerativa, tempo de doença, fragilidade (Edmonton Frail Scale - EFS), deglutição (Northwestern Dysphagia Patient CheckSheet- NDPCS, Eating Assessment Tool-EAT 10) e cognição (Mini-Mental State Examination-MMSE e Montreal Cognitive Assessment-MoCA). As variáveis quantitativas contínuas foram analisadas a partir de média e desvio padrão e as quantitativas categóricas a partir de frequência absoluta e relativa, assim como analisou-se a associação destas com o desfecho pelo teste Qui-Quadrado. As Razões de Prevalência brutas e ajustadas foram avaliadas a partir da Regressão de Poisson com variância robusta. Todos os testes estatísticos foram considerados significativos a um nível de 5%. Resultados: Os fatores significativos associados à fragilidade foram à presença de disfagia orofaríngea e desempenho cognitivo alterado. Indivíduos com a fragilidade apresentam maior prevalência de disfagia orofaríngea (RP=1,772(1,094-2,872)), enquanto a cognição alterada está associada a menor prevalência de fragilidade (RP=0,335(0,128-0,873). Conclusão: A disfagia orofaríngea pode ser um importante fator clínico preditivo a ser considerado em casos de fragilidade em pacientes com doenças neurodegenerativas.Purpose: To identify the factors associated with frailty in patients with neurodegenerative diseases. Methods: Cross-sectional study, whose sample consisted of 150 patients diagnosed with neurodegenerative diseases seen at a speech-language therapy clinic in a reference hospital in southern Brazil. A secondary exploratory analysis of the medical records of patients treated at this clinic between April 2016 and May 2019 was performed. The information collected was sex, age, education, type of neurodegenerative disease, time of disease, frailty (Edmonton Frail Scale-EFS), swallowing (Northwestern Dysphagia Patient CheckSheet-NDPCS, Eating Assessment ToolEAT 10), and cognition (Mini-Mental State Examination-MMSE and Montreal Cognitive Assessment-MoCA). Continuous quantitative variables were analyzed using mean and standard deviation and categorical quantitative variables from absolute and relative frequency, as well as their association with the outcome using the Chi-square test. Crude and adjusted Prevalence Ratios were assessed using Poisson regression with robust variance. All statistical tests were considered significant at a level of 5%. Results: The significant factors associated with frailty were the presence of oropharyngeal dysphagia and altered cognitive performance. Individuals with frailty have a higher prevalence of oropharyngeal dysphagia (PR= 1.772(1.094-2.872)), while cognition alteration presented a lower prevalence (PR= 0.335(0.128-0.873). Conclusion: Oropharyngeal dysphagia can be an important clinical predictive factor for consideration in cases of frailty in patients with neurodegenerative diseases

Person-centered Care for Institutionalized Older Adults in the Context of the Covid-19 Pandemic in Brazil

Objective: This study aims to discuss the caregiving practices developed by Long-term Care Facilities (LTCFs) during the COVID-19 pandemic and analyze the daily care practices in long-term institutions for older adults in Brazil, all in light of the PCC framework. Methods: This is a mixed methods study in which data were collected through interviews with managers from 10 LTCFs. The qualitative discussion was carried out through the PCC framework divided into 5 categories: leisure, accommodation, food, hygiene and comfort, and clinical care. The quantitative data collected were analyzed in a descriptive way, being discussed in the light of the literature. Results: Analyzed LTCFs are unaware of our present difficulties in the implementation of PCC, with a greater presence of the traditional biomedical model being recognized. Given the vulnerabilities that the LTCFs present, PCC is an important alternative for LTCFs to promote the quality of life and autonomy of residents. Deconstructing the vision of LTCFs as a last resort of care and investing in the quality of care is an urgent and essential imperative for dignified and comprehensive care. Conclusions: This study highlights the need for a change in culture and understanding of the LTCFs not only as a place to provide healthcare, but also as a residents’ home that fosters their autonomy, and feeling of belonging. Thus, it is essential to ensure that healthcare teams in LTCFs know about PCC and that further studies investigate the impact on the costs of PCC for institutionalized older adults

Dysarthria in hereditary spastic paraplegia type 4

Objective: To describe the speech pattern of patients with hereditary Spastic Paraplegia type 4 (SPG4) and correlated it with their clinical data. Methods: Cross-sectional study was carried out in two university hospitals in Brazil. Two groups participated in the study: the case group (n = 28) with a confirmed genetic diagnosis for SPG4 and a control group (n = 17) matched for sex and age. The speech assessment of both groups included: speech task recording, acoustic analysis, and auditory-perceptual analysis. In addition, disease severity was assessed with the Spastic Paraplegia Rating Scale (SPRS). Results: In the auditory-perceptual analysis, 53.5% (n = 15) of individuals with SPG4 were dysarthric, with mild to moderate changes in the subsystems of phonation and articulation. On acoustic analysis, SPG4 subjects’ performances were worse in measurements related to breathing (maximum phonation time) and articulation (speech rate, articulation rate). The articulation variables (speech rate, articulation rate) are related to the age of onset of the first motor symptom. Conclusion: Dysarthria in SPG4 is frequent and mild, and it did not evolve in conjunction with more advanced motor diseases. This data suggest that diagnosed patients should be screened and referred for speech therapy evaluation and those pathophysiological mechanisms of speech involvement may differ from the length-dependent degeneration of the corticospinal tract

Displasia do desenvolvimento do quadril, relação entre via de parto e impacto no tempo de tratamento: dysplasia of hip development, relationship between way of living and impact on time of treatment

Como uma das anomalias esqueléticas mais frequentes, a displasia do desenvolvimento do quadril (DDQ) é caracterizada por uma gama considerável de patologia, desde a frouxidão menor dos ligamentos na articulação do quadril até a luxação completa. Acredita-se que a detecção precoce e o tratamento subsequente da displasia do desenvolvimento do quadril (DDQ) melhorem seu prognóstico. Os fatores de risco frequentemente relatados para DDQ são história familiar positiva de DDQ, sexo feminino e apresentação pélvica, mas não há muito conhecimento sistemático sobre os fatores de risco, tempo de tratamento para DDQ com relação a via de parto. O objetivo deste estudo é verificar na literatura as possíveis relações entre DDQ e as via de parto, bem como sua influência no tempo de tratamento desses pacientes. Trata-se de uma revisão como bases publicações, dos último cinco anos, que abordem a relação entre via de parto e o tempo de tratamento da DDQ, extraídas de bases de dados eletrônicas como Scielo, PubMed, Lilacs, BVS, Embase e Medline, em língua inglesa e portuguesa. Dos estudo que se aproximaram do objetivo da pesquisa, muitos não relataram a estreita relação entre via de parto e tratamento da DDQ e aqueles que de alguma forma relataram, alegaram não haver uma relação direta entre as variáveis, pois a DDQ é multifatorial. Assim, espera-se que este estudo sirva de incentivo para que mais estudos sejam realizados sobre essa temática afim de estabelecer e conhecer se há alguma relação entre via de parto e tempo de tratamento de pacientes com DDQ

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Incidência da síndrome pré-menstrual na prática de esportes: aspectos atuais: Incidence of pre-menstrual syndrome in sports: current aspects

A síndrome pré-menstrual (SPM) é uma constelação complexa de alterações de humor, comportamentais e físicas que se limitam à fase pré-menstrual. Esses sintomas se recuperam dentro de alguns dias após o início da menstruação.&nbsp; Assim, o objetivo desse estudo é demonstrar a incidência da síndrome pré-menstrual na prática de esportes a partir de uma revisão integrativa sobre o tema. Para isso, foi realizado uma revisão integrativa sobre o tema, onde foi considerado textos publicados desde 2010, em inglês e português e que estejam disponíveis para leitura, no PUBMED, LILACs e Scielo. Esta revisão sistemática fornece algum suporte adicional para diretrizes clínicas que recomendam o exercício como um tratamento eficaz para a TPM. As análises secundárias realizadas também fornecem novas evidências de que o exercício pode ser útil no alívio de sintomas psicológicos, físicos e comportamentais específicos associados à TPM, além de auxiliar no gerenciamento do perfil global de sintomas