Cathepsin D SNP associated with increased risk of variant Creutzfeldt-Jakob disease

<p>Abstract</p> <p>Background</p> <p>Variant Creutzfeldt-Jakob disease (vCJD) originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (BSE) material, with 163 confirmed cases in the UK to date. Many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis) to identify genetic factors that may affect individual susceptibility to infection. This study looked at a polymorphism in the cathepsin D gene (refSNP ID: rs17571) previously examined in Alzheimer's disease (AD).</p> <p>Methods</p> <p>Blood samples taken from 110 vCJD patients were tested for the C-T base change, and genotype data were compared with published frequencies for a control population using multiple logistic regression.</p> <p>Results</p> <p>There was a significant excess of the cathepsin D polymorphism TT genotype in the vCJD cohort compared to controls. The TT genotype was found to have a 9.75 fold increase in risk of vCJD compared to the CT genotype and a 10.92 fold increase compared to the CC genotype.</p> <p>Conclusion</p> <p>This mutation event has been observed to alter the protease activity of the cathepsin D protein and has been linked to an increase in amyloid beta plaque formation in AD. vCJD neuropathology is characterised by the presence of amyloid plaques, formed from the prion protein, and therefore alterations in the amyloid processing activity of cathepsin D may affect the neuropathogenesis of this disease.</p

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding

Identifying and managing psoriasis-associated comorbidities: the IMPACT research programme

Background Psoriasis is a common, lifelong inflammatory skin disease, the severity of which can range from limited disease involving a small body surface area to extensive skin involvement. It is associated with high levels of physical and psychosocial disability and a range of comorbidities, including cardiovascular disease, and it is currently incurable. Objectives To (1) confirm which patients with psoriasis are at highest risk of developing additional long-term conditions and identify service use and costs to patient, (2) apply knowledge about risk of comorbid disease to the development of targeted screening services to reduce risk of further disease, (3) learn how patients with psoriasis cope with their condition and about their views of service provision, (4) identify the barriers to provision of best care for patients with psoriasis and (5) develop patient self-management resources and staff training packages to improve the lives of people with psoriasis. Design Mixed methods including two systematic reviews, one population cohort study, one primary care screening study, one discrete choice study, four qualitative studies and three mixed-methodology studies. Setting Primary care, secondary care and online surveys. Participants People with psoriasis and health-care professionals who manage patients with psoriasis. Results Prevalence rates for psoriasis vary by geographical location. Incidence in the UK was estimated to be between 1.30% and 2.60%. Knowledge about the cost-effectiveness of therapies is limited because high-quality clinical comparisons of interventions have not been done or involve short-term follow-up. After adjusting for known cardiovascular risk factors, psoriasis (including severe forms) was not found to be an independent risk factor for major cardiovascular events; however, co-occurrence of inflammatory arthritis was a risk factor. Traditional risk factors were high in patients with psoriasis. Large numbers of patients with suboptimal management of known risk factors were found by screening patients in primary care. Risk information was seldom discussed with patients as part of screening consultations, meaning that a traditional screening approach may not be effective in reducing comorbidities associated with psoriasis. Gaps in training of health-care practitioners to manage psoriasis effectively were identified, including knowledge about risk factors for comorbidities and methods of facilitating behavioural change. Theory-based, high-design-quality patient materials broadened patient understanding of psoriasis and self-management. A 1-day training course based on motivational interviewing principles was effective in increasing practitioner knowledge and changing consultation styles. The primary economic analysis indicated a high level of uncertainty. Sensitivity analysis indicated some situations when the interventions may be cost-effective. The interventions need to be assessed for long-term (cost-)effectiveness. Limitations The duration of patient follow-up in the study of cardiovascular disease was relatively short; as a result, future studies with longer follow-up are recommended. Conclusions Recognition of the nature of the psoriasis and its impact, knowledge of best practice and guideline use are all limited in those most likely to provide care for the majority of patients. Patients and practitioners are likely to benefit from the provision of appropriate support and/or training that broadens understanding of psoriasis as a complex condition and incorporates support for appropriate health behaviour change. Both interventions were feasible and acceptable to patients and practitioners. Cost-effectiveness remains to be explored. Future work Patient support materials have been created for patients and NHS providers. A 1-day training programme with training materials for dermatologists, specialist nurses and primary care practitioners has been designed. Spin-off research projects include a national study of responses to psoriasis therapy and a global study of the prevalence and incidence of psoriasis. A new clinical service is being developed locally based on the key findings of the Identification and Management of Psoriasis Associated ComorbidiTy (IMPACT) programme. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 10, No. 3. See the NIHR Journals Library website for further project information. </jats:sec

Packages of Care for Alcohol Use Disorders in Low- And Middle-Income Countries

In the fourth in a series of six articles on packages of care for mental disorders in low- and middle-income countries, Vivek Benegal and colleagues discuss the treatment of alcohol use disorders

Electrochemical promotion of CH4 oxidation on Pd nanoparticles, Pd/Co3O4 andPd/MnO2 nanodispersed catalysts deposited on O2- conductors (YSZ, CGO)

SSCI-VIDE+CARE+IKL:SNS:PVEInternational audienceStudies of CH4 oxidation are of special interest due to the difficulty in activating this particular hydrocarbon,to the demand of an active catalyst at low temperatures (T50 at 300oC) as well as due to possible deactivation of the catalyst upon exposure at higher temperatures. To address these issues, we have used Electrochemical Promotion of Catalysis (EPOC) which was discovered in the early 80's and has been studied for more than 100 catalytic systems. EPOC allows the controlled enhancement of the catalytic activity by potential or small current application between a catalyst (working electrode) supported on a solid electrolyte and an auxiliary electrode. In this study, the use of Pd nanoparticles (2-4 nm) as well as the use of nanodispersed Pd/Co3O4 and Pd/MnO2 catalysts deposited on O2- conductors (YSZ and CGO) is described. The aim is to demonstrate the feasibility of EPOC with nanodispersed catalysts and to enhance the reaction rate at temperatures lower than those that have been observed in previous studies

Electrochemical promotion of CH4 oxidation on Pd nanoparticles, Pd/Co3O4 andPd/MnO2 nanodispersed catalysts deposited on O2- conductors (YSZ, CGO)

SSCI-VIDE+CARE+IKL:SNS:PVEInternational audienceStudies of CH4 oxidation are of special interest due to the difficulty in activating this particular hydrocarbon,to the demand of an active catalyst at low temperatures (T50 at 300oC) as well as due to possible deactivation of the catalyst upon exposure at higher temperatures. To address these issues, we have used Electrochemical Promotion of Catalysis (EPOC) which was discovered in the early 80's and has been studied for more than 100 catalytic systems. EPOC allows the controlled enhancement of the catalytic activity by potential or small current application between a catalyst (working electrode) supported on a solid electrolyte and an auxiliary electrode. In this study, the use of Pd nanoparticles (2-4 nm) as well as the use of nanodispersed Pd/Co3O4 and Pd/MnO2 catalysts deposited on O2- conductors (YSZ and CGO) is described. The aim is to demonstrate the feasibility of EPOC with nanodispersed catalysts and to enhance the reaction rate at temperatures lower than those that have been observed in previous studies

Nouveaux catalyseurs zéolitiques pour la réduction catalytique sélective des NOx par le CH4

SSCI-VIDE+CARE+DLG:SNS:PVENational audienceLa réduction sélective catalytique (RSC) des NOx par le CH4 se présente comme une technologie très intéressante par la dépollution des NOx émis par moteurs à combustion interne au gaz naturel. Des zéolithes contenant différents métaux (Pd, Co, In ou Ga) sont considérées comme des matériaux prometteurs grâce à des paramètres structuraux et chimiques ajustables sur mesure, comme la taille et forme des pores, l’acidité ou la possibilité de modifier le cation compensateur par échange ionique ou imprégnation [1]. Dans ce travail, nous proposons différentes structures zéolitiques (FER, MOR, ZSM-5, BEA) en systèmes monométalliques (Co ou Pd) ou bimétalliques (Co et Pd) pour la RSC des NOx par le CH4. Les performances catalytiques sont mesurées entre 300°C et 700°C et les catalyseurs ont été vieillis sous mélange réactionnel à 700 ºC (12 heures). Les catalyseurs synthétisés associent du Pd à l’état cationique (échange ionique ≈ 0,5 % wt.) au Co déposé sur la surface (imprégnation ≈ 2 % wt.) sur différentes supports zéolitiques. La Figure 1 montre les performances catalytiques des différentes formulations zéolitiques étudiées. L’oxydation de CH4 commence vers 350 °C et atteint 80 % à 500 °C. L’activité catalytique est similaire pour toutes les zéolithes. Par rapport à la production de N2, les catalyseurs à base de MOR (2-Co-0.5Pd-MOR) et FER (2-Co-0.5Pd-FER) présentent les meilleures performances (33 % et 28 % de réduction de NOx en N2, respectivement) avec une pauvre activité du catalyseur à base de ZSM-5 (2-Co-0.5Pd-ZSM5). Par contre, à l’état vieilli, le catalyseur devient moins sélectif et produit plus de NO2 (pas montré) et la conversion de NOx descend à 3 % et à 17 % pour MOR et FER, respectivement. La désactivation si différente entre les deux catalyseurs peut être expliqué par la différent taille des pores (les rapports Si/Al ainsi que les surfaces spécifiques sont similaires (Figure 1)). Les petits pores peuvent servir pour mieux stabiliser les métaux échangés et pour protéger du frittage. Ces hypothèses ont été confirmées par la microscopie électronique en transmission (MET) réalisée sur ces catalyseurs après réaction. D’abord, le Co reste sous forme de nanoparticules en surface des cristallites de zéolithe sur le catalyseur à base de FER. La majorité des nanoparticules présentent une petite taille ( 20 nm) sont clairement observées, démontrant que le Pd n’est plus dans le réseau de la zéolithe. Cette étude a permis d’évaluer les performances catalytiques des catalyseurs zéolitiques dans des conditions proches à ceux des moteurs au gaz naturel travaillant en excès d’oxygène. Ces catalyseurs permettent d’obtenir une conversion des NOx en N2 élevée. Après vieillissement, l’activité baisse fortement, ce qui a été liée à la différente structure poreuse des zéolithes. [1] F. Lonyi, H.E. Solt, Z. Paszti, J. Valyon, Appl. Catal. B. 150-151 (2014) 218-229

Nouveaux catalyseurs zéolitiques pour la réduction catalytique sélective des NOx par le CH4

SSCI-VIDE+CARE+DLG:SNS:PVENational audienceLa réduction sélective catalytique (RSC) des NOx par le CH4 se présente comme une technologie très intéressante par la dépollution des NOx émis par moteurs à combustion interne au gaz naturel. Des zéolithes contenant différents métaux (Pd, Co, In ou Ga) sont considérées comme des matériaux prometteurs grâce à des paramètres structuraux et chimiques ajustables sur mesure, comme la taille et forme des pores, l’acidité ou la possibilité de modifier le cation compensateur par échange ionique ou imprégnation [1]. Dans ce travail, nous proposons différentes structures zéolitiques (FER, MOR, ZSM-5, BEA) en systèmes monométalliques (Co ou Pd) ou bimétalliques (Co et Pd) pour la RSC des NOx par le CH4. Les performances catalytiques sont mesurées entre 300°C et 700°C et les catalyseurs ont été vieillis sous mélange réactionnel à 700 ºC (12 heures). Les catalyseurs synthétisés associent du Pd à l’état cationique (échange ionique ≈ 0,5 % wt.) au Co déposé sur la surface (imprégnation ≈ 2 % wt.) sur différentes supports zéolitiques. La Figure 1 montre les performances catalytiques des différentes formulations zéolitiques étudiées. L’oxydation de CH4 commence vers 350 °C et atteint 80 % à 500 °C. L’activité catalytique est similaire pour toutes les zéolithes. Par rapport à la production de N2, les catalyseurs à base de MOR (2-Co-0.5Pd-MOR) et FER (2-Co-0.5Pd-FER) présentent les meilleures performances (33 % et 28 % de réduction de NOx en N2, respectivement) avec une pauvre activité du catalyseur à base de ZSM-5 (2-Co-0.5Pd-ZSM5). Par contre, à l’état vieilli, le catalyseur devient moins sélectif et produit plus de NO2 (pas montré) et la conversion de NOx descend à 3 % et à 17 % pour MOR et FER, respectivement. La désactivation si différente entre les deux catalyseurs peut être expliqué par la différent taille des pores (les rapports Si/Al ainsi que les surfaces spécifiques sont similaires (Figure 1)). Les petits pores peuvent servir pour mieux stabiliser les métaux échangés et pour protéger du frittage. Ces hypothèses ont été confirmées par la microscopie électronique en transmission (MET) réalisée sur ces catalyseurs après réaction. D’abord, le Co reste sous forme de nanoparticules en surface des cristallites de zéolithe sur le catalyseur à base de FER. La majorité des nanoparticules présentent une petite taille ( 20 nm) sont clairement observées, démontrant que le Pd n’est plus dans le réseau de la zéolithe. Cette étude a permis d’évaluer les performances catalytiques des catalyseurs zéolitiques dans des conditions proches à ceux des moteurs au gaz naturel travaillant en excès d’oxygène. Ces catalyseurs permettent d’obtenir une conversion des NOx en N2 élevée. Après vieillissement, l’activité baisse fortement, ce qui a été liée à la différente structure poreuse des zéolithes. [1] F. Lonyi, H.E. Solt, Z. Paszti, J. Valyon, Appl. Catal. B. 150-151 (2014) 218-229