Defectos de mantenimiento del ADN mitocondrial. Mutaciones en el gen POLG. A propósito de un caso.

En el presente trabajo se expone el caso de una paciente afecta de enfermedad mitocondrial por deficiencia de la polimerasa gamma. La paciente porta las variantes patogénicas H1134R e Y831C en el gen de la ADN polimerasa gamma. Se expone también el marco teórico fisiopatológico y bioquímico que subyace a estas patologías para intentar comprender el funcionamiento de las enfermedades mitocondriales, así como su diagnóstico y tratamiento.Además, se discute el proceso diagnóstico y terapéutico de las enfermedades mitocondriales actualizando el conocimiento sobre estas patologías, a fin de aportar las últimas evidencias científicas para el diagnóstico y las posibilidades terapéuticas disponibles en la actualidad, así como las que se encuentran en estudio y desarrollo.<br /

Combined impact of traditional and non-traditional health behaviors on mortality: A national prospective cohort study in Spanish older adults

Background: Data on the combined effect of lifestyles on mortality in older people have generally been collected from highly selected populations and have been limited to traditional health behaviors. In this study, we examined the combined impact of three traditional (smoking, physical activity and diet) and three non-traditional health behaviors (sleep duration, sedentary time and social interaction) on mortality among older adults. Methods: A cohort of 3,465 individuals, representative of the Spanish population aged ≥60 years, was established in 2000/2001 and followed-up prospectively through 2011. At baseline, the following positive behaviors were selfreported: never smoking or quitting tobacco >15 years, being very or moderately physically active, having a healthy diet score ≥ median in the cohort, sleeping 7 to 8 h/d, spending <8 h/d in sitting time, and seeing friends daily. Analyses were performed with Cox regression and adjusted for the main confounders. Results: During an average nine-year follow-up, 1,244 persons died. Hazard ratios (95% confidence interval) for allcause mortality among participants with two, three, four, five and six compared to those with zero to one positive behaviors were, respectively, 0.63 (0.46 to 0.85), 0.41 (0.31 to 0.55), 0.32 (0.24 to 0.42), 0.26 (0.20 to 0.35) and 0.20 (0.15 to 0.28) (P for trend <0.001). The results were similar regardless of age, sex and health status at baseline. Those with six vs. zero to one positive health behaviors had an all-cause mortality risk equivalent to being 14 years younger. Adding the three non-traditional to the four traditional behaviors improved the model fit (likelihood ratio test, P <0.001) and the accuracy of mortality prediction (c-statistic: + 0.0031, P = 0.040). Conclusions: Adherence to some traditional and non-traditional health behaviors may substantially reduce mortality risk in older adults.This work was funded by grants from the FIS (ref. 12/1166) and the ‘Plan Nacional sobre Drogas’ (ref. 06/2010), and by the ‘Cátedra UAM de Epidemiología y Control del Riesgo Cardiovascular’. DMG had a “Juan de la Cierva” contract from the Spanish Ministry of Scienc

Physical activity, sitting time, and mortality from inflammatory diseases in older adults

Objective: The aim of this study was to examine the independent and combined associations of physical activity (PA) and sitting time (ST) with long-term mortality attributed to inflammatory causes other than cardiovascular disease (CVD) and cancer in a national cohort of older adults in Spain. Design: Prospective study. Setting and Participants: A cohort of 3,677 individuals (1,626 men) aged =60 years was followed-up during 14.3 years. Measures: At baseline, individuals reported PA and ST. The study outcome was death from inflammatory diseases when CVD or cancer mortality was excluded. This outcome was classified into infectious and non-infectious conditions. Analyses were performed with Cox regression and adjusted for PA, ST, and other main confounders (age, sex, educational level, smoking, alcohol consumption, body mass index, and chronic conditions). Results: During follow-up, 286 deaths from inflammatory diseases (77 from infectious diseases) were identified. Compared to individuals who defined themselves as inactive/less active, mortality from inflammatory diseases was lower in those who were moderately active (hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.50-0.90) or very active (HR = 0.48, 95%CI = 0.33-0.68), independently of ST. Also, being seated ≥7 h/d vs. &lt; 7 h/d was linked to higher mortality (HR = 1.38, 95%CI = 1.02-1.87). The largest risk of mortality was observed in inactive/less active individuals with ST≥7 h/d (HR = 2.29, 95%CI = 1.59-3.29) compared to those with moderate/very PA and ST &lt; 7 h/d. Low PA and high ST were consistently associated with a higher risk of mortality from non-infectious inflammatory causes. Associations of PA and ST with mortality from infectious inflammatory causes showed a similar trend, but most of them did not reach statistical significance. Conclusions: Low PA and high ST were independently associated with higher mortality from inflammatory diseases other than CVD or cancer in older adults. Interventions addressing simultaneously both behaviors could have greater benefits than those focusing on only one of themThis work was supported by FIS grant 16/609 (Instituto de Salud Carlos III, State Secretary of R+D+I and FEDER/FSE), MINECO R+D+I grant (DEP2013-47786-R), MECD mobility grant (JC2015-00080), the FRAILOMIC Initiative (European Union FP7-HEALTH-2012-Proposal No. 305483-2), and the ATHLOS project (European project H2020- Project ID: 635316

Physical Activity, Sitting Time, and Mortality From Inflammatory Diseases in Older Adults

Objective: The aim of this study was to examine the independent and combined associations of physical activity (PA) and sitting time (ST) with long-term mortality attributed to inflammatory causes other than cardiovascular disease (CVD) and cancer in a national cohort of older adults in Spain.Design: Prospective study.Setting and Participants: A cohort of 3,677 individuals (1,626 men) aged ≥60 years was followed-up during 14.3 years.Measures: At baseline, individuals reported PA and ST. The study outcome was death from inflammatory diseases when CVD or cancer mortality was excluded. This outcome was classified into infectious and non-infectious conditions. Analyses were performed with Cox regression and adjusted for PA, ST, and other main confounders (age, sex, educational level, smoking, alcohol consumption, body mass index, and chronic conditions).Results: During follow-up, 286 deaths from inflammatory diseases (77 from infectious diseases) were identified. Compared to individuals who defined themselves as inactive/less active, mortality from inflammatory diseases was lower in those who were moderately active (hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.50–0.90) or very active (HR = 0.48, 95%CI = 0.33–0.68), independently of ST. Also, being seated ≥7 h/d vs. &lt;7 h/d was linked to higher mortality (HR = 1.38, 95%CI = 1.02–1.87). The largest risk of mortality was observed in inactive/less active individuals with ST≥7 h/d (HR = 2.29, 95%CI = 1.59–3.29) compared to those with moderate/very PA and ST &lt;7 h/d. Low PA and high ST were consistently associated with a higher risk of mortality from non-infectious inflammatory causes. Associations of PA and ST with mortality from infectious inflammatory causes showed a similar trend, but most of them did not reach statistical significance.Conclusions: Low PA and high ST were independently associated with higher mortality from inflammatory diseases other than CVD or cancer in older adults. Interventions addressing simultaneously both behaviors could have greater benefits than those focusing on only one of them

Sub-micro- and nano-sized polyethylene terephthalate deconstruction with engineered protein nanopores

The identification or design of biocatalysts to mitigate the accumulation of plastics, including sub-micro- and nano-sized polyethylene terephthalate (nPET), is becoming a global challenge. Here we computationally incorporated two hydrolytic active sites with geometries similar to that of Idionella sakaiensis PET hydrolase, to fragaceatoxin C (FraC), a membrane pore-forming protein. FraCm1/m2 could be assembled into octameric nanopores (7.0 nm high × 1.6–6.0 nm entry), which deconstructed (40 °C, pH 7.0) nPET from GoodFellow, commodities and plastic bottles. FraCm1 and FraCm2 degrade nPET by endo- and exo-type chain scission. While FraCm1 produces bis(2-hydroxyethyl) terephthalate as the main product, FraCm2 yields a high diversity of oligomers and terephthalic acid. Mechanistic and biochemical differences with benchmark PET hydrolases, along with pore and nPET dynamics, suggest that these pore-forming protein catalytic nanoreactors do not deconstruct macro-PET but are promising in nanotechnology for filtering, capturing and breaking down nPET, for example, in wastewater treatment plants. [Figure not available: see fulltext.]. © 2023, The Author(s).This study was conducted under the auspices of the FuturEnzyme Project funded by the European Union’s Horizon 2020 Research and Innovation Programme under the auspices of the FuturEnzyme Project (grant agreement no. 101000327) and the PlasticsFatE project (grant agreement no. 95921), and Horizon Europe Research and Innovation Programme under grant agreement no. GA101060625 (Nymphe project). We also acknowledge financial support under grants PID2020-112758RB-I00 (M.F.), PDC2021-121534-I00 (M.F.), TED2021-130544B-I00 (M.F.), PID2019-106370RB-I00 (V.G.) and PID2019-105838RB-C31 (F.J.P.) from the Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación (AEI) (Digital Object Identifier MCIN/AEI/10.13039/501100011033), Fondo Europeo de Desarrollo Regional (ERDF) A way of making Europe and the European Union NextGenerationEU/PRTR, UCM-Banco Santander Grants PR87/19-22556 and PR108/20-26896 and UnaEuropa (Unano) SF2106 (to A.M.P.). S.G.-L. was supported by a Real Colegio Complutense Postdoctoral Fellowship for Distinguished Junior Scholars. S.R. thanks the Spanish Ministry of Science and Innovation for a PhD fellowship (FPU19/00608). D.H.-M. thanks Complutense University of Madrid and Banco Santander for a PhD fellowship (CT82/20/CT83/20). A.R.-M. thanks the Spanish Ministry of Science and Innovation for a PhD fellowship (PRE2020-091825) and the project PID2019-106370RB-I00. We thank M. J. Vicente for the ESI–MS analysis, performed at the Servicio Interdepartamental de Investigación (SIDI) from the Autonomous University of Madrid, Spain.Supplementary dataPeer reviewe

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)

From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions

Correction: Combined Impact of Traditional and Non-Traditional Healthy Behaviors on Health-Related Quality of Life: A Prospective Study in Older Adults.

[This corrects the article DOI: 10.1371/journal.pone.0170513.]