A Genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology

We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and "TAU" transgenic mice (mutant human MAPT gene). Microarray data were validated by qPCR and by comparison to human studies, including genome-wide association study (GWAS) hits. Immune gene expression correlated tightly with plaques whereas synaptic genes correlated negatively with neurofibrillary tangles. Network analysis of immune gene modules revealed six hub genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal network in TAU mice was similar except that Trem2 had hub status only in amyloid mice. The cortical network of TAU mice was entirely different with more hub genes and few in common with the other networks, suggesting reasons for specificity of cortical dysfunction in FTDP17. This Resource opens up many areas for investigation. All data are available and searchable at http://www.mouseac.org

Observation of coherent many-body Rabi oscillations

A two-level quantum system coherently driven by a resonant electromagnetic field oscillates sinusoidally between the two levels at frequency $\Omega$ which is proportional to the field amplitude [1]. This phenomenon, known as the Rabi oscillation, has been at the heart of atomic, molecular and optical physics since the seminal work of its namesake and coauthors [2]. Notably, Rabi oscillations in isolated single atoms or dilute gases form the basis for metrological applications such as atomic clocks and precision measurements of physical constants [3]. Both inhomogeneous distribution of coupling strength to the field and interactions between individual atoms reduce the visibility of the oscillation and may even suppress it completely. A remarkable transformation takes place in the limit where only a single excitation can be present in the sample due to either initial conditions or atomic interactions: there arises a collective, many-body Rabi oscillation at a frequency $N^0.5\Omega$ involving all N >> 1 atoms in the sample [4]. This is true even for inhomogeneous atom-field coupling distributions, where single-atom Rabi oscillations may be invisible. When one of the two levels is a strongly interacting Rydberg level, many-body Rabi oscillations emerge as a consequence of the Rydberg excitation blockade. Lukin and coauthors outlined an approach to quantum information processing based on this effect [5]. Here we report initial observations of coherent many-body Rabi oscillations between the ground level and a Rydberg level using several hundred cold rubidium atoms. The strongly pronounced oscillations indicate a nearly complete excitation blockade of the entire mesoscopic ensemble by a single excited atom. The results pave the way towards quantum computation and simulation using ensembles of atoms

Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

BACKGROUND: The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS) may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx), the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. METHODS: Cultured human glomerular endothelial (HGEN), human glomerular visceral epithelial (HGEC) and human proximal tubule (HPT) cells were exposed to Stx-1 after pre-incubation with progesterone, β-estradiol or testosterone followed by determination of cytotoxicity. RESULTS: Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, β-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor) by any cell type at any time point. CONCLUSION: These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells

Confession Session: Learning from Others Mistakes

Accepted versio

Measuring body composition in overweight individuals by dual energy x-ray absorptiometry

BACKGROUND: Dual energy x-ray absorptiometry (DXA) is widely used for body composition measurements in normal-weight and overweight/obese individuals. The limitations of bone densitometers have been frequently addressed. However, the possible errors in assessing body composition in overweight individuals due to incorrect positioning or limitations of DXA to accurately assess both bone mineral density and body composition in obese individuals have not received much attention and are the focus of this report. DISCUSSION: We discuss proper ways of measuring overweight individuals and point to some studies where that might not have been the case. It appears that currently, the most prudent approach to assess body composition of large individuals who cannot fit under the scanning area would be to estimate regional fat, namely the regions of thigh and/or abdomen. Additionally, using two-half body scans, although time consuming, may provide a relatively accurate measurement of total body fat, however, more studies using this technique are needed to validate it. SUMMARY: Researchers using bone densitometers for body composition measurements need to have an understanding of its limitations in overweight individuals and address them appropriately when interpreting their results. Studies on accuracy and precision in measurements of both bone and soft tissue composition in overweight individuals using available densitometers are needed

Key Concepts for Estimating the Burden of Surgical Conditions and the Unmet Need for Surgical Care

Background: Surgical care is emerging as a crucial issue in global public health. Methodology is needed to assess the impact of surgical care from a public health perspective. Methods: A consensus opinion of a group of surgeons, anesthesiologists, and public health experts was established regarding the methodology for estimating the burden of surgical conditions and the unmet need for surgical care. Results: For purposes of analysis, we define surgical conditions as any disease state requiring the expertise of a surgically trained provider. Abnormalities resulting from a surgical condition or its treatment are termed surgical sequelae. Surgical care is defined as any measure that reduces the rates of physical disability or premature death associated with a surgical condition. To measure the burden of surgical conditions and unmet need for surgical care we propose using cumulative disability-adjusted life-year (DALY) curves generated from age-specific population-based data. This conceptual framework is based on the premise that surgically associated disability and death is determined by the incidence of surgical conditions and the quantity and quality of surgical care. The burden of surgical conditions is defined as the total disability and premature deaths that would occur in a population should there be no surgical care; the unmet need for surgical care is defined as the potentially treatable disability and premature deaths due to surgical conditions. Burden of surgical conditions should be expressed as DALYs and unmet need as potential DALYs avertable. Conclusions: Methodology is described for estimating the burden of surgical conditions and unmet need for surgical care. Using this approach it will be feasible to estimate the global burden of surgical conditions and help clarify where surgery fits among other global health priorities. These methods need to be validated using population-based data

The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987–2007

The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider. Subjects are enrolled prospectively to allow standardized clinical assessments during life. Funding comes primarily from competitive grants. The Program has made short postmortem brain retrieval a priority, with a 2.75-h median postmortem interval for the entire collection. This maximizes the utility of the resource for molecular studies; frozen tissue from approximately 82% of all cases is suitable for RNA studies. Studies performed in-house have shown that, even with very short postmortem intervals, increasing delays in brain retrieval adversely affect RNA integrity and that cerebrospinal fluid pH increases with postmortem interval but does not predict tissue viability

Pre-divorce problems in 3-year-olds: a prospective study in boys and girls

Objective: We examined to what extent internalizing and externalizing problems at age 3 preceded and predicted parental divorce, and if divorce and the time lapse since divorce were related to internalizing and externalizing problems at age 12. Methods: Parental ratings of internalizing and externalizing problems were collected with the Child Behavior Checklist (CBCL) in a large sample (N = 6,426) of 3-yearold children. All these children were followed through the age of 12 years, at which parents completed the CBCL again, while teachers completed the Teacher's Report Form. Children whose parents divorced between age 3 and age 12 were compared with children whose families remained intact. Results: Girls whose parents divorced between ages 3 and 12 already showed more externalizing problems at age 3 than girls whose parents stayed married. Higher levels of externalizing problems in girls at age 3 predicted later parental divorce. Parental reports indicated that 12-year-olds with divorced parents showed more internalizing and externalizing problems than children with married parents. Levels of teacher-reported problems were not different between children with married versus divorced parents. However, children whose parents divorced between ages 3 and 12 showed more teacher-rated internalizing problems at age 12 when the divorce was more recent than when the divorce was less recent. Parental ratings of both internalizing and externalizing problems at age 12 were not associated with the time lapse since divorce. Conclusion: Externalizing problems in girls precede and predict later parental divorce. Post-divorce problems in children vary by raters, and may depend on the time lapse since divorce

Spatiotemporal Infectious Disease Modeling: A BME-SIR Approach

This paper is concerned with the modeling of infectious disease spread in a composite space-time domain under conditions of uncertainty. We focus on stochastic modeling that accounts for basic mechanisms of disease distribution and multi-sourced in situ uncertainties. Starting from the general formulation of population migration dynamics and the specification of transmission and recovery rates, the model studies the functional formulation of the evolution of the fractions of susceptible-infected-recovered individuals. The suggested approach is capable of: a) modeling population dynamics within and across localities, b) integrating the disease representation (i.e. susceptible-infected-recovered individuals) with observation time series at different geographical locations and other sources of information (e.g. hard and soft data, empirical relationships, secondary information), and c) generating predictions of disease spread and associated parameters in real time, while considering model and observation uncertainties. Key aspects of the proposed approach are illustrated by means of simulations (i.e. synthetic studies), and a real-world application using hand-foot-mouth disease (HFMD) data from China.J.M. Angulo and A.E. Madrid have been partially supported by grants MTM2009-13250 and MTM2012-32666 of SGPI, and P08-FQM-3834 of the Andalusian CICE, Spain. H-L Yu has been partially supported by a grant from National Science Council of Taiwan (NSC101-2628-E-002-017-MY3 and NSC102-2221-E-002-140-MY3). A. Kolovos was supported by SpaceTimeWorks, LLC. G. Christakos was supported by a Yongqian Chair Professorship (Zhejiang University, China)

The heart healthy lenoir project-an intervention to reduce disparities in hypertension control: study protocol

Background Racial disparities in blood pressure control are well established; however the impact of low health literacy (LHL) on blood pressure has garnered less attention. Office based interventions that are created with iterative patient, practice and community stakeholder input and are rolled out incrementally, may help address these disparities in hypertension control. This paper describes our study protocol. Methods/design Using a community based participatory research (CBPR) approach, we designed and implemented a cohort study that includes both a practice level and patient level intervention to enhance the care and support of patients with hypertension in primary care practices in a rural region of eastern North Carolina. The study is divided into a formative phase and an ongoing 2.5 year implementation phase. Our main care enhancement activities include the integration of a community health coach, using home blood pressure monitoring in clinical decision making, standardizing care delivery processes, and working to improve medication adherence. Main outcomes include overall blood pressure change, the differential change in blood pressure by race (African American vs. White) and health literacy level (low vs. higher health literacy). Discussion Using a community based participatory approach in primary care practice settings has helped to engage patients and practice staff and providers in the research effort and in making practice changes to support hypertension care. Practices have engaged at varying levels, but progress has been made in implementing and iteratively improving upon the interventions to date