Recent Research Articles from UNTHSC

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Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model.

Tue, 05/13/2014 - 4:04am
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Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model.

Neurobiol Dis. 2013 Nov;59:18-25

Authors: Li W, Huang R, Shetty RA, Thangthaeng N, Liu R, Chen Z, Sumien N, Rutledge M, Dillon GH, Yuan F, Forster MJ, Simpkins JW, Yang SH

Abstract
Vascular dementia ranks as the second leading cause of dementia in the United States. However, its underlying pathophysiological mechanism is not fully understood and no effective treatment is available. The purpose of the current study was to evaluate long-term cognitive deficits induced by transient middle cerebral artery occlusion (tMCAO) in rats and to investigate the underlying mechanism. Sprague-Dawley rats were subjected to tMCAO or sham surgery. Behavior tests for locomotor activity and cognitive function were conducted at 7 or 30days after stroke. Hippocampal long term potentiation (LTP) and involvement of GABAergic neurotransmission were evaluated at 30days after sham surgery or stroke. Immunohistochemistry and Western blot analyses were conducted to determine the effect of tMCAO on cell signaling in the hippocampus. Transient MCAO induced a progressive deficiency in spatial performance. At 30days after stroke, no neuron loss or synaptic marker change in the hippocampus were observed. LTP in both hippocampi was reduced at 30days after stroke. This LTP impairment was prevented by blocking GABAA receptors. In addition, ERK activity was significantly reduced in both hippocampi. In summary, we identified a progressive decline in spatial learning and memory after ischemic stroke that correlates with suppression of hippocampal LTP, elevation of GABAergic neurotransmission, and inhibition of ERK activation. Our results indicate that the attenuation of GABAergic activity or enhancement of ERK/MAPK activation in the hippocampus might be potential therapeutic approaches to prevent or attenuate cognitive impairment after ischemic stroke.

PMID: 23845275 [PubMed - indexed for MEDLINE]

Comparison of the accuracy of kriging and IDW interpolations in estimating groundwater arsenic concentrations in Texas.

Tue, 05/13/2014 - 4:04am
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Comparison of the accuracy of kriging and IDW interpolations in estimating groundwater arsenic concentrations in Texas.

Environ Res. 2014 Apr;130:59-69

Authors: Gong G, Mattevada S, O'Bryant SE

Abstract
Exposure to arsenic causes many diseases. Most Americans in rural areas use groundwater for drinking, which may contain arsenic above the currently allowable level, 10µg/L. It is cost-effective to estimate groundwater arsenic levels based on data from wells with known arsenic concentrations. We compared the accuracy of several commonly used interpolation methods in estimating arsenic concentrations in >8000 wells in Texas by the leave-one-out-cross-validation technique. Correlation coefficient between measured and estimated arsenic levels was greater with inverse distance weighted (IDW) than kriging Gaussian, kriging spherical or cokriging interpolations when analyzing data from wells in the entire Texas (p<0.0001). Correlation coefficient was significantly lower with cokriging than any other methods (p<0.006) for wells in Texas, east Texas or the Edwards aquifer. Correlation coefficient was significantly greater for wells in southwestern Texas Panhandle than in east Texas, and was higher for wells in Ogallala aquifer than in Edwards aquifer (p<0.0001) regardless of interpolation methods. In regression analysis, the best models are when well depth and/or elevation were entered into the model as covariates regardless of area/aquifer or interpolation methods, and models with IDW are better than kriging in any area/aquifer. In conclusion, the accuracy in estimating groundwater arsenic level depends on both interpolation methods and wells' geographic distributions and characteristics in Texas. Taking well depth and elevation into regression analysis as covariates significantly increases the accuracy in estimating groundwater arsenic level in Texas with IDW in particular.

PMID: 24559533 [PubMed - indexed for MEDLINE]

Dual plating of humeral shaft fractures: orthogonal plates biomechanically outperform side-by-side plates.

Tue, 05/06/2014 - 4:04am
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Dual plating of humeral shaft fractures: orthogonal plates biomechanically outperform side-by-side plates.

Clin Orthop Relat Res. 2014 Apr;472(4):1310-7

Authors: Kosmopoulos V, Nana AD

Abstract
BACKGROUND: Single large-fragment plate constructs currently are the norm for internal fixation of middiaphyseal humerus fractures. In cases where humeral size is limited, however, dual small-fragment locking plate constructs may serve as an alternative. The mechanical effects of different possible plate configurations around the humeral diaphysis may be important, but to our knowledge, have yet to be investigated.
QUESTIONS/PURPOSES: We used finite element analysis to compare the simulated mechanical performance of five different dual small-fragment locking plate construct configurations for humeral middiaphyseal fracture fixation in terms of (1) stiffness, (2) stress shielding of bone, (3) hardware stresses, and (4) interfragmentary strain.
METHODS: Middiaphyseal humeral fracture fixation was simulated using the finite element method. Three 90° and two side-by-side seven-hole and nine-hole small-fragment dual locking plate configurations were tested in compression, torsion, and combined loading. The configurations chosen are based on implantation using either a posterior or anterolateral approach.
RESULTS: All three of the 90° configurations were more effective in restoring the intact compressive and torsional stiffness as compared with the side-by-side configurations, resulted in less stress shielding and stressed hardware, and showed interfragmentary strains between 5% to 10% in torsion and combined loading.
CONCLUSIONS: The nine-hole plate anterior and seven-hole plate lateral (90° apart) configuration provided the best fixation. Our findings show the mechanical importance of plate placement with relation to loading in dual-plate fracture-fixation constructs.
CLINICAL RELEVANCE: The results presented provide novel biomechanical information for the orthopaedic surgeon considering different treatment options for middiaphyseal humeral fractures.

PMID: 24218163 [PubMed - indexed for MEDLINE]

Thoracic and abdominal lymphatic pump techniques inhibit the growth of S. pneumoniae bacteria in the lungs of rats.

Tue, 05/06/2014 - 4:04am
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Thoracic and abdominal lymphatic pump techniques inhibit the growth of S. pneumoniae bacteria in the lungs of rats.

Lymphat Res Biol. 2013 Sep;11(3):183-6

Authors: Creasy C, Schander A, Orlowski A, Hodge LM

Abstract
BACKGROUND: Osteopathic physicians utilize manual medicine techniques called lymphatic pump techniques (LPT) to improve lymphatic flow and enhance immunity. Clinical studies report that LPT enhances antibody responses to bacterial vaccines, shortens duration of cough in patients with respiratory disease, and shortens the duration of intravenous antibiotic therapy and hospital stay in patients with pneumonia. The purpose of this study was to identify if thoracic LPT (Th-LPT) or abdominal LPT (Ab-LPT) would reduce Streptococcus pneumoniae colony-forming units (CFU) in the lungs of rats with acute pneumonia.
METHODS AND RESULTS: Rats were nasally infected with S. pneumoniae and received either control, sham, Ab-LPT, or Th-LPT once daily for 3 consecutive days. On day 4 post-infection, lungs were removed and bacteria were enumerated. Three daily applications of either Ab-LPT or Th-LPT were able to significantly (p<0.05) reduce the numbers of pulmonary bacteria compared to control and sham. There were no significant differences in the percentage or concentration of leukocytes in blood between groups, suggesting neither Ab-LPT nor Th-LPT release leukocytes into blood circulation.
CONCLUSIONS: Our data demonstrate that LPT may protect against pneumonia by inhibiting bacterial growth in the lung; however, the mechanism of protection is unclear. Once these mechanisms are understood, LPT can be optimally applied to patients with pneumonia, which may substantially reduce morbidity, mortality, and frequency of hospitalization.

PMID: 24024572 [PubMed - indexed for MEDLINE]

Assessment and management of back pain.

Tue, 05/06/2014 - 4:04am
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Assessment and management of back pain.

JAMA Intern Med. 2014 Mar;174(3):478-9

Authors: Licciardone JC, Gatchel R, Dagenais S

PMID: 24590092 [PubMed - indexed for MEDLINE]

A revised definition for cure of childhood acute lymphoblastic leukemia.

Sat, 05/03/2014 - 4:05am
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A revised definition for cure of childhood acute lymphoblastic leukemia.

Leukemia. 2014 Apr 30;

Authors: Pui CH, Pei D, Campana D, Cheng C, Sandlund JT, Bowman WP, Hudson MM, Ribeiro RC, Raimondi SC, Jeha S, Howard SC, Bhojwani D, Inaba H, Rubnitz JE, Metzger ML, Gruber TA, Coustan-Smith E, Downing JR, Leung WH, Relling MV, Evans WE

Abstract
With improved contemporary therapy, we re-assess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia to determine when cure can be declared with a high degree of confidence. In 6 successive clinical trials between 1984 and 2007, 1291(84.5%) patients completed all therapy in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% [P<0.001]) and overall survival (76.5% vs 81.1% vs 91.7% [P<0.001]) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5%, and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years off therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with acute lymphoblastic leukemia may relapse after completion of treatment, and those who remain in remission at 4 years post-treatment may be considered cured (i.e., less than 1% chance of relapse).Leukemia accepted article preview online, 30 April 2014; doi:10.1038/leu.2014.142.

PMID: 24781017 [PubMed - as supplied by publisher]

Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus.

Sat, 05/03/2014 - 4:05am
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Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus.

Neuroscience. 2014 Apr 26;

Authors: Chen Z, Huang R

Abstract
Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. The physiological relevance of pH modulation of GABAergic neurotransmission is not fully elucidated. In the present studies, we examined the influence of extracellular pH on the GABAA receptor-mediated inhibitory neurotransmission in rat hypothalamic neurons. The inhibitory postsynaptic currents (IPSCs), tonic currents, and the GABA-evoked currents were recorded with whole-cell patch techniques on the hypothalamic slices from Sprague-Dawley rats at 15-26 postnatal days. The amplitude and frequency of spontaneous GABA IPSCs were significantly increased while the external pH was changed from 7.3 to 8.4. In the acidic pH (6.4), the spontaneous GABA IPSCs were reduced in amplitude and frequency. The pH induced changes in miniature GABA IPSCs (mIPSCs) similar to that in spontaneous IPSCs. The pH effect on the postsynaptic GABA receptors was assessed with exogenously applied varying concentrations of GABA. The tonic currents and the currents evoked by sub-saturating concentration of GABA ([GABA]) (10 M) were inhibited by acidic pH and potentiated by alkaline pH. In contrast, the currents evoked by saturating [GABA] (1 mM) were not affected by pH changes. We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant 122 GABAA receptors stably expressed in HEK 293 cells, The pH influence on GABAA receptors was similar in HEPES- and MES-buffered medium, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission, which is mediated by both presynaptic and postsynaptic mechanisms.

PMID: 24780768 [PubMed - as supplied by publisher]

Arterial pressure and cerebral blood flow variability: friend or foe? A review.

Fri, 05/02/2014 - 4:05am
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Arterial pressure and cerebral blood flow variability: friend or foe? A review.

Front Physiol. 2014;5:120

Authors: Rickards CA, Tzeng YC

Abstract
Variability in arterial pressure and cerebral blood flow has traditionally been interpreted as a marker of cardiovascular decompensation, and has been associated with negative clinical outcomes across varying time scales, from impending orthostatic syncope to an increased risk of stroke. Emerging evidence, however, suggests that increased hemodynamic variability may, in fact, be protective in the face of acute challenges to perfusion, including significant central hypovolemia and hypotension (including hemorrhage), and during cardiac bypass surgery. This review presents the dichotomous views on the role of hemodynamic variability on clinical outcome, including the physiological mechanisms underlying these patterns, and the potential impact of increased and decreased variability on cerebral perfusion and oxygenation. We suggest that reconciliation of these two apparently discrepant views may lie in the time scale of hemodynamic variability; short time scale variability appears to be cerebroprotective, while mid to longer term fluctuations are associated with primary and secondary end-organ dysfunction.

PMID: 24778619 [PubMed - as supplied by publisher]

Future directions of forensic DNA databases.

Fri, 05/02/2014 - 4:05am
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Future directions of forensic DNA databases.

Croat Med J. 2014 Apr 28;55(2):163-6

Authors: Ge J, Sun H, Li H, Liu C, Yan J, Budowle B

PMID: 24778103 [PubMed - in process]

Somatic Dysfunction and Use of Osteopathic Manual Treatment Techniques During Ambulatory Medical Care Visits: A CONCORD-PBRN Study.

Fri, 05/02/2014 - 4:05am
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Somatic Dysfunction and Use of Osteopathic Manual Treatment Techniques During Ambulatory Medical Care Visits: A CONCORD-PBRN Study.

J Am Osteopath Assoc. 2014 May;114(5):344-54

Authors: Licciardone JC, Kearns CM, King HH, Seffinger MA, Crow WT, Zajac P, Devine WH, Abu-Sbaih RY, Miller SJ, Berkowitz MR, Dyer R, Heath DM, Treffer KD, Nevins NA, Aryal S

Abstract
CONTEXT: Osteopathic manual treatment (OMT) of somatic dysfunction is a unique approach to medical care that may be studied within a practice-based research network.
OBJECTIVE: To measure patient characteristics and osteopathic physician practice patterns within the Consortium for Collaborative Osteopathic Research Development-Practice-Based Research Network (CONCORD-PBRN). Design: Cross-sectional card study.
SETTING: Eleven member clinics within the CONCORD-PBRN coordinated by The Osteopathic Research Center.
PATIENTS: A total of 668 patients seen between January and March 2013. Main Study Measures: Patient age and sex; primary diagnoses; somatic dysfunction as manifested by tenderness, asymmetry, restricted motion, or tissue texture changes; and use of 14 OMT techniques. Results were stratified by anatomical region and adjusted for clustering within member clinics. Clustering was measured by the intracluster correlation coefficient.
RESULTS: Patient ages ranged from 7 days to 87 years (adjusted mean age, 49.2 years; 95% confidence interval [CI], 43.3-55.1 years). There were 450 females (67.4%) and 508 patient visits (76.0%) involved a primary diagnosis of disease of the musculoskeletal system and connective tissue. Structural examination was performed during 657 patient visits (98.4%), and 649 visits (97.2%) involved OMT. Restricted motion and tenderness were the most and least common palpatory findings, respectively. Cranial (1070 [14.5%]), myofascial release (1009 [13.7%]), muscle energy (1001 [13.6%]), and counterstrain (980 [13.3%]) techniques were most commonly used, accounting for more than one-half of the OMT provided. Pediatric patients were more likely than adults to receive OMT within the head (adjusted odds ratio [OR], 9.53; 95% CI, 1.28-71.14). Geriatric patients were more likely than adults to receive a structural examination (adjusted OR, 1.83; 95% CI, 1.09-3.07) and OMT (adjusted OR, 1.62; 1.02-2.59) within the lower extremity. Females were more likely than males to receive a structural examination (adjusted OR, 2.44; 95% CI, 1.44-4.16) and OMT (adjusted OR, 2.11; 95% CI, 1.26-3.52) within the sacrum and OMT within the pelvis (adjusted OR, 1.79; 95% CI, 1.12-2.88). Intracluster correlation coefficients for the 4 most commonly used OMT techniques ranged from 0.34 to 0.72.
CONCLUSION: This study provides proof of concept of the feasibility of studying osteopathic medical practice on a national level by developing and growing the CONCORD-PBRN.

PMID: 24777999 [PubMed - in process]

Association between Helicobacter pylori and Barrett's esophagus: a case-control study.

Fri, 05/02/2014 - 4:05am
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Association between Helicobacter pylori and Barrett's esophagus: a case-control study.

Am J Gastroenterol. 2014 Mar;109(3):357-68

Authors: Fischbach LA, Graham DY, Kramer JR, Rugge M, Verstovsek G, Parente P, Alsarraj A, Fitzgerald S, Shaib Y, Abraham NS, Kolpachi A, Gupta S, Vela MF, Velez M, Cole R, Anand B, El Serag HB

Abstract
OBJECTIVES: The estimated association between Helicobacter pylori and Barrett's esophagus (BE) has been heterogenous across previous studies. In this study, we aimed to examine the association between H. pylori and BE and to identify factors that may explain or modify this association.
METHODS: We conducted a case-control study in which we used screening colonoscopy controls recruited from primary care clinics as our primary control group in order to minimize selection bias. All participants underwent an esophagogastroduodenoscopy with gastric mapping biopsies. We used logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the association between H. pylori and BE while controlling for confounders.
RESULTS: We identified 218 cases and 439 controls. The overall OR for the association between H. pylori and BE after controlling for age and white race was 0.55 (95% CI: 0.35-0.84). We observed an even stronger inverse association (OR: 0.28; 95% CI: 0.15, 0.50) among participants with corpus atrophy or antisecretory drug use ≥ 1 time per week (factors thought to lower gastric acidity), and no inverse association in patients without these factors (OR: 1.32; 95% CI: 0.66, 2.63).
CONCLUSIONS: The association between H. pylori and a decreased risk for BE appears to occur in patients with factors that would likely lower gastric acidity (corpus atrophy or taking antisecretory drugs at least once a week).

PMID: 24419485 [PubMed - indexed for MEDLINE]