Expression profile of CREB knockdown in myeloid leukemia cells.

BackgroundThe cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells compared to normal hematopoietic stem cells. CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo, but does not affect long-term hematopoietic reconstitution.MethodsTo understand downstream pathways regulating CREB, we performed expression profiling with RNA from the K562 myeloid leukemia cell line transduced with CREB shRNA.ResultsBy combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. We performed extensive analyses on the top genes in this list as high confidence CREB targets. We found that this list is enriched for genes involved in cancer, and unexpectedly, highly enriched for histone genes. Furthermore, histone genes regulated by CREB were more likely to be specifically expressed in hematopoietic lineages. Decreased expression of specific histone genes was validated in K562, TF-1, and primary AML cells transduced with CREB shRNA.ConclusionWe have identified a high confidence list of CREB targets in K562 cells. These genes allow us to begin to understand the mechanisms by which CREB contributes to acute leukemia. We speculate that regulation of histone genes may play an important role by possibly altering the regulation of DNA replication during the cell cycle

Rabies Surveillance Identifies Potential Risk Corridors and Enables Management Evaluation

Intensive efforts are being made to eliminate the raccoon variant of rabies virus (RABV) from the eastern United States and Canada. The United States Department of Agriculture (USDA) Wildlife Services National Rabies Management Program has implemented enhanced rabies surveillance (ERS) to improve case detection across the extent of the raccoon oral rabies vaccination (ORV) management area. We evaluated ERS and public health surveillance data from 2006 to 2017 in three northeastern USA states using a dynamic occupancy modeling approach. Our objectives were to examine potential risk corridors for RABV incursion from the U.S. into Canada, evaluate the effectiveness of ORV management strategies, and identify surveillance gaps. ORV management has resulted in a decrease in RABV cases over time within vaccination zones (from occupancy (ψ) of 0.60 standard error (SE) = 0.03 in the spring of 2006 to ψ of 0.33 SE = 0.10 in the spring 2017). RABV cases also reduced in the enzootic area (from ψ of 0.60 SE = 0.03 in the spring of 2006 to ψ of 0.45 SE = 0.05 in the spring 2017). Although RABV occurrence was related to habitat type, greater impacts were associated with ORV and trap–vaccinate–release (TVR) campaigns, in addition to seasonal and yearly trends. Reductions in RABV occupancy were more pronounced in areas treated with Ontario Rabies Vaccine Bait (ONRAB) compared to RABORAL V-RG®. Our approach tracked changes in RABV occurrence across space and time, identified risk corridors for potential incursions into Canada, and highlighted surveillance gaps, while evaluating the impacts of management actions. Using this approach, we are able to provide guidance for future RABV management

Academic Performance of Students with Emotional and Behavioral Disorders Served in a Self-Contained Setting

This study describes the academic, social, and behavioral performance of elementary and secondary students with emotional and behavioral disorders (EBD) receiving services in a self-contained school for students with serious behavior problems, with an emphasis on how school adjustment and problem behavior patterns predict academic performance. Results revealed that elementary and secondary group scores were well below the 25th percentile on reading, math, and written expression measures. Further, a seven variable model representing academic, social, and behavioral domains was able to differentiate between age groups explaining 54% of the variance and correctly classifying 78.26% (n = 18) of the elementary students and 84.21% (n = 16) of the secondary students. Findings also suggested that behavioral variables (e.g., school adjustment, externalizing, and internalizing) were predictive of broad reading and broad written expression scores, with school adjustment (a protective factor) accounting for the most variance in the three-variable model. Limitations and recommendations for future research are addressed

Are there multiple kinds of episodic memory? An fMRI investigation comparing autobiographical and recognition memory tasks

What brain regions underlie retrieval from episodic memory? The bulk of research addressing this question with fMRI has relied upon recognition memory for materials encoded within the laboratory. Another, less dominant tradition has used autobiographical methods, whereby people recall events from their lifetime, often after being cued with words or pictures. The current study addresses how the neural substrates of successful memory retrieval differed as a function of the targeted memory when the experimental parameters were held constant in the two conditions (except for instructions). Human participants studied a set of scenes and then took two types of memory test while undergoing fMRI scanning. In one condition (the picture memory test), participants reported for each scene (32 studied, 64 nonstudied) whether it was recollected from the prior study episode. In a second condition (the life memory test), participants reported for each scene (32 studied, 64 nonstudied) whether it reminded them of a specific event from their preexperimental lifetime. An examination of successful retrieval (yes responses) for recently studied scenes for the two test types revealed pronounced differences; that is, autobiographical retrieval instantiated with the life memory test preferentially activated the default mode network, whereas hits in the picture memory test preferentially engaged the parietal memory network as well as portions of the frontoparietal control network. When experimental cueing parameters are held constant, the neural underpinnings of successful memory retrieval differ when remembering life events and recently learned events

Four Health Care Organizations' Efforts to Improve Patient Care and Reduce Costs

Synthesizes findings from four case studies in the Brookings-Dartmouth ACO Pilot Program about forming integrated systems that can deliver accountable care under shared-savings agreements with private payers

The Path to Eliminating Raccoon Rabies in the Eastern US-Obstacles and Opportunities in Urban-Suburban Landscapes

Rabies in terrestrial wildlife poses a significant public and animal health threat. Oral rabies vaccination (ORV) targeting specific vector species has proven effective in eliminating certain rabies variants in Europe and Canada. The goal of eliminating the raccoon rabies variant (RRV) in the US is achievable through an integrated ORV program at the landscape scale. Current wildlife rabies management in the US includes extensive air and ground ORV programs in 16 eastern states coordinated by Wildlife Services (WS)’ National Rabies Management Program. More than 10 million vaccine-baits are distributed annually targeting raccoons (Procyon lotor) and striped skunks (Mephitis mephitis) with the long-term goal of eliminating RRV. Achieving vaccine-induced herd immunity in target species in developed landscapes has proven challenging due to abundant anthropogenic food sources, higher wildlife densities, decreased home ranges, habitat fragmentation, and non-target bait competition. Effectively managing RRV in the urban-suburban landscape requires greater understanding of meso-carnivore ecology in these landscapes and critical analyses of current baiting strategies. Preliminary results from urban-suburban studies demonstrate fewer potential ORV bait encounters for target species than expected, lower seroconversion rates compared to rural habitats and patchy bait distribution patterns. New technologies including the use of Point of Interest GPS units to document ground bait distribution in combination with research conducted by WS including ORV field trials, urban density studies, and raccoon, skunk, and opossum (Didelphis virginiana) ecology have provided valuable insight to overcome the obstacles of urban rabies management and make eliminating RRV a reality

Data-driven management—a dynamic occupancy approach to enhanced rabies surveillance prioritization

Rabies lyssavirus (RABV) is enzootic in raccoons across the eastern United States. Intensive management of RABV by oral rabies vaccination (ORV) has prevented its spread westward and shown evidence of local elimination in raccoon populations of the northeastern US. The USDA, Wildlife Services, National Rabies Management Program (NRMP) collaborates with other agencies to implement broad-scale ORV and conducts extensive monitoring to measure the effectiveness of the management. Enhanced Rabies Surveillance (ERS) was initiated during 2005 and updated in 2016 to direct surveillance efforts toward higher-value specimens by assigning points to different methods of encountering specimens for collection (strange-acting, roadkill, surveillance-trapped, etc.; specimen point values ranged from 1 to 15). We used the 2016–2019 data to re-evaluate the point values using a dynamic occupancy model. Additionally, we used ERS data from 2012–2015 and 2016–2019 to examine the impact that the point system had on surveillance data. Implementation of a point system increased positivity rates among specimens by 64%, indicating a substantial increase in the efficiency of the ERS to detect wildlife rabies. Our re-evaluation found that most points accurately reflect the value of the surveillance specimens. The notable exception was that samples from animals found dead were considerably more valuable for rabies detection than originally considered (original points = 5, new points = 20). This work demonstrates how specimen prioritization strategies can be used to refine and improve ERS in support of wildlife rabies management

Cervical dystonia incidence and diagnostic delay in a multiethnic population.

BackgroundCurrent cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized.ObjectivesTo determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization.MethodsWe identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration.ResultsCD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68).ConclusionsCD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society