Sortilin receptor 1 predicts longitudinal cognitive change

The gene encoding sortilin receptor 1 (SORL1) has been associated with Alzheimer's disease risk. We examined 15 SORL1 variants and single nucleotide polymorphism (SNP) set risk scores in relation to longitudinal verbal, spatial, memory, and perceptual speed performance, testing for age trends and sex-specific effects. Altogether, 1609 individuals from 3 population-based Swedish twin studies were assessed up to 5 times across 16 years. Controlling for apolipoprotein E genotype (APOE), multiple simple and sex-moderated associations were observed for spatial, episodic memory, and verbal trajectories (p = 1.25E-03 to p = 4.83E-02). Five variants (rs11600875, rs753780, rs7105365, rs11820794, rs2070045) were associated across domains. Notably, in those homozygous for the rs2070045 risk allele, men demonstrated initially favorable performance but accelerating declines, and women showed overall lower performance. SNP set risk scores predicted spatial (Card Rotations, p = 5.92E-03) and episodic memory trajectories (Thurstone Picture Memory, p = 3.34E-02), where higher risk scores benefited men's versus women's performance up to age 75 but with accelerating declines. SORL1 is associated with cognitive aging, and might contribute differentially to change in men and women.     

Detecting EGFR alterations in clinical specimens—pitfalls and necessities

We investigated the epidermal growth factor receptor (EGFR) status in early stage lung cancer in Southern Sweden, a population for which there are no previous reports on the EGFR mutation frequency. Three hundred fifty small cell lung cancers, adenocarcinomas (AC), squamous cell carcinomas (SqCC), and large cell carcinomas were analyzed using a combination of techniques for the analysis of protein expression, gene copy numbers, and mutations. Immunohistochemical (IHC) staining with antibodies for the EGFR mutations L858R and del E746-A750 revealed intratumoral heterogeneity and several discrepant cases when compared to mutation-specific polymerase chain reaction (PCR)-based analysis. The frequencies of these two mutations, when considering IHC staining with mutation-specific antibodies in a cohort of 298 cases and subsequent confirmation by PCR, were 10 % in AC and <2 % in SqCC. Furthermore, screening by sequencing of EGFR in a cohort of 52 lung AC and squamous carcinomas demonstrated a more diverse mutation spectrum, not covered by the mutation-specific antibodies. High expression of total EGFR protein was correlated to high gene copy numbers but did not reflect the mutational status of the tumors. We believe that the mutation spectra in a Southern Swedish population is too diverse to be covered by the mutation-specific antibodies, and we also raise some other issues regarding the use of the mutation-specific antibodies, for example concerning heterogeneous expression of the mutated protein, optimal antibody dilution, and discrepancies between staining results and PCR.     

Coronary heart disease attack rate, incidence and mortality 1975-1994 in Goteborg, Sweden

MATERIAL AND METHODS: Data from the Göteborg myocardial infarction register wereused to investigate trends in attack rate, incidence of non-fatalmyocardial infarction and mortality from coronary heart diseasein persons aged 64 and below during the period 1975–1994. RESULTS: Myocardial infarction was defined according to strict criteriawhich remained the same throughout the study period. Attackrate and incidence were 3–5 times higher among men thanwomen. The ratio of recurrent infarcts out of all attacks increasedwith increasing age and was 14%, 20% and 24% for men aged 35–44,45–54, and 55–64, respectively. Corresponding ratesfor women were 8%, 14%, and 22%, respectively. Both attack rateand incidence decreased significantly by 2·1–3·9%per year during the study period for most age groups. The 28-dayfatality rate (hospitalized as well as non-hospitalized cases)tended to decline, but significantly so only in the oldest men.The same was true for 28-day fatality among hospitalized patients.The majority of all coronary heart disease deaths occurred outsidehospital in people unaware they had coronary heart disease.Mortality from coronary heart disease decreased by 2·0–68%per year during the study period. In-hospital treatment of myocardialinfarction with intravenous beta-blockers followed by oral treatment,nitroglycerin and thrombolytics increased during the study period.Coronary surgery and angioplasty were used in less than 5% ofpatients during the study period, but increased substantiallyin 1994. CONCLUSION: Coronary heart disease and mortality in ages below 65 yearsare now decreasing in Sweden. Decreasing short-term mortalityis almost certainly due to more efficient treatment in hospital,but as the majority of coronary heart disease deaths occur outsidehospital and in people unaware they have coronary heart disease,primary prevention is still very important.     

Assessment tool for hospital admissions related to medications: development and validation in older patients

International Journal of Clinical Pharmacy - Background Medication-related hospital admissions (MRAs) are frequently used to measure outcomes in studies involving medication reviews. The process of...     

Superior beta cell proliferation, function and gene expression in a subpopulation of rat islets identified by high blood perfusion

Aims/hypothesis  

The blood perfusion of individual pancreatic islets is highly variable, with a subgroup of islets having high perfusion and blood vessels responsive to further blood flow increase induced by glucose. This study tested the hypothesis that there is heterogeneity between islets with regard to beta cell proliferation, function and gene expression based on differences in their blood perfusion.