Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) S18Y polymorphism in Alzheimer's disease

Alzheimer's disease (AD) is characterized by protein aggregates, i.e. senile plaques and neurofibrillary tangles. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a de-ubiquitinating enzyme with important functions in recycling of ubiquitin. The S18Y polymorphism of the UCHL1 gene confers protection against Parkinson's disease. In this study, the genotype and allele frequencies of the UCHL1 S18Y polymorphism were investigated in 452 AD patients and 234 control subjects, recruited from four memory clinics in Sweden. Using a binary logistic regression model including UCHL1 allele A and APOE ε4 allele positivity, age and sex as covariates with AD diagnosis as dependent variable, an adjusted OR of 0.82 ([95% CI 0.55-1.24], P = 0.35) was obtained for a positive UCHL1 allele A carrier status. The present study thus do not support a protective effect of the UCHL1 S18Y polymorphism against AD

Oestradiol levels and superoxide dismutase activity in age-related cataract: a case-control study.

Background: It has been suggested that the higher prevalence of cataract in women is caused by a withdrawal effect of oestrogen at menopause. In vitro studies have demonstrated protection of serum oestradiol (E2) against oxidative stress through upregulation of antioxidant enzymes, including superoxide dismutase (SOD). The purpose of the present study was to investigate E2 levels and SOD erythrocyte activity in patients with age-related cataract. Methods: The studied subjects consisted of 103 patients with age-related cataract and 22 controls. Cataracts were classified as nuclear, cortical, or posterior subcapsular. Blood samples were collected and data on smoking, hormonal use, diabetes and age at menarche/menopause was obtained for all individuals. Serum oestradiol analyses were performed with radioimmunoassay (RIA) and SOD activity was measured in erythrocyte lysates. Results: A negative correlation between age and E2 concentration was seen in a linear regression analysis. No correlation was seen between SOD activity and age or gender and no correlation between E2 levels and SOD activity was found using multiple linear regression. The mean level of E2 for all male subjects was 50.1 +/- 16.3 pmol/L, significantly higher compared to 13.8 +/- 11.8 pmol/L for postmenopausal women. Conclusion: The present study does not support a role for E2-induced effects on SOD in cataract formation. The findings of higher E2 levels in men than in postmenopausal women may suggest that decreased oestrogen at menopause is partially responsible for the gender-related difference in cataract prevalence. However, the latter can only be verified through prospective randomized trials using hormonal replacement therapy

Mild cognitive impairment is associated with passive suicidal ideation in older adults: A population-based study

OBJECTIVE: To investigate the association between MCI and passive/active suicidal ideation in a population-based sample of older adults. METHOD: The sample included 916 participants without dementia acquired from the two population-based studies Prospective Population Study of Women (PPSW) and the H70-study. Cognitive status was assessed using a comprehensive neuropsychiatric examination and classified according to the Winblad et al. criteria: 182 participants were classified as cognitively intact, 448 had cognitive impairment but did not fulfill MCI criteria and 286 were diagnosed with MCI. Passive/active suicidal ideation was assessed using the Paykel questions. RESULTS: Passive or active suicidal ideation (any level) was reported by 16.0% of those with MCI and 1.1% of those who were cognitively intact. MCI was associated with past year life-weariness (OR 18.32, 95% CI 2.44-137.75) and death wishes (OR 5.30, 95% CI 1.19-23.64) in regression models adjusted for covariates including major depression. Lifetime suicidal ideation was reported more frequently in MCI (35.7%) than in cognitively intact participants (14.8%). MCI was associated with lifetime life-weariness (OR 2.90, 95% CI 1.67-5.05). Among individuals with MCI, impairments in memory and visuospatial ability were associated with both past year and lifetime life-weariness. CONCLUSION: Our findings suggest reports of past year as well as lifetime passive suicidal ideation to be more frequent among individuals with MCI compared to those cognitively intact, indicating that individuals with MCI may constitute a high-risk group for suicidal behavior

Ubiquitin Carboxyl-Terminal Esterase LI (UCHLI) SI8Y Polymorphism in Patients with Cataracts

Background: Cataract is characterized by light-scattering protein aggregates. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a de-ubiquitinating enzyme wit

BRain health and healthy AgeINg in retired rugby union players, the BRAIN Study: study protocol for an observational study in the UK.

INTRODUCTION: Relatively little is known about the long-term health of former elite rugby players, or former sportspeople more generally. As well as the potential benefits of being former elite sportspersons, there may be potential health risks from exposures occurring during an individual's playing career, as well as following retirement. Each contact sport has vastly different playing dynamics, therefore exposing its players to different types of potential traumas. Current evidence suggests that these are not necessarily comparable in terms of pathophysiology, and their potential long-term adverse effects might also differ. There is currently limited but increasing evidence that poorer age-related and neurological health exists among former professional sportsmen exposed to repetitive concussions; however the evidence is limited on rugby union players, specifically. METHODS AND ANALYSIS: We present the protocol for a cross-sectional study to assess the association between self-reported history of concussion during a playing career, and subsequent measures of healthy ageing and neurological and cognitive impairment. We are recruiting a sample of approximately 200 retired rugby players (former Oxford and Cambridge University rugby players and members of the England Rugby International Club) aged 50 years or more, and collecting a number of general and neurological health-related outcome measures though validated assessments. Biomarkers of neurodegeneration (neurofilaments and tau) will be also be measured. Although the study is focusing on rugby union players specifically, the general study design and the methods for assessing neurological health are likely to be relevant to other studies of former elite sportspersons. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Committee of London School of Hygiene and Tropical Medicine (reference: 11634-2). It is intended that results of this study will be published in peer-reviewed medical journals, communicated to participants, the general public and all relevant stakeholders

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio

Can values drive value for sustainable business? : An analyzing and interpreting case study of Konsum Värmland Value-creation

Abstract Historically, value was believed to be created and embedded in the manufacturing process, implying that companies were the creators of value. Conversely, the notion of value-creation changed during the last decades and has implemented the customer orientation and service centred view. Instead, researchers currently believe that companies only can offer value-propositions, which means that value is to be created by the customers. Services and goods are much about values and identity today, which people connect to therefore it is important that positive values are associated with the company. The purpose of this case study is to present if values can drive value for sustainable business. In order to illustrate this we have chosen Konsum Värmland for our investigation, an independent consumer co-operative own by its 126 000 members. Konsum Värmland has advantages by being independent from KF (the co-operative union in Sweden), this by being able to set its own strategies and visions. This thesis aspires to illustrate which values Konsum Värmland stands for and to see if Konsum Värmland has succeeded to communicate these values to their stakeholders. We will present the theoretical framework and how values-based management is an excellent performance measurement for co-creating values together with its stakeholders. We chose to use a narrative approach for our empirical analysis. The narratives are based on interviews, observations and secondary data that we obtained in forms of literature, articles and previous research. We have chosen to investigate four areas for our case study, which are obvious of creating values. The areas are; the history Konsum Värmland, the brands Nästgård and Värmlandsgrisen, and the adapting and developing Konsum Värmland. These areas give the reader an insight to the value creation efforts of Konsum Värmland. It is important for companies to differentiate themselves from others, in order to stay competitive in the everyday retail branch. This is something that Konsum Värmland has done by standing for values that contributes to the region of Värmland This case study shows how the consumer co-operative thinking is becoming more modern, in co-creating common values and meanings. The consumer co-operative thinking also tells us that is can be used as a competitive strategy, to be able to predict and to adapt to the market. In this study we can see that local produced goods generate value, which makes the customer want to buy the goods even if they are more expensive. The values are communicated through the brands Värmlandsgrisen and Nästgård and the goods are offered in form of values-based service quality. We have created a model that illustrates how the vision, organization and the value-creation have to be in balance, to create values that can drive value for sustainable business.Résumé Historiquement des valeurs et leur création étaient vues comme un élément de la procédure de fabrication ce qui voulait dire que seul l’entreprise prenait le rôle du créateur de valeur. En parallèle le regard sur la création de valeur a évolué pendant ses dernières décennies vers une perspective s’orientant plus vers le client et donc plus accentuée « service ». Ces deux approches sont complétées par un avis des experts modernes qui défend la position que seule une offre basée sur des vraies valeurs peut réussir et émerger de son univers concurrentiel. Uniquement les produits, proposant une base de valeur, réussissent à influencer la perception des clients de manière durable. Des services et des produits peuvent émerger donc seulement à travers de leurs valeurs, c’est à dire à travers de leur identité, puisque les gens arrivent mieux à se mettre en rapport ce qui crée idéalement un attachement. C’est pour ça que c’est important que l’entreprise associe des valeurs à ses marques et surtout de le rend percevable aux clients de manière crédible. Le but de cet analyse est de montrer comment des valeurs peuvent durablement porter le succès économique d’entreprises. Afin de l’illustrer pour notre étude nous avons choisi Konsum Värmland, qui compte 126 000 membres en tant que coopérative indépendante. Grâce à cela Konsum Värmland a des avantages, puisque il est indépendant du syndicat suédois KF et donc autonome de réaliser ses propres stratégies et visions. Au delà de ça cet analyse veut montre quelles valeurs Konsum Värmland représente, et veut également examiner si Konsum Värmland a réussi à les communiquer à ses membres et ses clients. A travers un model théorique nous allons montrer comment le management à base de valeur est un excellent indicateur pour la création de valeur mutuellement avec les membres de la coopérative. Nous avons donc choisi une approche narrative pour analyse empirique. Les conclusions se basent sur des interviews, nos observations ainsi que d’autres données que nous avons obtenu dans la litérature, des articles de la presse et par une recherche préliminaire. Pour cet étude de cas nous avons décidé d’examiner quatre secteurs de la création de valeur qui sont l’histoire d’entreprise de Konsum Värmland, ses deux marques Nästgård et Värmlandsgrisen, ainsi que leur adaptation et évolution menées par Konsum Värmland. Ces secteurs donnent au lecteur une compréhension approfondie de la création de valeur stratégique à Konsum Värmland. Dans l’intention de rester compétitif dans l’environnement quotidien de grand distribution, il est important pour l’entreprise de se différencier des autres. Konsum Värmland a réussi à le faire grâce à exploitation intelligente des valeurs ancrées dans la région de Värmland. Par ailleurs cet étude de cas montre comment le raisonnement des clients évolue vers une création mutuelle des valeurs communes entre demande et offre. Ce comportement nous amène à la conclusion qu’il utilisable davantage dans une stratégie de compétition afin d’anticiper des changements de marché dans l’objectif de s’adapter vite au nouveau contexte. Dans cette analyse nous pouvons voir comment des produits locaux peuvent profiter des valeurs éthiques ce qui favorise une relation dans laquelle les clients sont prêts à acheter des produits même s’ils sont plus chers qu’ailleurs. Ces valeurs sont communiquées à travers les marques Värmlandsgrisen et Nästgård dont on propose les produits en s’appuyant sur une qualité de service à valeur ajoutée. Nous avons développé un model qui montre quelle vision, organisation et création de valeur doivent être balancés l’un à l’autre. Seulement à ce moment là il est possible de créer des valeurs, qui portent durablement le succès économique de l’entreprise.Zusammenfassung Ursprünglich wurden Werte and Wertschöpfung in der Wirtschaftsgeschichte als Teil des Herstellungsprozesses angesehen, was wiederum bedeutet das Unternehmen als Werterzeuger auftraten. Parallel veränderte sich die Bedeutung von Wertschaffung in der letzten Jahrzehnten in Richtung einer mehr Kundenorientierten und damit service-ausgerichteten Ansicht. Diesen beiden Perspektiven gegenüber steht, dass Wirtschaftsforscher heute davon ausgehen, dass Unternehmen ausschliesslich durch wertebasierende Angebote im Markt erfolgreich sein können. Nur diese schaffen es durch deren Empfinden den Kunden nachhaltig zu beeinflussen. Dienstleistungen und Waren sind also durch deren Werte und damit deren Identität erfolgreich, da Menschen diese besser mit ihren eigenen in Verbindung bringen können was im Idealfall eine stärkere Bindung bedeutet. Daher ist es wichtig, dass Unternehmen positive Werte mit ihren Marken verbinden und vor allem für die Kunden glaubhaft erlebbar machen. Ziel dieser Arbeit ist es zu zeigen wie Werte den nachhaltigen wirtschaftlichen Erfolg von Unternehmen fördern können. Um dies zu veranschaulichen haben wir für unsere Untersuchung Konsum Värmland gewählt, welches als unabhängige Vereinigung 126 000 Mitglieder zählt. Konsum Värmland hat dadurch Vorteile, da es einerseits unabhängig von der schwedischen Gewerkschaft KF ist und andererseits damit in der Lage ist seine eigenen Strategien und Vision umzusetzen. Diese Arbeit hat den Anspruch zu erläutern für welche Werte Konsum Värmland steht, und darüberhinaus zu untersuchen, ob Konsum Värmland es gelungen ist diese erfolgreich seinen Mitgliedern sowie Kunden zu kommunizieren. Wir werden mit Hilfe eines theoretischen Rahmenmodells zeigen wie wertebasiertes Management ein exzellenter Ergebnismesser für gemeinsame Wertschaffung mit den Mitgliedern der Kooperative sein kann. Wir haben für diese empirische Analysis daher einen erzählerischen Ansatz gewählt. Die erzählerischen Schlussfolgerungen basieren auf Interviews, eigenen Beobachtungen sowie weiteren Daten welche wir aus Fachliteratur, Zeitungsartikeln and vorangegangener Forschung erhielten. Für dies Fallstudie haben wir uns entschieden vier Bereich der Wertschaffung zu untersuchen. Diese sind die Unternehmensgeschichte von Konsum Värmland, die beiden Handelsmarken Nästgård und Värmlandsgrisen, sowie deren Anpassung durch und Entwicklung von Konsum Värmland. Diese Bereiche geben dem Leser eine tiefere Einsicht in die strategische Wertschaffung von Konsum Värmland. In der Absicht im alltäglichen Einzelhandelsumfeld wettbewerbsfähig zu bleiben, ist es für Unternehmen dabei wichtig, sich selbst von anderen zu differenzieren. Dieses gelang Konsum Värmland durch deren erfolgreiche Nutzung von in der Värmland-Region verankerten Werten. Diese Fallstudie zeigt wie sich modernes Konsumentendenken hinzu einer kooperativen Schöpfung gemeinschaftlicher Werte und Bedeutungen entwickelt. Dieses Kundendenken veranlasst uns zu der Schlussfolgerung, dass es in einer Wertbewerbsstrategie genutzt werden kann um Marktveränderung rechtzeitig zu erkennen und sich daran anzupassen. In dieser Studie können wir sehen wie lokal erzeugte Güter ethische Werte zu nutzen, was die Kunden wiederum dazu bewegt die Produkte zu kaufen, selbst wenn diese leicht teurer sind. Die Werte werden mittels der Handelsmarken Värmlandsgrisen und Nästgård kommuniziert, indem deren Erzeugnisse über eine wertebasierte Servicequalität angeboten werden. Wir haben dazu ein Model entwickelt, welches zeigt wie Vision, Organisation und die Wertschaffung auf einander abgestimmt sein müssen. Nur dann können Werte geschaffen werden, welche den nachhaltigen wirtschaftlichen Erfolg von Unternehmen fördern können

Toric IOL implantation in a patient with keratoconus and previous penetrating keratoplasty: a case report and review of literature

Abstract Background Cataract surgery in patients with keratoconus with or without previous penetrating keratoplasty (PKP) can be demanding due to difficulties in selecting the intraocular lens (IOL) and predicting the refractive outcome. We report a case of cataract surgery in a patient with keratoconus and previous PKP in one eye. Case presentation A 71-year-old man with bilateral cataract and advanced bilateral keratoconus and previous PKP in the left eye. Preoperatively, best corrected visual acuity (BCVA) was 20/150, with − 5.75 sph − 9.75 cyl 72°, in the right eye and 20/40, with − 0.25 sph − 5.0 cyl 50°, in the left eye. The patient was subjected to phacoemulsification with implantation of a spherical IOL in the right eye and a toric IOL in the left eye. BCVA postoperatively was 20/80 with + 1.25 sph − 3 cyl 65° in the right eye and 20/25 with − 0.5 sph − 3.25 cyl 80° in the left eye. Conclusions Correction of post-PKP astigmatism and cataract with phacoemulsification and implantation of a toric IOL can be an effective and safe choice. Predicting the refractive outcome in cataract surgery is difficult in patients with advanced keratoconus even when using non-toric IOLs, and the surgeon should be aware of different sources of biometric errors and the possible consequences