Muscle Coordination Contributes to Function after Stroke; Proprioception Contributes to Control of Posture, Movement

More than half of stroke survivors experience persistent upper extremity motor impairments that can negatively impact quality of life and independence. Effective use of the upper extremity requires coordination of agonist/antagonist muscle pairs, as well as coordination of multiple control actions for stabilizing and moving the arm. In this dissertation, I present three studies in which I recorded isometric torque production, single joint movement and stabilization, and clinical measures of function and impairments after stroke to evaluate the extent to which changes in coordination of agonist/antagonist muscles and of sequential control actions contribute to deficits after stroke. In Aim 1, I quantified the extent to which stroke-related deficits in the coordination of agonist/antagonist muscle pairs degraded the ability to generate, maintain, and relax cued torques about the elbow. Participants who survived stroke (SP) and neurologically intact participants (NI) performed pursuit tracking of step-changes in isomeric torque targets to investigate coordination of activation magnitude in elbow agonist/antagonist muscle pairs. SP had marked hypertonia of the primary flexor muscles, which led to increased compensatory activity in the primary extensor muscles. These stroke-related deficits of muscle coordination degraded ability to generate, maintain, and relax cued torque production. In Aim 2, SP and NI performed sequential combinations of elbow stabilization and movements to investigate impairments in execution and coordination of these fundamental control actions. Impaired proprioception in SP was associated with increased impairments in stabilizing the arm against a perturbation compared with SP with intact proprioception. Surprisingly, SP with intact proprioception had greater impairments when moving than did SP with impaired proprioception. These results support the supposition that deficits of somatosensation can differentially impact neural control of limb stabilization and movement. Aim 3 used correlation and forward regression to compare deficits of muscle coordination (Aim 1) and control (Aim 2) to one another in order to quantify the extent to which each could explain deficits of motor function after stroke. Taken together, the three studies revealed that stroke-related deficits in coordination timing and magnitude of muscle activation impact clinically-measured function, and that somatosensory deficits can differentially impair neuromotor stabilization and movement control

A Fully Abstract Symbolic Semantics for Psi-Calculi

We present a symbolic transition system and bisimulation equivalence for psi-calculi, and show that it is fully abstract with respect to bisimulation congruence in the non-symbolic semantics. A psi-calculus is an extension of the pi-calculus with nominal data types for data structures and for logical assertions representing facts about data. These can be transmitted between processes and their names can be statically scoped using the standard pi-calculus mechanism to allow for scope migrations. Psi-calculi can be more general than other proposed extensions of the pi-calculus such as the applied pi-calculus, the spi-calculus, the fusion calculus, or the concurrent constraint pi-calculus. Symbolic semantics are necessary for an efficient implementation of the calculus in automated tools exploring state spaces, and the full abstraction property means the semantics of a process does not change from the original

Análise do discurso nas pesquisas em educação: perspectivas foucaultianas

The objective of this article is to assimilate the Discourse Analysis, according to Foucault, with the purpose of having this theoretical-methodological reference in the researches in Education. Based on the foucaultian perspective, the relation between discourse and power is elucidated, since for Foucault everything is practical and interconnected in the relations of power and knowledge. The discourse is more than the reference of things, as it allows a conceptual network that is its own. This study is justified due to the area of Education investigating and referring to the different discourses of segments of the school, such as: managers, teachers, students, employees, or even official texts on educational policies, etc., that is, the diverse and deep perspectives to investigate things said. In order to facilitate the understanding of the Foucaultian theory, we sought to exemplify it with research related to the field of Education in general, as well as specific researches developed by research groups of the Education, Culture and Subjectivity Line of the Post-Graduate Program in Education of the Federal University of São Carlos. O objetivo deste artigo é auxiliar os pesquisadores da área de Educação a compreenderem algumas possibilidades de aplicação da Análise do Discurso, segundo Foucault, com o propósito de dispor deste referencial teórico-metodológico nas pesquisas em Educação. Foucault (1979) trata da relação entre discurso e poder, visto que para o autor as práticas discursivas estão interligadas nas relações de poder e saber. O discurso é mais do que a referência das coisas, pois possibilita uma rede conceitual que lhe é própria. Este estudo justifica-se devido à necessidade da área de Educação investigar e referendar os diferentes discursos de segmentos da escola, como: gestores, professores, alunos, funcionários, ou mesmo de textos oficiais sobre políticas educacionais, etc., isto é, as diversas e profundas perspectivas de investigar as coisas ditas. Para facilitar a compreensão da Análise do Discurso, buscamos exemplificá-la com pesquisas referentes ao campo da Educação, em geral, como também pesquisas específicas desenvolvidas em 2017 e 2018, por grupos de pesquisa da Linha Educação, Cultura e Subjetividade do Programa de Pós-Graduação em Educação, da Universidade Federal de São Carlos

Lessons learned - resolving the enigma of genetic factors in IBS

IBS is the most prevalent functional gastrointestinal disorder and phenotypically characterized by chronic abdominal discomfort, pain and altered defecation patterns. The pathophysiology of IBS is multifactorial, albeit with a substantial genetic component. To date, studies using various methodologies, ranging from family and twin studies to candidate gene approaches and genome-wide association studies, have identified several genetic variants in the context of IBS. Yet, despite enlarged sample sizes, increased statistical power and meta-analyses in the past 7 years, positive associations are still scarce and/or have not been reproduced. In addition, epigenetic and pharmacogenetic approaches remain in their infancy. A major hurdle is the lack of large homogenized case-control cohorts recruited according to standardized and harmonized criteria. The COST Action BM1106 GENIEUR (GENes in Irritable Bowel Syndrome Research Network EURope) has been established to address these obstacles. In this Review, the (epi)genetic working group of GENIEUR reports on the current state-of-the-art in the field, highlights fundamental flaws and pitfalls in current IBS (epi) genetic research and provides a vision on how to address and improve (epi) genetic approaches in this complex disorder in the future.This is the peer reviewed version of the paper: Gazouli, M., Wouters, M. M., Kapur-Pojskić, L., Bengtson, M.-B., Friedman, E., Nikčević, G., Demetriou, C. A., Mulak, A., Santos, J., & Niesler, B. (2016). Lessons learned—Resolving the enigma of genetic factors in IBS. Nature Reviews Gastroenterology & Hepatology, 13(2), 77–87. [https://doi.org/10.1038/nrgastro.2015.206]Published version: [https://imagine.imgge.bg.ac.rs/handle/123456789/977

The Rqc2/Tae2 subunit of the ribosome-associated quality control (RQC) complex marks ribosome-stalled nascent polypeptide chains for aggregation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Ribosome stalling during translation can potentially be harmful, and is surveyed by a conserved quality control pathway that targets the associated mRNA and nascent polypeptide chain (NC). In this pathway, the ribosome-associated quality control (RQC) complex promotes the ubiquitylation and degradation of NCs remaining stalled in the 60S subunit. NC stalling is recognized by the Rqc2/Tae2 RQC subunit, which also stabilizes binding of the E3 ligase, Listerin/Ltn1. Additionally, Rqc2 modifies stalled NCs with a carboxy-terminal, Ala- and Thr-containing extension-the 'CAT tail'. However, the function of CAT tails and fate of CAT tail-modified ('CATylated') NCs has remained unknown. Here we show that CATylation mediates formation of detergent-insoluble NC aggregates. CATylation and aggregation of NCs could be observed either by inactivating Ltn1 or by analyzing NCs with limited ubiquitylation potential, suggesting that inefficient targeting by Ltn1 favors the Rqc2-mediated reaction. These findings uncover a translational stalling-dependent protein aggregation mechanism, and provide evidence that proteins can become specifically marked for aggregation.Ribosome stalling during translation can potentially be harmful, and is surveyed by a conserved quality control pathway that targets the associated mRNA and nascent polypeptide chain (NC). In this pathway, the ribosome-associated quality control (RQC) com5116CNQP - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)202144/2011-9We thank J Warner, A van Hoof, R Kopito, O Brandman, and S Lindquist for reagents. EBT gratefully acknowledges the Brazilian Council for Scientific and Technological Development (CNPq) for a Postdoctoral Fellowship. MK was supported by the Hartmut Hoffma

Longevity and relationships with children: the importance of the parental role

<p>Abstract</p> <p>Background</p> <p>Social networks predict longevity across societies but specific mechanisms are largely unknown. The aim of this work was to examine the role of children in the longevity of elderly men and women in a cohort of community dwelling elderly people in Spain.</p> <p>Methods</p> <p>The data were taken from the "Aging in Leganes" cohort study with 15 years of follow-up. The baseline population was an age- and sex-stratified random sample of community dwelling people over 65 living in Leganés (Madrid) in 1993. Poor relationship with at least one child, emotional support and the perceived roles elders play in the lives of their children, extended family, spouse and friends were assessed at baseline. Cox proportional hazards models were fit to investigate the effects of social roles variables on longevity, adjusting for a wide range of socioeconomic, behavioural and health covariates.</p> <p>Results</p> <p>In the fully adjusted model, having a poor relationship with at least one child increased mortality by 30%. Elderly persons who felt their role in their children's lives was important (HR = 0.70; 95% CI 0.54; 0.91) had a lower mortality risk than those who felt they played a small role. Feeling loved and listened to by one's children did not have an effect on survival. Maintaining an important role in the extended family was also significantly associated with survival.</p> <p>Conclusion</p> <p>In this Mediterranean population, maintaining an important role in the lives of one's children is associated with survival. Functions of social networks related to meaning of life and different forms of social support may have important effects on mortality, and these functions may vary across cultures according to family norms and values.</p

Old(er) Care home residents and sexual/intimate citizenship

Sexuality and intimacy in care homes for older people are overshadowed by concern with prolonging physical and/or psychological autonomy.When sexuality and intimacy have been addressed in scholarship, this can reflect a sexological focus concerned with howto continue sexual activitywithreduced capacity.We reviewthe (Anglophone) academic and practitioner literatures bearing on sexuality and intimacy in relation to older care home residents (though much of this applies to older people generally).We highlight how ageism (or ageist erotophobia), which defines older people as post-sexual, restricts opportunities for the expression of sexuality and intimacy. In doing so, we draw attention to more critical writing that recognises constraints on sexuality and intimacy and indicates solutions to some of the problems identified. We also highlight problems faced by lesbian, gay, bisexual and trans (LGB&T) residents who are doubly excluded from sexual/intimate citizenship because of ageism combined with the heterosexual assumption. Older LGB&T residents/individuals can feel obliged to deny or disguise their identity. We conclude by outlining an agenda for research based on more sociologically informed practitioner-led work

An adaptive phase II/III safety and efficacy randomized controlled trial of single day or three-day fixed-dose albendazole-ivermectin co-formulation versus albendazole for the treatment of Trichuris trichiura and other STH infections. ALIVE trial protocol

Background: Soil-transmitted helminths (STH) are targeted for control through mass drug-administration campaigns to prevent morbidity affecting at-risk groups in endemic regions. Although broadly successful, the use of albendazole and mebendazole achieved variable progress, with deficiencies against Trichuris trichiura and a predictable low efficacy against Strongyloides stercoralis. Novel drug combinations offer a potential solution, providing they can be delivered safely and maintain efficacy against all STH species. Here we present the protocol of a clinical trial to evaluate a fixed-dose combination (FDC) tablet containing albendazole and ivermectin that will be compared against albendazole against STH. Methods: An adaptive phase II/III randomized controlled trial will be undertaken in STH endemic sites in Ethiopia, Kenya and Mozambique to evaluate an oral FDC of 400 mg albendazole and either 9- or 18 mg ivermectin. FDC will be administered as a single dose or single doses over three-consecutive days and assessed against a single dose of 400 mg albendazole. In the phase II trial, 126 T. trichiura-infected children weighting 15 to 45 kg will be treated in a dose-escalation manner to determine safety objectives. In the phase III trial, 1097 participants aged 5 to 18 years old infected with T. trichiura, hookworm and S. stercoralis will be recruited to determine safety and efficacy. The trial will be open-label with blinded outcome assessors. Cure rate measured 21-days after-treatment in duplicate Kato-Katz is the primary efficacy outcome. Secondary objectives include efficacy evaluation by quantitative polymerase chain reaction (PCR) as an outcome measurement, description of pharmacokinetic parameters, palatability and acceptability evaluations, and monitoring of anthelmintic resistance. Conclusions: This trial with registrational goals seeks to evaluate an innovative fixed-dose combination of albendazole and ivermectin co-formulated tablets, with the goal of providing an anthelmintic regimen with improved efficacy and spectrum of coverage against STH. ClinicalTrials.gov registration: NCT05124691 (18/11/2021)