Recent Research Articles from UNTHSC

Syndicate content NCBI pubmed
NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
Updated: 5 hours 28 min ago

Attitudes Associated with Alcohol and Marijuana Referral Actions by Resident Assistants.

Thu, 09/25/2014 - 3:04am
Related Articles

Attitudes Associated with Alcohol and Marijuana Referral Actions by Resident Assistants.

J Prim Prev. 2014 Sep 23;

Authors: Thombs DL, Osborn CJ, Rossheim ME, Suzuki S

Abstract
This exploratory study examined associations between resident assistant (RA) attitudes and referral actions to identify training strategies for strengthening the ability of these paraprofessionals to recognize and refer college students in their living units who misuse alcohol and marijuana. The study's hypotheses were that (1) referral self-efficacy and perceived referral norms would be positively associated with RA referral actions and (2) perceived referral barriers and referral anticipatory anxiety would be negatively associated with RAs' referral actions. A total of 317 RAs at eight residential campuses in different regions of the U.S. took part in the study. All participating RAs had at least one semester of work experience. Just prior to the Fall semester of 2012, RA's responded to an online survey that assessed their alcohol and marijuana referral attitudes and referral actions. Overall, RAs reported considerable anxiety about approaching and referring students who may have an alcohol and/or marijuana problem. Perceived referral norms among RAs indicated substantial variability in perceptions about others' expectations of them for referring students who may have alcohol and marijuana problems. Results from two multivariable logistic regression analyses showed that referral self-efficacy distinguished RAs who took alcohol referral actions and marijuana referral actions from those who did not do so. Neither length of RA service nor time spent on campus was associated with referral actions. RA training programs could give attention to strengthening referral self-efficacy through a series of increasingly difficult skill-building activities during pre- and in-service training. In addition, senior residence life and housing professional staff may consider assessing the extent to which RAs under their supervision follow established protocols for assisting students with possible alcohol and marijuana problems. The development of evidence-based RA training programs will require additional research.

PMID: 25245491 [PubMed - as supplied by publisher]

Characterization of 114 insertion/deletion (INDEL) polymorphisms, and selection for a global INDEL panel for human identification.

Thu, 09/25/2014 - 3:04am
Related Articles

Characterization of 114 insertion/deletion (INDEL) polymorphisms, and selection for a global INDEL panel for human identification.

Leg Med (Tokyo). 2014 Jan;16(1):26-32

Authors: LaRue BL, Lagacé R, Chang CW, Holt A, Hennessy L, Ge J, King JL, Chakraborty R, Budowle B

Abstract
Bi-Allelic Insertions and Deletions (INDELs) are a powerful set of genetic markers for Human Identification (HID). They have certain desirable features, such as low mutation rates, no stutter, and potentially small amplicon sizes that could prove effective in some circumstances. In this study, we analyzed the distribution of 114 INDELs in four North American populations (Caucasian, African American, Southwest Hispanic, and Asian) to estimate their distribution in major global populations. Of the 114 INDELs a primary panel of 38 candidate markers was selected that met the criteria of (1) a minimum allele frequency of greater than 0.20 across the populations studied; (2) general concordance with Hardy-Weinberg equilibrium (HWE) expectations; (3) relatively low FST based on the major populations; (4) physical distance between markers greater than 40 Mbp; and (5) a lack of linkage disequilibria between syntenic markers. Additionally, another 11 supplemental markers were selected for an expanded panel of 49 markers which met the above criteria, with the exception that they are separated at least by 20 Mbp. The resulting panels had Random Match Probabilities that were at least 10(-16) and 10(-19), respectively, and combined FST values of approximately 0.02. Given these findings, these INDELs should be useful for HID.

PMID: 24296037 [PubMed - indexed for MEDLINE]

Autopsy rate in suicide is low among elderly in Denmark compared with Finland.

Wed, 09/24/2014 - 3:05am
Related Articles

Autopsy rate in suicide is low among elderly in Denmark compared with Finland.

Forensic Sci Int. 2014 Sep 6;244C:158-165

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

Abstract
National differences in the legislation on cause and manner of death investigation are reflected in a high autopsy rate in suicides in Finland and a low corresponding rate in Denmark. The consequences for mortality statistics of these different investigation practices on deaths classified as suicides in Denmark and Finland, respectively, are not known in detail. The aim of this article was to analyse autopsy rates in deaths classified as suicides, and to identify any differences in investigation practices in deaths with a comparable cause of death, but classified as unnatural deaths other than suicide. Data from the mortality registries were summarised for the years 2000, 2005 and 2010. Autopsy rates (total, forensic and medical) were analysed with regard to deaths classified as suicide, and they were compared for three age groups (1-50 years, 51-70 years and ≥71 years) and for causes of death. Deaths classified as suicide were compared with other unnatural classifications, and comparable causes of death were coded into six subgroups: poisonings, suffocations/strangulations, firearm discharges, drowning/submersions, explosions/flames and other/unspecified causes. The total autopsy rate for suicides was 99.8% in Finland and 13.2% in Denmark. Almost all of these autopsies were conducted as forensic autopsies. In the age group ≥71 years, Danish suicides outnumbered Finnish suicides (410 versus 283). The total autopsy rate was lower in the more senior age group in Denmark (19.5%, 9.9%, 5.6%), whereas it was consistently high in Finland (99.8%, 99.9%, 99.6%). Among Danish deaths due to poisonings, the autopsy rate was 89.5% when these were classified as accidents, but only 20.7% for cases classified as suicides. The number of deaths in the two Danish subgroups was comparable (550 versus 553). In Denmark, the decision regarding the need, if any, for a forensic autopsy is made during the external forensic examination of the body. Our study showed that the limited use of forensic autopsy to confirm the cause of death in deaths classified as suicides raises doubts about the accuracy of the Danish suicide mortality statistics. Our finding is emphasised by those cases in which the cause of death was registered as intentional self-poisoning. The high number of suicides among the elderly in Denmark is striking and begs further investigation and research. Overall, our data from Finland and Denmark reveal striking differences between the two countries and warrant further comparative studies on the subject in other countries.

PMID: 25244292 [PubMed - as supplied by publisher]

Associations between time spent sitting and cancer-related biomarkers in postmenopausal women: an exploration of effect modifiers.

Wed, 09/24/2014 - 3:05am
Related Articles

Associations between time spent sitting and cancer-related biomarkers in postmenopausal women: an exploration of effect modifiers.

Cancer Causes Control. 2014 Sep 20;

Authors: Paxton RJ, Jung SY, Vitolins MZ, Fenton J, Paskett E, Pollak M, Hays-Grudo J, Hursting SD, Chang S

Abstract
PURPOSE: Despite evidence that prolonged periods of sitting may influence biological mediators of cancer development, few studies have considered these relationships in a cancer-specific context.
METHODS: This cross-sectional study included 755 postmenopausal women enrolled in an ancillary study of the Women's Health Initiative. Plasma levels of Insulin-like growth factor-I (IGF-I), IGF-binding protein-3, leptin, insulin, C-peptide, C-reactive protein (CRP), and Interleukin (IL)-6 were measured. The time spent sitting per day was categorized as quartiles (Qs). The relationships between sedentary time and biomarkers were modified by race, physical activity, and exogenous estrogen use.
RESULTS: IGF-I levels among African American (AA) women were higher than those of white women across the Qs of sedentary time. Likewise, IL-6 levels in AA women were higher than those in white women at Q3 and Q4 of sedentary time. IGFBP-3 levels were higher and insulin levels were lower across the Qs of sedentary time among women meeting guidelines for physical activity than women who were not. Additionally, CRP levels were higher among estrogen users than nonusers at Q1, Q2, and Q4 of sedentary time.
CONCLUSIONS: These results suggest that relationship between time spent sitting and cancer-related biomarkers may not be simply linear, but differ in the context of effect modifiers.

PMID: 25238978 [PubMed - as supplied by publisher]

Cognitive Set Shifting Deficits and Their Relationship to Repetitive Behaviors in Autism Spectrum Disorder.

Wed, 09/24/2014 - 3:05am
Related Articles

Cognitive Set Shifting Deficits and Their Relationship to Repetitive Behaviors in Autism Spectrum Disorder.

J Autism Dev Disord. 2014 Sep 19;

Authors: Miller HL, Ragozzino ME, Cook EH, Sweeney JA, Mosconi MW

Abstract
The neurocognitive impairments associated with restricted and repetitive behaviors (RRBs) in autism spectrum disorder (ASD) are not yet clear. Prior studies indicate that individuals with ASD show reduced cognitive flexibility, which could reflect difficulty shifting from a previously learned response pattern or a failure to maintain a new response set. We examined different error types on a test of set-shifting completed by 60 individuals with ASD and 55 age- and nonverbal IQ-matched controls. Individuals with ASD were able to initially shift sets, but they exhibited difficulty maintaining new response sets. Difficulty with set maintenance was related to increased severity of RRBs. General difficulty maintaining new response sets and a heightened tendency to revert to old preferences may contribute to RRBs.

PMID: 25234483 [PubMed - as supplied by publisher]

Antigen-pulsed bone marrow-derived and pulmonary dendritic cells promote Th2 cell responses and immunopathology in lungs during the pathogenesis of murine Mycoplasma pneumonia.

Wed, 09/24/2014 - 3:05am
Related Articles

Antigen-pulsed bone marrow-derived and pulmonary dendritic cells promote Th2 cell responses and immunopathology in lungs during the pathogenesis of murine Mycoplasma pneumonia.

J Immunol. 2014 Aug 1;193(3):1353-63

Authors: Dobbs NA, Zhou X, Pulse M, Hodge LM, Schoeb TR, Simecka JW

Abstract
Mycoplasmas are a common cause of pneumonia in humans and animals, and attempts to create vaccines have not only failed to generate protective host responses, but they have exacerbated the disease. Mycoplasma pulmonis causes a chronic inflammatory lung disease resulting from a persistent infection, similar to other mycoplasma respiratory diseases. Using this model, Th1 subsets promote resistance to mycoplasma disease and infection, whereas Th2 responses contribute to immunopathology. The purpose of the present study was to evaluate the capacity of cytokine-differentiated dendritic cell (DC) populations to influence the generation of protective and/or pathologic immune responses during M. pulmonis respiratory disease in BALB/c mice. We hypothesized that intratracheal inoculation of mycoplasma Ag-pulsed bone marrow-derived DCs could result in the generation of protective T cell responses during mycoplasma infection. However, intratracheal inoculation (priming) of mice with Ag-pulsed DCs resulted in enhanced pathology in the recipient mice when challenged with mycoplasma. Inoculation of immunodeficient SCID mice with Ag-pulsed DCs demonstrated that this effect was dependent on lymphocyte responses. Similar results were observed when mice were primed with Ag-pulsed pulmonary, but not splenic, DCs. Lymphocytes generated in uninfected mice after the transfer of either Ag-pulsed bone marrow-derived DCs or pulmonary DCs were shown to be IL-13(+) Th2 cells, known to be associated with immunopathology. Thus, resident pulmonary DCs most likely promote the development of immunopathology in mycoplasma disease through the generation of mycoplasma-specific Th2 responses. Vaccination strategies that disrupt or bypass this process could potentially result in a more effective vaccination.

PMID: 24973442 [PubMed - indexed for MEDLINE]

Iatrogenic esophageal injuries: evidence-based management for diagnosis and timing of contrast studies after repair.

Fri, 09/19/2014 - 3:04am
Related Articles

Iatrogenic esophageal injuries: evidence-based management for diagnosis and timing of contrast studies after repair.

Int Surg. 2012 Jan-Mar;97(1):1-5

Authors: Ko E, O-Yurvati AH

Abstract
Leakage from gastroesophageal repair is considered a major complication and is often associated with increased hospital stay, morbidity, and mortality. Management of these patients is variable among surgeons. Cases managed by the thoracic surgical service from March 1, 2010 to March 1, 2011 were retrospectively reviewed. Eight patients met criteria for inclusion: 4 were repaired primarily, 2 by debridement with diversion, and 2 by Ivor-Lewis resection and reconstruction. Esophograms were completed between 1 and 7 days postoperatively. Of the 8 patients treated, there was 1 mortality (12%) due to fungal mediastinitis. Soluble contrast imaging revealed 2 leaks (25%), 1 contained and 1 diffuse, which was the only mortality. Changes in clinical status, even minor, require contrast imaging of the esophagus to assess repair integrity. Timing of contrast study is variable in the literature, averaging 5 to 14 days. A conservative time frame is 7 days, unless any clinical suspicion of an esophageal leak exists.

PMID: 23101993 [PubMed - indexed for MEDLINE]

Indoor air pollution from solid fuels and peripheral Blood DNA methylation: Findings from a population study in Warsaw, Poland.

Fri, 09/12/2014 - 3:05am
Related Articles

Indoor air pollution from solid fuels and peripheral Blood DNA methylation: Findings from a population study in Warsaw, Poland.

Environ Res. 2014 Sep 5;134C:325-330

Authors: Tao MH, Zhou J, Rialdi AP, Martinez R, Dabek J, Scelo G, Lissowska J, Chen J, Boffetta P

Abstract
DNA methylation is a potential mechanism linking indoor air pollution to adverse health effects. Fetal and early-life environmental exposures have been associated with altered DNA methylation and play a critical role in progress of diseases in adulthood. We investigated whether exposure to indoor air pollution from solid fuels at different lifetime periods was associated with global DNA methylation and methylation at the IFG2/H19 imprinting control region (ICR) in a population-based sample of non-smoking women from Warsaw, Poland. Global methylation and IFG2/H19 ICR methylation were assessed in peripheral blood DNA from 42 non-smoking women with Luminometric Methylation Assay (LUMA) and quantitative pyrosequencing, respectively. Linear regression models were applied to estimate associations between indoor air pollution and DNA methylation in the blood. Compared to women without exposure, the levels of LUMA methylation for women who had ever exposed to both coal and wood were reduced 6.70% (95% CI: -13.36, -0.04). Using both coal and wood before age 20 was associated with 6.95% decreased LUMA methylation (95% CI: -13.79, -0.11). Further, the negative correlations were more significant with exposure to solid fuels for cooking before age 20. There were no clear associations between indoor solid fuels exposure before age 20 and through the lifetime and IFG2/H19 ICR methylation. Our study of non-smoking women supports the hypothesis that exposure to indoor air pollution from solid fuels, even early-life exposure, has the capacity to modify DNA methylation that can be detected in peripheral blood.

PMID: 25199973 [PubMed - as supplied by publisher]

Alcohol Withdrawal and Cerebellar Mitochondria.

Fri, 09/12/2014 - 3:05am
Related Articles

Alcohol Withdrawal and Cerebellar Mitochondria.

Cerebellum. 2014 Sep 9;

Authors: Jung ME

Abstract
Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new therapy to manage cerebellar disorders associated with hyperexcitatory CNS disorders like ethanol withdrawal.

PMID: 25195804 [PubMed - as supplied by publisher]

Future directions of forensic DNA databases.

Fri, 09/12/2014 - 3:05am
Related Articles

Future directions of forensic DNA databases.

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

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

PMID: 24778103 [PubMed - indexed for MEDLINE]

Allele frequencies for 15 autosomal STR loci and haplotype data for 17 Y-STR loci in a population from Belize.

Wed, 09/10/2014 - 3:05am
Related Articles

Allele frequencies for 15 autosomal STR loci and haplotype data for 17 Y-STR loci in a population from Belize.

Int J Legal Med. 2014 Sep 6;

Authors: Flores S, Sun J, King J, Eisenberg A, Budowle B

Abstract
Allele frequencies for 15 autosomal STR loci (N = 290) and haplotype data for 17 Y-STR loci (N = 157) were determined for an admixed population from Belize. There were no detectable departures from Hardy-Weinberg equilibrium expectations at any autosomal STR loci except for the D8S1179 locus (p = 0.002). The combined power of discrimination (PD) and combined power of exclusion (PE) were greater than 0.99999999 and 0.99999951, respectively. In addition, a total of 144 distinct Y-STR haplotypes were observed with 133 Y-STR haplotypes observed only once. The most common Y-STR haplotype was observed three times for two separate haplotypes. The various analyses of these forensically relevant STR loci showed that these markers are informative in the Belize population for forensic and parentage testing applications.

PMID: 25193820 [PubMed - as supplied by publisher]

Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas.

Sun, 09/07/2014 - 3:04am
Related Articles

Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas.

Nat Genet. 2014 Jul;46(7):726-30

Authors: Zhang L, Chen LH, Wan H, Yang R, Wang Z, Feng J, Yang S, Jones S, Wang S, Zhou W, Zhu H, Killela PJ, Zhang J, Wu Z, Li G, Hao S, Wang Y, Webb JB, Friedman HS, Friedman AH, McLendon RE, He Y, Reitman ZJ, Bigner DD, Yan H

Abstract
Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic gliomas. We also performed targeted mutational analysis of an additional 24 such tumors and genome-wide methylation profiling of 45 gliomas. This study led to the discovery of tumor-specific mutations in PPM1D, encoding wild-type p53-induced protein phosphatase 1D (WIP1), in 37.5% of the BSGs that harbored hallmark H3F3A mutations encoding p.Lys27Met substitutions. PPM1D mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53 activation in vitro. PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2. These results define PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas.

PMID: 24880341 [PubMed - indexed for MEDLINE]

Changes in retinal aquaporin-9 (AQP9) expression in glaucoma.

Sun, 09/07/2014 - 3:04am
Related Articles

Changes in retinal aquaporin-9 (AQP9) expression in glaucoma.

Biosci Rep. 2013;33(2)

Authors: Yang MH, Dibas A, Tyan YC

Abstract
The eye contains numerous water channel proteins and the roles of AQPs (aquaporins) in the retina are blurred, especially under disease conditions. The purpose of this study was to investigate the expression of AQP9 gene and proteins affected by elevated IOP (intraocular pressure) in a rat model of glaucoma induced by intravitreous injection of hypertonic saline into the episcleral veins. The gene and protein expressions of AQP9 were investigated by real-time PCR and Western blotting. The immunoreactive expression of AQP9, AQP4 and GFAP (glial fibrillary acidic protein) in the optic nerve of rats exposed to experimentally elevated IOP was detected by immunofluorescence microscopy. The mRNA and protein expression levels of AQP9 were up-regulated in the retina of an animal model of glaucoma. The immunoreactivities of the AQP9, AQP4 and GFAP were also detected and increased in the optic nerve region. The expression of AQP9 was up-regulated in this glaucoma model and the immunoreactivities of the AQP4 and GFAP were also detected as co-localizing with AQP9 in the optic nerve region, indicating retina ganglion cells were surrounded by activated astrocytes. This may indicate that the injured neurons may rely on the astrocytes. The alterations of AQP expression may compensate the glaucomatous damage.

PMID: 23464865 [PubMed - indexed for MEDLINE]

Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

Fri, 09/05/2014 - 3:04am
Related Articles

Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

Invest Ophthalmol Vis Sci. 2014 Jun;55(6):3912-21

Authors: Tripathi T, Abdi M, Alizadeh H

Abstract
PURPOSE: Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim of this study was to explore if aPA stimulates proinflammatory cytokine in human corneal epithelial (HCE) cells via the protease-activated receptors (PARs) pathway.
METHODS: Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose for 7 days, and the supernatants were collected and centrifuged. The aPA was purified using the fast protein liquid chromatography system, and aPA activity was determined by zymography assays. Human corneal epithelial cells were incubated with or without aPA (100 μg/mL), PAR1 agonists (thrombin, 10 μM; TRAP-6, 10 μM), and PAR2 agonists (SLIGRL-NH2, 100 μM; AC 55541, 10 μM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60 μM) and PAR2 (FSLLRY-NH2, 100 μM) with or without aPA. Human corneal epithelial cells also were preincubated with PAR1 and PAR2 antagonists and then incubated with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2 and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was quantified by qRT-PCR and ELISA.
RESULTS: Human corneal epithelial cells constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold, respectively) (P < 0.05). Protease-activated receptor 2 antagonist significantly inhibited aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P < 0.05). Protease-activated receptor 1 agonists, but not aPA, significantly upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1 antagonist in HCE cells. Acanthamoeba plasminogen activator and PAR2 agonists stimulated IL-8 mRNA expression and protein production, which is significantly diminished by PAR2 antagonist (P < 0.05). Protease-activated receptor 1 antagonist did not alter aPA-stimulated IL-8 mRNA expression and protein production in HCE cells. Flow cytometry and immunocytochemistry showed that aPA and SLIGRL-NH2 (PAR2 agonist) upregulated PAR2 surface protein as compared to that in unstimulated HCE cells. Thrombin, but not aPA, stimulated PAR1 surface protein in HCE cells.
CONCLUSIONS: Acanthamoeba plasminogen activator specifically induces expression and production of IL-8 in HCE cells via PAR2 pathway, and PAR2 antagonists may be used as a therapeutic target in AK.

PMID: 24876278 [PubMed - indexed for MEDLINE]

Patient-centered medical home features and expenditures by medicare beneficiaries.

Thu, 09/04/2014 - 3:04am
Related Articles

Patient-centered medical home features and expenditures by medicare beneficiaries.

Am J Manag Care. 2014 May;20(5):379-385

Authors: Stockbridge EL, Philpot LM, Pagán JA

Abstract
Objectives To determine the impact of individual features of the patient-centered medical home (PCMH) care model on next-year healthcare expenditures including outpatient, inpatient, emergency department, pharmacy, and total healthcare expenditures among Medicare beneficiaries 65 years and older. Study Design Analysis of retrospective longitudinal survey data. Methods Longitudinal files from the Medical Expenditure Panel Survey were analyzed. Differences in expenditures for individuals whose usual sources of care did or did not have different PCMH features were estimated using recycled predictions from generalized linear regression models. Results Having little to no difficulty contacting the regular source of care over the telephone during regular business hours was associated with significantly lower total and inpatient expenditures over the next year (differences of $2867 and $3736, respectively). Having a regular source of care with office hours at night or on weekends was associated with significantly lower outpatient, emergency department, and other expenditures (differences of $535, $103, and $328, respectively). Pharmacy expenditures were significantly higher for individuals whose usual source of care inquired about medications and treatments prescribed by other doctors (difference of $362). Conclusions This study points out the need to identify how individual PCMH features impact healthcare expenditures across different policy-relevant categories. Practices that have not fully adopted a PCMH model can still make progress in improving quality and controlling costs by adopting even some modest features of the PCMH model.

PMID: 25181567 [PubMed - as supplied by publisher]

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.

Thu, 09/04/2014 - 3:04am
Related Articles

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 Aug 30;

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 - as supplied by publisher]

Neural stem cell protects aged rat brain from ischemia-reperfusion injury through neurogenesis and angiogenesis.

Thu, 09/04/2014 - 3:04am
Related Articles

Neural stem cell protects aged rat brain from ischemia-reperfusion injury through neurogenesis and angiogenesis.

J Cereb Blood Flow Metab. 2014 Jul;34(7):1138-47

Authors: Tang Y, Wang J, Lin X, Wang L, Shao B, Jin K, Wang Y, Yang GY

Abstract
Neural stem cells (NSCs) show therapeutic potential for ischemia in young-adult animals. However, the effect of aging on NSC therapy is largely unknown. In this work, NSCs were transplanted into aged (24-month-old) and young-adult (3-month-old) rats at 1 day after stroke. Infarct volume and neurobehavioral outcomes were examined. The number of differentiated NSCs was compared in aged and young-adult ischemic rats and angiogenesis and neurogenesis were also determined. We found that aged rats developed larger infarcts than young-adult rats after ischemia (P<0.05). The neurobehavioral outcome was also worse for aged rats comparing with young-adult rats. Brain infarction and neurologic deficits were attenuated after NSC transplantation in both aged and young-adult rats. The number of survived NSCs in aged rats was similar to that of the young-adult rats (P>0.05) and most of them were differentiated into glial fibrillary acidic protein(+) (GFAP(+)) cells. More importantly, angiogenesis and neurogenesis were greatly enhanced in both aged and young-adult rats after transplantation compared with phosphate-buffered saline (PBS) control (P<0.05), accompanied by increased expression of vascular endothelial growth factor (VEGF). Our results showed that NSC therapy reduced ischemic brain injury, along with increased angiogenesis and neurogenesis in aged rats, suggesting that aging-related microenvironment does not preclude a beneficial response to NSCs transplantation during cerebral ischemia.

PMID: 24714034 [PubMed - indexed for MEDLINE]

Molecular genetic investigative leads to differentiate monozygotic twins.

Wed, 09/03/2014 - 3:05am

Molecular genetic investigative leads to differentiate monozygotic twins.

Investig Genet. 2014;5:11

Authors: Budowle B

PMID: 25177480 [PubMed]

Risk Factors for and Assessment of Symptomatic Pseudarthrosis After Lumbar Pedicle Subtraction Osteotomy in Adult Spinal Deformity.

Tue, 09/02/2014 - 3:06am

Risk Factors for and Assessment of Symptomatic Pseudarthrosis After Lumbar Pedicle Subtraction Osteotomy in Adult Spinal Deformity.

Spine (Phila Pa 1976). 2014 Jul 1;39(15):1190-1195

Authors: Dickson DD, Lenke LG, Bridwell KH, Koester LA

Abstract
STUDY DESIGN.: Retrospective review of prospectively collected data.
OBJECTIVE.: To assess the prevalence, risk factors, and clinical outcomes for pseudarthrosis after a lumbar pedicle subtraction osteotomy (PSO).
SUMMARY OF BACKGROUND DATA.: There exists no large series that examines pseudarthrosis rates of PSOs.
METHODS.: Data of 171 consecutive patients with adult deformity who underwent a lumbar PSO by 2 surgeons at a single institution with a minimum 2-year follow-up were analyzed. Pseudarthrosis diagnosed through sagittal malalignment and instrumentation failure noted on radiograph was confirmed intraoperatively.
RESULTS.: Eighteen (10.5%) of 171 patients developed pseudarthrosis after a PSO. Eleven of the 18 patients (6.4% of all patients, 61.1% of the 18 patients with pseudarthrosis) had pseudarthrosis at the PSO site, L3 being the most common; other locations included the lumbosacral junction (4/18), thoracolumbar junction (2/18), and upper thoracic spine (1/18). Preoperative pseudarthrosis level was a predictor of the postoperative level of pseudarthrosis (93%). Fifteen of the 18 patients (83%) had no interbody fusion directly above or below the PSO site, 16 (88%) had a history of pseudarthrosis at the time of PSO surgery and 2 of 3 patients who had prior radiation to the lumbar region developed pseudarthrosis. Most pseudarthroses occurred within the first 2 years (n = 13/18), between 2 and 5 years (n = 3/18), and more than 5 years (n = 2/18) postoperatively. Prior pseudarthrosis (P < 0.0001), pseudarthrosis at the PSO site (P < 0.0001), prior decompression in the lumbar region (P = 0.0037), prior radiation to the lumbar region (P < 0.0001), and presence of inflammatory/neurological disorders (P < 0.0036) were identified as risk factors. All 18 patients with pseudarthroses required revision surgery (posterior-only surgery, n = 12; anteroposterior surgery, n = 6) due to loss of sagittal alignment and pain. The mean pre-revision Scoliosis Research Society score was 85, post-revision score was 95 (P = 0.0166), and the mean pre-revision Oswestry Disability Index score was 42.5, post-revision score was 34.5 (P = 0.0203).
CONCLUSION.: The overall prevalence of pseudarthrosis was 10.5% of which 61% occurred at the actual PSO site and Scoliosis Research Society and Oswestry Disability Index scores improved significantly after pseudarthrosis repair.Level of Evidence: 4.

PMID: 25171067 [PubMed - as supplied by publisher]

Evidence of brain tumor stem progenitor-like cells with low proliferative capacity in human benign pituitary adenoma.

Sat, 08/30/2014 - 3:06am
Related Articles

Evidence of brain tumor stem progenitor-like cells with low proliferative capacity in human benign pituitary adenoma.

Cancer Lett. 2014 Jul 10;349(1):61-6

Authors: Chen L, Ye H, Wang X, Tang X, Mao Y, Zhao Y, Wu Z, Mao XO, Xie L, Jin K, Yao Y

Abstract
Tumor stem cells have been implicated as cancer-initiating cells in malignant brain tumors. However, whether benign brain tumors also contain tumor stem cells are largely unexplored. Here, we investigated whether tumor stem-like cells were present in pituitary adenoma similar to malignant brain tumors. By immunocytochemistry, we found that pituitary adenoma tissues expressed neural stem cell marker. These cells could form neurospheres in vitro, expressed neural stem/progenitor cell markers and generated daughter cells with the capacity to differentiate into three neural lineages. Importantly, compared with non-invasive pituitary adenomas, we found that CD133 expression was significantly increased in invasive pituitary adenomas, suggesting that the proliferative capacity was correlated with the malignance of pituitary adenomas. Finally, invasive pituitary adenomas cells displayed lower proliferative ability than glioblastoma. Our data indicate that a subpopulation of stem/progenitor-like cells are present in pituitary adenomas, and these cells may be responsible for benign tumor initiation and maintenance.

PMID: 24732807 [PubMed - indexed for MEDLINE]