New DUMC Articles

Milestone Ratings and Supervisory Role Categorizations Swim Together, but is the Water Muddy?

4 hours 55 min ago

Milestone Ratings and Supervisory Role Categorizations Swim Together, but is the Water Muddy?

Acad Pediatr. 2018 Jun 17;:

Authors: Schumacher DJ, Bartlett KW, Elliott SP, Michelson C, Sharma T, Garfunkel LC, King B, Schwartz A, APPD LEARN CCC Study Group

Abstract
PURPOSE: This single specialty, multi-institutional study aimed to determine: 1) the association between milestone ratings for individual competencies and average milestone ratings (AMRs) and 2) the association between AMRs and recommended supervisory role categorizations made by individual clinical competency committee (CCC) members.
METHODS: During the 2015-16 academic year, CCC members at 14 pediatric residencies reported milestone ratings for 21 competencies and recommended supervisory role categories (may not supervise, may supervise in some settings, may supervise in all settings) for residents they reviewed. An exploratory factor analysis of competencies was conducted. The associations between individual competencies, the AMR, and supervisory role categorizations were determined by computing bivariate correlations. The relationship between AMRs and recommended supervisory role categorizations was examined using an ordinal mixed logistic regression model.
RESULTS: 68/155 CCC members completed both milestone assignments and supervision categorizations for 451 residents. Factor analysis of individual competencies controlling for clustering of residents in raters and sites resulted in a single-factor solution (cumulative variance 0.75). All individual competencies had large positive correlations with the AMR (correlation coefficient: 0.84-0.93), except for two professionalism competencies (Prof1: 0.63 and Prof4: 0.65). When combined across training year and time points, the AMR and supervisory role categorization had a moderately positive correlation (0.56).
DISCUSSION: This exploratory study identified a modest correlation between average milestone ratings and supervisory role categorization. Convergence of competencies on a single factor deserves further exploration, with possible rater effects warranting attention.

PMID: 29925038 [PubMed - as supplied by publisher]

Categories: New DUMC Articles

MIN1PIPE: A Miniscope 1-Photon-Based Calcium Imaging Signal Extraction Pipeline.

4 hours 55 min ago

MIN1PIPE: A Miniscope 1-Photon-Based Calcium Imaging Signal Extraction Pipeline.

Cell Rep. 2018 Jun 19;23(12):3673-3684

Authors: Lu J, Li C, Singh-Alvarado J, Zhou ZC, Fröhlich F, Mooney R, Wang F

Abstract
In vivo calcium imaging using a 1-photon-based miniscope and a microendoscopic lens enables studies of neural activities in freely behaving animals. However, the high and fluctuating background, the inevitable movements and distortions of imaging field, and the extensive spatial overlaps of fluorescent signals emitted from imaged neurons inherent in this 1-photon imaging method present major challenges for extracting neuronal signals reliably and automatically from the raw imaging data. Here, we develop a unifying algorithm called the miniscope 1-photon imaging pipeline (MIN1PIPE), which contains several stand-alone modules and can handle a wide range of imaging conditions and qualities with minimal parameter tuning and automatically and accurately isolate spatially localized neural signals. We have quantitatively compared MIN1PIPE with other existing partial methods using both synthetic and real datasets obtained from different animal models and show that MIN1PIPE has superior efficiency and precision in analyzing noisy miniscope calcium imaging data.

PMID: 29925007 [PubMed - in process]

Categories: New DUMC Articles

Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10.

4 hours 55 min ago

Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10.

Cell Rep. 2018 Jun 19;23(12):3525-3536

Authors: Jaslow SL, Gibbs KD, Fricke WF, Wang L, Pittman KJ, Mammel MK, Thaden JT, Fowler VG, Hammer GE, Elfenbein JR, Ko DC

Abstract
Salmonella enterica is an important foodborne pathogen that uses secreted effector proteins to manipulate host pathways to facilitate survival and dissemination. Different S. enterica serovars cause disease syndromes ranging from gastroenteritis to typhoid fever and vary in their effector repertoire. We leveraged this natural diversity to identify stm2585, here designated sarA (Salmonella anti-inflammatory response activator), as a Salmonella effector that induces production of the anti-inflammatory cytokine IL-10. RNA-seq of cells infected with either ΔsarA or wild-type S. Typhimurium revealed that SarA activates STAT3 transcriptional targets. Consistent with this, SarA is necessary and sufficient for STAT3 phosphorylation, STAT3 inhibition blocks IL-10 production, and SarA and STAT3 interact by co-immunoprecipitation. These effects of SarA contribute to intracellular replication in vitro and bacterial load at systemic sites in mice. Our results demonstrate the power of using comparative genomics for identifying effectors and that Salmonella has evolved mechanisms for activating an important anti-inflammatory pathway.

PMID: 29924996 [PubMed - in process]

Categories: New DUMC Articles

Continuous Interdomain Orientation Distributions Reveal Components of Binding Thermodynamics.

4 hours 55 min ago

Continuous Interdomain Orientation Distributions Reveal Components of Binding Thermodynamics.

J Mol Biol. 2018 Jun 17;:

Authors: Qi Y, Martin JW, Barb AW, Thélot F, Yan A, Donald BR, Oas TG

Abstract
The flexibility of biological macromolecules is an important structural determinant of function. Unfortunately, the correlations between different motional modes are poorly captured by discrete ensemble representations. Here, we present new ways to both represent and visualize correlated interdomain motions. Interdomain motions are determined directly from residual dipolar couplings (RDCs), represented as a continuous conformational distribution, and visualized using the disk-on-sphere (DoS) representation. Using the DoS representation, features of interdomain motions, including correlations, are intuitively visualized. The representation works especially well for multidomain systems with broad conformational distributions.This analysis also can be extended to multiple probability density modes, using a Bingham mixture model. We use this new paradigm to study the interdomain motions of staphylococcal protein A, which is a key virulence factor contributing to the pathogenicity of S. aureus. We capture the smooth transitions between important states and demonstrate the utility of continuous distribution functions for computing the reorientational components of binding thermodynamics. Such insights allow the dissection the dynamic structural components of functionally important intermolecular interactions.

PMID: 29924964 [PubMed - as supplied by publisher]

Categories: New DUMC Articles

Stemming Lung Disease?

4 hours 55 min ago

Stemming Lung Disease?

N Engl J Med. 2018 Jun 21;378(25):2439-2440

Authors: Hogan B

PMID: 29924948 [PubMed - in process]

Categories: New DUMC Articles

A mobile clinic approach to the delivery of community-based mental health services in rural Haiti.

4 hours 55 min ago

A mobile clinic approach to the delivery of community-based mental health services in rural Haiti.

PLoS One. 2018;13(6):e0199313

Authors: Fils-Aimé JR, Grelotti DJ, Thérosmé T, Kaiser BN, Raviola G, Alcindor Y, Severe J, Affricot E, Boyd K, Legha R, Daimyo S, Engel S, Eustache E

Abstract
This study evaluates the use of a mental health mobile clinic to overcome two major challenges to the provision of mental healthcare in resource-limited settings: the shortage of trained specialists; and the need to improve access to safe, effective, and culturally sound care in community settings. Employing task-shifting and supervision, mental healthcare was largely delivered by trained, non-specialist health workers instead of specialists. A retrospective chart review of 318 unduplicated patients assessed and treated during the mobile clinic's first two years (January 2012 to November 2013) was conducted to explore outcomes. These data were supplemented by a quality improvement questionnaire, illustrative case reports, and a qualitative interview with the mobile clinic's lead community health worker. The team evaluated an average of 42 patients per clinic session. The most common mental, neurological, or substance abuse (MNS) disorders were depression and epilepsy. Higher follow-up rates were seen among those with diagnoses of bipolar disorder and neurological conditions, while those with depression or anxiety had lower follow-up rates. Persons with mood disorders who were evaluated on at least two separate occasions using a locally developed depression screening tool experienced a significant reduction in depressive symptoms. The mental health mobile clinic successfully treated a wide range of MNS disorders in rural Haiti and provided care to individuals who previously had no consistent access to mental healthcare. Efforts to address these common barriers to the provision of mental healthcare in resource-limited settings should consider supplementing clinic-based with mobile services.

PMID: 29924866 [PubMed - in process]

Categories: New DUMC Articles

Classification of crystallization outcomes using deep convolutional neural networks.

4 hours 55 min ago

Classification of crystallization outcomes using deep convolutional neural networks.

PLoS One. 2018;13(6):e0198883

Authors: Bruno AE, Charbonneau P, Newman J, Snell EH, So DR, Vanhoucke V, Watkins CJ, Williams S, Wilson J

Abstract
The Machine Recognition of Crystallization Outcomes (MARCO) initiative has assembled roughly half a million annotated images of macromolecular crystallization experiments from various sources and setups. Here, state-of-the-art machine learning algorithms are trained and tested on different parts of this data set. We find that more than 94% of the test images can be correctly labeled, irrespective of their experimental origin. Because crystal recognition is key to high-density screening and the systematic analysis of crystallization experiments, this approach opens the door to both industrial and fundamental research applications.

PMID: 29924841 [PubMed - in process]

Categories: New DUMC Articles

Second harmonic generation microscopy provides accurate automated staging of liver fibrosis in patients with non-alcoholic fatty liver disease.

4 hours 55 min ago

Second harmonic generation microscopy provides accurate automated staging of liver fibrosis in patients with non-alcoholic fatty liver disease.

PLoS One. 2018;13(6):e0199166

Authors: Chang PE, Goh GBB, Leow WQ, Shen L, Lim KH, Tan CK

Abstract
BACKGROUND: Assessment of severity of liver fibrosis is essential in the management of non-alcoholic fatty liver disease (NAFLD). Second Harmonic Generation (SHG) microscopy is a novel optical tissue imaging system that provides automated quantification of fibrosis based on unique architectural features of collagen. This study aims to develop and validate a SHG-based index for automated staging of liver fibrosis in patients with NAFLD.
METHODS: SHG microscopy was performed on archived liver biopsy specimens from 83 patients with NAFLD. A unique algorithm was developed to identify specific SHG parameters that correlated with fibrosis stage. The accuracy of the algorithm was compared against clinical assessment by experienced liver histopathologists using the Brunt fibrosis staging and further validated using the leave-one-out cross-validation method.
RESULTS: Mean age of the study cohort was 51.8 ± 11.7 years, with 41% males. A fibrosis index (SHG B-index) was developed comprising 14 unique SHG-based collagen parameters that correlated with severity of NAFLD fibrosis in a continuous fashion. The SHG B-index had excellent correlation with Brunt fibrosis stage (Spearman's correlation 0.820, p<0.001). AUROCs for prediction of Brunt fibrosis stages 1, 2, 3 and 4 were 0.853, 0.967, 0.985 and 0.941 respectively. In the cross-validation analysis, the SHG B-index demonstrated high specificity for diagnosis of all grades of fibrosis. A SHG B-index score of >1.76 had an overall diagnostic accuracy of 98.5% for prediction of presence of bridging fibrosis (Brunt stage ≥3) with sensitivity of 87.5%, specificity 98.0%, positive predictive value 96.6% and negative predictive value 92.6%.
CONCLUSION: The SHG B-index is a unique SHG-based index that provides accurate automated assessment of fibrosis stage in NAFLD patients.

PMID: 29924825 [PubMed - in process]

Categories: New DUMC Articles

Markers of Renal Function in Older Adults Completing a Higher Protein Obesity Intervention and One Year Later: Findings from the MEASUR-UP Trial.

4 hours 55 min ago

Markers of Renal Function in Older Adults Completing a Higher Protein Obesity Intervention and One Year Later: Findings from the MEASUR-UP Trial.

J Nutr Gerontol Geriatr. 2018 Jun 20;:1-13

Authors: Porter Starr KN, McDonald SR, Jarman A, Orenduff M, Sloane R, Pieper CF, Bales CW

Abstract
Increases in rates of obesity in the older population are hastening the development of chronic illnesses, including chronic kidney disease (CKD). However, obesity reduction in older adults is besought with concerns about the long-term benefit/risk, especially regarding loss of muscle mass and its impact on function. Higher protein intakes have been advocated to help offset the tendency for loss of muscle during weight reduction but this raises concerns about possible negative effects on older kidneys. We assessed markers of renal function in venous blood samples collected during a six-month randomized controlled weight loss trial of higher protein intake in obese (n = 67; BMI ≥ 30 kg/m2) older (≥60 years) adults with physical frailty and age-normal renal status (glomerular filtration rate [GFR] ≥ 45); the Control diet (0.8 g protein/kg body weight/day; n = 21) was compared to a protein-enhanced (1.2 g/g protein/kg body weight/day with 30 g protein/meal; n = 41; Protein) diet. Results showed no group effect of the Protein treatment on markers of renal function (estimated GFR, blood urea nitrogen, and creatinine), either upon intervention completion or one year later. Our findings align with literature support for the benefits of higher protein in the diets of older individuals during obesity reduction and help to confirm the safety of moderate increases in protein intake during weight loss in this population.

PMID: 29924703 [PubMed - as supplied by publisher]

Categories: New DUMC Articles

Successful Identification of Anatomical Markers and Placement of Feeding Tubes in Critically Ill Patients via Camera-Assisted Technology with Real-Time Video Guidance.

4 hours 55 min ago

Successful Identification of Anatomical Markers and Placement of Feeding Tubes in Critically Ill Patients via Camera-Assisted Technology with Real-Time Video Guidance.

JPEN J Parenter Enteral Nutr. 2018 Jun 20;:

Authors: Wischmeyer PE, McMoon MM, Waldron NH, Dye EJ

Abstract
BACKGROUND: Enteral feeding via feeding tube (FT) provides essential nutrition support to critically ill patients or those who cannot intake adequate nutrition via the oral route. Unfortunately, 1%-2% of FTs placed blindly at bedside enter the airway undetected (as confirmed by x-ray), where they could result in adverse events. Misplaced FTs can cause complications including pneumothorax, vocal cord injury, bronchopleural fistula, pneumonia, and death. X-ray is typically performed to confirm FT placement before feeding, but may delay nutrition intake, may not universally identify misplacement, and adds cost and radiation exposure.
METHODS: A prospective case series was conducted to evaluate a novel FT with a camera to provide real-time visualization, guiding placement. The primary end point was the clinician's ability to identify anatomical markers in the gastrointestinal tract and/or airway using the camera.
RESULTS: The Kangaroo Feeding Tube with IRIS Technology tube was placed in 45 subjects with 1 misplaced tube; 3 placements were postpyloric, with the remainder gastric. Clinicians correctly identified the stomach in 44 of 45 placements at a median depth of 60.0 cm (range 45.0-85.0 cm). A stomach image was obtained in 42 subjects (93.3%). Agreement between camera image and radiographic confirmation of placement was 93% (P = .014) with small deviations in recognizing stomach vs small bowel. No device-related adverse events occurred.
CONCLUSIONS: Direct visualization of the stomach using a camera-equipped FT can assist with FT placement, help avoid misplacements, and with further studies to evaluate the safety of eliminating confirmatory x-ray before feeding, could potentially preclude the need for radiographic confirmation.

PMID: 29924386 [PubMed - as supplied by publisher]

Categories: New DUMC Articles

Another Look at Competencies and Clinical Evaluation: From 40 Years Ago.

4 hours 55 min ago

Another Look at Competencies and Clinical Evaluation: From 40 Years Ago.

Nurse Educ. 2018 Jul/Aug;43(4):167

Authors: Oermann MH

PMID: 29923956 [PubMed - in process]

Categories: New DUMC Articles

Magnesium Sulfate-Induced Motor Evoked Potential Changes.

4 hours 55 min ago

Magnesium Sulfate-Induced Motor Evoked Potential Changes.

Neurodiagn J. 2018;58(2):83-90

Authors: Johnson T, Kale EB, Husain AM

Abstract
Motor evoked potentials (MEPs) are commonly used during neurophysiologic intraoperative monitoring. Anesthetic, homeostatic, surgical, and technical factors can cause a change in MEPs. The authors describe a case in which a bolus of magnesium sulfate resulted in a loss of amplitude of MEPs. Responses returned to near baseline about 20 minutes later. The patient did not have any new postoperative deficits. When MEP changes occur, in addition to evaluating other causes, magnesium sulfate administration should be considered.

PMID: 29923809 [PubMed]

Categories: New DUMC Articles

Validation of the Nickel Biotic Ligand Model for Locally Relevant Species in Australian Freshwaters.

4 hours 55 min ago

Validation of the Nickel Biotic Ligand Model for Locally Relevant Species in Australian Freshwaters.

Environ Toxicol Chem. 2018 Jun 20;:

Authors: Peters A, Merrington G, Schlekat C, De Schamphelaere K, Stauber J, Batley G, Harford A, van Dam R, Pease C, Mooney T, Warne M, Hickey C, Glazebrook P, Chapman J, Smith R, Krassoi R

Abstract
Australian freshwaters have relatively low water hardness and different calcium to magnesium ratios compared with those in Europe. The hardness values of a substantial proportion of Australian freshwaters fall below the application boundary of the existing European nickel Biotic Ligand Models (NiBLMs) of 2 mg Ca/L. Toxicity testing was undertaken using Hydra viridissima to assess the predictive ability of the existing NiBLM for this species in extremely soft waters. This testing revealed an increased competitive effect of calcium and magnesium with nickel for binding to the biotic ligand in soft water (<10 mg CaCO3 /L) than at higher water hardness. Modifications were made to the NiBLM by increasing the binding constants for Ca and Mg at the biotic ligand to account for softer waters encountered in Australia and the more important competitive effect of calcium and magnesium on nickel toxicity. To validate the modified NiBLM, ecotoxicity testing was performed on five Australian test species in five different natural Australian waters. Overall, no single water chemistry parameter was able to indicate the trends in toxicity to all of the test species. The modified NiBLMs were able to predict the toxicity of nickel to the test species in the validation studies in natural waters better than the existing NiBLMs. This work suggests that the overarching mechanisms defining nickel bioavailability to freshwater species are globally similar, and that NiBLMs can be used in all freshwater systems with minor modifications. This article is protected by copyright. All rights reserved.

PMID: 29923627 [PubMed - as supplied by publisher]

Categories: New DUMC Articles

Quantitative simulation of extracellular single unit recording from the surface of cortex.

4 hours 55 min ago

Quantitative simulation of extracellular single unit recording from the surface of cortex.

J Neural Eng. 2018 Jun 20;:

Authors: Hill M, Rios E, Sudhakar SK, Roossien D, Caldwell CM, Cai D, Ahmed O, Lempka S, Chestek CA

Abstract
OBJECTIVE: Neural recording is important for a wide variety of clinical applications. Until recently, recording from the surface of the brain, even when using micro-electrocorticography (µECoG) arrays, was not thought to enable recording from individual neurons. Recent results suggest that when the surface electrode contact size is sufficiently small, it may be possible to record single neurons from the brain's surface. In this study, we use computational techniques to investigate the ability of surface electrodes to record the activity of single neurons.
APPROACH: The computational model included the rat head, µECoG electrode, two existing multi-compartmental neuron models, and a novel multi-compartmental neuron model derived from patch clamp experiments in layer 1 of the cortex.
MAIN RESULTS: Using these models, we reproduced single neuron recordings from µECoG arrays and elucidated their possible source. The model resembles the experimental data when spikes originate from layer 1 neurons that are less than 60 µm from the cortical surface. We further used the model to explore the design space for surface electrodes. Although this model does not include biological or thermal noise, the results indicate the electrode contact area should be 100 µm&lt;sup&gt;2&lt;/sup&gt; or smaller to maintain a detectable waveform amplitude. Furthermore, the model shows the width of lateral insulation could be reduced, which may reduce scar formation, while retaining 95% of signal amplitude.
SIGNIFICANCE: Overall, the model suggests single-unit surface recording is limited to neurons in layer 1 and further improvement in electrode design is needed.

PMID: 29923502 [PubMed - as supplied by publisher]

Categories: New DUMC Articles

Sex differences in management and outcomes of patients with type 2 diabetes and cardiovascular disease: A report from TECOS.

4 hours 55 min ago
Related Articles

Sex differences in management and outcomes of patients with type 2 diabetes and cardiovascular disease: A report from TECOS.

Diabetes Obes Metab. 2018 Jun 19;:

Authors: Alfredsson J, Green JB, Stevens SR, Reed SD, Armstrong PW, Angelyn Bethel M, Engel SS, McGuire DK, Van de Werf F, Hramiak I, White HD, Peterson ED, Holman RR, TECOS Study Group

Abstract
AIM: To examine sex differences in baseline characteristics and outcomes in patients with type 2 diabetes and atherosclerotic vascular disease.
MATERIALS AND METHODS: Cox models were used to analyse the association between sex and outcomes in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), a randomized, placebo-controlled trial assessing the impact of sitagliptin on cardiovascular (CV) outcomes in patients with type 2 diabetes and atherosclerotic vascular disease.
RESULTS: A total of 4297 women and 10 374 men were followed for a median of 3.0 years. Women were slightly older and more often had cerebrovascular disease and peripheral arterial disease but less often coronary heart disease than men. At baseline, women were less likely to use aspirin or statins. The primary composite outcome of CV death, myocardial infarction, stroke, or hospitalization for unstable angina occurred in 418 women (9.7%) and 1272 men (12.3%; 3.48 vs 4.38 events/100 participant-years, crude hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.71-0.89, adjusted HR 0.64, 95% CI 0.55-0.74; P < .0001). Women also had a significantly lower risk of secondary CV outcomes and all-cause death.
CONCLUSIONS: In this large prospective study of people with type 2 diabetes and CV disease, women had different CV disease burden, worse CV risk factor profiles, and less use of indicated medications than men. Despite this, women had significantly lower risk of CV events, suggesting that the cardioprotective effects of female sex extend to populations with type 2 diabetes.

PMID: 29923323 [PubMed - as supplied by publisher]

Categories: New DUMC Articles

"Faggot" neutrophils in acute promyelocytic leukaemia with ongoing tretinoin therapy.

4 hours 55 min ago
Related Articles

"Faggot" neutrophils in acute promyelocytic leukaemia with ongoing tretinoin therapy.

Br J Haematol. 2018 Jun 19;:

Authors: Ma S, Yang LH, Luedke C, Ingersoll K, Wang E

PMID: 29923183 [PubMed - as supplied by publisher]

Categories: New DUMC Articles

BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia.

4 hours 55 min ago
Related Articles

BMI1 enhancer polymorphism underlies chromosome 10p12.31 association with childhood acute lymphoblastic leukemia.

Int J Cancer. 2018 Jun 19;:

Authors: de Smith AJ, Walsh KM, Francis SS, Zhang C, Hansen HM, Smirnov I, Morimoto L, Whitehead TP, Kang A, Shao X, Barcellos LF, McKean-Cowdin R, Zhang L, Fu C, Wang R, Yu H, Hoh J, Dewan AT, Metayer C, Ma X, Wiemels JL

Abstract
Genome-wide association studies of childhood acute lymphoblastic leukemia (ALL) have identified regions of association at PIP4K2A and upstream of BMI1 at chromosome 10p12.31-12.2. The contribution of both loci to ALL risk and underlying functional variants remain to be elucidated. We carried out single nucleotide polymorphism (SNP) imputation across chromosome 10p12.31-12.2 in Latino and non-Latino white ALL cases and controls from two independent California childhood leukemia studies, and additional Genetic Epidemiology Research on Aging study controls. Ethnicity-stratified association analyses were performed using logistic regression, with meta-analysis including 3133 cases (1949 Latino, 1184 non-Latino white) and 12,135 controls (8584 Latino, 3551 non-Latino white). SNP associations were identified at both BMI1 and PIP4K2A. After adjusting for the lead PIP4K2A SNP, genome-wide significant associations remained at BMI1, and vice-versa (Pmeta <10-10 ), supporting independent effects. Lead SNPs differed by ethnicity at both peaks. We sought functional variants in tight linkage disequilibrium with both the lead Latino SNP among Admixed Americans and lead non-Latino white SNP among Europeans. This pinpointed rs11591377 (Pmeta =2.1x10-10 ) upstream of BMI1, residing within a hematopoietic stem cell enhancer of BMI1, and which showed significant preferential binding of the risk allele to MYBL2 (P=1.73x10-5 ) and p300 (P=1.55x10-3 ) transcription factors using binomial tests on ChIP-Seq data from a SNP heterozygote. At PIP4K2A, we identified rs4748812 (Pmeta =1.3x10-15 ), which alters a RUNX1 binding motif and demonstrated chromosomal looping to the PIP4K2A promoter. Fine-mapping chromosome 10p12 in a multi-ethnic ALL GWAS confirmed independent associations and identified putative functional variants upstream of BMI1 and at PIP4K2A. This article is protected by copyright. All rights reserved.

PMID: 29923177 [PubMed - as supplied by publisher]

Categories: New DUMC Articles

Single session real-time fMRI neurofeedback has a lasting impact on cognitive behavioral therapy strategies.

4 hours 55 min ago
Related Articles

Single session real-time fMRI neurofeedback has a lasting impact on cognitive behavioral therapy strategies.

Neuroimage Clin. 2018;19:868-875

Authors: MacDuffie KE, MacInnes J, Dickerson KC, Eddington KM, Strauman TJ, Adcock RA

Abstract
To benefit from cognitive behavioral therapy (CBT), individuals must not only learn new skills but also strategically implement them outside of session. Here, we tested a novel technique for personalizing CBT skills and facilitating their generalization to daily life. We hypothesized that showing participants the impact of specific CBT strategies on their own brain function using real-time functional magnetic imaging (rt-fMRI) neurofeedback would increase their metacognitive awareness, help them identify effective strategies, and motivate real-world use. In a within-subjects design, participants who had completed a clinical trial of a standardized course of CBT created a personal repertoire of negative autobiographical stimuli and mood regulation strategies. From each participant's repertoire, a set of experimental and control strategies were identified; only experimental strategies were practiced in the scanner. During the rt-fMRI neurofeedback session, participants used negative stimuli and strategies from their repertoire to manipulate activation in the anterior cingulate cortex, a region implicated in emotional distress. The primary outcome measures were changes in participant ratings of strategy difficulty, efficacy, and frequency of use. As predicted, ratings for unscanned control strategies were stable across observations, whereas ratings for experimental strategies changed after neurofeedback. At follow-up one month after the session, efficacy and frequency ratings for scanned strategies were predicted by neurofeedback during the rt-fMRI session. These results suggest that rt-fMRI neurofeedback created a salient and durable learning experience for patients, extending beyond the scan session to guide and motivate CBT skill use weeks later. This metacognitive approach to neurofeedback offers a promising model for increasing clinical benefits from cognitive behavioral therapy by personalizing skills and facilitating generalization.

PMID: 29922575 [PubMed - in process]

Categories: New DUMC Articles

Navigation Patterns and Scent Marking: Underappreciated Contributors to Hippocampal and Entorhinal Spatial Representations?

4 hours 55 min ago
Related Articles

Navigation Patterns and Scent Marking: Underappreciated Contributors to Hippocampal and Entorhinal Spatial Representations?

Front Behav Neurosci. 2018;12:98

Authors: Lebedev MA, Pimashkin A, Ossadtchi A

Abstract
According to the currently prevailing theory, hippocampal formation constructs and maintains cognitive spatial maps. Most of the experimental evidence for this theory comes from the studies on navigation in laboratory rats and mice, typically male animals. While these animals exhibit a rich repertoire of behaviors associated with navigation, including locomotion, head movements, whisking, sniffing, raring and scent marking, the contribution of these behavioral patterns to the hippocampal spatially-selective activity has not been sufficiently studied. Instead, many publications have considered animal position in space as the major variable that affects the firing of hippocampal place cells and entorhinal grid cells. Here we argue that future work should focus on a more detailed examination of different behaviors exhibited during navigation to better understand the mechanism of spatial tuning in hippocampal neurons. As an inquiry in this direction, we have analyzed data from two datasets, shared online, containing recordings from rats navigating in square and round arenas. Our analyses revealed patchy navigation patterns, evident from the spatial maps of animal position, velocity and acceleration. Moreover, grid cells available in the datasets exhibited similar periodicity as the navigation parameters. These findings indicate that activity of grid cells could affect navigation parameters and/or vice versa. Additionally, we speculate that scent marks left by navigating animals could contribute to neuronal responses while rats and mice sniff their environment; the act of sniffing could modulate neuronal discharges even in virtual visual environments. Accordingly, we propose that future experiments should contain additional controls for navigation patterns, whisking, sniffing and maps composed of scent marks.

PMID: 29922134 [PubMed]

Categories: New DUMC Articles

Predicting treatment course and outcome using a promotion and prevention framework in a community sample of arthritis sufferers.

4 hours 55 min ago
Related Articles

Predicting treatment course and outcome using a promotion and prevention framework in a community sample of arthritis sufferers.

Patient Prefer Adherence. 2018;12:981-991

Authors: Blalock DV, McKnight PE, Kashdan TB, Franz SC

Abstract
Objective: The present study examined the proposition that patients need to focus on something beyond simply "getting better". In a sample of arthritis sufferers, we distinguished individuals by the goals that motivated them - moving toward aspirational goals and maximizing gains (promotion focus) rather than obligations and minimizing losses (prevention focus) - and how these motivational styles influenced treatment.
Methods: Patients (N=254) participated in a randomized controlled trial of resistance training and self-management, providing 6 time points of data over 2 years. Promotion and prevention focus at baseline were used to predict the course (compliance and changes in coping self-efficacy) and outcome (changes in physical functioning) of treatment.
Results: Arthritis sufferers with strong promotion orientations showed significant improvements in physical functioning (a direct positive impact on physical health); there were no significant associations with treatment compliance and coping self-efficacy. Arthritis sufferers with strong prevention orientations complied less with the treatment and showed little change in coping self-efficacy during treatment, which, in turn, predicted worse physical functioning over time (a pernicious, indirect influence on treatment outcome).
Conclusion: A focus on positive approach-oriented goals may improve overall treatment response, whereas a focus on negative avoidance-oriented goals may degrade treatment response through reduced compliance and self-efficacy.

PMID: 29922044 [PubMed]

Categories: New DUMC Articles

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