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Changes in inflammatory biomarkers following spinal manipulation.

Recent Research Articles from UNTHSC - Wed, 05/24/2017 - 07:35
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Changes in inflammatory biomarkers following spinal manipulation.

Musculoskelet Sci Pract. 2017 May 17;:

Authors: Licciardone JC

PMID: 28533071 [PubMed - as supplied by publisher]

HIV-1 Tat Induces Unfolded Protein Response and Endoplasmic Reticulum Stress in Astrocytes and Causes Neurotoxicity through Glial Fibrillary Acidic Protein (GFAP) Activation and Aggregation.

Recent Research Articles from UNTHSC - Tue, 05/23/2017 - 07:34
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HIV-1 Tat Induces Unfolded Protein Response and Endoplasmic Reticulum Stress in Astrocytes and Causes Neurotoxicity through Glial Fibrillary Acidic Protein (GFAP) Activation and Aggregation.

J Biol Chem. 2016 Oct 21;291(43):22819-22829

Authors: Fan Y, He JJ

Abstract
HIV-1 Tat is a major culprit for HIV/neuroAIDS. One of the consistent hallmarks of HIV/neuroAIDS is reactive astrocytes or astrocytosis, characterized by increased cytoplasmic accumulation of the intermediate filament glial fibrillary acidic protein (GFAP). We have shown that that Tat induces GFAP expression in astrocytes and that GFAP activation is indispensable for astrocyte-mediated Tat neurotoxicity. However, the underlying molecular mechanisms are not known. In this study, we showed that Tat expression or GFAP expression led to formation of GFAP aggregates and induction of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress in astrocytes. In addition, we demonstrated that GFAP up-regulation and aggregation in astrocytes were necessary but also sufficient for UPR/ER stress induction in Tat-expressing astrocytes and for astrocyte-mediated Tat neurotoxicity. Importantly, we demonstrated that inhibition of Tat- or GFAP-induced UPR/ER stress by the chemical chaperone 4-phenylbutyrate significantly alleviated astrocyte-mediated Tat neurotoxicity in vitro and in the brain of Tat-expressing mice. Taken together, these results show that HIV-1 Tat expression leads to UPR/ER stress in astrocytes, which in turn contributes to astrocyte-mediated Tat neurotoxicity, and raise the possibility of developing HIV/neuroAIDS therapeutics targeted at UPR/ER stress.

PMID: 27609520 [PubMed - indexed for MEDLINE]

HIV-1 Tat Promotes Lysosomal Exocytosis in Astrocytes and Contributes to Astrocyte-mediated Tat Neurotoxicity.

Recent Research Articles from UNTHSC - Tue, 05/23/2017 - 07:34
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HIV-1 Tat Promotes Lysosomal Exocytosis in Astrocytes and Contributes to Astrocyte-mediated Tat Neurotoxicity.

J Biol Chem. 2016 Oct 21;291(43):22830-22840

Authors: Fan Y, He JJ

Abstract
Tat interaction with astrocytes has been shown to be important for Tat neurotoxicity and HIV/neuroAIDS. We have recently shown that Tat expression leads to increased glial fibrillary acidic protein (GFAP) expression and aggregation and activation of unfolded protein response/endoplasmic reticulum (ER) stress in astrocytes and causes neurotoxicity. However, the exact molecular mechanism of astrocyte-mediated Tat neurotoxicity is not defined. In this study, we showed that neurotoxic factors other than Tat protein itself were present in the supernatant of Tat-expressing astrocytes. Two-dimensional gel electrophoresis and mass spectrometry revealed significantly elevated lysosomal hydrolytic enzymes and plasma membrane-associated proteins in the supernatant of Tat-expressing astrocytes. We confirmed that Tat expression and infection of pseudotyped HIV.GFP led to increased lysosomal exocytosis from mouse astrocytes and human astrocytes. We found that Tat-induced lysosomal exocytosis was tightly coupled to astrocyte-mediated Tat neurotoxicity. In addition, we demonstrated that Tat-induced lysosomal exocytosis was astrocyte-specific and required GFAP expression and was mediated by ER stress. Taken together, these results show for the first time that Tat promotes lysosomal exocytosis in astrocytes and causes neurotoxicity through GFAP activation and ER stress induction in astrocytes and suggest a common cascade through which aberrant astrocytosis/GFAP up-regulation potentiates neurotoxicity and contributes to neurodegenerative diseases.

PMID: 27609518 [PubMed - indexed for MEDLINE]

Current Alcohol Use is Associated with Sleep Patterns in First-Year College Students.

Recent Research Articles from UNTHSC - Tue, 05/23/2017 - 07:34
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Current Alcohol Use is Associated with Sleep Patterns in First-Year College Students.

Sleep. 2016 06 01;39(6):1321-6

Authors: Van Reen E, Roane BM, Barker DH, McGeary JE, Borsari B, Carskadon MA

Abstract
STUDY OBJECTIVES: To examine whether differences exist in self-reported sleep patterns and self-reported alcohol use for first-semester college students who do or do not report drinking during the last 6 months (mo) of high school.
METHODS: Participants were 878 first-year college students. Students completed a survey in late May/early June about alcohol use and consequences, during the last 6 mo of high school; they later completed a daily record of sleep behavior and alcohol use across the first 9 weeks of the first semester of college. High school drinking status (past 6 mo) was classified as positive (HS-6 mo+) or negative (HS-6mo-) based on any indication of drinking on the May/June survey. Collegiate drinking was determined from first-semester daily diary alcohol reports as non-drinkers (0 reported drinks), drinkers (one or fewer heavy episodic drinking episodes (HED)), and drinkers reporting more than one HED episode. Sleep patterns were compared for non-drinkers, drinkers, and HED with no high school drinking history (HS-6mo-/HED). In addition, a separate analysis compared sleep patterns for college HED with (HS-6mo+/HED) and without (HS-6mo-/HED) high school self-reported alcohol use.
RESULTS: Increased alcohol consumption in the first semester of college was associated with later bedtimes and rise times. We found no association of high school alcohol use and sleep in those with collegiate HED.
CONCLUSIONS: Later sleep timing in those with greater alcohol use, supports a connection between sleep patterns and alcohol use. Such an early appearance of this connection may herald the development of alcohol use disorder in some individuals.

PMID: 27070138 [PubMed - indexed for MEDLINE]

Breaking Up Sedentary Behavior: Perceptions From Cancer Survivors.

Recent Research Articles from UNTHSC - Tue, 05/23/2017 - 07:34
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Breaking Up Sedentary Behavior: Perceptions From Cancer Survivors.

Cancer Nurs. 2016 Jul-Aug;39(4):272-8

Authors: Paxton RJ, Anderson A, Sarkar S, Taylor WC

Abstract
BACKGROUND: Limited data exist on the benefits of, barriers to, and potential strategies to break up time spent sitting in cancer survivors. Such data will be meaningful given the consequences of prolonged sitting.
OBJECTIVES: The aim of this study was to conduct a mixed-method research study consisting of semistructured telephone interviews to identify recurrent themes associated with prolonged sitting in cancer survivors.
METHODS: African American breast cancer survivors (N = 31) were recruited from a local tumor registry. Telephone interviews were conducted and group consensus processes were used to identify recurrent themes. The a priori categories were benefits, barriers, and potential strategies to breaking up prolonged periods of sitting.
RESULTS: Recurrent themes contributing most to prolonged sitting were leisure time interest (45%: eg, watching television and reading) and health challenges (27%: eg, pain and fatigue). Most (66%) women perceived improved health as benefits to breaking up time spent sitting. Nonetheless, many (41%) survivors reported health (eg, pain and fatigue) as the biggest challenge to interrupt time spent sitting. Engaging in light intensity activities (eg, staying active, keep moving) was the most commonly reported strategy for breaking up prolonged sitting.
CONCLUSIONS: African American breast cancer survivors identified the benefits and barriers to breaking up time spent sitting as well as potential strategies to interrupt time-spent sitting.
IMPLICATIONS FOR PRACTICE: Clinicians are integral in promoting breaks from prolonged sitting throughout the initial phases of the cancer continuum. Successful studies will begin with early intervention in the clinical setting, with increasing intensity as survivors transition to the recovery phase.

PMID: 26713501 [PubMed - indexed for MEDLINE]

Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU.

Recent Research Articles from UNTHSC - Fri, 05/19/2017 - 07:39

Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU.

PLoS One. 2017;12(5):e0176286

Authors: Durrer KE, Allen MS, Hunt von Herbing I

Abstract
Phenylketonuria (PKU) is a genetic disease characterized by the inability to convert dietary phenylalanine to tyrosine by phenylalanine hydroxylase. Given the importance of gut microbes in digestion, a genetically engineered microbe could potentially degrade some ingested phenylalanine from the diet prior to absorption. To test this, a phenylalanine lyase gene from Anabaena variabilis (AvPAL) was codon-optimized and cloned into a shuttle vector for expression in Lactobacillus reuteri 100-23C (pHENOMMenal). Functional expression of AvPAL was determined in vitro, and subsequently tested in vivo in homozygous PAHenu2 (PKU model) mice. Initial trials of two PAHenu2 homozygous (PKU) mice defined conditions for freeze-drying and delivery of bacteria. Animals showed reduced blood phe within three to four days of treatment with pHENOMMenal probiotic, and blood phe concentrations remained significantly reduced (P < 0.0005) compared to untreated controls during the course of experiments. Although pHENOMMenal probiotic could be cultured from fecal samples at four months post treatment, it could no longer be cultivated from feces at eight months post treatment, indicating eventual loss of the microbe from the gut. Preliminary screens during experimentation found no immune response to AvPAL. Collectively these studies provide data for the use of a genetically engineered probiotic as a potential treatment for PKU.

PMID: 28520731 [PubMed - in process]

Extracellular Superoxide Dismutase Enhances Recruitment of Immature Neutrophils to the Liver.

Recent Research Articles from UNTHSC - Fri, 05/19/2017 - 07:39
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Extracellular Superoxide Dismutase Enhances Recruitment of Immature Neutrophils to the Liver.

Infect Immun. 2016 Dec;84(12):3302-3312

Authors: Break TJ, Witter AR, Indramohan M, Mummert ME, Dory L, Berg RE

Abstract
Listeria monocytogenes is a Gram-positive intracellular pathogen that causes spontaneous abortion in pregnant women, as well as septicemia, meningitis, and gastroenteritis, primarily in immunocompromised individuals. Although L. monocytogenes can usually be effectively treated with antibiotics, there is still around a 25% mortality rate with individuals who develop clinical listeriosis. Neutrophils are innate immune cells required for the clearance of pathogenic organisms, including L. monocytogenes The diverse roles of neutrophils during both infectious and noninfectious inflammation have recently gained much attention. However, the impact of reactive oxygen species, and the enzymes that control their production, on neutrophil recruitment and function is not well understood. Using congenic mice with varying levels of extracellular superoxide dismutase (ecSOD) activity, we have recently shown that the presence of ecSOD decreases clearance of L. monocytogenes while increasing the recruitment of neutrophils that are not protective in the liver. The data presented here show that ecSOD activity does not lead to a cell-intrinsic increase in neutrophil-homing potential or a decrease in protection against L. monocytogenes Instead, ecSOD activity enhances the production of neutrophil-attracting factors and protects hyaluronic acid (HA) from damage. Furthermore, neutrophils from the livers of ecSOD-expressing mice have decreased intracellular and surface-bound myeloperoxidase, are less capable of killing phagocytosed L. monocytogenes, and have decreased oxidative burst. Collectively, our data reveal that ecSOD activity modulates neutrophil recruitment and function in a cell-extrinsic fashion, highlighting the importance of the enzyme in protecting tissues from oxidative damage.

PMID: 27600509 [PubMed - indexed for MEDLINE]

Therapeutic drug monitoring of posaconazole oral suspension in paediatric patients younger than 13 years of age: a retrospective analysis and literature review.

Recent Research Articles from UNTHSC - Thu, 05/18/2017 - 07:40
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Therapeutic drug monitoring of posaconazole oral suspension in paediatric patients younger than 13 years of age: a retrospective analysis and literature review.

J Clin Pharm Ther. 2017 Feb;42(1):75-79

Authors: Jancel T, Shaw PA, Hallahan CW, Kim T, Freeman AF, Holland SM, Penzak SR

Abstract
WHAT IS KNOWN AND OBJECTIVE: Posaconazole is an extended-spectrum triazole antifungal with activity against a variety of clinically significant yeasts and moulds. Posaconazole is not currently approved by the U.S. Food and Drug Administration for use in children younger than 13 years of age. Our primary objective was to describe the dosing and observed trough concentrations with posaconazole oral suspension in paediatric patients at the National Institutes of Health Clinical Center (Bethesda, MD).
METHODS: This retrospective single-centre study reviewed paediatric patients younger than 13 years of age initiated on posaconazole oral suspension. Patients were included if they were initiated on posaconazole for prophylaxis or treatment for fungal infections from September 2006 through March 2013 with at least one trough concentration collected after at least 7 days of therapy.
RESULTS AND DISCUSSION: A total of 20 male patients were included, of whom 15 (75%) had chronic granulomatous disease. The median age of patients was 6·5 years (range: 2·8-10·7). A total of 79 posaconazole trough concentrations were measured in patients receiving posaconazole as prophylaxis (n = 8) or treatment (n = 12). Posaconazole dose referenced to total body weight ranged from 10·0 to 49·2 mg/kg/day. Posaconazole trough concentrations ranged from undetectable (<50 ng/mL) up to 3620 ng/mL and were ≥500, ≥700 and ≥1250 ng/mL in 95%, 60% and 25% of patients, respectively.
WHAT IS NEW AND CONCLUSIONS: Patients younger than 13 years of age had highly variable trough concentrations, and recommendations for the appropriate dosing of posaconazole oral suspension remain challenging. Until studies are conducted to determine the appropriate dosing of posaconazole in this patient population, therapeutic drug monitoring should be considered to ensure adequate posaconazole exposure.

PMID: 27982447 [PubMed - indexed for MEDLINE]

Reiteration of the Statistical Basis of DNA Source Attribution Determinations in View of the Attorney General's Directive on "Reasonable Scientific Certainty" Statements.

Recent Research Articles from UNTHSC - Wed, 05/17/2017 - 10:01
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Reiteration of the Statistical Basis of DNA Source Attribution Determinations in View of the Attorney General's Directive on "Reasonable Scientific Certainty" Statements.

J Forensic Sci. 2017 May 16;:

Authors: Moretti TR, Budowle B

PMID: 28508395 [PubMed - as supplied by publisher]

Evolving Relevance of Neuroproteomics in Alzheimer's Disease.

Recent Research Articles from UNTHSC - Wed, 05/17/2017 - 10:01
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Evolving Relevance of Neuroproteomics in Alzheimer's Disease.

Methods Mol Biol. 2017;1598:101-115

Authors: Lista S, Zetterberg H, O'Bryant SE, Blennow K, Hampel H

Abstract
Substantial progress in the understanding of the biology of Alzheimer's disease (AD) has been achieved over the past decades. The early detection and diagnosis of AD and other age-related neurodegenerative diseases, however, remain a challenging scientific frontier. Therefore, the comprehensive discovery (relating to all individual, converging or diverging biochemical disease mechanisms), development, validation, and qualification of standardized biological markers with diagnostic and prognostic functions with a precise performance profile regarding specificity, sensitivity, and positive and negative predictive value are warranted.Methodological innovations in the area of exploratory high-throughput technologies, such as sequencing, microarrays, and mass spectrometry-based analyses of proteins/peptides, have led to the generation of large global molecular datasets from a multiplicity of biological systems, such as biological fluids, cells, tissues, and organs. Such methodological progress has shifted the attention to the execution of hypothesis-independent comprehensive exploratory analyses (opposed to the classical hypothesis-driven candidate approach), with the aim of fully understanding the biological systems in physiology and disease as a whole. The systems biology paradigm integrates experimental biology with accurate and rigorous computational modelling to describe and foresee the dynamic features of biological systems. The use of dynamically evolving technological platforms, including mass spectrometry, in the area of proteomics has enabled to rush the process of biomarker discovery and validation for refining significantly the diagnosis of AD. Currently, proteomics-which is part of the systems biology paradigm-is designated as one of the dominant matured sciences needed for the effective exploratory discovery of prospective biomarker candidates expected to play an effective role in aiding the early detection, diagnosis, prognosis, and therapy development in AD.

PMID: 28508359 [PubMed - in process]

Altered levels of blood proteins in Alzheimer's disease longitudinal study: Results from Australian Imaging Biomarkers Lifestyle Study of Ageing cohort.

Recent Research Articles from UNTHSC - Wed, 05/17/2017 - 10:01
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Altered levels of blood proteins in Alzheimer's disease longitudinal study: Results from Australian Imaging Biomarkers Lifestyle Study of Ageing cohort.

Alzheimers Dement (Amst). 2017;8:60-72

Authors: Gupta VB, Hone E, Pedrini S, Doecke J, O'Bryant S, James I, Bush AI, Rowe CC, Villemagne VL, Ames D, Masters CL, Martins RN, AIBL Research Group

Abstract
INTRODUCTION: A blood-based biomarker panel to identify individuals with preclinical Alzheimer's disease (AD) would be an inexpensive and accessible first step for routine testing.
METHODS: We analyzed 14 biomarkers that have previously been linked to AD in the Australian Imaging Biomarkers lifestyle longitudinal study of aging cohort.
RESULTS: Levels of apolipoprotein J (apoJ) were higher in AD individuals compared with healthy controls at baseline and 18 months (P = .0003) and chemokine-309 (I-309) were increased in AD patients compared to mild cognitive impaired individuals over 36 months (P = .0008).
DISCUSSION: These data suggest that apoJ may have potential in the context of use (COU) of AD diagnostics, I-309 may be specifically useful in the COU of identifying individuals at greatest risk for progressing toward AD. This work takes an initial step toward identifying blood biomarkers with potential use in the diagnosis and prognosis of AD and should be validated across other prospective cohorts.

PMID: 28508031 [PubMed - in process]

Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study.

Recent Research Articles from UNTHSC - Sun, 05/14/2017 - 07:36

Treatment of refractory epilepsy patients with autologous mesenchymal stem cells reduces seizure frequency: An open label study.

Adv Med Sci. 2017 May 10;62(2):273-279

Authors: Hlebokazov F, Dakukina T, Ihnatsenko S, Kosmacheva S, Potapnev M, Shakhbazau A, Goncharova N, Makhrov M, Korolevich P, Misyuk N, Dakukina V, Shamruk I, Slobina E, Marchuk S

Abstract
PURPOSE: Existing anti-epileptic drugs (AED) have limited efficiency in many patients, necessitating the search for alternative approaches such as stem cell therapy. We report the use of autologous patient-derived mesenchymal stem cells (MSC) as a therapeutic agent in symptomatic drug-resistant epilepsy in a Phase I open label clinical trial (registered as NCT02497443).
PATIENTS AND METHODS: The patients received either standard treatment with AED (control group), or AED supplemented with single intravenous administration of undifferentiated autologous MSC (target dose of 1×10(6)cells/kg), followed by a single intrathecal injection of neurally induced autologous MSC (target dose of 0.1×10(6)cells/kg).
RESULTS: MSC injections were well tolerated and did not cause any severe adverse effects. Seizure frequency was designated as the main outcome and evaluated at 1 year time point. 3 out of 10 patients in MSC therapy group achieved remission (no seizures for one year and more), and 5 additional patients became responders to AEDs, while only 2 out of 12 patients became responders in control group (difference significant, P=0.0135).
CONCLUSIONS: MSC possess unique immunomodulatory properties and are a safe and promising candidate for cell therapy in AED resistant epilepsy patients.

PMID: 28500900 [PubMed - as supplied by publisher]

European survey on forensic applications of massively parallel sequencing.

Recent Research Articles from UNTHSC - Sat, 05/13/2017 - 07:33
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European survey on forensic applications of massively parallel sequencing.

Forensic Sci Int Genet. 2017 Apr 26;:

Authors: Alonso A, Müller P, Roewer L, Willuweit S, Budowle B, Parson W

PMID: 28495357 [PubMed - as supplied by publisher]

A pilot mobile integrated healthcare program for frequent utilizers of emergency department services.

Recent Research Articles from UNTHSC - Sat, 05/13/2017 - 07:33
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A pilot mobile integrated healthcare program for frequent utilizers of emergency department services.

Am J Emerg Med. 2017 Apr 27;:

Authors: Nejtek VA, Aryal S, Talari D, Wang H, O'Neill L

Abstract
PURPOSE: To examine whether or not a mobile integrated health (MIH) program may improve health-related quality of life while reducing emergency department (ED) transports, ED admissions, and inpatient hospital admissions in frequent utilizers of ED services.
METHODS: A small retrospective evaluation assessing pre- and post-program quality of life, ED transports, ED admissions, and inpatient hospital admissions was conducted in patients who frequently used the ED for non-emergent or emergent/primary care treatable conditions.
RESULTS: Pre- and post-program data available on 64 program completers are reported. Of those with mobility problems (n=42), 38% improved; those with problems performing usual activities (N=45), 58% reported improvement; and of those experiencing moderate to extreme pain or discomfort (N=48), 42% reported no pain or discomfort after program completion. Frequency of ED transports decreased (5.34±6.0 vs. 2.08±3.3; p <0.000), as did ED admissions (9.66±10.2 vs. 3.30±4.6; p<0.000), and inpatient hospital admissions (3.11±5.5 vs. 1.38±2.5; p=0.003).
CONCLUSION: Results suggest that MIH participation is associated with improved quality of life, reduced ED transports, ED admissions, and inpatient hospital admissions. The MIH program may have potential to improve health outcomes in patients who are frequent ED users for non-emergent or emergent/primary care treatable conditions by teaching them how to proactively manage their health and adhere to therapeutic regimens. Programmatic reasons for these improvements may include psychosocial bonding with participants who received in-home care, health coaching, and the MIH team's 24/7 availability that provided immediate healthcare access.

PMID: 28495031 [PubMed - as supplied by publisher]

Intermittent Hypoxia Training Blunts Cerebrocortical Presenilin 1 Overexpression and Amyloid β Accumulation in Ethanol-Withdrawn Rats.

Recent Research Articles from UNTHSC - Fri, 05/12/2017 - 07:36
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Intermittent Hypoxia Training Blunts Cerebrocortical Presenilin 1 Overexpression and Amyloid β Accumulation in Ethanol-Withdrawn Rats.

Am J Physiol Regul Integr Comp Physiol. 2017 May 10;:ajpregu.00050.2017

Authors: Ryou MG, Mallet RT, Metzger DB, Jung ME

Abstract
Abrupt cessation of chronic alcohol consumption triggers signaling cascades that harm vulnerable brain regions and produce neurobehavioral deficits. We have demonstrated that a program of intermittent, normobaric hypoxia training (IHT) in rats prevents neurobehavioral impairment resulting from abrupt ethanol withdrawal (EW). Moreover, EW induced expression of stress-activated protein kinase p38 and presenilin 1 (PS1), the γ-secretase component that produces the neurotoxic amyloid-β (Aβ) peptides, Aβ40 and Aβ42. We tested the hypotheses that (1) IHT limits EW-induced activation of the p38-PS1 axis, thereby attenuating γ-secretase activation and Aβ accumulation, and (2) EW disables heat shock protein 25 (HSP25), a p38 substrate, molecular chaperone and antioxidant, and provokes protein carbonylation in a manner suppressed by IHT. Adult male rats completed two cycles of 4 wk ethanol diet (0 or 6.5% w/v) and 3 wk EW. A 20 d IHT program of cyclic, 5-8 min exposures to 9.5-10% FIO2 was administered during the first EW phase. PS1, phosphorylated p38 (P-p38) and HSP25 were analyzed by immunoblot, PS1 messenger RNA by quantitative polymerase chain reaction, protein carbonyl content by spectrometry, and Aβ40 and Aβ42 contents by enzyme-linked immunosorbent assay, in prefrontal cortical extracts. IHT attenuated the EW-associated increases in PS1, P-p38, Aβ40, Aβ42 and protein carbonyl contents, but not that of PS1 messenger RNA, while preserving functionally competent HSP25 dimers in EW rats. Collectively, these findings demonstrate that IHT attenuates EW-activation of the p38-PS1-γ-secretase axis, thereby dampening Aβ accumulation, and prevents EW-induced oxidative protein damage.

PMID: 28490448 [PubMed - as supplied by publisher]

Rapid-eye-movement sleep-predominant central sleep apnea relieved by positive airway pressure: a case report.

Recent Research Articles from UNTHSC - Wed, 05/10/2017 - 07:33
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Rapid-eye-movement sleep-predominant central sleep apnea relieved by positive airway pressure: a case report.

Physiol Rep. 2017 May;5(9):

Authors: Jouett NP, Smith ML, Watenpaugh DE, Siddiqui M, Ahmad M, Siddiqui F

Abstract
Central Sleep Apnea (CSA) is characterized by intermittent apneas and hypopneas during sleep that result from absent central respiratory drive. CSA occurs almost exclusively during non-rapid-eye-movement (NREM) sleep due to enhanced neuronal ventilatory drive during REM sleep that makes central apneas highly unlikely to form. A 45-year-old obese African American female presented with co-existing Obstructive Sleep Apnea (OSA) and CSA, not in the form of mixed or complex sleep apnea. Peculiarly, her CSA occurred only during rapid-eye-movement (REM) sleep, which is exceedingly rare. The patient's CSA was resolved when appropriate positive airway pressure (PAP) was prescribed. Our patient remains stable and has reported significant benefit from PAP usage. We offer possible neuro-physiological mechanisms herein, including enhanced loop gain and/or malfunction or malformation of the pre-Botzinger nucleus or other neurological process, that could explain the unique findings of this case.

PMID: 28483860 [PubMed - in process]

Detecting Gene-Gene Interactions Associated with Multiple Complex Traits with U-Statistics.

Recent Research Articles from UNTHSC - Wed, 05/10/2017 - 07:33
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Detecting Gene-Gene Interactions Associated with Multiple Complex Traits with U-Statistics.

Curr Genomics. 2016 Oct;17(5):403-415

Authors: Li M, Wei C, Wen Y, Wang T, Lu Q

Abstract
Many complex diseases, such as psychiatric and behavioral disorders, are commonly characterized through various measurements that reflect physical, behavioral and psychological aspects of diseases. While it remains a great challenge to find a unified measurement to characterize a disease, the available multiple phenotypes can be analyzed jointly in the genetic association study. Simultaneously testing these phenotypes has many advantages, including considering different aspects of the disease in the analysis, and utilizing correlated phenotypes to improve the power of detecting disease-associated variants. Furthermore, complex diseases are likely caused by the interplay of multiple genetic variants through complicated mechanisms. Considering gene-gene interactions in the joint association analysis of complex diseases could further increase our ability to discover genetic variants involving complex disease pathways. In this article, we propose a stepwise U-test for joint association analysis of multiple loci and multiple phenotypes. Through simulations, we demonstrated that testing multiple phenotypes simultaneously could attain higher power than testing one single phenotype at a time, especially when there are shared genes contributing to multiple phenotypes. We also illustrated the proposed method with an application to Nicotine Dependence (ND), using datasets from the Study of Addition, Genetics and Environment (SAGE). The joint analysis of three ND phenotypes identified two SNPs, rs10508649 and rs2491397, and reached a nominal P-value of 3.79e-13. The association was further replicated in two independent datasets with P-values of 2.37e-05 and 7.46e-05.

PMID: 28479869 [PubMed - in process]

RE: "Letter to the Editor concerning Webber et al. Exp Eye Res. 148:97-102, 2016".

Recent Research Articles from UNTHSC - Wed, 05/10/2017 - 07:33
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RE: "Letter to the Editor concerning Webber et al. Exp Eye Res. 148:97-102, 2016".

Exp Eye Res. 2017 May 03;:

Authors: Webber HC, Bermudez JY, Sethi A, Clark AF, Mao W

PMID: 28478122 [PubMed - as supplied by publisher]

Testicular torsion: A retrospective investigation of predictors of surgical outcomes and of remaining controversies.

Recent Research Articles from UNTHSC - Wed, 05/10/2017 - 07:33
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Testicular torsion: A retrospective investigation of predictors of surgical outcomes and of remaining controversies.

J Pediatr Urol. 2017 Apr 21;:

Authors: Castañeda-Sánchez I, Tully B, Shipman M, Hoeft A, Hamby T, Palmer BW

Abstract
INTRODUCTION: Testicular torsion (TT), a common surgical emergency worldwide, is typically treated with orchiectomy or orchiopexy. It is widely accepted that the chance of salvaging the testicle declines with time and degree of torsion. The impact of ethnicity on outcome is less well understood, and the association between weather and onset of TT remains a controversy.
OBJECTIVES: It is important to know the signs of TT so that appropriate treatment can be given quickly. The purpose of this study was to provide a detailed analysis of registered cases of TT in adolescent patients diagnosed at a single institution to better understand the association between clinical indicators and surgical outcomes and to examine some remaining controversies in the literature on TT.
STUDY DESIGN: A retrospective chart review was conducted, using medical records from the present institution. Data were collected for 165 patients who met the following inclusion criteria: 1) adolescent males between 10 and 18 years of age at the time of diagnosis, and 2) TT between January 2001 and June 2013.
RESULTS: Of the 165 patients, 38% had orchiectomies. Patients with orchiectomies had longer wait times for surgery (p < 0.0001)-but not greater driving times, driving distances, or degrees of torsion-than those with orchiopexies (Table). Yet, among patients who waited less than the median wait time to surgery (197 min), patients with orchiectomies had greater degrees of torsion than did those with orchiopexies (p = 0.02). Assuming that patients without reference to presence of bell clapper deformity in their medical notes did not have the deformity, those with orchiectomies were less likely to have bell clapper deformity than were those with orchiopexies (p < 0.01). Although mean atmospheric temperature was unassociated with onset of TT and with surgical outcome in general, patients without bell clapper deformity had TT on relatively colder days (p = 0.02).
DISCUSSION AND CONCLUSION: Wait time to surgery positively correlates with orchiectomy. Early identification and intervention is vital to testicular salvage. As the degree of torsion increases, the blood supply to the affected testis decreases and the time required to inflict testicular vascular damage decreases. Our results showed the presence of the bell clapper deformity moderated the relationship between temperature and TT: Those without the deformity had torsions on colder days than did those with the deformity. A comprehensive multi-centered study could help draw further conclusions regarding temperature correlation and the bell clapper deformity.

PMID: 28476481 [PubMed - as supplied by publisher]

Statin Effects on Exacerbation Rates, Mortality, and Inflammatory Markers in Patients with Chronic Obstructive Pulmonary Disease: A Review of Prospective Studies.

Recent Research Articles from UNTHSC - Wed, 05/10/2017 - 07:33
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Statin Effects on Exacerbation Rates, Mortality, and Inflammatory Markers in Patients with Chronic Obstructive Pulmonary Disease: A Review of Prospective Studies.

Pharmacotherapy. 2016 05;36(5):536-47

Authors: Howard ML, Vincent AH

Abstract
Chronic obstructive pulmonary disease (COPD) is a debilitating, irreversible disease with currently available therapies targeting symptom control and exacerbation reduction. A need for alternative disease-modifying therapies remains, specifically those that may have antiinflammatory and immunomodulatory properties that impact the pathophysiologic components of COPD. Statin drugs, the current gold standard for the treatment of dyslipidemia and prevention of cardiovascular disease (CVD), contain properties that affect the inflammatory disease processes seen in COPD. Several retrospective studies have demonstrated that statins may have a benefit in the reduction of morbidity and mortality in patients with COPD. This has led to prospective trials evaluating the impact of statins on various COPD-related outcomes. This article reviews the current body of prospective evidence for use of statins in patients with COPD. A search of the PubMed/Medline database of English-language articles was conducted from 1964 through November 2015; references of relevant articles were also reviewed for qualifying studies. Prospective studies of all types relating to statin use in patients with COPD were included if they had COPD- or respiratory-related outcomes; ultimately, eight studies were identified for this review. Statin effects on exacerbation rates, mortality, and inflammatory markers in patients with COPD are discussed. Strong prospective evidence does not currently exist to suggest that statins provide a clinical benefit in patients with COPD who do not have other CVD risk factors. Benefits from statins that have been illustrated are likely explained by their impact on underlying CVD risk factors rather than the COPD disease process. An opportunity exists for unanswered questions to be addressed in future studies.

PMID: 26990316 [PubMed - indexed for MEDLINE]

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