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Nonetheless, the axial knee joint reaction force increases for all exoskeleton cases due to the added weight and higher GRFs. In summary, the results provide sound evidence of the efficacy of the proposed controllers on reducing the wearer's musculoskeletal loadings. And it is shown the human-in-the-loop simulation paradigm presented here can be used for virtual design and evaluation of powered exoskeletons and pave the way for building optimized exoskeleton prototypes for experimental evaluation.Pathogenic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene belong to the most common genetic causes of inherited Parkinson's disease (PD) and variations in its locus increase the risk to develop sporadic PD. Extensive research efforts aimed at understanding how changes in the LRRK2 function result in molecular alterations that ultimately lead to PD. Cellular LRRK2-based models revealed several potential pathophysiological mechanisms including apoptotic cell death, LRRK2 protein accumulation and deficits in neurite outgrowth. BSJ-4-116 mouse However, highly variable outcomes between different cellular models have been reported. Here, we have investigated the effect of different experimental conditions, such as the use of different tags and gene transfer methods, in various cellular LRRK2 models. Readouts included cell death, sensitivity to oxidative stress, LRRK2 relocalization, α-synuclein aggregation and neurite outgrowth in cell culture, as well as neurite maintenance in vivo. We show that overexpression levels and/or the tag fused to LRRK2 affect the relocalization of LRRK2 to filamentous and skein-like structures. We found that overexpression of LRRK2 per se is not sufficient to induce cellular toxicity or to affect α-synuclein-induced toxicity and aggregate formation. Finally, neurite outgrowth/retraction experiments in cell lines and in vivo revealed that secondary, yet unknown, factors are required for the pathogenic LRRK2 effects on neurite length. Our findings stress the importance of technical and biological factors in LRRK2-induced cellular phenotypes and hence imply that conclusions based on these types of LRRK2-based assays should be interpreted with caution.Coronavirus disease 2019 (COVID-19) is an emerging disease that has reached pandemic status by rapidly spreading worldwide. Elderly individuals and patients with comorbidities such as obesity, diabetes, and hypertension show a higher risk of hospitalization, severe disease, and mortality by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. These patients frequently show exacerbated secretion of proinflammatory cytokines associated with an overreaction of the immune system, the so-called cytokine storm. Host nutritional status plays a pivotal role in the outcome of a variety of different infectious diseases. It is known that the immune system is highly affected by malnutrition, leading to decreased immune responses with consequent augmented risk of infection and disease severity. Body composition, especially low lean mass and high adiposity, has consistently been linked to worsened prognosis in many different diseases. In this review, evidence concerning the impact of nutritional status on viral infection outcomes is discussed.At the start of the COVID-19 pandemic, mounting demand overwhelmed critical care surge capacities, triggering implementation of triage protocols to determine ventilator allocation. Relying on triage scores to ration care, while relieving clinicians from making morally distressing decisions under high situational pressure, distracts clinicians from what is essentially deeply humanistic issues entrenched in this protracted public health crisis. Such an approach will become increasingly untenable as countries flatten their epidemic curves. Decisions regarding intensive care unit admission are particularly challenging in older people, who are most likely to require critical care, but for whom benefits are most uncertain. Before applying score-based triage, physicians must first discern if older people will benefit from critical care (beneficence) and second, if he wants critical care (autonomy). When deliberating beneficence, physicians should steer away from solely using age-stratified survival probabilities from epidemiological data. Instead, decisions must be based on individualised risk-stratification that encompasses evidence-based predictors of adverse outcomes specific to older adults. Survival will also need to be weighed against burden of treatment, as well as longer term functional deficits and quality-of-life. By identifying the robust older people who may benefit from critical care, clinicians should proceed to elicit his values and preferences that would determine the treatment most aligned with his best interest. During these dialogues, physicians must truthfully convey the emergent clinical reality, discern the older person's therapeutic goals and discuss the feasibility of achieving them. Given that COVID-19 is here to stay, these conversations aimed at achieving goal-cordant care must become a new clinical norm.

Individuals with multiple myeloma (MM) often have reduced functional performance due to the cancer itself or as a direct side effect of cancer treatments. Physical therapy is a part of cancer rehabilitation; however, no guidelines are available to provide information and direction for physical therapists managing patients with MM. The goal of this guideline is to provide recommendations based on a systematic review and consensus process that physical therapists can use to manage patients with MM.

A systematic review of the literature published until August 2018 was performed in 8 databases with 2 independent reviewers assessing quality. Seventeen articles were identified as relevant, and a draft guideline was developed in the form of action statements. A total of 10 physical therapists with hematology experience and 10 patients with MM were recruited for consensus process. A priori threshold of 80% agreement was used to establish a consensus for each statement. The draft guidelines were reviewed externally by 4 methodologists using the AGREE II tool and a stakeholder representing OH (Cancer Care Ontario) Program in Evidence Based Care, McMaster University. The final guideline was reviewed and officially endorsed by the Canadian Physiotherapy Association.

A total of 30 action statements were developed that achieved consensus, indicating physical therapy recommendations based on physiological markers (ie, hemoglobin, platelet count), complete patient presentation, and the stage of medical treatment.

These clinical practice guidelines were developed to aid physical therapists in implementing evidence-based and best-practice care for patients with MM to optimize rehabilitation outcomes.

These guidelines fill an important knowledge gap and are the first to provide information specifically for physical therapist management of patients with MM.

These guidelines fill an important knowledge gap and are the first to provide information specifically for physical therapist management of patients with MM.

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