Recent Research Articles from UNTHSC

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Bilateral symmetrical supernumerary heads of biceps brachii with rare pectoralis major insertion.

Fri, 05/16/2014 - 4:05am

Bilateral symmetrical supernumerary heads of biceps brachii with rare pectoralis major insertion.

Surg Radiol Anat. 2014 May 10;

Authors: Fraser PR, Howard LW, Rosales AA, Guttmann GD

Abstract
During a routine dissection of a 51-year-old Caucasian male cadaver, bilateral symmetrical supernumerary heads (SH) of the biceps brachii muscles with insertion into the pectoralis major (PM) muscles were discovered. Multiple case reports have documented supernumerary heads for the biceps brachii; however, none have shown bilateral insertion into the pectoralis major. This study describes a previously undocumented variation of the SH that has potential for clinical impact. Healthcare providers could be confounded by patients presenting with shoulder pain or muscle tears as a result of the anomaly. Furthermore, MRI studies on patients with possible shoulder muscle tears could reveal unexpected results. Such cases would warrant consideration of SH anomaly and treatment should be adjusted accordingly. The significant bulk and angle of the SH insertion on the PM we observed changes force vectors which would have an unknown effect in performance, surgical interventions and pain syndromes. A second biceps brachii anomaly was observed on the left brachium in addition to the bilateral SH. We postulate that these variants provide the potential for clinical complications regarding muscular injury to these aforementioned muscle groups.

PMID: 24817560 [PubMed - as supplied by publisher]

Developmental validation of the EX20+4 system.

Fri, 05/16/2014 - 4:05am

Developmental validation of the EX20+4 system.

Forensic Sci Int Genet. 2014 Mar 19;11C:207-213

Authors: Li S, Liu C, Liu H, Ge J, Budowle B, Liu C, Zheng W, Li F, Ge B

Abstract
The EX20+4Y System is a polymerase chain reaction (PCR)-based amplification kit that enables typing of 19 autosomal short tandem repeat (STR) loci (i.e., CSF1PO, D13S317, D16S539, D18S51, D21S11, D3S1358, D5S818, D7S820, D8S1179, FGA, TH01, TPOX, vWA, Penta D, Penta E, D2S1338, D19S433, D12S391, D6S1043), four widely used Y chromosome-specific STR (Y-STR) loci (DYS458, DYS456, DYS391, DYS635), and amelogenin. In this study, this multiplex system was validated for sensitivity of detection, DNA mixtures, inhibitor tolerance, species specificity based on the Scientific Working Group on DNA Analysis methods (SWGDAM) developmental validation guidelines, and the Chinese criteria for the human fluorescent STR multiplex PCR reagent. The results show that the EX20+4 System is a robust and reliable amplification kit which can be used for human identification testing.

PMID: 24815370 [PubMed - as supplied by publisher]

Pharmacology, benefits, unaddressed questions, and pragmatic issues of the newer oral anticoagulants for stroke prophylaxis in non-valvular atrial fibrillation and proposal of a management algorithm.

Fri, 05/16/2014 - 4:05am

Pharmacology, benefits, unaddressed questions, and pragmatic issues of the newer oral anticoagulants for stroke prophylaxis in non-valvular atrial fibrillation and proposal of a management algorithm.

Int J Cardiol. 2014 Apr 26;

Authors: Rosanio S, Keylani AM, D'Agostino DC, Delaughter CM, Vitarelli A

Abstract
This systematic review aims to provide an update on pharmacology, efficacy and safety of the newer oral direct thrombin and factor Xa inhibitors, which have emerged for the first time in ~60years as cogent alternatives to warfarin for stroke prophylaxis in non-valvular atrial fibrillation. We also discuss on four of the most common clinical scenarios with several unsolved questions and areas of uncertainty that may play a role in physicians' reluctance to prescribe the newer oral anticoagulants such as 1) patients with renal failure; 2) the elderly; 3) patients presenting with atrial fibrillation and acute coronary syndromes and/or undergoing coronary stenting; and 4) patients planning to receive AF ablation with the use of pulmonary vein isolation. New aspects presented in current guidelines are covered and we also propose an evidence-based anticoagulation management algorithm.

PMID: 24814537 [PubMed - as supplied by publisher]

Assessment of the role of DNA repair in damaged forensic samples.

Tue, 05/13/2014 - 4:04am

Assessment of the role of DNA repair in damaged forensic samples.

Int J Legal Med. 2014 May 3;

Authors: Ambers A, Turnbough M, Benjamin R, King J, Budowle B

Abstract
Previous studies on DNA damage and repair have involved in vitro laboratory procedures that induce a single type of lesion in naked templates. Although repair of singular, sequestered types of DNA damage has shown some success, forensic and ancient specimens likely contain a number of different types of lesions. This study sought to (1) develop protocols to damage DNA in its native state, (2) generate a pool of candidate samples for repair that more likely emulate authentic forensic samples, and (3) assess the ability of the PreCR(TM) Repair Mix to repair the resultant lesions. Complexed, native DNA is more difficult to damage than naked DNA. Modified procedures included the use of higher concentrations and longer exposure times. Three types of samples, those that demonstrated damage based on short tandem repeat (STR) profile signals, were selected for repair experiments: environmentally damaged bloodstains, bleach-damaged whole blood, and human skeletal remains. Results showed trends of improved performance of STR profiling of bleach-damaged DNA. However, the repair assay did not improve DNA profiles from environmentally damaged bloodstains or bone, and in some cases resulted in lower RFU values for STR alleles. The extensive spectrum of DNA damage and myriad combinations of lesions that can be present in forensic samples appears to pose a challenge for the in vitro PreCR(TM) assay. The data suggest that the use of PreCR in casework should be considered with caution due to the assay's varied results.

PMID: 24792635 [PubMed - as supplied by publisher]

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]

Feasability and reception of a post-match boot cAMP for fourth-year students based on milestone 1.

Wed, 04/30/2014 - 4:04am
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Feasability and reception of a post-match boot cAMP for fourth-year students based on milestone 1.

Obstet Gynecol. 2014 May;123 Suppl 1:18S

Authors: Hinkle K

Abstract
INTRODUCTION: Milestone 1 was developed to help students prepare for starting an obstetrics-gynecology residency. Although most current students are naive to Milestone 1, it has the potential to be very useful in designing a "boot camp" curriculum for students before leaving medical school. Milestone 1 should help ease the transition for both the future resident and the residency program.
METHODS: We developed an intensive elective opportunity in April of the fourth year to specifically address the objectives of Milestone 1. We held 4 half-day sessions each week for 4 weeks. An anonymous questionnaire (5-point Likert) was used at the end of the experience for evaluation, covering the Milestone Objectives and students' overall impressions of the course.
RESULTS: Eight of 10 students matching in obstetrics-gynecology participated in the elective and completed the questionnaire. The results were heavily weighted toward being better able to explain and discuss a topic or complete a task covered by the objectives. All respondents strongly supported the focused, small group structure and the timing of the course after the match. All felt it was an important part of their education and would recommend it to other students.
CONCLUSIONS: Designing a "boot camp" experience based on Milestone 1 is both feasible and well received by fourth-year medical students. Placing it after match and before graduation is also well received by students. Program director feedback will be the next step in developing better "boot camp" experiences for students.

PMID: 24770123 [PubMed - in process]

Mitochondrial genome interrogation for forensic casework and research studies.

Tue, 04/29/2014 - 4:04am
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Mitochondrial genome interrogation for forensic casework and research studies.

Curr Protoc Hum Genet. 2014;81:14.9.1-14.9.23

Authors: Roby RK, Sprouse M, Phillips N, Alicea-Centeno A, Shewale S, Shore S, Paul N

Abstract
This unit describes methods used in the analysis of mitochondrial DNA (mtDNA) for forensic and research applications. UNIT describes procedures specifically for forensic casework where the DNA from evidentiary material is often degraded or inhibited. In this unit, protocols are described for quantification of mtDNA before amplification; amplification of the entire control region from high-quality samples as well as procedures for interrogating the whole mitochondrial genome (mtGenome); quantification of mtDNA post-amplification; and, post-PCR cleanup and sequencing. The protocols for amplification were developed for high-throughput databasing applications for forensic DNA testing such as reference samples and population studies. However, these same protocols can be applied to biomedical research such as age-related disease and health disparities research. Curr. Protoc. Hum. Genet. 81:14.9.1-14.9.23. © 2014 by John Wiley & Sons, Inc.

PMID: 24763992 [PubMed - in process]

Autonomic Neural Control of Heart Rate during Dynamic Exercise: Revisited.

Sat, 04/26/2014 - 4:05am
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Autonomic Neural Control of Heart Rate during Dynamic Exercise: Revisited.

J Physiol. 2014 Apr 22;

Authors: White DW, Raven PB

Abstract
The accepted model of autonomic control of heart rate (HR) during dynamic exercise indicates that the initial increase is due entirely to withdrawal of parasympathetic nervous system activity (PSNA) and that subsequent increases in HR are entirely due to increases in cardiac sympathetic activity. In the present review we sought to re-evaluate the model of autonomic neural control of HR in humans during progressive increases in dynamic exercise workloads. We analyzed data from both new and previously published studies involving baroreflex stimulation and pharmacological blockade of the autonomic nervous system. Results identify that the parasympathetic nervous system remains functionally active throughout exercise and that increases in HR from rest through maximal exercise result from an increasing workload-related transition from a 4:1 vagal-sympatho balance to a 4:1 sympatho-vagal balance. Furthermore, the beat to beat autonomic reflex control of HR was found to be dependent on the PSNA's ability to modulate the HR as it was progressively restrained by increasing workload-related sympathetic nerve activity. In conclusion the: i) increases in exercise workload related HR are not caused by a total withdrawal of the parasympathetic nervous system followed by an increase in sympathetic tone; ii) reciprocal antagonism is key to the transition from vagal to sympathetic dominance; and iii) resetting of the arterial baroreflex causes immediate exercise-onset reflexive increases in HR, which are parasympathetically mediated followed by slower increases in sympathetic tone as workloads are increased.

PMID: 24756637 [PubMed - as supplied by publisher]

Pyruvate minimizes rtPA toxicity from in vitro oxygen-glucose deprivation and reoxygenation.

Sat, 04/26/2014 - 4:05am
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Pyruvate minimizes rtPA toxicity from in vitro oxygen-glucose deprivation and reoxygenation.

Brain Res. 2013 Sep 12;1530:66-75

Authors: Ryou MG, Choudhury GR, Winters A, Xie L, Mallet RT, Yang SH

Abstract
Clinical application of recombinant tissue plasminogen activator (rtPA) for stroke is limited by hemorrhagic transformation, which narrows rtPA's therapeutic window. In addition, mounting evidence indicates that rtPA is potentially neurotoxic if it traverses a compromised blood brain barrier. Here, we demonstrated that pyruvate protects cultured HT22 neuronal and primary microvascular endothelial cells co-cultured with primary astrocytes from oxygen glucose deprivation (OGD)/reoxygenation stress and rtPA cytotoxicity. After 3 or 6h OGD, cells were reoxygenated with 11mmol/L glucose±pyruvate (8mmol/L) and/or rtPA (10µg/ml). Measured variables included cellular viability (calcein AM and annexin-V/propidium iodide), reactive oxygen species (ROS; mitosox red and 2',7'-dichlorofluorescein diacetate), NADPH, NADP(+) and ATP contents (spectrophotometry), matrix metalloproteinase-2 (MMP2) activities (gelatin zymography), and cellular contents of MMP2, tissue inhibitor of metalloproteinase-2 (TIMP2), and phosphor-activation of anti-apoptotic p70s6 kinase, Akt and Erk (immunoblot). Pyruvate prevented the loss of HT22 cells after 3h OGD±rtPA. After 6h OGD, rtPA sharply lowered cell viability; pyruvate dampened this effect. Three hours OGD and 4h reoxygenation with rtPA increased ROS formation by about 50%. Pyruvate prevented this ROS formation and doubled cellular NADPH/NADP(+) ratio and ATP content. In endothelial cell monolayers, 3h OGD and 24h reoxygenation increased FITC-dextran leakage, indicating disruption of intercellular junctions. Although rtPA exacerbated this effect, pyruvate prevented it while sharply lowering MMP2/TIMP2 ratio and increasing phosphorylation of p70s6 kinase, Akt and Erk. Pyruvate protects neuronal cells and microvascular endothelium from hypoxia-reoxygenation and cytotoxic action of rtPA while reducing ROS and activating anti-apoptotic signaling. These results support the proposed use of pyruvate as an adjuvant to dampen the side effects of rtPA treatment, thereby extending rtPA's therapeutic window.

PMID: 23891792 [PubMed - indexed for MEDLINE]

Reducing the Burden of Suicide in the U.S.: The Aspirational Research Goals of the National Action Alliance for Suicide Prevention Research Prioritization Task Force.

Thu, 04/24/2014 - 8:04am
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Reducing the Burden of Suicide in the U.S.: The Aspirational Research Goals of the National Action Alliance for Suicide Prevention Research Prioritization Task Force.

Am J Prev Med. 2014 Apr 18;

Authors: Claassen CA, Pearson JL, Khodyakov D, Satow PM, Gebbia R, Berman AL, Reidenberg DJ, Feldman S, Molock S, Carras MC, Lento RM, Sherrill J, Pringle B, Dalal S, Insel TR

Abstract
BACKGROUND: The National Action Alliance for Suicide Prevention Research Prioritization Task Force (RPTF) has created a prioritized national research agenda with the potential to rapidly and substantially reduce the suicide burden in the U.S. if fully funded and implemented.
PURPOSE: Viable, sustainable scientific research agendas addressing challenging public health issues such as suicide often need to incorporate perspectives from multiple stakeholder groups (e.g., researchers, policymakers, and other end-users of new knowledge) during an agenda-setting process. The Stakeholder Survey was a web-based survey conducted and analyzed in 2011-2012 to inform the goal-setting step in the RPTF agenda development process. The survey process, and the final list of "aspirational" research goals it produced, are presented here.
METHODS: Using a modified Delphi process, diverse constituent groups generated and evaluated candidate research goals addressing pressing suicide prevention research needs.
RESULTS: A total of 716 respondents representing 49 U.S. states and 18 foreign countries provided input that ultimately produced 12 overarching, research-informed aspirational goals aimed at reducing the U.S. suicide burden. Highest-rated goals addressed prevention of subsequent suicidal behavior after an initial attempt, strategies to retain patients in care, improved healthcare provider training, and generating care models that would ensure accessible treatment.
CONCLUSIONS: The Stakeholder Survey yielded widely valued research targets. Findings were diverse in focus, type, and current phase of research development but tended to prioritize practical solutions over theoretical advancement. Other complex public health problems requiring input from a broad-based constituency might benefit from web-based tools that facilitate such community input.

PMID: 24750971 [PubMed - as supplied by publisher]