In Patients With Acute Myocardial Infarction, the Impact of Hyperglycemia as a Risk Factor for Mortality Is Not Homogeneous Across Age-Groups

OBJECTIVE To assess the impact of hyperglycemia in different age-groups of patients with acute myocardial infarction (AM I). RESEARCH DESIGN AND METHODS A total of 2,027 patients with AMI were categorized into one of five age-groups: <50 years (n = 301), >= 50 and <60 (n = 477),>= 60 and <70 (n = 545), >= 70 and <80 (n = 495), and years (n = 209). Hyperglycemia was defined as initial glucose >= 115 mg/dL. RESULTS The adjusted odds ratios for hyperglycemia predicting hospital mortality in groups 1-5 were, respectively, 7.57 (P = 0.004), 3.21 (P 0.046), 3.50 (P = 0.003), 3.20 (P < 0.001.), and 2.16 (P = 0.021). The adjusted P values for correlation between glucose level (as a continuous variable) and mortality were 0.007, <0.001, 0.043, <0.001, and 0.064. The areas under the ROC curves (AUCs) were 0.785, 0.709, 0.657, 0.648, and 0.613. The AUC in group 1 was significantly higher than those in groups 3-5. CONCLUSIONS The impact of hyperglycemia as a risk factor for hospital mortality in AMI is more pronounced in younger patients.

ER stress is associated with reduced ABCA-1 protein levels in macrophages treated with advanced glycated albumin - Reversal by a chemical chaperone

ATP-binding cassette transporter A1 mediates the export of excess cholesterol from macrophages, contributing to the prevention of atherosclerosis. Advanced glycated albumin (AGE-alb) is prevalent in diabetes mellitus and is associated with the development of atherosclerosis. Independently of changes in ABCA-1 mRNA levels, AGE-alb induces oxidative stress and reduces ABCA-1 protein levels, which leads to macrophage lipid accumulation. These metabolic conditions are known to elicit endoplasmic reticulum (ER) stress. We sought to determine if AGE-alb induces ER stress and unfolded protein response (UPR) in macrophages and how disturbances to the ER could affect ABCA-1 content and cholesterol efflux in macrophages. AGE-alb induced a time-dependent increase in ER stress and UPR markers. ABCA-1 content and cellular cholesterol efflux were reduced by 33% and 47%, respectively, in macrophages treated with AGE-alb, and both were restored by treatment with 4-phenyl butyric acid (a chemical chaperone that alleviates ER stress), but not MG132 (a proteasome inhibitor). Tunicamycin, a classical ER stress inductor, also impaired ABCA-1 expression and cholesterol efflux (showing a decrease of 61% and 82%, respectively), confirming the deleterious effect of ER stress in macrophage cholesterol accumulation. Glycoxidation induces macrophage ER stress, which relates to the reduction in ABCA-1 and in reverse cholesterol transport, endorsing the adverse effect of macrophage ER stress in atherosclerosis. Thus, chemical chaperones that alleviate ER stress may represent a useful tool for the prevention and treatment of atherosclerosis in diabetes. (C) 2012 Elsevier Ltd. All rights reserved.

Tradition, Change and Variation : Past and Present Trends in Public Old-age Care

The general aim of this dissertation is to describe and analyse how public old-age care in Sweden has developed and changed during the last century. The study applies a provider perspective on how care has been planned and professionally carried out. A broader social policy perspective, studying old-age care at central/national as well as local/municipal level, is also developed. A special focus is directed at the large local variation in care and services for the elderly. The empirical base is comprised of official documents and other public sources, survey data from interviews with elderly recipients of public old-age care, and official statistics on publicly financed and controlled old-age care and services. Study I addresses the development of old-age care in Sweden during the twentieth century by studying an important occupation in this field – the supervisors and their professional roles, tasks and working conditions. Throughout, the roles of supervisors have followed the prevailing official policy on the proper way to provide care for elderly people in Sweden; from poor relief at the beginning of the 1900s, via a generous level of services in the 1960s and 1970s, to today’s restricted and economy-controlled mode of operation. Study II describes and compares two main forms of public old-age care in Sweden today, home help services and institutional care. The care-load found in home-based care was comparable to and sometimes even larger than in service-homes and other institutions, indicating that large care needs among elderly people in Sweden today can be met in their homes as well as in institutional settings. Studies III and IV analyse the local variation in public old-age care in Sweden. During the last decades there has been an overall decline in home help services. The coverage of home help for elderly people shows large differences between municipalities throughout this period, and the relative variation has increased. The local disparity seems to depend more on historical factors, e.g., previous coverage rates, than on the present municipal situation in levels of need or local economy and politics. In an introductory part the four papers are linked together by an outline of the demographic situation and the social policy model for old-age care in Sweden. Trends that have been apparent over time, e.g. professionalisation and market orientation, are traced and discussed. Conflicts between prevailing ideologies are analysed, in regards to for instance home-based and institution-based care, social and medical culture, and local and central levels of decision-making. ’Welfare municipality’, ‘path dependency’, and ‘decentralisation’ are suggested as a conceptual framework for describing the large and increasing local variations in old-age care. Finally, implications of the four studies with regard to old-age care policy and further research are discussed.

Norm and difference : Stone Age dietary practice in the Baltic region

Stone Age research on Northern Europe frequently makes gross generalizations about the Mesolithic and Neolithic, although we still lack much basic knowledge on how the people lived. The transition from the Mesolithic to the Neolithic in Europe has been described as a radical shift from an economy dominated by marine resources to one solely dependent on farming. Both the occurrence and the geographical extent of such a drastic shift can be questioned, however. It is therefore important to start out at a more detailed level of evidence in order to present the overall picture, and to account for the variability even in such regional or chronological overviews. Fifteen Stone Age sites were included in this study, ranging chronologically from the Early Mesolithic to the Middle or Late Neolithic, c. 8300–2500 BC, and stretching geographically from the westernmost coast of Sweden to the easternmost part of Latvia within the confines of latitudes 55–59° N. The most prominent sites in terms of the number of human and faunal samples analysed are Zvejnieki, Västerbjers and Skateholm I–II. Human and faunal skeletal remains were subjected to stable carbon and nitrogen isotope analysis to study diet and ecology at the sites. Stable isotope analyses of human remains provide quantitative information on the relative importance of various food sources, an important addition to the qualitative data supplied by certain artefacts and structures or by faunal or botanical remains. A vast number of new radiocarbon dates were also obtained. In conclusion, a rich diversity in Stone Age dietary practice in the Baltic Region was demonstrated. Evidence ranging from the Early Mesolithic to the Late Neolithic show that neither chronology nor location alone can account for this variety, but that there are inevitably cultural factors as well. Food habits are culturally governed, and therefore we cannot automatically assume that people at similar sites will have the same diet. Stable isotope studies are very important here, since they tell us what people actually consumed, not only what was available, or what one single meal contained. We should not be deceived in inferring diet from ritually deposited remains, since things that were mentally important were not always important in daily life. Thus, although a ritual and symbolic norm may emphasize certain food categories, these may in fact contribute very little to the diet. By the progress of analysis of intra-individual variation, new data on life history changes have been produced, revealing mobility patterns, breastfeeding behaviour and certain dietary transitions. The inclusion of faunal data has proved invaluable for understanding the stable isotope ecology of a site, and thereby improve the precision of the interpretations of human stable isotope data. The special case of dogs, though, demonstrates that these animals are not useful for inferring human diet, since, due to the number of roles they possess in human society, dogs could deviate significantly from humans in their diet, and in several cases have been proved to do so. When evaluating radiocarbon data derived from human and animal remains from the Pitted-Ware site of Västerbjers on Gotland, the importance of establishing the stable isotope ecology of the site before making deductions on reservoir effects was further demonstrated. The main aim of this thesis has been to demonstrate the variation and diversity in human practices, challenging the view of a “monolithic” Stone Age. By looking at individuals and not only at populations, the whole range of human behaviour has been accounted for, also revealing discrepancies between norm and practice, which are frequently visible both in the archaeological record and in present-day human behaviour.

La casa ellenistica in Epiro ed Illiria meridionale

Il ritrovamento della Casa dei due peristili a Phoinike ha aperto la strada a un’intensa opera di revisione di tutti i dati relativi all’edilizia domestica nella regione, con studi comparativi verso nord (Illiria meridionale) e verso sud (il resto dell’Epiro, ovvero Tesprozia e Molossia). Tutta quest’area della Grecia nord-occidentale è stata caratterizzata nell’antichità da un’urbanizzazione scarsa numericamente e tardiva cronologicamente (non prima del IV sec. a.C.), a parte ovviamente le colonie corinzio-corciresi di area Adriatico- Ionica d’età arcaica (come Ambracia, Apollonia, Epidamnos). A un’urbanistica di tipo razionale e programmato (ad es. Cassope, Orraon, Gitani in Tesprozia, Antigonea in Caonia) si associano numerosi casi di abitati cresciuti soprattutto in rapporto alla natura del suolo, spesso diseguale e montagnoso (ad es. Dymokastro/Elina in Tesprozia, Çuka e Aitoit nella Kestrine), talora semplici villaggi fortificati, privi di una vera fisionomia urbana. D’altro canto il concetto classico di polis così come lo impieghiamo normalmente per la Grecia centro-meridionale non ha valore qui, in uno stato di tipo federale e dominato dall’economia del pascolo e della selva. In questo contesto l’edilizia domestica assume caratteri differenti fra IV e I sec. a.C.: da un lato le città ortogonali ripetono schemi egualitari con poche eccezioni, soprattutto alle origini (IV sec. a.C., come a Cassope e forse a Gitani), dall’altro si delinea una spiccata differenziazione a partire dal III sec., quando si adottano modelli architettonici differenti, come i peristili, indizio di una più forte differenziazione sociale (esemplari i casi di Antigonea e anche di Byllis in Illiria meridionale). I centri minori e fortificati d’altura impiegano formule abitative più semplici, che sfruttano l’articolazione del terreno roccioso per realizzare abitazioni a quote differenti, utilizzando la roccia naturale anche come pareti o pavimenti dei vani.

The effects of a flexible visual acuity-driven ranibizumab treatment regimen in age-related macular degeneration: outcomes of a drug and disease model

Differences in treatment responses to ranibizumab injections observed within trials involving monthly (MARINA and ANCHOR studies) and quarterly (PIER study) treatment suggest that an individualized treatment regimen may be effective in neovascular age-related macular degeneration. In the present study, a drug and disease model was used to evaluate the impact of an individualized, flexible treatment regimen on disease progression.

Vertical bias in neglect: A question of time?

Neglect is defined as the failure to attend and to orient to the contralesional side of space. A horizontal bias towards the right visual field is a classical finding in patients who suffered from a right-hemispheric stroke. The vertical dimension of spatial attention orienting has only sparsely been investigated so far. The aim of this study was to investigate the specificity of this vertical bias by means of a search task, which taps a more pronounced top-down attentional component. Eye movements and behavioural search performance were measured in thirteen patients with left-sided neglect after right hemispheric stroke and in thirteen age-matched controls. Concerning behavioural performance, patients found significantly less targets than healthy controls in both the upper and lower left quadrant. However, when targets were located in the lower left quadrant, patients needed more visual fixations (and therefore longer search time) to find them, suggesting a time-dependent vertical bias.

Ten-year comparison of pericardial tissue valves versus mechanical prostheses for aortic valve replacement in patients younger than 60 years of age

Aortic valve replacement using a tissue valve is controversial for patients younger than 60 years old. The long-term survival in this age group, the expected event rates during long-term follow-up, and valve-related complications are not clearly determined.

Verteporfin plus Ranibizumab for Choroidal Neovascularization in Age-related Macular Degeneration: Twelve-month MONT BLANC Study Results

To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration.

Distinct proteinase K-resistant prion protein fragment in goats with no signs of disease in a classical scrapie outbreak

Considerable efforts have been directed toward the identification of small-ruminant prion diseases, i.e., classical and atypical scrapie as well as bovine spongiform encephalopathy (BSE). Here we report the in-depth molecular analysis of the proteinase K-resistant prion protein core fragment (PrP(res)) in a highly scrapie-affected goat flock in Greece. The PrP(res) profile by Western immunoblotting in most animals was that of classical scrapie in sheep. However, in a series of clinically healthy goats we identified a unique C- and N-terminally truncated PrP(res) fragment, which is akin but not identical to that observed for atypical scrapie. These findings reveal novel aspects of the nature and diversity of the molecular PrP(res) phenotypes in goats and suggest that these animals display a previously unrecognized prion protein disorder.

Caprine PRNP polymorphisms at codons 171, 211, 222 and 240 in a Greek herd and their association with classical scrapie

The association between PRNP variation and scrapie incidence was investigated in a highly affected Greek goat herd. Four mutations were identified at codons 171Q/R, 211R/Q, 222Q/K and 240P/S. Lysine at codon 222 was found to be associated with the protection from natural scrapie (P=0.0111). Glutamine at codon 211 was observed in eight animals, all of them being scrapie-negative, indicating a possible protective role of this polymorphism although statistical analysis failed to support it (P=0.1074). A positive association (P=0.0457) between scrapie-affected goats and the wild-type Q(171)R(211)Q(222)S(240) allele is presented for the first time. In addition, a novel R(171)RQS allele, which is identical to the A(136)R(154)R(171) allele that has been associated with resistance to classical scrapie in sheep, was observed in low frequency. Resistant alleles that include K(222) and Q(211) are absent or rare in sheep and can provide the basis for the development of a feasible breeding programme for scrapie eradication in goats.

Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts

Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

Age at diagnosis and loss of heterozygosity on chromosome 1p and 19q in oligodendroglial tumors

The age distribution and incidence of loss of heterozygosity (LOH) of 1p and 19q was analyzed in 85 oligodendroglial tumors WHO II and III. The peak of tumor manifestation was in the age group of 35 to 55 years. There was no association between age at diagnosis and LOH incidence. We conclude that the prognostic effect of age on survival is not mediated by LOH 1p/19q.

Postmortem unenhanced magnetic resonance imaging of myocardial infarction in correlation to histological infarction age characterization

AIMS: Postmortem magnetic resonance (MRI) imaging is currently evaluated as alternative to traditional autopsy and myocardial infarction plays a key role therein. The aim of this study is to determine the suitability of postmortem MRI in infarction age staging. METHODS AND RESULTS: In eight human forensic corpses presenting with a total of 11 myocardial infarcted areas, short-axis, transversal, and longitudinal long-axis images (T1, T2, stir, flair) were acquired in situ on a 1.5 T system. During subsequent autopsy, the section technique was adapted to short-axis images. Histological investigations were performed along the entire circumference of the left ventricle to correlate the signal alteration in MR to the histological appearance. Two peracute infarctions were not detected in MRI and autopsy. Four acute infarcted areas presented with decreased signal in necrotic centres and increased signal in marginal myocardial regions (T2-weighted). T1-weighted images showed local hyperintensities when intramyocardial haemorrhage occurred. Four cases showed subacute infarctions with hyperintense regions in T2-weighted images and no signal alteration in T1-weighted images. Four chronic myocardial infarctions showed distinctively decreased signals in all applied sequences. CONCLUSION: Postmortem MRI demonstrates myocardial infarction in situ and allows for an infarction age estimation based on the signal behaviour.

Methacholine responsiveness in mice from 2 to 8 wk of age

Many chronic human lung diseases have their origin in early childhood, yet most murine models used to study them utilize adult mice. An important component of the asthma phenotype is exaggerated airway responses, frequently modelled by methacholine (MCh) challenge. The present study was undertaken to characterize MCh responses in mice from 2 to 8 wk of age measuring absolute lung volume and volume-corrected respiratory mechanics as outcome variables. Female BALB/c mice aged 2, 3, 4, 6, and 8 wk were studied during cumulative intravenous MCh challenge. Following each MCh dose, absolute lung volume was measured plethysmographically at functional residual volume and during a slow inflation to 20-hPa transrespiratory pressure. Respiratory system impedance was measured continuously during the inflation maneuver and partitioned into airway and constant-phase parenchymal components by model fitting. Volume-corrected (specific) estimates of respiratory mechanics were calculated. Intravenous MCh challenge induced a predominantly airway response with no evidence of airway closure in any age group. No changes in functional residual volume were seen in mice of any age during the MCh challenge. The specific airway resistance MCh dose response curves did not show significant differences between the age groups. The results from the present study do not show systematic differences in MCh responsiveness in mice from 2 to 8 wk of age.