Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses

peer reviewedContext: Sarcopenia is a progressive and generalized skeletal muscle disorder associated with an increased risk of adverse outcomes such as falls, disability, and death. The Belgian Society of Gerontology and Geriatrics has developed evidencebased guidelines for the prevention and treatment of sarcopenia. This umbrella review presents the results of the Working Group on Nutritional Interventions. Objective: The aim of this umbrella review was to provide an evidence-based overview of nutritional interventions targeting sarcopenia or at least 1 of the 3 sarcopenia criteria (ie, muscle mass, muscle strength, or physical performance) in persons aged 65 years. Data sources: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the PubMed and Web of Science databases were searched for systematic reviews and meta-analyses reporting the effect of nutritional supplementation on sarcopenia or muscle mass, strength, or physical performance. Data extraction: Two authors extracted data on the key characteristics of the reviews, including participants, treatment, and outcomes. Methodological quality of the reviews was assessed using the product A Measurement Tool to Assess Systematic Reviews. Three authors synthesized the extracted data and generated recommendations on the basis of an overall synthesis of the effects of each intervention. Quality of evidence was rated with the Grading of Recommendations Assessment, Development and Evaluation approach. Data analysis: A total of 15 systematic reviews were included. The following supplements were examined: proteins, essential amino acids, leucine, b-hydroxy-b-methylbutyrate, creatine, and multinutrient supplementation (with or without physical exercise). Because of both the low amount and the low to moderate quality of the reviews, the level of evidence supporting most recommendations was low to moderate. Conclusions: Best evidence is available to recommend leucine, because it has a significant effect on muscle mass in elderly people with sarcopenia. Protein supplementation on top of resistance training is recommended to increase muscle mass and strength, in particular for obese persons and for >=24weeks. Effects on sarcopenia as a construct were not reported in the included reviews

T Cells Recognizing a Peptide Contaminant Undetectable by Mass Spectrometry

Synthetic peptides are widely used in immunological research as epitopes to stimulate their cognate T cells. These preparations are never completely pure, but trace contaminants are commonly revealed by mass spectrometry quality controls. In an effort to characterize novel major histocompatibility complex (MHC) Class I-restricted β-cell epitopes in non-obese diabetic (NOD) mice, we identified islet-infiltrating CD8+ T cells recognizing a contaminating peptide. The amount of this contaminant was so small to be undetectable by direct mass spectrometry. Only after concentration by liquid chromatography, we observed a mass peak corresponding to an immunodominant islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)206-214 epitope described in the literature. Generation of CD8+ T-cell clones recognizing IGRP206-214 using a novel method confirmed the identity of the contaminant, further underlining the immunodominance of IGRP206-214. If left undetected, minute impurities in synthetic peptide preparations may thus give spurious results

Statins: Could an old friend help the fight against COVID-19?

This is the peer reviewed version of the following article: "Statins: Could an old friend help the fight against COVID-19?" . British Journal of Pharmacology (2020): 19 June, which has been published in final form at https://doi.org/10.1111/bph.15166. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versionshe COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasomes, could limit the "cytokine storm" in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID-19 outcomesThis work and data discussed here were supported by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119 and Red de Investigación Renal (REDINREN): RD16/0009, to M.R-O, PI17/01495 to J.E, PI18/01133 to AMR, PI19/00815 to A.O); Comunidad de Madrid (“NOVELREN” B2017/BMD3751 to M.R-O, B2017/BMD-3686 CIFRA2-CM to A.O); Spanish Ministry of Economy and Competitiveness MINECO (DTS17/00203, DTS19/00093) to J,E; “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R-O and SR-M); ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071) and DTS18/00032 to A.O; The “Sara Borrell” postdoctoral training program of the ISCIII supported the salary of SR-M (CD19/00021), IMPROVE-PD project (“Identification and Management of Patients at Risk–Outcome and Vascular Events in Peritoneal Dialysis”) funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 812699 to M.R.O

Falsification of biotechnology drugs: current dangers and/or future disasters?

Falsified medical products have become a global threat since they were first mentioned to the general public at the conference of experts on the rational use of drugs organized by the world health organization (WHO) in 1985. Today, official estimates of the annual death toll due to falsified medical products range between two hundred thousand and one million. Although the extent of this global problem is the most significant in the developing world, an increasing number of reports have demonstrated the presence of a substantial (black) market for falsified medical products in the developed world. In recent years, also biotechnology drugs (synthetic peptide drugs and protein drugs) have been reported to be prone for falsifications. Next to the traditional doping related substances and image-enhancing polypeptides (e.g., human growth hormone, melanotan II) also essential medicines such as insulin, oxytocin and monoclonal antibodies have been falsified. The danger regarding the use of these falsified polypeptide drugs lies in the fact that end-users have no guarantee of the safety and efficacy of these preparations. Multiple reports have namely described the presence of the wrong active pharmaceutical ingredient (API), the wrong dosage or the absence of the API. Additionally, adverse health effects have been reported in the past due to toxic contaminations and product or process related impurities. Moreover, also unauthorized polypeptides or polypeptides which failed clinical trials or are still subject of clinical or pre-clinical assessments have been found in seizures of regulatory agencies. It stands to reason that regulatory agencies and analytical laboratories handling falsified biotechnology drugs have stepped up efforts to counter these grievous practices. The analysis of these falsified polypeptides and putative impurities is however not always straightforward. Often (bio)analytical laboratories have to resort to a combination of electrophoretic techniques, immunological assays and mass spectrometry based approaches to merely identify the content of seized samples. In addition, the difference in size (peptide vs proteins vs monoclonal antibodies), complexity (e.g., isoforms, glycosylations) and different synthesis techniques (chemical synthesis, recombinant expression, native protein isolation) result in a wide range of putative health risks. This review therefore aims to provide a brief overview of the genuine biotherapeutics present on the market and their quality prerequisites. Next, we describe the identification strategy utilised by our lab to identify the API in falsified biotherapeutics, followed by a discussion of the putative hazards due to impurities and contaminations that were found or could be encountered in falsified biotherapeutics. Finally, we terminate with an educational prediction of what may happen in the future and possible ways to counteract putative future&nbsp;disasters.</p