Does Resistance Training Reduce Falls and Improve Quality of Life in People with Parkinson’s Disease using Strength Training Exercise Programmes?

Background: Parkinson’s Disease (PD) is the second most common neurodegenerative disorder behind Alzheimer’s, affecting around 1% of the population over 50 years old. PD is associated with inhibited motor functions including tremors, muscle rigidity, impaired posture, bradykinesia (slowed movement) and loss of balance. Physical activity is thought to be one of the most important non-pharmacological strategies to target and improve the management of motor symptoms of PD. Objective: To identify the effect of Strength Training (ST) on Falls and Quality of Life (QOL) on people suffering with PD. Method: A systematic search of AMED, Cinahl, Cinhal Plus, CSP Online Library Catalogue, Medline and SportDiscus was conducted; articles were searched until November 2018. Results: Eleven studies were included in this review, with a total of 549 participants of which 539 had a confirmed diagnosis of PD, 10 did not. All eleven included studies were randomised control trials. The training volume including repetitions, sets, frequency and intensity varied between all studies. Interventions showed positive trends in reducing the proportion of fallers and improving QOL Scores. Conclusion: There is some evidence to show that ST is effective at improving strength in People with Parkinson’s Disease (PwPD) and has some passover effects in reducing falls and improving QOL. Future research is required to determine if optimum guideline training volumes for PwPD better support the secondary effects on falls and QOL

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Concesión de viático a fray Buenaventura Malaquías, fray Guillermo Siredan y fray Bernardino Cornelio, religiosos de la orden de San Francisco, para ir a la Misión de Irlanda

Fecha del documento: 1640-11-21. 3 páginasAndrés de Rozas al secretario Juan de Otalora sobre la resolución regia de conceder a fray Buenaventura Malaquías, fray Guillermo Siredan y fray Bernardino Cornelio, religiosos de la orden de San Francisco, un viático de 100 ducados a cada uno para ir a la Misión de Irlanda. Acudan de Antonio de Campo Redondo. Orden del Antonio de Campo Redondo al secretario Juan García Dávila Muñoz para que haga la cédula para que el tesorero general Pedro Baza de Herrera libre el dinero del arca de las tres llaves y pueda entregarlo a don Alonso Pérez de Guzmán, patriarca de Indias. Hecha la cédula.Proyecto Proyección Política y Social de la Comunidad Irlandesa en la Monarquía hispánica y en la América Colonial de la Edad Moderna(siglos XVI-XVIII) (HAR2009-11339 - subprograma HIST) del Ministerio de Economía y Competitividad en colaboración con el Consejo Superior de Investigaciones Científicas (CSIC), Embajada de Irlanda en Madrid, National University of Ireland (NUI) Maynooth, University College Dublin y Trinity College DublinAndrés de Rozas, secretario del Consejo de EstadoJuan de Otalora, secretario del Consejo de HaciendaOrden de San FranciscoSí300 ducados (100x3)NoN

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease