Recent Research Articles from UNTHSC

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Novel Split Chest Tube Improves Post-Surgical Thoracic Drainage.

Tue, 12/09/2014 - 3:29am
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Novel Split Chest Tube Improves Post-Surgical Thoracic Drainage.

J Clin Exp Cardiolog. 2014;5

Authors: Olivencia-Yurvati AH, Cherry BH, Gurji HA, White DW, Newton JT, Scott GF, Hoxha B, Gourlay T, Mallet RT

Abstract
OBJECTIVE: Conventional, separate mediastinal and pleural tubes are often inefficient at draining thoracic effusions.
DESCRIPTION: We developed a Y-shaped chest tube with split ends that divide within the thoracic cavity, permitting separate intrathoracic placement and requiring a single exit port. In this study, thoracic drainage by the split drain vs. that of separate drains was tested.
METHODS: After sternotomy, pericardiotomy, and left pleurotomy, pigs were fitted with separate chest drains (n=10) or a split tube prototype (n=9) with internal openings positioned in the mediastinum and in the costo-diaphragmatic recess. Separate series of experiments were conducted to test drainage of D5W or 0.58 M sucrose, an aqueous solution with viscosity approximating that of plasma. One litre of fluid was infused into the thorax, and suction was applied at -20 cm H2O for 30 min.
RESULTS: When D5W was infused, the split drain left a residual volume of 53 ± 99 ml (mean value ± SD) vs. 148 ± 120 for the separate drain (P=0.007), representing a drainage efficiency (i.e. drained vol/[drained + residual vol]) of 95 ± 10% vs. 86 ± 12% for the separate drains (P = 0.011). In the second series, the split drain evacuated more 0.58 M sucrose in the first minute (967 ± 129 ml) than the separate drains (680 ± 192 ml, P<0.001). By 30 min, the split drain evacuated a similar volume of sucrose vs. the conventional drain (1089 ± 72 vs. 1056 ± 78 ml; P = 0.5). Residual volume tended to be lower (25 ± 10 vs. 62 ± 72 ml; P = 0.128) and drainage efficiency tended to be higher (98 ± 1 vs. 95 ± 6%; P = 0.111) with the split drain vs. conventional separate drains.
CONCLUSION: The split chest tube drained the thoracic cavity at least as effectively as conventional separate tubes. This new device could potentially alleviate postoperative complications.

PMID: 25478289 [PubMed - as supplied by publisher]

Postmortem medicolegal genetic diagnostics also require reporting guidance.

Fri, 12/05/2014 - 7:30pm

Postmortem medicolegal genetic diagnostics also require reporting guidance.

Eur J Hum Genet. 2014 Dec 3;

Authors: Sajantila A, Budowle B

PMID: 25469540 [PubMed - as supplied by publisher]

The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades.

Fri, 12/05/2014 - 7:30pm

The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades.

Mol Biol Evol. 2014 Dec 2;

Authors: Hallast P, Batini C, Zadik D, Maisano Delser P, Wetton JH, Arroyo-Pardo E, Cavalleri GL, de Knijff P, Destro Bisol G, Myhre Dupuy B, Eriksen HA, Jorde LB, King TE, Larmuseau MH, López de Munain A, López-Parra AM, Loutradis A, Milasin J, Novelletto A, Pamjav H, Sajantila A, Schempp W, Sears M, Tolun A, Tyler-Smith C, Van Geystelen A, Watkins S, Winney B, Jobling MA

Abstract
Many studies of human populations have used the male-specific region of the Y chromosome (MSY) as a marker, but MSY sequence variants have traditionally been subject to ascertainment bias. Also, dating of haplogroups has relied on Y-specific short tandem repeats (STRs), involving problems of mutation rate choice, and possible long-term mutation saturation. Next-generation sequencing can ascertain single nucleotide polymorphisms (SNPs) in an unbiased way, leading to phylogenies in which branch-lengths are proportional to time, and allowing the times-to-most-recent-common-ancestor (TMRCAs) of nodes to be estimated directly. Here we describe the sequencing of 3.7 Mb of MSY in each of 448 human males at a mean coverage of 51 ×, yielding 13,261 high-confidence SNPs, 65.9% of which are previously unreported. The resulting phylogeny covers the majority of the known clades, provides date estimates of nodes, and constitutes a robust evolutionary framework for analysing the history of other classes of mutation. Different clades within the tree show subtle but significant differences in branch lengths to the root. We also apply a set of 23 Y-STRs to the same samples, allowing SNP- and STR-based diversity and TMRCA estimates to be systematically compared. Ongoing purifying selection is suggested by our analysis of the phylogenetic distribution of non-synonymous variants in 15 MSY single-copy genes.

PMID: 25468874 [PubMed - as supplied by publisher]

Positive oxidative stress in aging and aging-related disease tolerance.

Wed, 12/03/2014 - 11:30pm

Positive oxidative stress in aging and aging-related disease tolerance.

Redox Biol. 2014 Jan 9;2C:165-169

Authors: Yan LJ

Abstract
It is now well established that reactive oxygen species (ROS), reactive nitrogen species (RNS), and a basal level of oxidative stress are essential for cell survival. It is also well known that while severe oxidative stress often leads to widespread oxidative damage and cell death, a moderate level of oxidative stress, induced by a variety of stressors, can yield great beneficial effects on adaptive cellular responses to pathological challenges in aging and aging-associated disease tolerance such as ischemia tolerance. Here in this review, I term this moderate level of oxidative stress as positive oxidative stress, which usually involves imprinting molecular signatures on lipids and proteins via formation of lipid peroxidation by-products and protein oxidation adducts. As ROS/RNS are short-lived molecules, these molecular signatures can thus execute the ultimate function of ROS/RNS. Representative examples of lipid peroxidation products and protein oxidation adducts are presented to illustrate the role of positive oxidative stress in a variety of pathological settings, demonstrating that positive oxidative stress could be a valuable prophylactic and/or therapeutic approach targeting aging and aging-associated diseases.

PMID: 25460727 [PubMed - as supplied by publisher]

Urine osmolality in the US population: Implications for environmental biomonitoring.

Wed, 12/03/2014 - 11:30pm

Urine osmolality in the US population: Implications for environmental biomonitoring.

Environ Res. 2014 Nov 25;136C:482-490

Authors: Yeh HC, Lin YS, Kuo CC, Weidemann D, Weaver V, Fadrowski J, Neu A, Navas-Acien A

Abstract
BACKGROUND: For many environmental chemicals, concentrations in spot urine samples are considered valid surrogates of exposure and internal dose. To correct for urine dilution, spot urine concentrations are commonly adjusted for urinary creatinine. There are, however, several concerns about the use of urine creatinine. While urine osmolality is an attractive alternative; its characteristics and determinants in the general population remain unknown. Our objective was to describe the determinants of urine osmolality and to contrast the difference between osmolality and creatinine in urine.
METHODS: From the National Health and Nutrition Examination Survey (NHANES) (2009-2010), 10,769 participants aged 16 years or older with measured urine osmolality and creatinine were used in the analysis. Very dilute and very concentrated urine was defined as urine creatinine lower than 0.3g/l and higher than 3g/l, respectively. Linear and logistic regression analyses were performed to investigate the associations of interest.
RESULTS: Urine osmolality and creatinine were highly correlated (Pearson correlation coefficient=0.75) and their respective median values were 648mOsm/kg and 1.07g/l. The prevalence of very dilute and very concentrated urine samples was 8.1% and 3.1%, respectively. Factors associated in the same direction with both urine osmolality and urine creatinine included age, sex, race, body mass index (BMI), hypertension, water intake, and blood osmolality. The magnitude of associations expressed as percent change was significantly stronger with creatinine than osmolality. Compared to urine creatinine, urine osmolality did not vary by diabetes status but was affected by daily total protein intake. Participants with chronic kidney disease (CKD) had significantly higher urine creatinine concentrations but lower urine osmolality. Both very dilute and concentrated urine were associated with a diverse array of sociodemographic, medical conditions, and dietary factors. For instance, females were approximately 3.3 times more likely to have urine over-dilution than male [the adjusted odds ratios (95% CI)=3.27 (2.10-5.10)].
CONCLUSION: Although the determinants of urine osmolality were generally similar to those of urine creatinine, the relative influence of socio-demographic and medical conditions was less on urine osmolality than on urine creatinine. Protocols for spot urine sample collection could recommend avoiding excessive and insufficient water intake before urine sampling to improve urine adequacy. The feasibility of adopting urine osmolality adjustment and water intake recommendations before providing spot urine samples for environmental biomonitoring merits further investigation.

PMID: 25460670 [PubMed - as supplied by publisher]

Sequencing the hypervariable regions of human mitochondrial DNA using massively parallel sequencing: Enhanced data acquisition for DNA samples encountered in forensic testing.

Wed, 12/03/2014 - 11:30pm

Sequencing the hypervariable regions of human mitochondrial DNA using massively parallel sequencing: Enhanced data acquisition for DNA samples encountered in forensic testing.

Leg Med (Tokyo). 2014 Oct 25;

Authors: Davis C, Peters D, Warshauer D, King J, Budowle B

Abstract
Mitochondrial DNA testing is a useful tool in the analysis of forensic biological evidence. In cases where nuclear DNA is damaged or limited in quantity, the higher copy number of mitochondrial genomes available in a sample can provide information about the source of a sample. Currently, Sanger-type sequencing (STS) is the primary method to develop mitochondrial DNA profiles. This method is laborious and time consuming. Massively parallel sequencing (MPS) can increase the amount of information obtained from mitochondrial DNA samples while improving turnaround time by decreasing the numbers of manipulations and more so by exploiting high throughput analyses to obtain interpretable results. In this study 18 buccal swabs, three different tissue samples from five individuals, and four bones samples from casework were sequenced at hypervariable regions I and II using STS and MPS. Sample enrichment for STS and MPS was PCR-based. Library preparation for MPS was performed using Nextera® XT DNA Sample Preparation Kit and sequencing was performed on the MiSeq™ (Illumina, Inc.). MPS yielded full concordance of base calls with STS results, and the newer methodology was able to resolve length heteroplasmy in homopolymeric regions. This study demonstrates short amplicon MPS of mitochondrial DNA is feasible, can provide information not possible with STS, and lays the groundwork for development of a whole genome sequencing strategy for degraded samples.

PMID: 25459369 [PubMed - as supplied by publisher]

Cause and manner of death and phase of the blood alcohol curve.

Wed, 12/03/2014 - 11:30pm

Cause and manner of death and phase of the blood alcohol curve.

Forensic Sci Int. 2014 Sep 28;244C:306-312

Authors: Lahti RA, Pitkäniemi J, Jones AW, Sajantila A, Poikolainen K, Vuori E

Abstract
In a large number of forensic autopsies (N=28,184) the concentrations of ethanol in femoral blood and bladder urine were determined and the urine-to-blood concentration ratios of ethanol were calculated. Based on the differences in ethanol concentration between urine and blood, the deaths were classified as having occurred during the absorptive, the peak or the post-absorptive phase of the blood-alcohol curve. Most people died in the post-absorptive phase, N=24,223 (86%), whereas 1538 individuals (5.5%) were still absorbing alcohol and 2423 (8.6%) were at or close to the peak BAC at time of death. Both blood-alcohol concentration (BAC) and urine-alcohol concentration (UAC) were significantly higher in the post-absorptive phase (p<0.001). The proportions of people dying in the absorptive and peak phases increased with advancing age. The cause of death (CoD) and manner of death (MoD) according to death certificates were compared with phase of the blood-alcohol curve using a multinomial regression model with and without making adjustment for possible effects of age, gender and BAC. The relative risk (RR) and relative risk ratios (RRR) showed some associations between CoD and phase of the blood-alcohol curve. Undetermined MoD was significantly higher in the absorptive phase compared with the post-absorptive phase (RRR=2.12). Deaths related to esophagus, stomach and duodenum (RRR=2.04) and alcoholic liver diseases (RRR=1.85) were significantly higher at or close to peak phase compared to the post-absorptive phase. Road-traffic fatalities were more prevalent in the peak BAC phase (RRR=1.33) and deaths by accidental falls were less in the absorptive phase (RRR=0.58) compared with the post-absorptive phase. The phase of alcohol intoxication seems relevant to consider by forensic experts when alcohol-related deaths are investigated.

PMID: 25452205 [PubMed - as supplied by publisher]

STRait Razor v2.0: The improved STR Allele Identification Tool - Razor.

Wed, 12/03/2014 - 11:30pm

STRait Razor v2.0: The improved STR Allele Identification Tool - Razor.

Forensic Sci Int Genet. 2014 Oct 22;14C:182-186

Authors: Warshauer DH, King JL, Budowle B

Abstract
STRait Razor (the STR Allele Identification Tool - Razor) was developed as a bioinformatic software tool to detect short tandem repeat (STR) alleles in massively parallel sequencing (MPS) raw data. The method of detection used by STRait Razor allows it to make reliable allele calls for all STR types in a manner that is similar to that of capillary electrophoresis. STRait Razor v2.0 incorporates several new features and improvements upon the original software, such as a larger default locus configuration file that increases the number of detectable loci (now including X-chromosome STRs and Amelogenin), an enhanced custom locus list generator, a novel output sorting method that highlights unique sequences for intra-repeat variation detection, and a genotyping tool that emulates traditional electropherogram data. Users also now have the option to choose whether the program detects autosomal, X-chromosome, Y-chromosome, or all STRs. Concordance testing was performed, and allele calls produced by STRait Razor v2.0 were completely consistent with those made by the original software.

PMID: 25450790 [PubMed - as supplied by publisher]

Exosome-Associated Hepatitis C Virus in Cell Cultures and Patient Plasma.

Wed, 12/03/2014 - 11:30pm

Exosome-Associated Hepatitis C Virus in Cell Cultures and Patient Plasma.

Biochem Biophys Res Commun. 2014 Nov 4;

Authors: Liu Z, Zhang X, Yu Q, He JJ

Abstract
Hepatitis C virus (HCV) infects its target cells in the form of cell-free viruses and through cell-cell contact. Here we report that HCV is associated with exosomes. Using highly purified exosomes and transmission electron microscopic imaging, we demonstrated that HCV occurred in both exosome-free and exosome-associated forms. Exosome-associated HCV was infectious and resistant to neutralization by an anti-HCV neutralizing antibody. There were more exosome-associated HCV than exosome-free HCV detected in the plasma of HCV-infected patients. These results suggest exosome-associated HCV as an alternative form for HCV infection and transmission.

PMID: 25449270 [PubMed - as supplied by publisher]

Clinical and laboratory profiles of refractory Mycoplasma pneumoniae pneumonia in children.

Wed, 12/03/2014 - 11:30pm

Clinical and laboratory profiles of refractory Mycoplasma pneumoniae pneumonia in children.

Int J Infect Dis. 2014 Oct 22;29C:18-23

Authors: Wang M, Wang Y, Yan Y, Zhu C, Huang L, Shao X, Xu J, Zhu H, Sun X, Ji W, Chen Z

Abstract
OBJECTIVES: The purpose of this study was to explore the clinical and laboratory characteristics of children with refractory Mycoplasma pneumoniae pneumonia (RMPP).
METHODS: Seventy-six children with RMPP and 26 children with non-refractory M. pneumoniae pneumonia (NRMPP), confirmed by both serology and fluorescent quantitation PCR in bronchoalveolar lavage fluid (BALF), were evaluated retrospectively.
RESULTS: Compared to those with NRMPP, children with RMPP were older (66.6±39.0 vs. 48.4±35.4 months, p=0.038) and had a longer duration of fever (12.7±2.6 vs. 7.5±1.8 days) and hospital stay (12.1±3.2 vs. 7.4±2.9 days). Children with RMPP presented neutrophil infiltration both in serum and BALF, as well as severe pulmonary lesions with pleural effusion. Children with RMPP had a significantly higher M. pneumoniae DNA load in BALF compared to NRMPP patients, and the M. pneumoniae load in BALF was significantly correlated with neutrophils and inversely correlated with macrophages for both the NRMPP and RMPP groups. The serum concentrations of tumor necrosis factor alpha (median 114.5 pg/ml, range 49.1-897.9 pg/ml) and interferon gamma (median 376.9 pg/ml, range 221.4-1997.6 pg/ml) were significantly higher in children with RMPP compared to children with NRMPP.
CONCLUSIONS: This study indicates that a direct microbe effect and the subsequent induced excessive host immune response contribute in part to the progression of RMPP.

PMID: 25449230 [PubMed - as supplied by publisher]

Cost-consequence analysis of cause of death investigation in Finland and in Denmark.

Wed, 12/03/2014 - 11:30pm

Cost-consequence analysis of cause of death investigation in Finland and in Denmark.

Forensic Sci Int. 2014 Oct 31;245C:133-142

Authors: Ylijoki-Sørensen S, Boldsen JL, Lalu K, Sajantila A, Baandrup U, Boel LW, Ehlers LH, Bøggild H

Abstract
The 1990s 12-16% total autopsy rate in Denmark has until now declined to 4%, while in Finland, it has remained between 25 and 30%. The decision to proceed with a forensic autopsy is based on national legislation, but it can be assumed that the financing of autopsies influences the decision process. Only little is known about the possible differences between health economics of Finnish and Danish cause of death investigation systems. The aims of this article were to analyse costs and consequences of Finnish and Danish cause of death investigations, and to develop an alternative autopsy practice in Denmark with another cost profile. Data on cause of death investigation systems and costs were derived from Departments of Forensic Medicine, Departments of Pathology, and the National Police. Finnish and Danish autopsy rates were calculated in unnatural (accident, suicide, homicide and undetermined intent) and natural (disease) deaths, and used to develop an alternative autopsy practice in Denmark. Consequences for society were analysed. The estimated unit cost (€) for one forensic autopsy is 3.2 times lower in Finland than in Denmark (€1400 versus €4420), but in Finland the salaries for forensic pathologists working at the National Institute for Health and Welfare are not included in the unit cost. The unit cost for one medical autopsy is also lower in Finland than in Denmark; €700 versus €1070. In our alternative practice in Denmark, the forensic autopsy rate was increased from 2.2% to 8.5%, and the medical autopsy rate from 2.4% to 5.8%. Costs per 10,000 deaths were estimated to be 50% (±25%) higher than now; i.e. €3,678,724 (2,759,112-4,598,336), but would result in a lower unit cost for forensic autopsies €3,094 (2,320-3,868) and for medical autopsies €749 (562-936). This practice would produce a higher accuracy of national mortality statistics, which, consequently, would entail higher quality in public health, an accurate basis for decision-making in health politics, and better legislative safety in society. The implementation of this alternative practice in Denmark requires that legislation demands that forensic autopsy be performed if causality between unnatural death and cause of death cannot be clarified or if cause of death remains unknown. The Danish Health and Medicines Authority should provide guidelines that request a medical autopsy in natural deaths where more information about disease as a cause of death is needed. Our study results warrant similar health economic analyses of different cause of death investigations in other countries.

PMID: 25447186 [PubMed - as supplied by publisher]

Temperature as a predictive tool for plantar triaxial loading.

Wed, 12/03/2014 - 11:30pm

Temperature as a predictive tool for plantar triaxial loading.

J Biomech. 2014 Nov 28;47(15):3767-3770

Authors: Yavuz M, Brem RW, Davis BL, Patel J, Osbourne A, Matassini MR, Wood DA, Nwokolo IO

Abstract
Diabetic foot ulcers are caused by moderate repetitive plantar stresses in the presence of peripheral neuropathy. In severe cases, the development of these foot ulcers can lead to lower extremity amputations. Plantar pressure measurements have been considered a capable predictor of ulceration sites in the past, but some investigations have pointed out inconsistencies when solely relying on this method. The other component of ground reaction forces/stresses, shear, has been understudied due to a lack of adequate equipment. Recent articles reported the potential clinical significance of shear in diabetic ulcer etiology. With the lack of adequate tools, plantar temperature has been used as an alternative method for determining plantar triaxial loading and/or shear. However, this method has not been previously validated. The purpose of this study was to analyze the potential association between exercise-induced plantar temperature increase and plantar stresses. Thirteen healthy individuals walked on a treadmill for 10minutes at 3.2km/h. Pre and post-exercise temperature profiles were obtained with a thermal camera. Plantar triaxial stresses were quantified with a custom-built stress plate. A statistically significant correlation was observed between peak shear stress (PSS) and temperature increase (r=0.78), but not between peak resultant stress (PRS) and temperature increase (r=0.46). Plantar temperature increase could predict the location of PSS and PRS in 23% and 39% of the subjects, respectively. Only a moderate linear relationship was established between triaxial plantar stresses and walking-induced temperature increase. Future research will investigate the value of nonlinear models in predicting plantar loading through foot temperature.

PMID: 25446272 [PubMed - as supplied by publisher]

Innovative diagnostic tools for early detection of Alzheimer's disease.

Wed, 12/03/2014 - 11:30pm

Innovative diagnostic tools for early detection of Alzheimer's disease.

Alzheimers Dement. 2014 Nov 15;

Authors: Laske C, Sohrabi HR, Frost SM, López-de-Ipiña K, Garrard P, Buscema M, Dauwels J, Soekadar SR, Mueller S, Linnemann C, Bridenbaugh SA, Kanagasingam Y, Martins RN, O'Bryant SE

Abstract
Current state-of-the-art diagnostic measures of Alzheimer's disease (AD) are invasive (cerebrospinal fluid analysis), expensive (neuroimaging) and time-consuming (neuropsychological assessment) and thus have limited accessibility as frontline screening and diagnostic tools for AD. Thus, there is an increasing need for additional noninvasive and/or cost-effective tools, allowing identification of subjects in the preclinical or early clinical stages of AD who could be suitable for further cognitive evaluation and dementia diagnostics. Implementation of such tests may facilitate early and potentially more effective therapeutic and preventative strategies for AD. Before applying them in clinical practice, these tools should be examined in ongoing large clinical trials. This review will summarize and highlight the most promising screening tools including neuropsychometric, clinical, blood, and neurophysiological tests.

PMID: 25443858 [PubMed - as supplied by publisher]

Nicotine Enhances Inhibition of Mouse Vagal Motor Neurons by Modulating Excitability of Premotor GABAergic Neurons in the Nucleus Tractus Solitarius.

Tue, 12/02/2014 - 3:30pm

Nicotine Enhances Inhibition of Mouse Vagal Motor Neurons by Modulating Excitability of Premotor GABAergic Neurons in the Nucleus Tractus Solitarius.

J Neurophysiol. 2014 Nov 26;:jn.00614.2014

Authors: Xu H, Boychuk JA, Boychuk CR, Uteshev VV, Smith BN

Abstract
The caudal nucleus of the solitary tract (NTS) serves as the site of the first synapse for visceral sensory inputs to the central nervous system. The NTS sends functional projections to multiple brain nuclei, with gastric-related projections primarily targeting the dorsal motor nucleus of the vagus (DMV). Previous studies have demonstrated that the majority of caudal NTS neurons that project to the DMV respond robustly to nicotine and express nicotinic acetylcholine receptors (nAChRs). However, the cytochemical identity and relationship with specific viscera of DMV-projecting, nicotine-responsive caudal NTS neurons have not been determined. The present study uses transgenic mice that express EGFP under a GAD67 promoter in a subset of GABAergic neurons, in vivo retrograde pseudorabies viral labeling to identify gastric-related vagal complex neurons, and patch-clamp electrophysiology in acute brainstem slices to test the hypothesis that gastric-related and GABAergic inhibitory synaptic input to the DMV from the caudal NTS is under a robust modulatory control by nAChRs. Our results suggest that activation of nAChRs in the caudal NTS, but not DMV, potentiates GABAergic, but not glutamatergic, input to the DMV. Gastric-related caudal NTS and DMV neurons are directly involved in this nicotine-sensitive circuitry. Understanding the central patterns of nicotinic modulation of visceral sensory-motor circuitry may help develop therapeutic interventions to restore autonomic homeostasis in patients with autonomic impairments.

PMID: 25429117 [PubMed - as supplied by publisher]

Chronic Pain and Health Care Spending: An Analysis of Longitudinal Data from the Medical Expenditure Panel Survey.

Thu, 11/27/2014 - 11:27am

Chronic Pain and Health Care Spending: An Analysis of Longitudinal Data from the Medical Expenditure Panel Survey.

Health Serv Res. 2014 Nov 25;

Authors: Stockbridge EL, Suzuki S, Pagán JA

Abstract
OBJECTIVE: To estimate average incremental health care expenditures associated with chronic pain by health care service category, expanding on prior research that focused on specific pain conditions instead of general pain, excluded low levels of pain, or did not incorporate pain duration.
DATA SOURCE: Medical Expenditure Panel Survey (MEPS) data (2008-2011; N = 26,671).
STUDY DESIGN: Differences in annual expenditures for adults at different levels of pain that interferes with normal work, as measured by the SF-12, were estimated using recycled predictions from two-part logit-generalized linear regression models.
PRINCIPAL FINDINGS: "A little bit" of chronic pain-related interference was associated with a $2,498 increase in total adjusted expenditures over no pain interference (p < .0001) and a $1,008 increase over nonchronic pain interference (p = .0001). Moderate and severe chronic pain-related interference was associated with a $3,707 and $5,804 increase in expenditures over no pain interference and a $2,218 and $4,315 increase over nonchronic interference, respectively (p < .0001). Expenditure increases were most pronounced for inpatient and hospital outpatient expenditures compared to other types of health care expenditures.
CONCLUSIONS: Chronic pain limitations are associated with higher health care expenditures. Results underscore the substantial cost of pain to the health care system.

PMID: 25424348 [PubMed - as supplied by publisher]

Role of C/EBP Homologous Protein in Retinal Ganglion Cell Death after Ischemia/Reperfusion Injury.

Wed, 11/26/2014 - 3:12pm

Role of C/EBP Homologous Protein in Retinal Ganglion Cell Death after Ischemia/Reperfusion Injury.

Invest Ophthalmol Vis Sci. 2014 Nov 20;

Authors: Nashine S, Liu Y, Kim BJ, Clark AF, Pang IH

Abstract
Purpose: To investigate the role of C/EBP homologous protein (CHOP), a pro-apoptotic protein and unfolded protein response (UPR) marker that is involved in ER-stress mediated apoptosis, in mouse retinal ganglion cell (RGC) death following ischemia/reperfusion (I/R) injury. Methods: Retinal I/R was induced in adult C57BL/6J (wild type; WT) and CHOP knockout (Chop-/-) mice by raising intraocular pressure to 120 mmHg for 60 min. Expression of CHOP and other UPR markers was studied by Western blot and immunohistochemistry. RGC counts were performed in retinal flatmounts stained with an RGC marker. RGC function was evaluated by the scotopic threshold response (STR) electroretinography. Results: In WT mice, retinal CHOP was up-regulated by 30% in I/R-injured eyes compared to uninjured eyes 3 d after injury (p<0.05). Immunohistochemistry confirmed CHOP up-regulation specifically in RGCs. CHOP knockout did not affect baseline RGC density or STR amplitude. I/R decreased RGC densities and STR amplitudes in both WT and Chop-/- mice. However, survival of RGCs in I/R-injured Chop-/- mouse was 48% higher (p<0.05) than that of I/R-injured WT mouse 3 d after I/R injury. Similarly, RGC density was significantly higher in Chop-/- eyes at 7, 14, and 28 d after I/R. STR amplitudes of Chop-/- mice were significantly higher at 3 and 7 d after I/R than the WT mice. Conclusions: Absence of CHOP partially protects against RGC loss and reduction in retinal function after I/R injury, indicating that CHOP and thus ER-stress play an important role in RGC apoptosis in retinal I/R injury.

PMID: 25414185 [PubMed - as supplied by publisher]

Massively parallel sequencing of forensically relevant single nucleotide polymorphisms using TruSeq™ forensic amplicon.

Sat, 11/22/2014 - 4:05pm
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Massively parallel sequencing of forensically relevant single nucleotide polymorphisms using TruSeq™ forensic amplicon.

Int J Legal Med. 2014 Nov 19;

Authors: Warshauer DH, Davis CP, Holt C, Han Y, Walichiewicz P, Richardson T, Stephens K, Jager A, King J, Budowle B

Abstract
The TruSeq™ Forensic Amplicon library preparation protocol, originally designed to attach sequencing adapters to chromatin-bound DNA for chromatin immunoprecipitation sequencing (TruSeq™ ChIP-Seq), was used here to attach adapters directly to amplicons containing markers of forensic interest. In this study, the TruSeq™ Forensic Amplicon library preparation protocol was used to detect 160 single nucleotide polymorphisms (SNPs), including human identification SNPs (iSNPs), ancestry, and phenotypic SNPs (apSNPs) in 12 reference samples. Results were compared with those generated by a second laboratory using the same technique, as well as to those generated by whole genome sequencing (WGS). The genotype calls made using the TruSeq™ Forensic Amplicon library preparation protocol were highly concordant. The protocol described herein represents an effective and relatively sensitive means of preparing amplified nuclear DNA for massively parallel sequencing (MPS).

PMID: 25408291 [PubMed - as supplied by publisher]

Dual small fragment plating improves screw-to-screw load sharing for mid-diaphyseal humeral fracture fixation: A finite element study.

Sat, 11/22/2014 - 4:05pm
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Dual small fragment plating improves screw-to-screw load sharing for mid-diaphyseal humeral fracture fixation: A finite element study.

Technol Health Care. 2014 Nov 18;

Authors: Kosmopoulos V, Luedke C, Nana AD

Abstract
BACKGROUND: A smaller humerus in some patients makes the use of a large fragment fixation plate difficult. Dual small fragment plate constructs have been suggested as an alternative.
OBJECTIVE: This study compares the biomechanical performance of three single and one dual plate construct for mid-diaphyseal humeral fracture fixation.
METHODS: Five humeral shaft finite element models (1 intact and 4 fixation) were loaded in torsion, compression, posterior-anterior (PA) bending, and lateral-medial (LM) bending. A comminuted fracture was simulated by a 1-cm gap. Fracture fixation was modelled by: (A) 4.5-mm 9-hole large fragment plate (wide), (B) 4.5-mm 9-hole large fragment plate (narrow), (C) 3.5-mm 9-hole small fragment plate, and (D) one 3.5-mm 9-hole small fragment plate and one 3.5-mm 7-hole small fragment plate.
RESULTS: Model A showed the best outcomes in torsion and PA bending, whereas Model D outperformed the others in compression and LM bending. Stress concentrations were located near and around the unused screw holes for each of the single plate models and at the neck of the screws just below the plates for all the models studied. Other than in PA bending, Model D showed the best overall screw-to-screw load sharing characteristics.
CONCLUSION: The results support using a dual small fragment locking plate construct as an alternative in cases where crutch weight-bearing (compression) tolerance may be important and where anatomy limits the size of the humerus bone segment available for large fragment plate fixation.

PMID: 25408282 [PubMed - as supplied by publisher]

Aberrant Histone Acetylation Promotes Mitochondrial Respiratory Suppression In the Brain of Alcoholic Rats.

Sat, 11/22/2014 - 4:05pm
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Aberrant Histone Acetylation Promotes Mitochondrial Respiratory Suppression In the Brain of Alcoholic Rats.

J Pharmacol Exp Ther. 2014 Nov 18;

Authors: Jung ME, Metzger DB

Abstract
The acetylation of histone proteins in the core of DNA regulates gene expression, including those affecting mitochondria. Both histone acetylation and mitochondrial deficit have been implicated in neuronal damage associated with drinking problems. Many alcoholics repeat unsuccessful attempts at abstaining, developing a pattern of repeated withdrawal from ethanol exposure. Here, we investigated whether aberrant histone acetylation contributes to mitochondrial and cellular damage induced by repeated ethanol withdrawal (EW). We also investigated whether this effect of histone acetylation involves a small non-coding RNA (microRNA) let-7f. Male rats receive two cycles of ethanol diet (7.5%, four weeks) and withdrawal. Prefrontal cortex was collected to measure mitochondrial respiration and histone acetylation using XF real-time respirometry and gold immunostaining, respectively. Separately, HT22 (mouse hippocampal) cells received two cycles of ethanol exposure (100 mM, 20 hours) and withdrawal. Histone acetylation promoter (Trichostatin A, TSA) and let-7f antagomir were applied during withdrawal. Mitochondrial respiration, let-7f level, and cell viability were assessed using XF respirometry, qPCR, TaqMan let-7f primers, and Calcein-AM assay, respectively. Repeated ethanol withdrawn rats show more than a twofold increase in histone acetylation, accompanied by mitochondrial respiratory suppression. EW-induced mitochondrial respiratory suppression is exacerbated by TSA treatment in a manner that is attenuated by let-7f antagomir cotreatment. TSA treatment does not alter the increasing effect of EW on let-7f level but dramatically exacerbates cell death induced by EW. These data suggest that the multiple episodes of withdrawal from chronic ethanol impede mitochondrial and cellular integrity through upregulating histone acetylation, independently or additively with let-7f.

PMID: 25406171 [PubMed - as supplied by publisher]

Pathogenic strains of Acanthamoeba are recognized by TLR4 and initiated inflammatory responses in the cornea.

Thu, 11/20/2014 - 4:05am
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Pathogenic strains of Acanthamoeba are recognized by TLR4 and initiated inflammatory responses in the cornea.

PLoS One. 2014;9(3):e92375

Authors: Alizadeh H, Tripathi T, Abdi M, Smith AD

Abstract
Free-living amoebae of the Acanthamoeba species are the causative agent of Acanthamoeba keratitis (AK), a sight-threatening corneal infection that causes severe pain and a characteristic ring-shaped corneal infiltrate. Innate immune responses play an important role in resistance against AK. The aim of this study is to determine if Toll-like receptors (TLRs) on corneal epithelial cells are activated by Acanthamoeba, leading to initiation of inflammatory responses in the cornea. Human corneal epithelial (HCE) cells constitutively expressed TLR1, TLR2, TLR3, TLR4, and TLR9 mRNA, and A. castellanii upregulated TLR4 transcription. Expression of TLR1, TLR2, TLR3, and TLR9 was unchanged when HCE cells were exposed to A. castellanii. IL-8 mRNA expression was upregulated in HCE cells exposed to A. castellanii. A. castellanii and lipopolysaccharide (LPS) induced significant IL-8 production by HCE cells as measured by ELISA. The percentage of total cells positive for TLR4 was higher in A. castellanii stimulated HCE cells compared to unstimulated HCE cells. A. castellanii induced upregulation of IL-8 in TLR4 expressing human embryonic kidney (HEK)-293 cells, but not TLR3 expressing HEK-293 cells. TLR4 neutralizing antibody inhibited A. castellanii-induced IL-8 by HCE and HEK-293 cells. Clinical strains but not soil strains of Acanthamoeba activated TLR4 expression in Chinese hamster corneas in vivo and in vitro. Clinical isolates but not soil isolates of Acanthamoeba induced significant (P< 0.05) CXCL2 production in Chinese hamster corneas 3 and 7 days after infection, which coincided with increased inflammatory cells in the corneas. Results suggest that pathogenic species of Acanthamoeba activate TLR4 and induce production of CXCL2 in the Chinese hamster model of AK. TLR4 may be a potential target in the development of novel treatment strategies in Acanthamoeba and other microbial infections that activate TLR4 in corneal cells.

PMID: 24633052 [PubMed - indexed for MEDLINE]