Cancer/Testis Antigen MAGE-C1/CT7: New Target for Multiple Myeloma Therapy

Cancer/Testis Antigens (CTAs) are a promising class of tumor antigens that have a limited expression in somatic tissues (testis, ovary, fetal, and placental cells). Aberrant expression of CTAs in cancer cells may lead to abnormal chromosome segregation and aneuploidy. CTAs are regulated by epigenetic mechanisms (DNA methylation and acetylation of histones) and are attractive targets for immunotherapy in cancer because the gonads are immune privileged organs and anti-CTA immune response can be tumor-specific. Multiple myeloma (MM) is an incurable hematological malignancy, and several CTAs have been detected in many MM cell lines and patients. Among CTAs expressed in MM we must highlight the MAGE-C1/CT7 located on the X chromosome and expressed specificity in the malignant plasma cells. MAGE-C1/CT7 seems to be related to disease progression and functional studies suggests that this CTA might play a role in cell cycle and mainly in survival of malignant plasma cells, protecting myeloma cells against spontaneous as well as drug-induced apoptosis

Does early specialization provide an advantage in physical fitness development in youth basketball?

The present study examined the influence of the specialization onset on the magnitude and patterns of changes in basketball-specific physical fitness within a competitive season and developmental fitness trends between 11 and 17 years in young basketball players. Repeated measures of 181 young basketball players (female, n = 40; male, n = 141) were examined. Anthropometry, age, estimated maturity status, and basketball-specific physical fitness (assessed with the countermovement jump, line drill, and yo-yo intermittent recovery level-1 and fitness score) were considered. Players were grouped by the onset of specialization as related to biological maturation milestones (pre-puberty, mid-puberty, and late-puberty specialization). The within-season and developmental changes in physical fitness were fitted using multilevel modeling in a fully Bayesian framework. The fitness outcomes were similar between-player and within-player changes when grouped by specialization across a season. Fitness improvements across a season were apparent for female players, while male players maintained their performance levels. There was no variation in the patterns of physical fitness development between 11 and 17 years associated with the onset of specialization. Conditional on our data and models, the assumption that early sport specialization provides a physical fitness advantage for future athletic success does not hold

Modelagem em larga escala utilizando técnicas multi-declive em ambientes urbanos arborizados / Large-scale modeling using multi-declive techniques in urban wooded environments

Há inúmeros desafios no planejamento de redes sem fio, visto que a predição da perda no percurso e consequentemente da potência recebida em um dado instante e local é complexo. Desse modo o sistema tem que ser projetado para funcionar sob condições de grande variabilidade, considerando as atenuações e interferências. E assim, a modelagem matemática do canal torna-se uma ferramenta eficiente nesse processo, uma vez que ela é prediz o nível médio do sinal recebido e as variabilidades em torno dele. Sabendo que o ambiente influencia diretamente a propagação do sinal e que modelos com vários expoentes de atenuação podem ser mais precisos frente aos modelos com apenas um expoente de atenuação (log-distance). Este trabalho propõe um modelo em larga escala ajustado com técnicas de multi-declive para ambientes urbanos arborizados, utilizando a cidade de Belém/Pa como cenário, com vias públicas potencialmente arborizadas como cidades amazônicas. Os resultados obtidos demonstram que o modelo proposto foi satisfatório para representar o ambiente em estudo, com RMSE no valor 2,93

Beneficial effects of whole-body vibration exercise for brain disorders in experimental studies with animal models:A systematic review

Brain disorders have been a health challenge and is increasing over the years. Early diagnosis and interventions are considered essential strategies to treat patients at risk of brain disease. Physical exercise has shown to be beneficial for patients with brain diseases. A type of exercise intervention known as whole-body vibration (WBV) exercise gained increasing interest. During WBV, mechanical vibrations, produced by a vibrating platform are transmitted, to the body. The purpose of the current review was to summarize the effects of WBV exercise on brain function and behavior in experimental studies with animal models. Searches were performed in EMBASE, PubMed, Scopus and Web of Science including publications from 1960 to July 2021, using the keywords "whole body vibration" AND (animal or mice or mouse or rat or rodent). From 1284 hits, 20 papers were selected. Rats were the main animal model used (75%) followed by mice (20%) and porcine model (5%), 16 studies used males species and 4 females. The risk of bias, accessed with the SYRCLE Risk of Bias tool, indicated that none of the studies fulfilled all methodological criteria, resulting in possible bias. Despite heterogeneity, the results suggest beneficial effects of WBV exercise on brain functioning, mainly related to motor performance, coordination, behavioral control, neuronal plasticity and synapse function. In conclusion, the findings observed in animal studies justifies continued clinical research regarding the effectiveness and potential of WBV for the treatment of various types of brain disorders such as trauma, developmental disorders, neurogenetic diseases and other neurological diseases

Prioridades Axiológicas, Tempo de Serviço e Cidadania Organizacional

The objective of this research was to study the relationship between value priorities, tenure, and organizationalcitizenship. To our knowledge, personal value priorities have not been studied as antecedents of organizational behavior. Thesample was composed of 300 employees, men and women, with average age of 38.07 years. Two instruments were used: theSchwartz Value Inventory and the Organizational Citizenship Scale. Two groups of value priorities' subjects were considered:a high score group and a low score group. Three levels of organizational tenure were considered. The four second-order factorsof value priorities and the five organizational citizenship factors were considered for the analysis (Anova 2X3). Priorities ofself-transcendence, self-enhancement, collectivism and individualism values had a significant influence on several factors oforganizational citizenship. The impact of organizational tenure was limited to two factors: organizational climate and protectionof organizational patrimonyFoi objetivo desta pesquisa estudar a relação entre as prioridades axiológicas, o tempo de serviço e a cidadania organizacional. Os autores não têm conhecimento de que as prioridades axiológicas do indivíduo tenham sido estudadas comoantecedentes da cidadania organizacional. A amostra foi composta por 300 empregados, homens e mulheres, com idade média de 38,07 anos. Dois instrumentos de medida foram utilizados: o Inventário de Valores de Schwartz e a Escala de Cidadania Organizacional. Os sujeitos foram divididos em dois grupos de acordo com as suas prioridades axiológicas (escore alto e baixo). Os quatro fatores axiológicos de ordem superior e  os cinco fatores de cidadania organizacional foram considerados para a análise estatística (Anova 2X3). As prioridades ao nível dos valores de autotranscendência, autopromoção, individualismo e coletivismo tiveram influência significativa sobre vários fatores de cidadania organizacional. O impacto do tempo de serviço foi limitado a dois fatores: clima organizacional externo e proteção  ao patrimônio organizacional

Food addiction: Prevalence, psychopathological correlates and associations with quality of life in a large sample

Objective: To determine the prevalence of food addiction in a large Brazilian non-clinical sample. Sociodemographic and psychopathological correlates of food addiction as well as associations with quality (QoL) domains were also investigated. Methods: This cross-sectional study obtained data from a Brazilian anonymous web-based research platform (N = 7639; 71.3% females). Participants provided sociodemographic data and completed the modified Yale Food Addiction Scale 2.0, PHQ-9, hypomania checklist (HCL-32), Fagerström Test for Nicotine Dependence, AUDIT, modified Skin picking-Stanford questionnaire, Minnesota impulsive disorders interview, Symptom Checklist-90-Revised inventory (SCL-90R), early trauma inventory self report-short form, and the WHO Quality of Life instrument-Abbreviated version (WHOQOL-Bref). Associations were adjusted to potential confounders through multivariable models. Results: The prevalence of food addiction was 4.32% (95%CI: 3.89-4.80%), and was more common among females. Food addiction was associated with a positive screen for a major depressive episode (OR = 4.41; 95%CI: 3.46-5.62), bipolar spectrum disorder (OR = 1.98; 95%CI: 1.43-2.75), and skin picking disorder (OR = 2.02; 95%CI: 1.31-3.09). Food addiction was also independently associated with exposure to early life psychological and sexual abuse (P = 0.008) as well as with reduced physical, psychological, social, and environment QoL (all P < 0.001). Conclusions: Food addiction may be common in low and middle-income countries, though possibly less prevalent than in the US. Food addiction was associated with co-occurring mood disorders and skin picking disorder as well as with early life psychological and sexual abuse. Finally, food addiction was independently associated with broad reductions in QoL. Public health efforts towards the early recognition and management of food addiction are warranted

Dominant negative effect of polyglutamine expansion perturbs normal function of ataxin-3 in neuronal cells

The physiological function of Ataxin-3 (ATXN3), a deubiquitylase (DUB) involved in Machado–Joseph Disease (MJD), remains elusive. In this study, we demonstrate that ATXN3 is required for neuronal differentiation and for normal cell morphology, cytoskeletal organization, proliferation and survival of SH-SY5Y and PC12 cells. This cellular phenotype is associated with increased proteasomal degradation of a5 integrin subunit (ITGA5) and reduced activation of integrin signalling and is rescued by ITGA5 overexpression. Interestingly, silencing of ATXN3, overexpression of mutant versions of ATXN3 lacking catalytic activity or bearing an expanded polyglutamine (polyQ) tract led to partially overlapping phenotypes. In vivo analysis showed that both Atxn3 knockout and MJD transgenic mice had decreased levels of ITGA5 in the brain. Furthermore, abnormal morphology and reduced branching were observed both in cultured neurons expressing shRNA for ATXN3 and in those obtained from MJD mice. Our results show that ATXN3 rescues ITGA5 from proteasomal degradation in neurons and that polyQ expansion causes a partial loss of this cellular function, resulting in reduced integrin signalling and neuronal cytoskeleton modifications, which may be contributing to neurodegeneration.National Institutes of Health (NIH) ‘(R01NS038712)Fundação para a Ciência e a Tecnologia (FCT) and COMPETE through the project ‘(PTDC/SAU-GMG/ 101572/2008)Fundação para a Ciência e a Tecnologia (FCT) - fellowships SFRH/BD/51059/2010, SFRH/BD/ 78388/2011 and SFRH/BPD/91562/201

A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.OBJECTIVE: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT). SUMMARY BACKGROUND DATA: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. Additionally, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation. METHODS: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 y follow up, 32% beyond Milan criteria). The resulting four gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict. RESULTS: HepatoPredict identifies 99% disease-free patients (>5 y) from a retrospective cohort, including many outside clinical criteria (16%-24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88,5%-94,4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term. CONCLUSIONS: HepatoPredict outperforms conventional clinical-pathologic selection criteria, (Milan, UCSF) providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs.publishersversionepub_ahead_of_prin

Magnetic dehydrodipeptide-based self-assembled hydrogels for theragnostic applications

Self-assembled peptide hydrogels have emerged in recent years as the new paradigm in biomaterials research. We have contributed to this field the development of hydrogels based on dehydrodipeptides N-capped with naproxen. The dehydrodipeptide hydrogels can be loaded with drugs, thus being potential nanocarriers for drug delivery. In this work novel dehydrodipeptides containing tyrosine and aspartic acid amino acid residues N-capped with naproxen and C-terminal dehydrophenylalanine were prepared and characterized. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated into the dehydrodipeptide-based hydrogels and their effect on the self-assembly, structure and rheological and magnetic properties of the hydrogels was studied. Magnetic hydrogels, with incorporated SPIONs, displayed concentration-dependent T2-MRI contrast enhancement. Moreover, upon magnetic excitation (alternating magnetic field –AMF–) the SPIONs were able to generate a significant amount of heat. Hence, magnetic hyperthermia can be used as a remote trigger for release of drug cargos and SPIONs incorporated into the self-assembled dehydrodipeptide hydrogels.This work is funded by National Funds through FCT - Portuguese Foundation for Science and Technology under the Project PTDC/QUI-QOR/29015/2017 and CQ/UM UID/QUI/00686/2013 and UID/QUI/0686/2016. The NMR spectrometers are part of the National NMR Network (PTNMR) and are partially supported by Infrastructure Project No 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC).info:eu-repo/semantics/publishedVersio