Harmonisation and Between-Country Differences of the Lifetime of Experiences Questionnaire in Older Adults

Background: The Lifetime of Experiences Questionnaire (LEQ) assesses complex mental activity across the life-course and has been associated with brain and cognitive health. The different education systems and occupation classifications across countries represent a challenge for international comparisons. The objectives of this study were four-fold: to adapt and harmonise the LEQ across four European countries, assess its validity across countries, explore its association with brain and cognition and begin to investigate between-country differences in life-course mental activities. Method: The LEQ was administered to 359 cognitively unimpaired older adults (mean age and education: 71.2, 13.2 years) from IMAP and EU-funded Medit-Ageing projects. Education systems, classification of occupations and scoring guidelines were adapted to allow comparisons between France, Germany, Spain and United Kingdom. We assessed the LEQ's (i) concurrent validity with a similar instrument (cognitive activities questionnaire - CAQ) and its structural validity by testing the factors' structure across countries, (ii) we investigated its association with cognition and neuroimaging, and (iii) compared its scores between countries. Results: The LEQ showed moderate to strong positive associations with the CAQ and revealed a stable multidimensional structure across countries that was similar to the original LEQ. The LEQ was positively associated with global cognition. Between-country differences were observed in leisure activities across the life-course. Conclusions: The LEQ is a promising tool for assessing the multidimensional construct of cognitive reserve and can be used to measure socio-behavioural determinants of cognitive reserve in older adults across countries. Longitudinal studies are warranted to test further its clinical utility

Wiring of Photosystem II to Hydrogenase for Photoelectrochemical Water Splitting.

In natural photosynthesis, light is used for the production of chemical energy carriers to fuel biological activity. The re-engineering of natural photosynthetic pathways can provide inspiration for sustainable fuel production and insights for understanding the process itself. Here, we employ a semiartificial approach to study photobiological water splitting via a pathway unavailable to nature: the direct coupling of the water oxidation enzyme, photosystem II, to the H2 evolving enzyme, hydrogenase. Essential to this approach is the integration of the isolated enzymes into the artificial circuit of a photoelectrochemical cell. We therefore developed a tailor-made hierarchically structured indium-tin oxide electrode that gives rise to the excellent integration of both photosystem II and hydrogenase for performing the anodic and cathodic half-reactions, respectively. When connected together with the aid of an applied bias, the semiartificial cell demonstrated quantitative electron flow from photosystem II to the hydrogenase with the production of H2 and O2 being in the expected two-to-one ratio and a light-to-hydrogen conversion efficiency of 5.4% under low-intensity red-light irradiation. We thereby demonstrate efficient light-driven water splitting using a pathway inaccessible to biology and report on a widely applicable in vitro platform for the controlled coupling of enzymatic redox processes to meaningfully study photocatalytic reactions.This work was supported by the U.K. Engineering and Physical Sciences Research Council (EP/H00338X/2 to E.R. and EP/G037221/1, nanoDTC, to D.M.), the UK Biology and Biotechnological Sciences Research Council (BB/K002627/1 to A.W.R. and BB/K010220/1 to E.R.), a Marie Curie Intra-European Fellowship (PIEF-GA-2013-625034 to C.Y.L), a Marie Curie International Incoming Fellowship (PIIF-GA-2012-328085 RPSII to J.J.Z) and the CEA and the CNRS (to J.C.F.C.). A.W.R. holds a Wolfson Merit Award from the Royal Society.This is the final version of the article. It first appeared from ACS Publications via http://dx.doi.org/10.1021/jacs.5b0373

Enhanced oxygen-tolerance of the full heterotrimeric membrane-bound [NiFe]-hydrogenase of ralstonia eutropha.

Hydrogenases are oxygen-sensitive enzymes that catalyze the conversion between protons and hydrogen. Water-soluble subcomplexes of membrane-bound [NiFe]-hydrogenases (MBH) have been extensively studied for applications in hydrogen-oxygen fuel cells as they are relatively tolerant to oxygen, although even these catalysts are still inactivated in oxidative conditions. Here, the full heterotrimeric MBH of Ralstonia eutropha, including the membrane-integral cytochrome b subunit, was investigated electrochemically using electrodes modified with planar tethered bilayer lipid membranes (tBLM). Cyclic voltammetry and chronoamperometry experiments show that MBH, in equilibrium with the quinone pool in the tBLM, does not anaerobically inactivate under oxidative redox conditions. In aerobic environments, the MBH is reversibly inactivated by O2, but reactivation was found to be fast even under oxidative redox conditions. This enhanced resistance to inactivation is ascribed to the oligomeric state of MBH in the lipid membrane

Dynamic electrochemical investigations of hydrogen oxidation and production by enzymes and implications for future technology.

This tutorial review describes studies of hydrogen production and oxidation by biological catalysts--metalloenzymes known as hydrogenases--attached to electrodes. It explains how the electrocatalytic properties of hydrogenases are studied using specialised electrochemical techniques and how the data are interpreted to allow assessments of catalytic rates and performance under different conditions, including the presence of O2, CO and H2S. It concludes by drawing some comparisons between the enzyme active sites and platinum catalysts and describing some novel proof-of-concept applications that demonstrate the high activities and selectivities of these 'alternative' catalysts for promoting H2 as a fuel

Association and progression of multi-morbidity with Chronic Kidney Disease stage 3a secondary to Type 2 Diabetes Mellitus, grouped by albuminuria status in the multi-ethnic population of Northwest London: A real-world study.

IntroductionThe prevalence of Diabetic Kidney Disease (DKD) secondary to Type 2 Diabetes Mellitus (T2DM) is rising worldwide. However, real-world data linking glomerular function and albuminuria to the degree of multi-morbidity is lacking. We thus utilised the Discover dataset, to determine this association.MethodPatients with T2DM diagnosed prior to 1st January 2015 with no available biochemical evidence of CKD were included. Patients subsequently diagnosed and coded for CKD3a in 2015, were grouped by the degree of albuminuria. Baseline and 5-year co-morbidity was determined, as were prescribing practices with regards to prognostically beneficial medication.ResultsWe identified 56,261 patients with T2DM, of which 1082 had CKD stage 3a diagnosed in 2015 (224-CKD3aA1,154-CKD3aA2,93-CKD3aA1; 611 patients with CKD3a but no uACR available in 2015 were excluded from follow up). No statistically significant difference was observed in the degree of co-morbidities at baseline. A significant difference in the degree of hypertension, retinopathy, ischaemic heart disease and vascular disease from baseline compared to study end point was observed for all 3 study groups. Comparing co-morbidities developed at study end point, highlighted a statistical difference between CKD3aA1 Vs CKD3aA3 for retinopathy alone and for hypertension and heart failure between CKD3aA2 Vs CKD3aA3. 40.8% of patients with CKD3aA2 or A3 were prescribed Renin Angiotensin Aldosterone inhibitors (RAASi) therapy between June-December 2021. Survival analysis showed 15% of patients with CKD3aA3 developed CKD stage 5 within 5 years of diagnosis.DiscussionCKD3a secondary to DKD is associated with significant multimorbidity at baseline and 5 years post diagnosis, with CKD3aA3 most strongly associated with CKD progression to CKD 5, heart failure, hypertension and retinopathy compared to CKD3aA1 or CKD3aA2 at 5 years post diagnosis. The lack of uACR testing upon diagnosis and poor prescribing of RAASi, in those with CKD3aA2/A3, raises significant cause for concern.ConclusionDKD is associated with significant multimorbidity. Significant work is needed to be done to ensure patients undergo testing for uACR, to allow for future risk stratification and ability to be started on prognostically beneficial medication

How oxygen attacks [FeFe] hydrogenases from photosynthetic organisms

Green algae such as Chlamydomonas reinhardtii synthesize an [FeFe] hydrogenase that is highly active in hydrogen evolution. However, the extreme sensitivity of [FeFe] hydrogenases to oxygen presents a major challenge for exploiting these organisms to achieve sustainable photosynthetic hydrogen production. In this study, the mechanism of oxygen inactivation of the [FeFe] hydrogenase CrHydA1 from C. reinhardtii has been investigated. X-ray absorption spectroscopy shows that reaction with oxygen results in destruction of the [4Fe-4S] domain of the active site H-cluster while leaving the di-iron domain (2FeH) essentially intact. By protein film electrochemistry we were able to determine the order of events leading up to this destruction. Carbon monoxide, a competitive inhibitor of CrHydA1 which binds to an Fe atom of the 2FeH domain and is otherwise not known to attack FeS clusters in proteins, reacts nearly two orders of magnitude faster than oxygen and protects the enzyme against oxygen damage. These results therefore show that destruction of the [4Fe-4S] cluster is initiated by binding and reduction of oxygen at the di-iron domain—a key step that is blocked by carbon monoxide. The relatively slow attack by oxygen compared to carbon monoxide suggests that a very high level of discrimination can be achieved by subtle factors such as electronic effects (specific orbital overlap requirements) and steric constraints at the active site

Vitamin D and COVID-19 Severity in Hospitalized Older Patients: Potential Benefit of Prehospital Vitamin D Supplementation

International audienceStudies involving the associations between vitamin D supplementation taken before the onset of COVID-19 infection and the clinical outcomes are still scarce and this issue remains controversial. This study aimed to assess the relationships between vitamin D (VitD) status and supplementation and coronavirus disease 2019 (COVID-19) severity in older adults (average age of 78 years) hospitalized for COVID-19. We conducted an observational retrospective cohort study with 228 older hospitalized patients during the first wave of the COVID-19 pandemic. The outcomes were in-hospital mortality secondary to COVID-19 or critically severe COVID-19. A logistic regression analysis was conducted to test whether pre-hospital VitD supplementation was independently associated with severity. In this study, 46% of patients developed a severe form and the overall in-hospital mortality was 15%. Sixty-six (29%) patients received a VitD supplement during the 3 months preceding the infection onset. Additionally, a VitD supplement was associated with fewer severe COVID-19 forms (OR = 0.426, p = 0.0135) and intensive care unit (ICU) admissions (OR = 0.341, p = 0.0076). As expected, age > 70 years, male gender and BMI ≥ 35 kg/m(2) were independent risk factors for severe forms of COVID-19. No relationship between serum 25(OH)D levels and the severity of the COVID-19 was identified. VitD supplementation taken during the 3 months preceding the infection onset may have a protective effect on the development of severe COVID-19 forms in older adults. Randomized controlled trials and large-scale cohort studies are necessary to strengthen this observation

Photosynthetic Hydrogen Production by a Hybrid Complex of Photosystem I and [NiFe]-Hydrogenase

Krassen H, Schwarze A, Friedrich B, Ataka K, Lenz O, Heberle J. Photosynthetic Hydrogen Production by a Hybrid Complex of Photosystem I and [NiFe]-Hydrogenase. ACS NANO. 2009;3(12):4055-4061.Nature provides key components for generating fuels from renewable resources in the form of enzymatic nanomachines which catalyze crucial steps in biological energy conversion, for example, the photosynthetic apparatus, which transforms solar power into chemical energy, and hydrogenases, capable of generating molecular hydrogen. As sunlight is usually used to synthesize carbohydrates, direct generation of hydrogen from light represents an exception in nature. On the molecular level, the crucial step for conversion of solar energy into H-2 lies in the efficient electronic coupling of photosystem I and hydrogenase. Here we show the stepwise assembly of a hybrid complex consisting of photosystem I and hydrogenase on a solid gold surface. This device gave rise to light-induced H-2 evolution. Hydrogen production is possible at far higher potential and thus lower energy compared to those of previously described (bio)nanoelectronic devices that did not employ the photosynthesis apparatus. The successful demonstration of efficient solar-to-hydrogen conversion may serve as a blueprint for the establishment of this system in a living organism with the paramount advantage of self-replication