Chronic Fragmentation of the Daily Sleep-Wake Rhythm Increases Amyloid-beta Levels and Neuroinflammation in the 3xTg-AD Mouse Model of Alzheimer's Disease.

Fragmentation of the daily sleep-wake rhythm with increased nighttime awakenings and more daytime naps is correlated with the risk of development of Alzheimer's disease (AD). To explore whether a causal relationship underlies this correlation, the present study tested the hypothesis that chronic fragmentation of the daily sleep-wake rhythm stimulates brain amyloid-beta (Aß) levels and neuroinflammation in the 3xTg-AD mouse model of AD. Female 3xTg-AD mice were allowed to sleep undisturbed or were subjected to chronic sleep fragmentation consisting of four daily sessions of enforced wakefulness (one hour each) evenly distributed during the light phase, five days a week for four weeks. Piezoelectric sleep recording revealed that sleep fragmentation altered the daily sleep-wake rhythm to resemble the pattern observed in AD. Levels of amyloid-beta (Aß40 and Aß42) determined by ELISA were higher in hippocampal tissue collected from sleep-fragmented mice than from undisturbed controls. In contrast, hippocampal levels of tau and phospho-tau differed minimally between sleep fragmented and undisturbed control mice. Sleep fragmentation also stimulated neuroinflammation as shown by increased expression of markers of microglial activation and proinflammatory cytokines measured by q-RT-PCR analysis of hippocampal samples. No significant effects of sleep fragmentation on Aß, tau, or neuroinflammation were observed in the cerebral cortex. These studies support the concept that improving sleep consolidation in individuals at risk for AD may be beneficial for slowing the onset or progression of this devastating neurodegenerative disease.

Pre- and post-fire pollutant loads in an urban fringe watershed in Southern California.

Post-fire runoff has the potential to be a large source of contaminants to downstream areas. However, the magnitude of this effect in urban fringe watersheds adjacent to large sources of airborne contaminants is not well documented. The current study investigates the impacts of wildfire on stormwater contaminant loading from the upper Arroyo Seco watershed, burned in 2009. This watershed is adjacent to the Greater Los Angeles, CA, USA area and has not burned in over 60 years. Consequently, it acts as a sink for regional urban pollutants and presents an opportunity to study the impacts of wildfire. Pre- and post-fire storm samples were collected and analyzed for basic cations, trace metals, and total suspended solids. The loss of vegetation and changes in soil properties from the fire greatly increased the magnitude of storm runoff, resulting in sediment-laden floods carrying high concentrations of particulate-bound constituents. Post-fire concentrations and loads were up to three orders of magnitude greater than pre-fire values for many trace metals, including lead and cadmium. A shift was also observed in the timing of chemical delivery, where maximum suspended sediment, trace metal, and cation concentrations coincided with, rather than preceded, peak discharge in the post-fire runoff, amplifying the fire's impacts on mass loading. The results emphasize the importance of sediment delivery as a primary mechanism for post-fire contaminant transport and suggest that traditional management practices that focus on treating only the early portion of storm runoff may be less effective following wildfire. We also advocate that watersheds impacted by regional urban pollutants have the potential to pose significant risk for downstream communities and ecosystems after fire.

Anosovite-type V3O5: a new binary oxide of vanadium.

The reaction of either V(2)F(6)·4H(2)O or a mixture of 60 wt % VF(2)·4H(2)O and 40 wt % VF(3)·3H(2)O with a water-saturated gaseous mixture of 15-20 vol % hydrogen in argon leads to the formation of a new polymorph of V(3)O(5) crystallizing in the orthorhombic anosovite-type structure. Quantum-chemical calculations show that the anosovite-type structure is about 15 kJ/mol less stable than the corresponding monoclinic Magnéli phase. In addition, there are no imaginary modes in the phonon density of states, supporting the classification of the anosovite-type phase as a metastable V(3)O(5) polymorph. Susceptibility measurements down to 3 K reveal no hint for magnetic ordering.

Electronic structure and thermodynamics of V2O3 polymorphs.

A metastable bixbyite-type polymorph of vanadium sesquioxide, V(2)O(3), has recently been synthesized, and it transforms to the corundum-type phase at temperatures around 550 °C. The possibility of a paramagnetic to canted antiferromagnetic or even spin-glass-like transition has been discussed. Quantum-chemical calculations on the density-functional theory level including explicit electronic correlation confirm the metastability as well as the semiconducting behavior of the material and predict that the bixbyite-type structure is about 0.1 eV less stable than the well-known corundum-type phase. Nonetheless, quasiharmonic phonon calculations manifest that bixbyite-type vanadium sesquioxide is a dynamically stable compound. Other possible V(2)O(3) polymorphs are shown to be even less suitable candidates for the composition V(2)O(3).

Bixbyite-type V2O3--a metastable polymorph of vanadium sesquioxide.

A metastable polymorph of vanadium sesquioxide was prepared by the reaction of vanadium trifluoride with a water-saturated gaseous mixture of 10 vol % hydrogen in argon. The new polymorph crystallizes in the bixbyite-type structure. At temperatures around 823 K a transformation to the well-known corundum-type phase is observed. Quantum-chemical calculations show that the bixbyite-type structure is about 9 kJ/mol less stable than the known corundum-based one. This result, in combination with the absence of imaginary modes in the phonon density of states, supports the classification of the bixbyite-type phase as a metastable V(2)O(3) polymorph. At ~50 K a paramagnetic to canted antiferromagnetic transition is detected.

Continued multidisciplinary project-based learning - implementation in health informatics.

OBJECTIVES: Problem- and project-based learning are approved methods to train students, graduates and post-graduates in scientific and other professional skills. The students are trained on realistic scenarios in a broader context. For students specializing in health informatics we introduced continued multidisciplinary project-based learning (CM-PBL) at a department of medical informatics. The training approach addresses both students of medicine and students of computer science. METHODS: The students are full members of an ongoing research project and develop a project-related application or module, or explore or evaluate a sub-project. Two teachers guide and review the students' work. The training on scientific work follows a workflow with defined milestones. The team acts as peer group. By participating in the research team's work the students are trained on professional skills. RESULTS: A research project on a web-based information system on hospitals built the scenario for the realistic context. The research team consisted of up to 14 active members at a time, who were scientists and students of computer science and medicine. The well communicated educational approach and team policy fostered the participation of the students. Formative assessment and evaluation showed a considerable improvement of the students' skills and a high participant satisfaction. CONCLUSIONS: Alternative education approaches such as project-based learning empower students to acquire scientific knowledge and professional skills, especially the ability of life-long learning, multidisciplinary team work and social responsibility.

Implementing software development guidelines in a medical informatics research project.

OBJECTIVES: Due to the non-commercial, research-oriented context, software in medical informatics research projects is often developed by researchers as a proof-of-concept without applying structured software development process models. A guideline for software development can bring sufficient structure to the development process while avoiding the complexity of industry-standard methods. METHODS: We adapted the common evidence-based guideline development process from medicine to build a guideline for software development in our medical informatics teaching and research project. RESULTS: Our guideline development used the six steps of problem identification, first proposal, review, revision, gaining consensus and periodic guideline review. Since the developers had taken part in guideline development, our guideline clearly states the consensus of the development team over critical topics. The guideline improved the quality of our source code in structure and understandability. CONCLUSIONS: A software development guideline that is developed following a consensus panel approach is a good instrument for basic software quality assurance in domains where complex, industry-standard software development methods cannot be applied. This is especially the case in non-commercial, research-oriented medical informatics projects where mainly non-software engineers like students do the development work.

[Effects of extracorporeal shock waves (ESW) on human bone marrow cell cultures]. / Einwirkung extrakorporaler Stosswellen (ESW) auf humane Knochenmarkszellkulturen.

INTRODUCTION: Extracorporeal shockwave therapy (ESWT) is a new method of treating insertion tendopathy and pseudo-arthrosis, the clinical importance of which cannot yet be definitively assessed, and the underlying mechanisms of which are still unclear. AIM: To develop an experimental set-up enabling the standardised application of ESWT to human bone marrow cell culture and the determination of the effect of ESWT. MATERIAL AND METHODS: After 14 days incubation, human bone marrow cell cultures were subjected to ESWT using 200/500 pulses at an energy flux densities ED + of 0.03, 0.04, 0.07, 0.11 and 0.25 millijoule/mm2. Samples were obtained for LDH measurement 15 minutes, 4 h and 18 h after ESWT. Transmission light microscopy was carried out before and after ESWT to determine cell numbers and for morphological analysis. RESULTS: Gaps in the cellular tissue first appear at an energy of 0.01 millijoule/mm2. At energies of 0.25 millijoule/mm2, morphologically altered cells, thinned out cellular tissue with a cell-free focal zone are found. At low energy levels, defects have been repaired ca. 1 week after ESWT. No significant increase in LDH was detected at any of the energy levels applied. CONCLUSION: Increasing energy and higher pulse frequency is associated with an increase in the size and number of holes in cellular tissue and in cell separation. Regeneration capability (regrowth, sprouting, normal cell form) decreases as the energy level increases. Changes can be detected even at the lowest energy flux densities, which up until now had been assumed to have no effect on cell morphology or number. The standardised application of ESWT to human bone marrow cell cultures provides reproducible results that can be controlled by a placebo ESWT application.

Academic medical center libraries on the Web.

Academic medical center libraries are moving towards publishing electronically, utilizing networked technologies, and creating digital libraries. The catalyst for this movement has been the Web. An analysis of academic medical center library Web pages was undertaken to assess the information created and communicated in early 1997. A summary of present uses and suggestions for future applications is provided. A method for evaluating and describing the content of library Web sites was designed. The evaluation included categorizing basic information such as description and access to library services, access to commercial databases, and use of interactive forms. The main goal of the evaluation was to assess original resources produced by these libraries.

Quality filtering of the clinical literature by librarians and physicians.

A study was conducted at the University of Pittsburgh to determine the effectiveness of the selection process by clinical medical librarians and to identify the criteria used by librarians and physicians to select relevant articles. The study analyzed the similarity between librarian and physician selections, the decision-making processes used by librarians and physicians, and the utility of librarian selections versus those of physicians. No significant difference in utility between librarian and physician selection was found, suggesting that librarians can recognize and select useful articles as effectively as physicians. Both librarians and physicians based selection decisions primarily on article title, abstract, and journal title. Librarians were more likely to focus on Medical Subject Headings (MeSH) descriptors, while physicians focused on clinical applicability or similarity to a specific case. Journal selection data indicate that the principle internal medicine journals were the most frequently selected sources. The study demonstrates that librarians can effectively serve a quality filtering function in the clinical environment, and they should consider extending quality filtering activities to other arenas.

Isolated systolic hypertension in Dutch middle aged and all-cause mortality: a 25-year prospective study.

In the early 1950s, the blood pressure of 3901 Dutch civil servants and their spouses aged 40-65 years was measured in a general health survey. Isolated systolic hypertension (systolic pressure greater than 160 mmHg, diastolic pressure less than 90 mmHg) was observed in 6.3% of the women and 3.0% of the men. The prevalence increased with age and it was more common in women in all age groups. Using logistic regression, with adjustment for potential confounders (age, smoking, serum cholesterol, Quetelet index, alcohol consumption, haemoglobin level, pulse rate and diastolic blood pressure) the association of 15- and 25-year total mortality with isolated systolic hypertension was determined. Compared to normotensive people (systolic pressure less than or equal to 135 mmHg, diastolic pressure less than 90 mmHg), the risk of death from all causes was significantly higher for men with isolated systolic hypertension after 15 and 25 years of follow-up (odds ratio OR = 2.4, 95% confidence interval (CI) 1.2-4.8 and OR = 3.2, 95% CI 1.3-8.0). For women 15-years mortality risk was strongly associated with isolated systolic hypertension (OR = 3.7, 95% CI 1.4-9.7). The increased risk was less pronounced after 25 years of follow-up (OR = 1.7, 95% CI 0.96-3.0). Our results support those of other studies and indicate that isolated systolic hypertension is an important independent risk factor for all-cause mortality. Since isolated systolic hypertension may be an indicator for the early onset of ageing, it is important to study its determinants and to pay more attention to its diagnosis and treatment in middle-aged populations.

Scoring of prudent dietary habits and its relation to 25-year survival.

To evaluate the effect on longevity of a diet that is concurrent with common dietary guidelines, a simple diet scoring system was developed and applied in a follow-up study of 2,820 middle-aged Dutch civil servants and their spouses. In the early 1950s those civil servants were seen for a health examination that included a dietary survey. Consumption frequency data of the quantitatively most important food items at that time were used for the diet scoring. Overall survival after 25 years was 46.8% among men and 68.6% among women. In men, a significant positive association between prudent diet score and 25-year, age-adjusted survival could be demonstrated. Of the 10 food items that constituted the diet score, a higher intake of brown bread, porridge and/or yogurt, vegetables, fish, and fruit was associated with a slightly better survival. In a separate analysis we had found a significant inverse relationship between coffee consumption and survival. A similar trend, which, however, was not significant, was observed for alcohol intake. In women, the results for the separate food items were inconsistent, and no effect of a prudent diet score on longevity was observed. The proposed diet scoring system provides a means for evaluating the effects of the individual's food choice behavior on subsequent health and longevity.

Dietary sodium, calcium, and potassium, and blood pressure.

The cross-sectional association of systolic blood pressure with dietary sodium, calcium, and potassium, as estimated from dietary histories, was investigated by multiple regression analysis of data gathered in the Netherlands in the early 1950s in a general health examination of 2,291 middle-aged civil servants and spouses of civil servants. A statistically significant negative trend with systolic blood pressure was seen for calcium intake in both males and females, even after adjustments for covariates. For sodium and potassium intake, the observed negative trends were not significant after multivariate analyses. In addition, no consistent associations were found between diastolic blood pressure and the micronutrients after multivariate analyses, except for a significant negative association with calcium intake in females. In this study population, blood pressure was a strong independent risk factor of total mortality: 15- and 25-year mortality was about twice as high for hypertensives (greater than or equal to 160 mmHg) as for normotensives (less than 160 mmHg). These findings support the conclusion in recent epidemiologic studies that higher intakes of calcium are associated with lower systolic blood pressure, and they extend the evidence to an earlier time period.

Retinopathy as an independent indicator of all-causes mortality.

The association between retinopathy and mortality in hypertensive patients is well established. At the same level of blood pressure the prognosis gets worse with increasing seriousness of retinopathy. To assess the prognostic value of retinopathy for all-causes mortality, we studied the data from a general health survey of 1583 men and 1508 women after 15 and 25 years of follow up. Among the men a clear association was found in the first 15 years. Among the women a weaker association was found only after 25 years of follow-up. This association was independent of hypertension or other cardiovascular risk indicators, such as obesity, serum cholesterol, smoking or proteinuria.

Weight, smoking, and mortality.

A controversy has existed concerning the relationship between body habitus and mortality. Original studies found that overweight persons were at risk for increased mortality, but later studies suggested that the very lean were also at high risk. The existence of a U-shaped relationship between mortality and body mass index was confirmed in a reanalysis of a 25-year follow-up of 1,503 men and 1,464 women, initially aged 40 to 65 years. Cigarette smoking did not explain the higher mortality among persons in the lowest body mass index category.