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The maintenance of protein homeostasis (proteostasis) is a fundamental aspect of cell physiology that is essential for the survival of organisms under a variety of environmental and/or intracellular stress conditions. Acute and/or persistent stress exceeding the capacity of the intracellular homeostatic systems results in protein aggregation and/or damaged organelles that leads to pathological cellular states often resulting in cell death. These events are continuously suppressed by a complex macromolecular...
Protein homeostasis (proteostasis) is an essential pillar for correct cellular function. Impairments in proteostasis are encountered both in aging and in several human disease conditions. Molecular chaperones are important players for proteostasis; in particular, heat shock protein 70 (Hsp70) has an essential role in protein folding, disaggregation, and degradation. We have recently proposed a model for Hsp70 functioning as a "multiple socket". In the model, Hsp70 provides a physical platform for the bindin...
While numerous tools are available to better incorporate equity into population health actions, they are limited mainly by their lack of adaptation to professional practices and organizational realities. A study was conducted in Québec to identify and understand, from the perspective of future users, conditions that would facilitate use of a tool (Reflex-ISS) targeted at supporting collaborative action to improve consideration of social inequalities in health (SIH) within population health actions. Concept...
Dextropropoxyphene (DXP), a step 2 analgesic commonly prescribed in France, was withdrawn from the French market in 2011 following a European decision due to its poor risk-benefit ratio. The purpose of this study was to explore the perceptions of French general practitioners (GPs) and patients regarding DXP withdrawal.
This article proposes an update and summary of current knowledge in the management of alcohol withdrawal, based on a review of recent literature. The issues open to debate and the areas whith new developments will be addressed, such as: the entry into treatment, the withdrawal setting, the withdrawal medications, the various possible protocols and the introduction of relapse prevention treatments.
Maintaining protein homeostasis (proteostasis) is essential for a functional proteome. A wide range of extrinsic and intrinsic factors perturb proteostasis, causing protein misfolding, misassembly and aggregation. This compromises cellular integrity and leads to aging and disease, including neurodegeneration and cancer. At the cellular level, protein aggregation is counteracted by powerful mechanisms comprising of a cascade of enzymes and chaperones that operate in a coordinated multistep manner to sense, p...
Benzodiazepine-resistant alcohol withdrawal (RAW), defined by a requirement of ≥ 40 mg of diazepam in 1 h, represents a severe form of withdrawal without predictive parameters. This study was designed to identify risk factors associated with RAW versus withdrawal without benzodiazepine resistance (nRAW).
In the last decade numerous publications highlighted the connection between metabolism and epigenetics in different physiological and pathological conditions. The availability of metabolites for cells represents indeed a crucial factor, which is able to condition cell fate and development, differentiation and proliferation partially trough epigenetic control. This tight link provides novel therapeutic possibilities to treat many pathological conditions induced by epigenetic alterations, by manipulating meta...
Rates of participation in physical activity are often not the same between groups in a given demographic category. These differences have been termed 'inequities,' and major health organizations are advocating large-scale initiatives to create 'equity' in physical activity. The aim of this paper is to explain why equity in physical activity is a misguided goal. Equity is a misguided goal because it ignores absolute rates of physical activity (i.e., it is a metric of how one group compares with another), and...
High altitude associated hypobaric hypoxia is one of the cellular and environmental perturbation that alters proteostasis network and push the healthy cell towards loss of muscle mass. The present study has elucidated the robust proteostasis network and signaling mechanism for skeletal muscle atrophy under chronic hypobaric hypoxia (CHH).
Occupational therapists value the principles of health and health care equity and often face challenges addressing inequities within the systems in which they work.
We explored the definition of health equity being used by public health departments and the extent of engagement of public health departments in activities to improve health equity, as well as facilitators and barriers to this work.
Pharmacologic therapies for management of heroin withdrawal have been studied and reviewed widely. Opium dependence is generally associated with less severe dependence and milder withdrawal symptoms than heroin. The evidence on withdrawal management of heroin might therefore not be exactly applicable for opium.
The objective of the current study was to determine the effects of market type (super market - SM, indoor market - IM, open market - OM) and sampling time (at the opening - T0 and 4 h after the opening - T4) on antioxidant capacity, lipid oxidation, and descriptive sensory attributes of beef in Vietnam. Values of FC and TEAC were greater in OM beef than IM and SM (P
In 2010, Congress created an abbreviated application pathway for biosimilars, versions of approved biologics made by different manufacturers. However, as of November 1, 2018, the Food and Drug Administration had approved only 13 biosimilars under this pathway, of which just 6 were available for patients to use. We review the history of US regulation of biologics and identify manufacturing, regulatory, and marketing issues that have limited biosimilar market entry and uptake, concluding with recommendations ...
Population health approaches are visible among multidisciplinary methods used in urban design and planning, but attention to health equity is not always an explicit focus. Population and Public Health-Saskatoon Health Region recognized the need for frameworks to prioritize, integrate and measure health equity within local built environments.
Although aging-regulating pathways were discovered a few decades ago, it is not entirely clear how their activities are orchestrated, to govern lifespan and proteostasis at the organismal level. Here we utilized the nematode to examine whether the alteration of aging, by reducing the activity of the Insulin/IGF signaling (IIS) cascade, affects protein SUMOylation. We found that IIS activity promotes the SUMOylation of the germline protein, CAR-1, thereby shortening lifespan and impairing proteostasis. In c...
Cellular protein homeostasis (proteostasis) is maintained by a broad network of proteins involved in synthesis, folding, triage, repair and degradation. Chief among these are molecular chaperones and their cofactors that act as powerful protein remodelers. The growing realization that many human pathologies are fundamentally diseases of protein misfolding (proteopathies) has generated interest in understanding how the proteostasis network impacts onset and progression of these diseases. In this minireview, ...
Several fluoroquinolone antibiotics have been associated with cardiac adverse effects, leading to the withdrawal of some of these agents from the market. Cardiac side effects such as QT prolongation and torsades de pointes (TdP) have also been observed with fluoroquinolones currently on the market. In order to evaluate the cardiac risk of fluoroquinolones as a class, and the comparative risk for each individual drug, we conducted a systematic review, meta-analysis, and network meta-analysis.
The fat-tail financial data and cyclical financial market makes it difficult for the fixed structure model based on Gaussian distribution to characterize the dynamics of corporate bonds spreads. Using a flexible structure model based on generalized error distribution, this paper focuses on the impact of macro-level factors on the spreads of corporate bonds in China. It is found that in China's corporate bonds market, macroeconomic conditions have obvious structural transformational effects on bonds spreads,...
Maintaining protein homeostasis (proteostasis) is essential for cellular health and is governed by a network of quality control machinery comprising over 800 genes. When proteostasis becomes imbalanced, proteins can abnormally aggregate or become mislocalized. Inappropriate protein aggregation and proteostasis imbalance are two of the central pathological features of common neurodegenerative diseases including Alzheimer, Parkinson, Huntington, and motor neuron diseases. How aggregation contributes to the pa...
Heat-shock factor 1 (HSF1) is the master transcription factor that regulates the response to proteotoxic stress by controlling the transcription of many stress-responsive genes including the heat-shock proteins. Here, we show a novel molecular mechanism controlling the activation of HSF1. We demonstrate that transglutaminase type 2 (TG2), dependent on its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1 regulating adaptation to stress and proteostasis impairment. In p...