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Zhang C, Murphy SV, Atala A.
Semin Pediatr Surg. 2014 Jun ;23(3):106-11.
PMID: 24994523
Repair and reconstruction of damaged tissues and organs has been a major issue in the medical field. Regenerative medicine and tissue engineering, as rapid evolving technologies, may offer alternative treatments and hope for patients with serious defects and end-stage diseases. Most urologic diseases could benefit from the development of regenerative medicine and tissue engineering. This article discusses the role of cells and materials in regenerative medicine, as well as the status of current role of regenerative medicine for the generation of specific urologic organs.
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Zeidan F, Martucci KT, Kraft RA, McHaffie JG, Coghill RC.
Soc Cogn Affect Neurosci. 2014 Jun ;9(6):751-9.
PMID: 23615765
Anxiety is the cognitive state related to the inability to control emotional responses to perceived threats. Anxiety is inversely related to brain activity associated with the cognitive regulation of emotions. Mindfulness meditation has been found to regulate anxiety. However, the brain mechanisms involved in meditation-related anxiety relief are largely unknown. We employed pulsed arterial spin labeling MRI to compare the effects of distraction in the form of attending to the breath (ATB; before meditation training) to mindfulness meditation (after meditation training) on state anxiety across the same subjects. Fifteen healthy subjects, with no prior meditation experience, participated in 4 d of mindfulness meditation training. ATB did not reduce state anxiety, but state anxiety was significantly reduced in every session that subjects meditated. Meditation-related anxiety relief was associated with activation of the anterior cingulate cortex, ventromedial prefrontal cortex and anterior insula. Meditation-related activation in these regions exhibited a strong relationship to anxiety relief when compared to ATB. During meditation, those who exhibited greater default-related activity (i.e. posterior cingulate cortex) reported greater anxiety, possibly reflecting an inability to control self-referential thoughts. These findings provide evidence that mindfulness meditation attenuates anxiety through mechanisms involved in the regulation of self-referential thought processes.
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Pichardo-Geisinger R, Mora DC, Newman JC, Arcury TA, Feldman SR, Quandt SA.
South Med J. 2014 Jun ;107(6):374-9.
PMID: 24945173
Latino immigrant workers experience elevated rates of skin disease that result from their working and living conditions. Working in manual occupations exposes workers to a variety of challenges, including occlusive shoes, vigorous physical activity, and wet conditions. These challenges predispose workers to fungal infection. The objectives of this article are to examine the comorbidity of tinea pedis and onychomycosis and to identify possible risk factors among Latino immigrant poultry and nonpoultry workers in western North Carolina.
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McClure LA, Kleindorfer DO, Kissela BM, Cushman M, Soliman EZ, Howard G.
Stroke. 2014 Jun ;45(6):1716-20.
PMID: 24736237
The most well-known stroke risk score is the Framingham Stroke Risk Score (FSRS), which was developed during the higher stroke risk period of the 1990s and has not been validated for blacks. We assessed the performance of the FSRS among participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine whether it is useful in both blacks and whites.
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O'Neal WT, Efird JT, Davies SW, O'Neal JB, Anderson CA, Chitwood WR, Ferguson TB, Kypson AP.
Thorac Cardiovasc Surg. 2014 Jun ;62(4):308-16.
PMID: 24163260
Diabetes is a known predictor of decreased long-term survival after coronary artery bypass grafting (CABG). Differences in survival by race have not been examined.
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Gilmont RR, Raghavan S, Somara S, Bitar KN.
Tissue Eng Part A. 2014 Jun ;20(11-12):1603-11.
PMID: 24328537
Muscle replacement for patients suffering from extensive tissue loss or dysfunction is a major objective of regenerative medicine. To achieve functional status, bioengineered muscle replacement constructs require innervation. Here we describe a method to bioengineer functionally innervated gut smooth muscle constructs using neuronal progenitor cells and smooth muscle cells isolated and cultured from intestinal tissues of adult human donors. These constructs expressed markers for contractile smooth muscle, glial cells, and mature neuronal populations. The constructs responded appropriately to physiologically relevant neurotransmitters, and neural network integration was demonstrated by responses to electrical field stimulation. The ability of enteric neuroprogenitor cells to differentiate into neuronal populations provides enormous potential for functional innervation of a variety of bioengineered muscle constructs in addition to gut. Functionally innervated muscle constructs offer a regenerative medicine-based therapeutic approach for neuromuscular replacement after trauma or degenerative disorders.
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Randall LM, Manta B, Hugo M, Gil M, Batthyàny C, Trujillo M, Poole LB, Denicola A.
J Biol Chem. 2014 May 30;289(22):15536-15543.
PMID: 24719319
Peroxiredoxins (Prx) are efficient thiol-dependent peroxidases and key players in the mechanism of H2O2-induced redox signaling. Any structural change that could affect their redox state, oligomeric structure, and/or interaction with other proteins could have a significant impact on the cascade of signaling events. Several post-translational modifications have been reported to modulate Prx activity. One of these, overoxidation of the peroxidatic cysteine to the sulfinic derivative, inactivates the enzyme and has been proposed as a mechanism of H2O2 accumulation in redox signaling (the floodgate hypothesis). Nitration of Prx has been reported in vitro as well as in vivo; in particular, nitrated Prx2 was identified in brains of Alzheimer disease patients. In this work we characterize Prx2 tyrosine nitration, a post-translational modification on a noncatalytic residue that increases its peroxidase activity and its resistance to overoxidation. Mass spectrometry analysis revealed that treatment of disulfide-oxidized Prx2 with excess peroxynitrite renders mainly mononitrated and dinitrated species. Tyrosine 193 of the YF motif at the C terminus, associated with the susceptibility toward overoxidation of eukaryotic Prx, was identified as nitrated and is most likely responsible for the protection of the peroxidatic cysteine against oxidative inactivation. Kinetic analyses suggest that tyrosine nitration facilitates the intermolecular disulfide formation, transforming a sensitive Prx into a robust one. Thus, tyrosine nitration appears as another mechanism to modulate these enzymes in the complex network of redox signaling.
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Colaco M, Mettu J, Badlani G.
BJU Int. 2014 May 29. [Epub ahead of print]
PMID: 24889349
Pelvic floor diseases (PFDS) such as stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are common and vexing disorders. While synthetic mesh based repairs have long been considered an option for PFD treatment, and their efficacy established in RCT trials, safety of its use has recently been called into question. In order to better understand this controversy we reviewed the scientific and clinical literature to assess the basis for its use.
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Waugh CE, Koster EH.
Clin Psychol Rev. 2014 May 29. [Epub ahead of print]
PMID: 24930712
A significant proportion of people in remission from depression will experience a recurrence of depression. One theoretical mechanism for this recurrence is that with each additional episode of depression, people become more sensitive to the deleterious effects of less powerful stressors. We propose that research on resilience - the ability to adapt to and recover from stress - can inform interventions to prevent recurrence in people in remission. We conceptualize resilience as a dynamic process that may be deficient in people in remission from depression, rather than as a static personal quality that is unattainable to people who have experienced psychopathology. The three aspects of resilience that we suggest are the most important to target to prevent recurrence are (1) improving stress recovery from minor daily stressors that may aid remitted people in coping with major stressors, (2) increasing positivity, like promoting positive emotions during stress, and (3) and training flexibility-the ability to identify different demands in the environment and employ the appropriate coping strategy to meet those demands. We offer suggestions for the appropriate assessment of changes in resilience in remitted people and provide some examples of effective resilience interventions.
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Armstrong DL, Zidovetzki R, Alarcón-Riquelme ME, Tsao BP, Criswell LA, Kimberly RP, Harley JB, Sivils KL, Vyse TJ, Gaffney PM, Langefeld CD, Jacob CO.
Genes Immun. 2014 May 29. [Epub ahead of print]
PMID: 24871463
In a genome-wide association study (GWAS) of individuals of European ancestry afflicted with systemic lupus erythematosus (SLE) the extensive utilization of imputation, step-wise multiple regression, lasso regularization and increasing study power by utilizing false discovery rate instead of a Bonferroni multiple test correction enabled us to identify 13 novel non-human leukocyte antigen (HLA) genes and confirmed the association of four genes previously reported to be associated. Novel genes associated with SLE susceptibility included two transcription factors (EHF and MED1), two components of the NF-κB pathway (RASSF2 and RNF114), one gene involved in adhesion and endothelial migration (CNTN6) and two genes involved in antigen presentation (BIN1 and SEC61G). In addition, the strongly significant association of multiple single-nucleotide polymorphisms (SNPs) in the HLA region was assigned to HLA alleles and serotypes and deconvoluted into four primary signals. The novel SLE-associated genes point to new directions for both the diagnosis and treatment of this debilitating autoimmune disease.Genes and Immunity advance online publication, 29 May 2014; doi:10.1038/gene.2014.23.
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Carlsen AT, Zahid OK, Ruzicka JA, Taylor EW, Hall AR.
Nano Lett. 2014 May 29. [Epub ahead of print]
PMID: 24821614
We demonstrate a solid-state nanopore assay for the unambiguous discrimination and quantification of modified DNA. Individual streptavidin proteins are employed as high-affinity tags for DNA containing a single biotin moiety. We establish that the rate of translocation events corresponds directly to relative concentration of protein-DNA complexes and use the selectivity of our approach to quantify modified oligonucleotides from among a background of unmodified DNA in solution.
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Carlsen AT, Zahid OK, Ruzicka J, Taylor EW, Hall AR.
ACS Nano. 2014 May 27;8(5):4754-60.
PMID: 24758739
Solid-state nanopore electrical signatures can be convoluted and are thus challenging to interpret. In order to better understand the origin of these conductance changes, we investigate the translocation of DNA through small, thin pores over a range of voltage. We observe multiple, discrete populations of conductance blockades that vary with applied voltage. To describe our observations, we develop a simple model that is applicable to solid-state nanopores generally. These results represent an important step toward understanding the dynamics of the electrokinetic translocation process.
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Olex AL, Turkett WH, Fetrow JS, Loeser RF.
Gene. 2014 May 25;542(1):38-45.
PMID: 24630964
Osteoarthritis (OA) is characterized by remodeling and degradation of joint tissues. Microarray studies have led to a better understanding of the molecular changes that occur in tissues affected by conditions such as OA; however, such analyses are limited to the identification of a list of genes with altered transcript expression, usually at a single time point during disease progression. While these lists have identified many novel genes that are altered during the disease process, they are unable to identify perturbed relationships between genes and gene products. In this work, we have integrated a time course gene expression dataset with network analysis to gain a better systems level understanding of the early events that occur during the development of OA in a mouse model. The subnetworks that were enriched at one or more of the time points examined (2, 4, 8, and 16 weeks after induction of OA) contained genes from several pathways proposed to be important to the OA process, including the extracellular matrix-receptor interaction and the focal adhesion pathways and the Wnt, Hedgehog and TGF-β signaling pathways. The genes within the subnetworks were most active at the 2 and 4 week time points and included genes not previously studied in the OA process. A unique pathway, riboflavin metabolism, was active at the 4 week time point. These results suggest that the incorporation of network-type analyses along with time series microarray data will lead to advancements in our understanding of complex diseases such as OA at a systems level, and may provide novel insights into the pathways and processes involved in disease pathogenesis.
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Remer EM, Papanicolaou N, Casalino DD, Bishoff JT, Blaufox MD, Coursey CA, Dighe M, Eberhardt SC, Goldfarb S, Harvin HJ, Heilbrun ME, Leyendecker JR, Nikolaidis P, Oto A, Preminger GM, Raman SS, Sheth S, Vikram R, Weinfeld RM.
Am J Med. 2014 May 24. [Epub ahead of print]
PMID: 24865874
Imaging plays a role in the management of patients with acute kidney injury or chronic kidney disease However, clinical circumstances strongly impact the appropriateness of imaging use. In patients with newly detected renal dysfunction, ultrasonography can assess for reversible causes, assess renal size and echogenicity and, thus, establish the chronicity of disease. Urinary obstruction can be detected, but imaging is most useful in high-risk groups or in patients in whom there is a strong clinical suspicion for obstruction. CT, CT or MR arteriography, and percutaneous ultrasound-guided renal biopsy are valuable in other clinical situations. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
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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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