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Sarwal A, Cartwright MS, Walker FO, Mitchell E, Buj-Bello A, Beggs AH, Childers MK.
Muscle Nerve. 2014 May 23. [Epub ahead of print]
PMID: 24861988
Introduction: We tested the feasibility of using neuromuscular ultrasound for non-invasive real time assessment of diaphragmatic structure and function in a canine model of X-Linked Myotubular Myopathy (XLMTM). Methods: Ultrasound images in 3 dogs (Wild Type WT, n=1; XLMTM untreated, n=1; XLMTM post AAV8-mediated MTM1 gene replacement, n=1) were analyzed for diaphragm thickness, change in thickness with respiration, muscle echogenicity, and diaphragm excursion amplitude during spontaneous breathing. Results: Quantitative parameters of diaphragm structure were different among the animals. WT diaphragm was thicker and less echogenic than the XLMTM control, whereas the diaphragm measurements of the MTM1-treated XLMTM dog were comparable to the WT dog. Discussion: This pilot demonstrates the feasibility of using ultrasound for quantitative assessment of the diaphragm in a canine model. Ultrasonography may potentially replace invasive measures of diaphragm function in canine models and in humans in the future, for non-invasive respiratory monitoring and evaluation of neuromuscular disease. © 2014 Wiley Periodicals, Inc.
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Wang W, Wang M, Wang L, Adams TS, Tian Y, Xu J.
Sci Rep. 2014;4():5012.
PMID: 24852453
The role of [-2]proPSA (p2PSA) based diagnostic tests for the detection of aggressive prostate cancer (PCa) has not been fully evaluated. We conducted a meta-analysis to evaluate the diagnostic performance of p2PSA/free PSA (%p2PSA) and prostate health index (Phi) tests for PCa and to evaluate their ability in discriminating between aggressive and non-aggressive PCa. A total of 16 articles were included in this meta-analysis. For the detection of PCa, the pooled sensitivity, specificity, and AUC were 0.86 (95% CI, 0.84-0.87), 0.40 (95% CI, 0.39-042) and 0.72 (95% CI, 0.67-0.77) for %p2PSA respectively, and were 0.85 (95% CI, 0.83-0.86), 0.45 (95% CI, 0.44-0.47) and 0.70 (95% CI=0.65-0.74) for Phi, respectively. In addition, the sensitivity for discriminating PCa between higher Gleason score (≥7) and lower Gleason score (<7) was 0.96 (95% CI, 0.93-0.98) and 0.90 (95% CI, 0.87-0.92) for %p2PSA and Phi respectively, and the specificity was low, only 0.09 (95% CI, 0.06-0.12) and 0.17 (95% CI, 0.14-0.19) for %p2PSA and Phi, respectively. Phi and %p2PSA have a high diagnostic accuracy rates and can be used in PCa diagnosis. Phi and %p2PSA may be useful as tumor markers in predicating patients harboring more aggressive disease and guiding biopsy decisions.
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Maldjian JA, Daunais JB, Friedman DP, Whitlow CT.
Neuroinformatics. 2014 May 22. [Epub ahead of print]
PMID: 24850577
Currently available non-human primate templates typically require input of a skull-stripped brain for structural processing. This can be a manually intensive procedure, and considerably limits their utility. The purpose of this study was to create a vervet MRI population template, associated tissue probability maps (TPM), and a label atlas to facilitate true fully automated Magnetic Resonance Imaging (MRI) structural analyses for morphometric analyses. Structural MRI scans of ten vervet monkeys (Chlorocebus aethiops) scanned at three time points were used in this study. An unbiased population average template was created using a symmetric diffeomorphic registration (SyN) procedure. Skull stripping, segmentation, and label map generation were performed using the publically available rhesus INIA19 MRI template and NeuroMap label atlas. A six-class TPM and a six-layer two-class normalization template was created from the vervet segmentation for use within the Statistical Parametric Mapping (SPM) framework. Fully automated morphologic processing of all of the vervet MRI scans was then performed using the vervet TPM and vervet normalization template including skull-stripping, segmentation and normalization. The vervet template creation procedure resulted in excellent skull stripping, segmentation, and NeuroMap atlas labeling with 720 structures successfully registered. Fully automated processing was accomplished for all vervet scans, demonstrating excellent skull-stripping, segmentation, and normalization performance. We describe creation of an unbiased vervet structural MRI population template and atlas. The template includes an associated six-class TPM and DARTEL six-layer two-class normalization template for true fully automated skull-stripping, segmentation, and normalization of vervet structural T1-weighted MRI scans. We provide the most detailed vervet label atlas currently available based on the NeuroMaps atlas with 720 labels successfully registered. We additionally describe a novel method for atlas label generation that capitalizes on previous work in this area using high-dimensional highly accurate image matching procedures for inter-species morphologic normalization.
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Sniderman AD, Toth PP, Thanassoulis G, Pencina MJ, Furberg CD.
BMJ. 2014;348():g3047.
PMID: 24850828
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McDermott MM, Guralnik JM, Criqui MH, Ferrucci L, Zhao L, Liu K, Domanchuk K, Spring B, Tian L, Kibbe M, Liao Y, Lloyd Jones D, Rejeski WJ.
J Am Heart Assoc. 2014 Jun ;3(3):e000711.
PMID: 24850615
We studied whether a 6-month group-mediated cognitive behavioral (GMCB) intervention for peripheral artery disease (PAD) participants, which promoted home-based walking exercise, improved 6-minute walk and other outcomes at 12-month follow-up, 6 months after completing the intervention, compared to a control group.
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Rowland BA, Jiang W, Stein BE.
J Neurosci. 2014 May 21;34(21):7198-202.
PMID: 24849354
Detecting and locating environmental events are markedly enhanced by the midbrain's ability to integrate visual and auditory cues. Its capacity for multisensory integration develops in cats 1-4 months after birth but only after acquiring extensive visual-auditory experience. However, briefly deactivating specific regions of association cortex during this period induced long-term disruption of this maturational process, such that even 1 year later animals were unable to integrate visual and auditory cues to enhance their behavioral performance. The data from this animal model reveal a window of sensitivity within which association cortex mediates the encoding of cross-modal experience in the midbrain. Surprisingly, however, 3 years later, and without any additional intervention, the capacity appeared fully developed. This suggests that, although sensitivity degrades with age, the potential for acquiring or modifying multisensory integration capabilities extends well into adulthood.
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Pasche B, Grant SC.
JAMA. 2014 May 21;311(19):1975-6.
PMID: 24846033
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Mock JR, Garibaldi BT, Aggarwal NR, Jenkins J, Limjunyawong N, Singer BD, Chau E, Rabold R, Files DC, Sidhaye V, Mitzner W, Wagner EM, King LS, D'Alessio FR.
Mucosal Immunol. 2014 May 21. [Epub ahead of print]
PMID: 24850425
Acute respiratory distress syndrome (ARDS) causes significant morbidity and mortality each year. There is a paucity of information regarding the mechanisms necessary for ARDS resolution. Foxp3(+) regulatory T cells (Foxp3(+) Treg cells) have been shown to be an important determinant of resolution in an experimental model of lung injury. We demonstrate that intratracheal delivery of endotoxin (lipopolysaccharide) elicits alveolar epithelial damage from which the epithelium undergoes proliferation and repair. Epithelial proliferation coincided with an increase in Foxp3(+) Treg cells in the lung during the course of resolution. To dissect the role that Foxp3(+) Treg cells exert on epithelial proliferation, we depleted Foxp3(+) Treg cells, which led to decreased alveolar epithelial proliferation and delayed lung injury recovery. Furthermore, antibody-mediated blockade of CD103, an integrin, which binds to epithelial expressed E-cadherin decreased Foxp3(+) Treg numbers and decreased rates of epithelial proliferation after injury. In a non-inflammatory model of regenerative alveologenesis, left lung pneumonectomy, we found that Foxp3(+) Treg cells enhanced epithelial proliferation. Moreover, Foxp3(+) Treg cells co-cultured with primary type II alveolar cells (AT2) directly increased AT2 cell proliferation in a CD103-dependent manner. These studies provide evidence of a new and integral role for Foxp3(+) Treg cells in repair of the lung epithelium.Mucosal Immunology advance online publication, 21 May 2014; doi:10.1038/mi.2014.33.
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Chilton FH, Murphy RC, Wilson BA, Sergeant S, Ainsworth H, Seeds MC, Mathias RA.
Nutrients. 2014 May ;6(5):1993-2022.
PMID: 24853887
The "modern western" diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.
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Newburger JW, Sleeper LA, Frommelt PC, Pearson GD, Mahle WT, Chen S, Dunbar-Masterson C, Mital S, Williams IA, Ghanayem NS, Goldberg CS, Jacobs JP, Krawczeski CD, Lewis AB, Pasquali SK, Pizarro C, Gruber PJ, Atz AM, Khaikin S, Gaynor JW, Ohye RG, .
Circulation. 2014 May 20;129(20):2013-20.
PMID: 24705119
In the Single Ventricle Reconstruction (SVR) trial, 1-year transplantation-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS). At 3 years, we compared transplantation-free survival, echocardiographic right ventricular ejection fraction, and unplanned interventions in the treatment groups.
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Chrispin J, Jain A, Soliman EZ, Guallar E, Alonso A, Heckbert SR, Bluemke DA, Lima JA, Nazarian S.
J Am Coll Cardiol. 2014 May 20;63(19):2007-13.
PMID: 24657688
This study sought to examine the association between left ventricular hypertrophy (LVH), defined by cardiac magnetic resonance (CMR) and electrocardiography (ECG), with incident atrial fibrillation (AF).
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Nader MA, Balster RL, Henningfield JE.
Neuropharmacology. 2014 May 20. [Epub ahead of print]
PMID: 24859612
Clinical findings suggest that the most promising strategy for cocaine addiction is a combination of indirect-acting monoamine agonists with some form of behavioral intervention. This approach can be traced back to preclinical research, some of which was conducted by William L. Woolverton. The goal of this brief review is to provide readers with an appreciation for the experimental breadth involving both behavior and pharmacology that encompassed Woolverton's amazing career, from the evaluation of abuse liability of drugs to the use of complex behavioral contingencies to better model the human condition. We begin with Woolverton's research using simple and complex schedules of reinforcement to evaluate abuse liability and how that has impacted current animal models. We also discuss his use of cocaine vs. food choice schedules of reinforcement as a model to evaluate potential medications for treating cocaine use disorders. Woolverton concluded that drug taking behavior was not "impulsive" and "out of control" as has often been proposed, but rather directly determined by the environmental contingencies and the context of its availability, providing a nuanced understanding of drug-behavior interactions. This article is part of a Special Issue entitled 'CNS Stimulants'
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Wilson CL, Stratton K, Leisenring WM, Oeffinger KC, Nathan PC, Wasilewski-Masker K, Hudson MM, Castellino SM, Stovall M, Armstrong GT, Brinkman TM, Krull KR, Robison LL, Ness KK.
Cancer Epidemiol Biomarkers Prev. 2014 May 19. [Epub ahead of print]
PMID: 24842624
Background: We aimed to identify demographic and health-related predictors of declining physical activity levels over a four year period among participants in the Childhood Cancer Survivor Study. Methods: Analyses included 7287 >5 year childhood cancer survivors and 2107 siblings who completed multiple follow-up questionnaires. Participants were classified as active if they met the Centers for Disease Control and Prevention guidelines for physical activity. Generalized linear models were used to compare participants whose physical activity levels declined from active to inactive over the study to those who remained active. Additionally, selected chronic conditions (CTCAE v4.03 Grade 3 and 4) were evaluated as risk factors in an analysis limited to survivors only. Results: The median age at last follow-up among survivors and siblings was 36 (range: 21-58) and 38 (range: 21-62) years, respectively. The rate of decline did not accelerate over time among survivors when compared with siblings. Factors that predicted declining activity included BMI ≥30kg/m2 (RR=1.32, 95%CI=1.19-1.46, p<0.01), not completing high school (RR=1.31, 95%CI=1.08-1.60, p<0.01), and female sex (RR=1.33, 95%CI=1.22-1.44, p<0.01). Declining physical activity levels were associated with the presence of chronic musculoskeletal conditions (p=0.034), but not with the presence of cardiac (p=0.10), respiratory (p=0.92) or neurological conditions (p=0.21). Conclusions: Interventions designed to maximize physical activity should target female, obese, and less educated survivors. Survivors with chronic musculoskeletal conditions should be monitored, counseled and/or referred for physical therapy. Impact: Clinicians should be aware of low activity levels among sub-populations of childhood cancer survivors which may heighten their risk for chronic illness.
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Zeyl C.
Curr Biol. 2014 May 19;24(10):R394-6.
PMID: 24845668
Different strains of one genetic model species after another are turning out to have limited abilities to interbreed, as if they were on the way to becoming different species. Are model organisms aberrations, or are the first steps in speciation easier than they seem?
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Yamaleyeva LM, Merrill DC, Ebert TJ, Smith TL, Mertz HL, Brosnihan KB.
Hypertens Pregnancy. 2014 May 19. :1-14.[Epub ahead of print]
PMID: 24842292
Background: To understand the role of Angiotensin-(1-7) (Ang-(1-7)) in vasculature of pregnant women, we compared cardiac output (CO), total peripheral resistance (TPR) and forearm blood flow (FBF) responses to Ang-(1-7) infusion between normotensive pregnant women in their third trimester and healthy age matched non-pregnant women. The responses of skin microcirculation to Ang-(1-7) were tested in preeclamptic, normotensive pregnant and non-pregnant women. Responses to Angiotensin II (Ang II) were also determined. Methods: Non-invasive methods for systemic (bioimpedance and VascuMAP), FBF (venous occlusion strain gauge plethysmography), and skin (laser Doppler) hemodynamics assessments were used. Results: Compared to non-pregnant women, systemic infusion of Ang-(1-7) (2000 pmol/min) resulted in a greater increase in CO (9.4 ± 6.4 versus -3.3 ± 2.1%, n = 9-10) in normotensive pregnant women. Brachial local infusion of Ang-(1-7) had no effect on FBF in either group. In non-pregnant and normotensive pregnant women, local Ang II induced a dose-dependent decrease in FBF and increase in forearm resistance at 50 and 100 pmol/min (p < 0.05 versus corresponding baseline, n = 7-10). Following iontophoretic application of 5 mmol/l dose of Ang-(1-7), the change in skin flow was higher in normotensive pregnant versus preeclamptic women (182.5 ± 93 versus 15.76 ± 19.46%, n = 14-15). Skin flow was lower in normotensive pregnant versus preeclamptic women (-46.5 ± 48.7 versus 108.7 ± 49.1%, n = 14-15) following Ang II infusion at 1.0 pmol/min. Conclusion: In the third trimester of pregnancy, Ang-(1-7) induces alterations in CO and differentially regulates micro- and macro-circulations, depending on the dose. Dysregulation in skin vasculature may contribute to the development of vascular dysfunction and hypertension in preeclampsia.
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Vaidya D, Bennett WL, Sibley CT, Polak JF, Herrington DM, Ouyang P.
Hypertension. 2014 May 19. [Epub ahead of print]
PMID: 24842921
Pregnancy and childbirth are associated with hemodynamic changes and vascular remodeling. It is not known whether parity is associated with later adverse vascular properties such as larger arterial diameter, wall thickness, and lower distensibility. We used baseline data from 3283 women free of cardiovascular disease aged 45 to 84 years enrolled in the population-based Multi-Ethnic Study of Atherosclerosis. Participants self-reported parity status. Ultrasound-derived carotid artery lumen diameters and brachial artery blood pressures were measured at peak-systole and end-diastole. Common carotid intima-media thickness was also measured. Regression models to determine the association of carotid distensibility coefficient, lumen diameter, and carotid intima-media thickness with parity were adjusted for age, race, height, weight, diabetes mellitus, current smoking, blood pressure medication use, and total and high-density lipoprotein cholesterol levels. The prevalence of nulliparity was 18%. In adjusted models, carotid distensibility coefficient was 0.09×10(-5) Pa(-1) lower (P=0.009) in parous versus nulliparous women. Among parous women, there was a nonlinear association with the greatest carotid distensibility coefficient seen in women with 2 live births and significantly lower distensibility seen in primiparas (P=0.04) or with higher parity >2 (P=0.005). No such pattern of association with parity was found for lumen diameter or carotid intima-media thickness. Parity is associated with lower carotid artery distensibility, suggesting arterial remodeling that lasts beyond childbirth. These long-term effects on the vasculature may explain the association of parity with cardiovascular events later in life.
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Colaco M, Koslov DS, Keys T, Evans RJ, Badlani GH, Andersson KE, Walker SJ.
J Urol. 2014 May 17. [Epub ahead of print]
PMID: 24840534
Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression.
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Bolandzadeh N, Liu-Ambrose T, Aizenstein H, Harris T, Launer L, Yaffe K, Kritchevsky SB, Newman A, Rosano C.
Neuroimage. 2014 May 17;99C():7-13.[Epub ahead of print]
PMID: 24841418
Cerebral white matter hyperintensities (WMHs) are involved in the evolution of impaired mobility and executive functions. Executive functions and mobility are also associated. Thus, WMHs may impair mobility directly, by disrupting mobility-related circuits, or indirectly, by disrupting circuits responsible for executive functions. Understanding the mechanisms underlying impaired mobility in late life will increase our capacity to develop effective interventions.
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Casey BM, Mele L, Landon MB, Spong CY, Ramin SM, Wapner RJ, Varner MW, Rouse DJ, Thorp JM, Catalano P, Harper M, Saade G, Sorokin Y, Peaceman AM, .
Am J Perinatol. 2014 May 16. [Epub ahead of print]
PMID: 24839145
Objective The aim of the article is to determine whether maternal body mass index (BMI) influences the beneficial effects of diabetes treatment in women with gestational diabetes mellitus (GDM). Study Design Secondary analysis of a multicenter randomized treatment trial of women with GDM. Outcomes of interest were elevated umbilical cord c-peptide levels (> 90th percentile 1.77 ng/mL), large for gestational age (LGA) birth weight (> 90th percentile), and neonatal fat mass (g). Women were grouped into five BMI categories adapted from the World Health Organization International Classification of normal, overweight, and obese adults. Outcomes were analyzed according to treatment group assignment. Results A total of 958 women were enrolled (485 treated and 473 controls). Maternal BMI at enrollment was not related to umbilical cord c-peptide levels. However, treatment of women in the overweight, Class I, and Class II obese categories was associated with a reduction in both LGA birth weight and neonatal fat mass. Neither measure of excess fetal growth was reduced with treatment in normal weight (BMI < 25 kg/m(2)) or Class III (BMI ≥ 40 kg/m(2)) obese women. Conclusion There was a beneficial effect of treatment on fetal growth in women with mild GDM who were overweight or Class I and Class II obese. These effects were not apparent for normal weight and very obese women.
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Barnes LE, Al-Dabagh A, Huang WW, Feldman SR.
Dermatol Online J. 2014 May ;20(5):22609.
PMID: 24852769
Communication between physicians and patients is essential to providing proper medical care. At times, patients leave visits with insufficiently addressed questions. These questions prompt patients to call the clinic for additional information, which disrupts the flow of care, delays proper treatment, and reduces patient satisfaction.
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