Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer's disease

Introduction

We examined whether cortical microvascular blood volume and hemodynamics in Alzheimer's disease (AD) are consistent with tissue hypoxia and whether they correlate with cognitive performance and the degree of cortical thinning.

The Norwegian Arthroplasty Register: 11 years and 73,000 arthroplasties

In 1985, the Norwegian Orthopaedic Association decided to establish a national hip register, and the Norwegian Arthroplasty Register was started in 1987. In January 1994, it was extended to include all artificial joints. The main purpose of the register is to detect inferior results of implants as early as possible. All hospitals participate, and the orthopedic surgeons are supposed to report all primary operations and all revisions. Using the patient's unique national social security number, the revision can be linked to the primary operation, and survival analyses of the implants are done. In general, the survival analyses are performed with the Kaplan-Meier method or using Cox multiple regression analysis with adjustment for possible confounding factors such as age, gender, and diagnosis. Survival probabilities can be calculated for each of the prosthetic components. The end-point in the analyses is revision surgery, and we can assess the rate of revision due to specific causes like aseptic loosening, infection, or dislocation. Not only survival, but also pain, function, and satisfaction have been registered for subgroups of patients. We receive reports about more than 95% of the prosthesis operations. The register has detected inferior implants 3 years after their introduction, and several uncemented prostheses were abandoned during the early 1990s due to our documentation of poor performance. Further, our results also contributed to withdrawal of the Boneloc cement. The register has published papers on economy, prophylactic use of antibiotics, patients' satisfaction and function, mortality, and results for different hospital categories. In the analyses presented here, we have compared the results of primary cemented and uncemented hip pros theses in patients less than 60 years of age, with 0-11 years' follow-up. The uncemented circumferentially porous- or hydroxyapatite (HA)-coated femoral stems had better survival rates than the cemented ones. In young patients, we found that cemented cups had better survival than uncemented porous-coated cups, mainly because of higher rates of revision from wear and osteolysis among the latter. The uncemented HA-coated cups with more than 6 years of follow-up had an increased revision rate, compared to cemented cups due to aseptic loosening as well as wear and osteolysis. We now present new findings about the six commonest cemented acetabular and femoral components. Generally, the results were good, with a prosthesis survival of 95% or better at 10 years, and the differences among the prosthesis brands were small. Since the practice of using undocumented implants has not changed, the register will continue to survey these implants. We plan to assess the mid- and long-term results of implants that have so far had good short-term results.     

Influenza hospitalizations during childhood in children born preterm

ObjectiveThe objective is to determine if children born preterm were at increased risk of influenza hospitalization up to age five.MethodsNational registry data on all children born in Norway between 2008 and 2011 were used in Cox regression models to estimate adjusted hazard ratios (aHRs) for influenza hospitalizations up to age five in children born preterm (<37 pregnancy weeks). HRs were also estimated separately for very preterm (<32 weeks), early term (37–38 weeks), and post‐term (≥42 weeks) children.ResultsAmong 238,628 children born in Norway from January 2008 to December 2011, 15,086 (6.3%) were born preterm. There were 754 (0.3%) children hospitalized with influenza before age five. The rate of hospitalizations in children born preterm was 13.8 per 10,000 person‐years (95% confidence interval [CI] [11.3, 16.7]), and 5.9 per 10,000 person‐years (95% CI [5.5, 6.4]) in children born at term (≥37 weeks). Children born preterm had a higher risk of influenza hospitalization before age 5: aHR 2.33 (95% CI [1.85, 2.93]). The risk increased with decreasing gestational age and was highest among those born extremely/very preterm; aHR 4.07 (95% CI [2.63, 6.31]). Compared with children born at 40–41 weeks, children born early term also had an elevated risk of influenza hospitalization; aHR (37 weeks) 1.89 (95% CI [1.43, 2.50]), aHR (38 weeks) 1.43 (95% CI [1.15, 1.78]).ConclusionChildren born preterm had a higher risk of influenza hospitalizations before age five. An elevated risk was also present among children born at an early term. Children born preterm could benefit from influenza vaccinations.     

A prediction model to identify hospitalised,older adults with reduced physical performance

Background

Identifying older adults with reduced physical performance at the time of hospital admission can significantly affect patient management and trajectory. For example, such patients could receive targeted hospital interventions such as routine mobilisation. Furthermore, at the time of discharge, health systems could offer these patients additional therapy to maintain or improve health and prevent institutionalisation or readmission. The principle aim of this study was to identify predictors for persisting, reduced physical performance in older adults following acute hospitalisation.

Methods

This was a prospective cohort study that enrolled 117 medical patients, ages 65 or older, who were admitted to a short-stay unit in a Danish emergency department. Patients were included in the study if at the time of admission they performed ≤8 repetitions in the 30-s Chair-Stand Test (30s–CST). The primary outcome measure was the number of 30s–CST repetitions (≤ 8 or >8) performed at the time of follow-up, 34 days after admission. Potential predictors within the first 48 h of admission included: age, gender, ability to climb stairs and walk 400 m, difficulties with activities of daily living before admission, falls, physical activity level, self-rated health, use of a walking aid before admission, number of prescribed medications, 30s–CST, and the De Morton Mobility Index.

Results

A total of 78 (67%) patients improved in physical performance in the interval between admission and follow-up assessment, but 76 patients (65%) had persistent reduced physical performance when compared to their baseline (30s–CST?≤?8). The number of potential predictors was reduced in order to create a simplified prediction model based on 4 variables, namely the use of a walking aid before hospitalisation (score?=?1.5), a 30s–CST?≤?5 (1.8), age?>?85 (0.1), and female gender (0.6). A score?>?1.8 identified 78% of the older adults who continued to have reduced physical performance following acute hospitalisation.

Conclusion

At the time of admission, the variables of age, gender, walking aid use, and a 30s–CST score?≤?5 enabled clinicians to identify 78% of older adults who had persisting reduced physical performance following acute hospitalisation.

Trial registration

ClinicalTrials.gov Identifier: NCT02474277. (12.10.2014).

     

Quality of life and self-esteem in 7-year-old children with familial high risk of schizophrenia or bipolar disorder: the Danish High Risk and Resilience Study-VIA 7—a population-based cohort study

European Child & Adolescent Psychiatry - It is well established that children with familial high risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) have a higher risk of developing...     

Test-retest reliability and validity of self-reported duration of computer use at work

OBJECTIVES: The aims of this study were to evaluate the test-retest reliability and the validity of self-reported duration of computer use at work. METHODS: Test-retest reliability was studied among 81 employees of a research department of a university medical center. The employees filled out a web-based questionnaire twice with an in-between period of 14 days. Validity was studied among a group of 572 office workers who participated in an epidemiologic field study. A software program recorded the duration of computer use at work during the 3 months preceding the questionnaire. RESULTS: The percentages of agreement for test-retest reliability were 75% [95% confidence interval (95% CI) 64-84] for total computer use and 67% (95% CI 55-77) for mouse use. The percentages of agreement between self-report and registration were 18% (95% CI 15-21) for total computer use and 16% (95% CI 13-19) for mouse use. Misclassification was mainly nondifferential in nature, since all of the evaluated subgroups showed at least 75% misclassification. CONCLUSIONS: The use of self-reports lead to the misclassification of exposure to computer use for more than 80% of all persons. This misclassification is predominantly nondifferential in nature and can only partly be explained by limited test-retest reliability.     

Up‐regulation of metastasis‐promoting S100A4 (Mts‐1) in rheumatoid arthritis: Putative involvement in the pathogenesis of rheumatoid arthritis

Objective

To examine the involvement of the metastasis‐inducing protein S100A4 (Mts‐1) in the pathogenesis of rheumatoid arthritis (RA).

Methods

Synovial tissue, synovial fluid, and plasma were obtained from RA and osteoarthritis (OA) patients who were undergoing joint surgery. Immunohistochemical and immunofluorescence analyses and enzyme‐linked immunosorbent assays were used to determine the locations and concentrations of S100A4. The conformational structure of S100A4 in plasma and synovial fluid was determined after fractionation by size‐exclusion chromatography, protein separation by sodium dodecyl sulfate–polyacrylamide gel electrophoresis, and Western blot analysis. Expression of various S100 proteins in RA synovium was determined by immunofluorescence and double‐staining using specific anti‐S100 antibodies.

Results

We found an up‐regulation of S100A4 in cells infiltrating RA synovial tissue. Most cell types identified by cell‐specific markers (fibroblasts, immune cells, and vascular cells) contributed to the production of S100A4 in RA synovial tissue. The pattern of S100A4 expression differed significantly from that of the proinflammatory proteins S100A9 and S100A12, which were restricted to phagocytes and granulocytes. The up‐regulation of S100A4 in RA synovial tissue was consistent with the high concentrations of the protein in RA versus OA plasma (mean 1,100 versus 211 ng/ml) and synovial fluid (mean 1,980 versus 247 ng/ml). Moreover, we found that S100A4 in RA plasma and synovial fluid was present in bioactive multimeric (M‐S100A4) conformations, whereas in OA, the majority of extracellular S100A4 was detected as the less active dimeric form. Consistent with our observations in tumor models, extracellular S100A4 stabilized the p53 tumor suppressor in RA synovial fibroblast–like cells and affected the regulation of p53 target genes, including Bcl‐2, p21^WAF, and Hdm‐2, as well as matrix metalloproteinases.

Conclusion

Overexpression of S100A4 in RA synovial tissue and its release as M‐S100A4 can influence p53 function and modulate the expression of several genes that are potentially implicated in the disease process. Thus, S100A4 might play an important role in the pathogenesis of RA and might represent a new target for the treatment of RA.