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

Management of Hypertension in Patients With Diabetic Kidney Disease: Summary of the Joint Association of British Clinical Diabetologists and UK Kidney Association (ABCD-UKKA) Guideline 2021.

Diabetic kidney disease (DKD) accounts for >40% cases of chronic kidney disease (CKD) globally. Hypertension is a major risk factor for progression of DKD and the high incidence of cardiovascular disease and mortality in these people. Meticulous management of hypertension is therefore crucial to slow down the progression of DKD and reduce cardiovascular risk. Randomized controlled trial evidence differs in type 1 and type 2 diabetes and in different stages of DKD in terms of target blood pressure (BP). Renin-angiotensin blocking agents reduce progression of DKD and cardiovascular events in both type 1 and type 2 diabetes, albeit differently according to the stage of CKD. There is emerging evidence for the benefit of sodium glucose cotransporter 2, nonsteroidal selective mineralocorticoid antagonists, and endothelin-A receptor antagonists in slowing progression and reducing cardiovascular events in DKD. This UK guideline, developed jointly by diabetologists and nephrologists, has reviewed all available current evidence regarding the management of hypertension in DKD to produce a set of comprehensive individualized recommendations for BP control and the use of antihypertensive agents according to age, type of diabetes, and stage of CKD (https://ukkidney.org/sites/renal.org/files/Management-of-hypertension-and-RAAS-blockade-in-adults-with-DKD.pdf). A succinct summary of the guideline, including an infographic, is presented here

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

Electrochemical investigations of H2-producing enzymes

Hydrogenases are a family of enzyme that catalyses the bidirectional interconversion of H+ and H2. There are two major classes of hydrogenases: the [NiFe(Se)]- and [FeFe]-hydrogenases. Both of these benefit from characteristics which would be advantageous to their use in technological devices for H2 evolution and the generation of energy. These features are explored in detail in this thesis, with a particular emphasis placed on defining the conditions that limit the activity of hydrogenases when reducing H+ to produce H2. Electrochemistry can be used as a direct measure of enzymatic activity; thus, Protein Film Electrochemistry, in which the protein is adsorbed directly onto the electrode, has been employed to probe catalysis by hydrogenases. Various characteristics of hydrogenases were probed. The catalytic bias for H2 production was interrogated and the inhibition of H2 evolution by H2 itself (a major drawback to the use of some hydrogenases in technological devices to produce H2) was quantified for a number of different hydrogenase. Aerobic inactivation of hydrogenases is also a substantial technological limitation; thus, inactivation of both H2 production and H2 oxidation by O2 was studied in detail. This was compared to inhibition of hydrogenases by CO so as to elucidate the mechanism of binding of diatomic molecules and determine the factors limiting inactivation. This allows for a preliminary proposal for the genetic redesigning of hydrogenases for biotechnological purposes to be made. Finally, preliminary investigation of the binding of formaldehyde, potentially at a site integral to proton transfer, opens the field for further research into proton transfer pathways, the structural implications thereof and their importance in catalysis.</p

Understanding GRADE: an introduction.

OBJECTIVE: Grading of recommendations, assessment, development, and evaluations (GRADE) is arguably the most widely used method for appraising studies to be included in systematic reviews and guidelines. In order to use the GRADE system or know how to interpret it when reading reviews, reading several articles and attending a workshop are required. Moreover, the GRADE system is not covered in standard medical textbooks. Here, we explain GRADE concisely with the use of examples so that students and other researchers can understand it. BACKGROUND: In order to use or interpret the GRADE system, reading several articles and attending a workshop is currently required. Moreover, the GRADE system is not covered in standard medical textbooks. METHODS: We read, synthesized, and digested the GRADE publications and contacted GRADE contributors for explanations where required. We composed a digested version of the system in a concise way a general medical audience could understand. RESULTS: We were able to explain the GRADE basics clearly and completely in under 1500 words. CONCLUSIONS: While advanced critical appraisal requires judgment, training, and practice, it is possible for a non-specialist to grasp GRADE basics very quickly

The difference a Se makes? Oxygen-tolerant hydrogen production by the [NiFeSe]-hydrogenase from Desulfomicrobium baculatum.

Protein film voltammetry studies of the [NiFeSe]-hydrogenase from Desulfomicrobium baculatum show it to be a highly efficient H2 cycling catalyst. In the presence of 100% H2, the ratio of H2 production to H2 oxidation activity is higher than for any conventional [NiFe]-hydrogenases (lacking a selenocysteine ligand) that have been investigated to date. Although traces of O2 (&lt;&lt; 1%) rapidly and completely remove H2 oxidation activity, the enzyme sustains partial activity for H2 production even in the presence of 1% O2 in the atmosphere. That H2 production should be partly allowed, whereas H2 oxidation is not, is explained because the inactive product of O2 attack is reductively reactivated very rapidly, but this requires a potential that is almost as negative as the thermodynamic potential for the 2H(+)/H2 couple. The study provides further encouragement and clues regarding the feasibility of microbial/enzymatic H2 production free from restrictions of anaerobicity

Electrochemical kinetic investigations of the reactions of [FeFe]-hydrogenases with carbon monoxide and oxygen: comparing the importance of gas tunnels and active-site electronic/redox effects.

A major obstacle for future biohydrogen production is the oxygen sensitivity of [FeFe]-hydrogenases, the highly active catalysts produced by bacteria and green algae. The reactions of three representative [FeFe]-hydrogenases with O(2) have been studied by protein film electrochemistry under conditions of both H(2) oxidation and H(2) production, using CO as a complementary probe. The hydrogenases are DdHydAB and CaHydA from the bacteria Desulfovibrio desulfuricans and Clostridium acetobutylicum , and CrHydA1 from the green alga Chlamydomonas reinhardtii . Rates of inactivation depend on the redox state of the active site 'H-cluster' and on transport through the protein to reach the pocket in which the H-cluster is housed. In all cases CO reacts much faster than O(2). In the model proposed, CaHydA shows the most sluggish gas transport and hence little dependence of inactivation rate on H-cluster state, whereas DdHydAB shows a large dependence on H-cluster state and the least effective barrier to gas transport. All three enzymes show a similar rate of reactivation from CO inhibition, which increases upon illumination: the rate-determining step is thus assigned to cleavage of the labile Fe-CO bond, a reaction likely to be intrinsic to the atomic and electronic state of the H-cluster and less sensitive to the surrounding protein