Recent Research Articles from UNTHSC

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Mitochondrial DNA deletions in Alzheimer's brains: a review.

Wed, 12/17/2014 - 3:29am
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Mitochondrial DNA deletions in Alzheimer's brains: a review.

Alzheimers Dement. 2014 May;10(3):393-400

Authors: Phillips NR, Simpkins JW, Roby RK

Abstract
Mitochondrial dysfunction and increased oxidative stress have been associated with normal aging and are possibly implicated in the etiology of late-onset Alzheimer's disease (AD). DNA deletions, as well as other alterations, can result from oxidative damage to nucleic acids. Many studies during the past two decades have investigated the incidence of mitochondrial DNA deletions in postmortem brain tissues of late-onset AD patients compared with age-matched normal control subjects. Published studies are not entirely concordant, but their differences might shed light on the heterogeneity of AD itself. Our understanding of the role that mitochondrial DNA deletions play in disease progression may provide valuable information that could someday lead to a treatment.

PMID: 23850329 [PubMed - indexed for MEDLINE]

Risk of future offense among probationers with co-occurring substance use and mental health disorders.

Wed, 12/17/2014 - 3:29am
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Risk of future offense among probationers with co-occurring substance use and mental health disorders.

Community Ment Health J. 2014 Apr;50(3):288-95

Authors: Balyakina E, Mann C, Ellison M, Sivernell R, Fulda KG, Sarai SK, Cardarelli R

Abstract
The criminal justice system is the primary service delivery system for many adults with drug and alcohol dependence, mental health, and other health service needs. The purpose of this study was to examine the relationship between risk of future offense, mental health status and co-occurring disorders in a large substance abuse diversion probationer population. A purposive sample of 2,077 probationers completed an assessment to screen for mental health disorders, substance use disorders, risk of future crime and violence, and several demographic characteristics. Probationers who screened positive for co-occurring substance use and mental health disorders were significantly more likely to be at higher risk of future crime and violence compared to probationers who screened positive for only substance use, only a mental health disorder, or no substance use or mental health disorder. Implications for substance use and mental health service delivery are discussed, and recommendations are made for further research.

PMID: 23765181 [PubMed - indexed for MEDLINE]

c-Jun NH2-terminal kinase-induced proteasomal degradation of c-FLIPL/S and Bcl2 sensitize prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine.

Wed, 12/17/2014 - 3:29am
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c-Jun NH2-terminal kinase-induced proteasomal degradation of c-FLIPL/S and Bcl2 sensitize prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine.

Biochem Pharmacol. 2014 Oct 15;91(4):457-73

Authors: Chaudhary P, Vishwanatha JK

Abstract
Tetrandrine, a constituent of Chinese herb Stephania tetrandra, causes cell death in prostate cancer, but the molecular mechanisms leading to apoptosis is not known. Here we demonstrated that tetrandrine selectively inhibits the growth of prostate cancer PC3 and DU145 cells compared to normal prostate epithelial PWR-1E cells. Tetrandrine-induced cell death in prostate cancer cells is caused by reactive oxygen species (ROS)-mediated activation of c-Jun NH2-terminal kinase (JNK1/2). JNK1/2-mediated proteasomal degradation of c-FLIPL/S and Bcl2 proteins are key events in the sensitization of prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine. Tetrandrine-induced JNK1/2 activation caused the translocation of Bax to mitochondria by disrupting its association with Bcl2 which was accompanied by collapse of mitochondrial membrane potential (MMP), cytosolic release of cytochrome c and Smac, and apoptotic cell death. Additionally, tetrandrine-induced JNK1/2 activation increased the phosphorylation of Bcl2 at Ser70 and facilitated its degradation via the ubiquitin-mediated proteasomal pathway. In parallel, tetrandrine-mediated ROS generation also caused the induction of ligand-independent Fas-mediated apoptosis by activating procaspase-8 and Bid cleavage. Inhibition of procaspase-8 activation attenuated the cleavage of Bid, loss of MMP and caspase-3 activation suggest that tetrandrine-induced Fas-mediated apoptosis is associated with the mitochondrial pathway. Furthermore, most of the signaling effects of tetrandrine on apoptosis were significantly attenuated in the presence of antioxidant N-acetyl-l-cysteine, thereby confirming the involvement of ROS in these events. In conclusion, the results of the present study indicate that tetrandrine-induced apoptosis in prostate cancer cells is initiated by ROS generation and that both intrinsic and extrinsic pathway contributes to cell death.

PMID: 25181458 [PubMed - indexed for MEDLINE]

The spatial distribution of actin and mechanical cycle of Myosin are different in right and left ventricles of healthy mouse hearts.

Mon, 12/15/2014 - 11:30am
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The spatial distribution of actin and mechanical cycle of Myosin are different in right and left ventricles of healthy mouse hearts.

Biochemistry. 2014 Dec 9;53(48):7641-9

Authors: Nagwekar J, Duggal D, Rich R, Raut S, Fudala R, Gryczynski I, Gryczynski Z, Borejdo J

Abstract
The contraction of the right ventricle (RV) expels blood into the pulmonary circulation, and the contraction of the left ventricle (LV) pumps blood into the systemic circulation through the aorta. The respective afterloads imposed on the LV and RV by aortic and pulmonary artery pressures create very different mechanical requirements for the two ventricles. Indeed, differences have been observed in the contractile performance between left and right ventricular myocytes in dilated cardiomyopathy, in congestive heart failure, and in energy usage and speed of contraction at light loads in healthy hearts. In spite of these functional differences, it is commonly believed that the right and left ventricular muscles are identical because there were no differences in stress development, twitch duration, work performance, or power among the RV and LV in dogs. This report shows that on a mesoscopic scale [when only a few molecules are studied (here three to six molecules of actin) in ex vivo ventricular myofibrils], the two ventricles in rigor differ in the degree of orientational disorder of actin within in filaments and during contraction in the kinetics of the cross-bridge cycle.

PMID: 25488019 [PubMed - in process]

M2b Macrophage Elimination and Improved Resistance of Mice with Chronic Alcohol Consumption to Opportunistic Infections.

Wed, 12/10/2014 - 3:29am

M2b Macrophage Elimination and Improved Resistance of Mice with Chronic Alcohol Consumption to Opportunistic Infections.

Am J Pathol. 2014 Dec 5;

Authors: Ohama H, Asai A, Ito I, Suzuki S, Kobayashi M, Higuchi K, Suzuki F

Abstract
Alcohol abuse was found to predispose persons to opportunistic infections. In this study, we tried to improve the host antibacterial resistance of chronic alcohol-consuming (CAC) mice to opportunistic infections. Bactericidal macrophages with functions to produce IL-12 and to express mRNAs for CXCL9 and inducible nitric oxide synthase (M1 macrophages) were characterized as the main effector cells in host antibacterial innate immunities against infections with opportunistic pathogens. However, CAC mice were found to be carriers of M2b macrophages [macrophages with functions to produce IL-10 and to express mRNAs for CD163, chemokine ligand (CCL)1, and LIGHT (homologous to lymphotoxin, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for high-voltage electron microscopy on T cells)], which were inhibitory on macrophage conversion from resident macrophages to M1 macrophages. Under treatment with CCL1 antisense oligodeoxynucleotides, a specific inhibitor of M2b macrophages, CAC mouse macrophages reverted to resident macrophages, and M1 macrophages were induced by a bacterial antigen from macrophages of CAC mice that were previously treated with the oligodeoxynucleotides. Opportunistic infections (enterococcal translocation and Klebsiella pneumonia) in CAC mice were completely controlled by CCL1 antisense oligodeoxynucleotides. These results indicate that certain opportunistic infections in alcoholics are controllable through the modulation of M2b macrophages.

PMID: 25485859 [PubMed - as supplied by publisher]

Abuse liability of the dietary supplement dimethylamylamine.

Tue, 12/09/2014 - 3:29am

Abuse liability of the dietary supplement dimethylamylamine.

Drug Alcohol Depend. 2014 Nov 25;

Authors: Dolan SB, Gatch MB

Abstract
BACKGROUND: Dimethylamylamine (DMAA) is a component of many dietary supplements and has recently been associated with numerous adverse effects, prompting the US military and World Anti-Doping Agency to ban its use as a supplement. The current study aimed to elucidate the abuse liability profile of DMAA.
METHODS: Dose-response studies of DMAA were performed with Swiss-Webster mice in locomotor and conditioned place-preference assays. The discriminative stimulus effects of DMAA were investigated in Sprague-Dawley rats trained to discriminate either cocaine or methamphetamine from saline.
RESULTS: DMAA produced dose-dependent locomotor depression and fully substituted for cocaine and partially substituted for methamphetamine. In the conditioned place-preference assay, DMAA produced an inverted-U-shaped dose-response curve, with intermediate doses producing significant place preference.
CONCLUSIONS: The cocaine- and methamphetamine-like discriminative stimulus effects and the conditioned place preference produced by DMAA suggest that is has potential for abuse. These findings in combination with reports of substantial adverse effects of DMAA in humans suggest that control of DMAA may warrant further consideration.

PMID: 25481853 [PubMed - as supplied by publisher]

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]

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