Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

Subscribe to Recent Research Articles from UNTHSC  feed Recent Research Articles from UNTHSC
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: 1 hour 1 min ago

Biomechanical behavior of novel composite PMMA-CaP bone cements in an anatomically accurate cadaveric vertebroplasty model.

Wed, 10/11/2017 - 07:42
Related Articles

Biomechanical behavior of novel composite PMMA-CaP bone cements in an anatomically accurate cadaveric vertebroplasty model.

J Orthop Res. 2017 Sep;35(9):2067-2074

Authors: Aghyarian S, Hu X, Haddas R, Lieberman IH, Kosmopoulos V, Kim HKW, Rodrigues DC

Abstract
Vertebral compression fractures are caused by many factors including trauma and osteoporosis. Osteoporosis induced fractures are a result of loss in bone mass and quality that weaken the vertebral body. Vertebroplasty and kyphoplasty, involving cement augmentation of fractured vertebrae, show promise in restoring vertebral mechanical properties. Some complications however, are reported due to the performance characteristics of commercially available bone cements. In this study, the biomechanical performance characteristics of two novel composite (PMMA-CaP) bone cements were studied using an anatomically accurate human cadaveric vertebroplasty model. The study involves mechanical testing on two functional cadaveric spinal unit (2FSU) segments which include monotonic compression and cyclical fatigue tests, treatment by direct cement injection, and microscopic visualization of sectioned vertebrae. The 2FSU segments were fractured, treated, and mechanically tested to investigate the stability provided by two novel bone cements; using readily available commercial acrylic cement as a control. Segment height and stiffness were tracked during the study to establish biomechanical performance. The 2FSU segments were successfully stabilized with all three cement groups. Stiffness values were restored to initial levels following fatigue loading. Cement interdigitation was observed with all cement groups. This study demonstrates efficient reinforcement of the fractured vertebrae through stiffness restoration. The pre-mixed composite cements were comparable to the commercial cement in their performance and interdigitative ability, thus holding promise for future clinical use. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2067-2074, 2017.

PMID: 27891670 [PubMed - indexed for MEDLINE]

Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic.

Wed, 10/11/2017 - 07:42
Related Articles

Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic.

Alzheimers Dement. 2017 Jan;13(1):45-58

Authors: O'Bryant SE, Mielke MM, Rissman RA, Lista S, Vanderstichele H, Zetterberg H, Lewczuk P, Posner H, Hall J, Johnson L, Fong YL, Luthman J, Jeromin A, Batrla-Utermann R, Villarreal A, Britton G, Snyder PJ, Henriksen K, Grammas P, Gupta V, Martins R, Hampel H, Biofluid Based Biomarker Professional Interest Area

Abstract
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patient acceptance. Despite these advantages and increased research efforts, the field has been hampered by lack of reproducibility and an unclear path for moving basic discovery toward clinical utilization. Here we reviewed the recent literature on blood-based biomarkers in AD to provide a current state of the art. In addition, a collaborative model is proposed that leverages academic and industry strengths to facilitate the field in moving past discovery only work and toward clinical use. Key resources are provided. This new public-private partnership model is intended to circumvent the traditional handoff model and provide a clear and useful paradigm for the advancement of biomarker science in AD and other neurodegenerative diseases.

PMID: 27870940 [PubMed - indexed for MEDLINE]

HIV-1 Tat-shortened neurite outgrowth through regulation of microRNA-132 and its target gene expression.

Wed, 10/11/2017 - 07:42
Related Articles

HIV-1 Tat-shortened neurite outgrowth through regulation of microRNA-132 and its target gene expression.

J Neuroinflammation. 2016 Sep 15;13(1):247

Authors: Rahimian P, He JJ

Abstract
BACKGROUND: Synaptodendritic damage is a pathological hallmark of HIV-associated neurocognitive disorders, and HIV-1 Tat protein is known to cause such injury in the central nervous system. In this study, we aimed to determine the molecular mechanisms of Tat-induced neurite shortening, specifically the roles of miR-132, an important regulator of neurite morphogenesis in this process.
METHODS: The relationship between Tat expression and miR-132 expression was first determined using reverse transcription quantitative PCR (qRT-PCR) in Tat-transfected astrocytes and neurons, astrocytes from Tat-transgenic mice, and HIV-infected astrocytes. qRT-PCR and Western blotting were performed to determine Tat effects on expression of miR-132 target genes methyl CpG-binding protein 2, Rho GTPase activator p250GAP, and brain-derived neurotrophic factor. Exosomes were isolated from Tat-expressing astrocytes, and exosomal microRNA (miRNA) uptake into neurons was studied using miRNA labeling and flow cytometry. The lactate dehydrogenase release was used to determine the cytotoxicity, while immunostaining was used to determine neurite lengths and synapse formation. Tat basic domain deletion mutant and miR-132 mimic and inhibitor were used to determine the specificity of the relationship between Tat and miR-132 and its effects on astrocytes and neurons and the underlying mechanisms of Tat-induced miR-132 expression.
RESULTS: Tat significantly induced miR-132 expression, ensuing down-regulation of miR-132 target genes in astrocytes and neurons. miR-132 induction was associated with phosphorylation of cAMP response element-binding protein and required the basic domain of Tat. miRNA-132 induction had no effects on astrocyte activation or survival but was involved in the direct neurotoxicity of Tat. miR-132 was present in astrocyte-derived exosomes and was taken up by neurons, causing neurite shortening.
CONCLUSIONS: Tat-induced miR-132 expression contributes to both direct and astrocyte-mediated Tat neurotoxicity and supports the important roles of miR-132 in controlling neurite outgrowth.

PMID: 27634380 [PubMed - indexed for MEDLINE]

CRISPR-Cas9-based treatment of myocilin-associated glaucoma.

Thu, 10/05/2017 - 07:39

CRISPR-Cas9-based treatment of myocilin-associated glaucoma.

Proc Natl Acad Sci U S A. 2017 Oct 02;:

Authors: Jain A, Zode G, Kasetti RB, Ran FA, Yan W, Sharma TP, Bugge K, Searby CC, Fingert JH, Zhang F, Clark AF, Sheffield VC

Abstract
Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss worldwide, with elevated intraocular pressure (IOP) a major risk factor. Myocilin (MYOC) dominant gain-of-function mutations have been reported in ∼4% of POAG cases. MYOC mutations result in protein misfolding, leading to endoplasmic reticulum (ER) stress in the trabecular meshwork (TM), the tissue that regulates IOP. We use CRISPR-Cas9-mediated genome editing in cultured human TM cells and in a MYOC mouse model of POAG to knock down expression of mutant MYOC, resulting in relief of ER stress. In vivo genome editing results in lower IOP and prevents further glaucomatous damage. Importantly, using an ex vivo human organ culture system, we demonstrate the feasibility of human genome editing in the eye for this important disease.

PMID: 28973933 [PubMed - as supplied by publisher]

First-year Student Pharmacists' Spirituality and Perceptions Regarding the Role of Spirituality in Pharmacy Education.

Wed, 10/04/2017 - 07:43

First-year Student Pharmacists' Spirituality and Perceptions Regarding the Role of Spirituality in Pharmacy Education.

Am J Pharm Educ. 2017 Aug;81(6):108

Authors: Jacob B, White A, Shogbon A

Abstract
Objective: To measure student pharmacists' spirituality utilizing validated survey instruments and to determine perceptions regarding the anticipated role of spirituality in academic course work and professional practice. Methods: This was a cross-sectional, descriptive study. The survey was offered to all first-year student pharmacists during the first week of the fall semester (2012-2015). Descriptive and inferential statistics were used to analyze data. Results: A total of 580 students (98%) participated. The majority of students reported having each of the spiritual experiences on most days of the week or more frequently (58% to 89% based on individual item). Furthermore, 57% of students anticipate that matters of spirituality would be significant components of academic course work and 75% anticipate they would be incorporated into eventual professional practice settings. These perceptions were positively correlated to measures of spirituality and religiosity. Conclusion: These findings suggest that faculty should evaluate current and future incorporation of topics related to spirituality and health in pharmacy curriculum.

PMID: 28970609 [PubMed - in process]

Age-related Impairment of Vascular Structure and Functions.

Tue, 10/03/2017 - 07:37

Age-related Impairment of Vascular Structure and Functions.

Aging Dis. 2017 Oct;8(5):590-610

Authors: Xu X, Wang B, Ren C, Hu J, Greenberg DA, Chen T, Xie L, Jin K

Abstract
Among age-related diseases, cardiovascular and cerebrovascular diseases are major causes of death. Vascular dysfunction is a key characteristic of these diseases wherein age is an independent and essential risk factor. The present work will review morphological alterations of aging vessels in-depth, which includes the discussion of age-related microvessel loss and changes to vasculature involving the capillary basement membrane, intima, media, and adventitia as well as the accompanying vascular dysfunctions arising from these alterations.

PMID: 28966804 [PubMed]

Aging Systemic Milieu Impairs Outcome after Ischemic Stroke in Rats.

Tue, 10/03/2017 - 07:37

Aging Systemic Milieu Impairs Outcome after Ischemic Stroke in Rats.

Aging Dis. 2017 Oct;8(5):519-530

Authors: Pan M, Wang P, Zheng C, Zhang H, Lin S, Shao B, Zhuge Q, Jin K

Abstract
Compelling evidence indicates that factors in the blood can profoundly reverse aging-related impairments, as exposure of aged mice to young blood rejuvenates adult stem cell function, improves cognition, and ameliorates cardiac hypertrophy. Systemic factors from mice can also extend the life span of a partner exposed to a lethal treatment or disease. These findings suggest that the systemic milieu of a healthy young partner may be beneficial for an aged organism. However, it is unknown whether a healthy young systemic milieu can improve functional recovery after ischemic stroke. Intraperitoneal administration of young plasma into aged rats after ischemic stroke induced by distal middle cerebral artery occlusion (dMCAO) reduced infarct volume and motor impairment, compared with vehicle group. On the contrary, intraperitoneal administration of plasma from aged rats into young ischemic rats worsened brain injury and motor deficits. Using a proteomic approach, we found that haptoglobin levels were significantly increased in serum of aged rats and that intraperitoneal administration of haptoglobin impaired outcome after ischemic stroke in young rats. Our data suggest that the aging systemic milieu plays a critical role in functional outcome after ischemic stroke.

PMID: 28966798 [PubMed]

Severe hypercholesterolemia and liver disease in a 3-year old.

Tue, 10/03/2017 - 07:37
Related Articles

Severe hypercholesterolemia and liver disease in a 3-year old.

J Clin Lipidol. 2016 May-Jun;10(3):650-3

Authors: Patel AM, Brautbar A, Desai NK, Wilson DP

Abstract
Lipoprotein-X, which is composed of phospholipids and non-esterified cholesterol, is an abnormal lipoprotein with a density range similar to LDL-C. The two most common ways which lipoprotein-X accumulates is from reflux of bile salts into plasma or deficiency in lecithin cholesterol acyltransferase. This is a case of severe hypercholesterolemia and liver disease in a 3- year old male that presented with pruritus, pale stool, scleral ictus, and abdominal distention. He was diagnosed with primary sclerosing cholangitis which was confirmed by liver biopsy. Our patient was treated with steroids and immunomodulator therapy which was associated with significant reduction in cholestasis and LDL-C levels. Lipoprotein-X has several properties that make it anti-atherogenic, which raises the question if treatment for hypercholesterolemia should be initiated.

PMID: 27206954 [PubMed - indexed for MEDLINE]

Risk of psychological ill health and methods of organisational downsizing: a cross-sectional survey in four European countries.

Sun, 10/01/2017 - 07:36

Risk of psychological ill health and methods of organisational downsizing: a cross-sectional survey in four European countries.

BMC Public Health. 2017 Sep 29;17(1):758

Authors: Andreeva E, Brenner MH, Theorell T, Goldberg M

Abstract
BACKGROUND: The manner in which organizational downsizing is implemented can make a substantial difference as to whether the exposed workers will suffer from psychological ill health. Surprisingly, little research has directly investigated this issue. We examined the likelihood of psychological ill health associated with strategic and reactive downsizing.
METHODS: A cross-sectional survey included 1456 respondents from France, Sweden, Hungary and the United Kingdom: 681 employees in stable workplaces (reference group) and 775 workers from downsized companies. Reactive downsizing was exemplified by the exposures to compulsory redundancies of medium to large scale resulting in job loss or surviving a layoff while staying employed in downsized organizations. The workforce exposed to strategic downsizing was represented by surplus employees who were internally redeployed and supported through their career change process within a policy context of "no compulsory redundancy". Symptoms of anxiety, depression and emotional exhaustion were assessed in telephone interviews with brief subscales from Hospital Anxiety Scale (HADS-A), Hopkins Symptom Checklist (SCL-CD6) and Maslach Burnout Inventory (MBI-GS). Data were analyzed using logistic regression.
RESULTS: We observed no increased risk of psychological ill health in the case of strategic downsizing. The number of significant associations with psychological ill health was the largest for the large-scale reactive downsizing: surviving a layoff was consistently associated with all three outcome measures; returning to work after the job loss experience was related to anxiety and depression, while persons still unemployed at interview had elevated odds of anxiety. After reactive medium-scale downsizing, unemployment at interview was the only exposure associated with anxiety and depression.
CONCLUSIONS: The manner in which organizational downsizing is implemented can be important for the psychological wellbeing of workers. If downsizing is unavoidable, it should be achieved strategically. Greater attention is needed to employment and health policies supporting the workers after reactive downsizing.

PMID: 28962605 [PubMed - in process]

Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

Sat, 09/30/2017 - 07:34
Related Articles

Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

J Glaucoma. 2016 Oct;25(10):e834-e842

Authors: McDonnell FS, McNally SA, Clark AF, O'Brien CJ, Wallace DM

Abstract
BACKGROUND: Glaucoma is an optic neuropathy that affects 60 million people worldwide. There is an underlying fibrosis associated with the lamina cribrosa (LC) in glaucoma. DNA methylation is well established in regulating fibrosis and may be a therapeutic target for glaucoma. The purpose of this study was to compare global DNA methylation levels in primary human normal (NLC) and glaucomatous (GLC) cells, and to investigate DNA methylation in driving fibrosis through regulation of transforming growth factor β1 (TGFβ1).
MATERIALS AND METHODS: LC cells were cultured from normal and glaucomatous human donors. Global methylation was assessed by ELISA. qPCR was conducted for DNA methyltransferases (DNMTs), methyl-CpG-binding protein 2 (MeCP2), TGFβ 1 and 2, collagen 1α1 (COL1A1), and α-smooth muscle actin (αSMA). TGFβ1 and DNMT1 were examined by immunofluorescence. Methylation of the TGFβ1 promoter was determined by methylation-specific PCR (MSP).
RESULTS: Global DNA methylation demonstrated an increase in GLC compared with NLC cells (P<0.05). The previously mentioned methylation and matrix genes were increased in GLC compared with NLC cells (P<0.05). Immunofluorescence showed increased TGFβ1 and DNMT1 in GLC compared with NLC cells. MSP showed increased unmethylated DNA in the TGFβ1 promoter of GLC compared with NLC cells.
CONCLUSIONS: We found increased expression of fibrotic genes in GLC cells and demonstrated an increase in global DNA methylation and in associated enzymes in GLC cells. Furthermore, we showed decreased promoter methylation of TGFβ1 in GLC cells. Determining a role for methylation in glaucoma and in regulating TGFβ1 may provide a novel therapeutic approach.

PMID: 27300643 [PubMed - indexed for MEDLINE]

Comparative tolerance of two massively parallel sequencing systems to common PCR inhibitors.

Fri, 09/29/2017 - 07:34
Related Articles

Comparative tolerance of two massively parallel sequencing systems to common PCR inhibitors.

Int J Legal Med. 2017 Sep 27;:

Authors: Elwick K, Zeng X, King J, Budowle B, Hughes-Stamm S

Abstract
Human remains can be severely affected by the environment, and the DNA may be damaged, degraded, and/or inhibited. In this study, a DNA sample (at 1 ng DNA target input in triplicate) was spiked with five concentrations of five inhibitors (humic acid, melanin, hematin, collagen, and calcium) and sequenced with both the HID-Ion AmpliSeq™ Library Kit and ID panel on the Ion PGM™ System and the ForenSeq DNA Signature Prep Kit on the MiSeq FGx™. The objective of this study was to compare the baseline tolerance of the two sequencing chemistries and platforms to common inhibitors encountered in human remains recovered from missing person cases. The two chemistries generally were comparable but not always susceptible to the same inhibitors or at the same capacity. The HID-Ion AmpliSeq™ Library Kit and ID panel and the ForenSeq DNA Signature Prep Kit both were susceptible to humic acid, melanin, and collagen; however, the ForenSeq kit showed greater inhibition to melanin and collagen than the AmpliSeq™ kit. In contrast, the ForenSeq kit was resistant to the effects of hematin and calcium, whereas the AmpliSeq™ kit was highly inhibited by hematin. Short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) showed the same trend among inhibitors when using the ForenSeq kit. Generally, locus read depth, heterozygote allele balance, and the numbers of alleles typed were inversely correlated with increasing inhibitor concentration. The larger STR loci were affected more so by the presence of inhibitors compared to smaller STR amplicons and SNP loci. Additionally, it does not appear that sequence noise is affected by the inhibitors. The noise percentage, however, does increase as the inhibitor concentration increases, due to the decrease in locus read depth and not likely because of chemistry effects.

PMID: 28956146 [PubMed - as supplied by publisher]

Validation of droplet digital PCR for the detection and absolute quantification of Borrelia DNA in Ixodes scapularis ticks.

Fri, 09/29/2017 - 07:34
Related Articles

Validation of droplet digital PCR for the detection and absolute quantification of Borrelia DNA in Ixodes scapularis ticks.

Parasitology. 2017 Apr;144(4):359-367

Authors: King JL, Smith AD, Mitchell EA, Allen MS

Abstract
We evaluated the QX200 Droplet Digital PCR (ddPCR™, Bio-Rad) system and protocols for the detection of the tick-borne pathogens Borrelia burgdorferi and Borrelia miyamotoi in Ixodes scapularis nymphs and adults collected from North Truro, Massachusetts. Preliminary screening by nested PCR determined positive infection levels of 60% for B. burgdorferi in these ticks. To investigate the utility of ddPCR as a screening tool and to calculate the absolute number of bacterial genome copies in an infected tick, we adapted previously reported TaqMan®-based qPCR assays for ddPCR. ddPCR proved to be a reliable means for detection and absolute quantification of control bacterial DNA with precision as low as ten spirochetes in an individual sample. Application of this method revealed the average carriage level of B. burgdorferi in infected I. scapularis nymphs to be 2291 spirochetes per nymph (range: 230-5268 spirochetes) and 51 179 spirochetes on average in infected adults (range: 5647-115 797). No ticks naturally infected with B. miyamotoi were detected. The ddPCR protocols were at least as sensitive to conventional qPCR assays but required fewer overall reactions and are potentially less subject to inhibition. Moreover, the approach can provide insight on carriage levels of parasites within vectors.

PMID: 27806739 [PubMed - indexed for MEDLINE]

Vascular endothelium: a potential source of podocalyxin in serum from pregnancies with preeclampsia.

Thu, 09/28/2017 - 07:31
Related Articles

Vascular endothelium: a potential source of podocalyxin in serum from pregnancies with preeclampsia.

J Hypertens. 2017 Nov;35(11):2176-2177

Authors: Goulopoulou S

PMID: 28953590 [PubMed - in process]

δ-Opioid receptors: Pivotal role in intermittent hypoxia-augmentation of cardiac parasympathetic control and plasticity.

Thu, 09/28/2017 - 07:31
Related Articles

δ-Opioid receptors: Pivotal role in intermittent hypoxia-augmentation of cardiac parasympathetic control and plasticity.

Auton Neurosci. 2016 Jul;198:38-49

Authors: Estrada JA, Barlow MA, Yoshishige D, Williams AG, Downey HF, Mallet RT, Caffrey JL

Abstract
BACKGROUND: Intermittent hypoxia training (IHT) produces robust myocardial protection against ischemia-reperfusion induced infarction and arrhythmias. Blockade of this cardioprotection by antagonism of either β1-adrenergic or δ-opioid receptors (δ-OR) suggests autonomic and/or opioidergic adaptations.
PURPOSE: To test the hypothesis that IHT shifts cardiac autonomic balance toward greater cholinergic and opioidergic influence.
METHODS: Mongrel dogs completed 20d IHT, non-hypoxic sham training, or IHT with the δ-OR antagonist naltrindole (200μg/kgsc). The vagolytic effect of the δ-OR agonist met-enkephalin-arg-phe delivered by sinoatrial microdialysis was evaluated following IHT. Sinoatrial, atrial and left ventricular biopsies were analyzed for changes in δ-OR, the neurotrophic monosialoganglioside, GM-1, and cholinergic and adrenergic markers.
RESULTS: IHT enhanced vagal bradycardia vs. sham dogs (P<0.05), and blunted the δ2-OR mediated vagolytic effect of met-enkephalin-arg-phe. The GM-1 labeled fibers overlapped strongly with cholinergic markers, and IHT increased the intensity of both signals (P<0.05). IHT increased low and high intensity vesicular acetylcholine transporter labeling of sinoatrial nodal fibers (P<0.05) suggesting an increase in parasympathetic arborization. IHT reduced select δ-OR labeled fibers in both the atria and sinoatrial node (P<0.05) consistent with moderation of the vagolytic δ2-OR signaling described above. Furthermore, blockade of δ-OR signaling with naltrindole during IHT increased the protein content of δ-OR (atria and ventricle) and vesicular acetylcholine transporter (atria) vs. sham and untreated IHT groups. IHT also reduced the sympathetic marker, tyrosine hydroxylase in ventricle (P<0.05).
SUMMARY: IHT shifts cardiac autonomic balance in favor of parasympathetic control via adaptations in opioidergic, ganglioside, and adrenergic systems.

PMID: 27498137 [PubMed - indexed for MEDLINE]

Modeling the Cost-Effectiveness of Interventions to Reduce Suicide Risk Among Hospital Emergency Department Patients.

Tue, 09/26/2017 - 07:35

Modeling the Cost-Effectiveness of Interventions to Reduce Suicide Risk Among Hospital Emergency Department Patients.

Psychiatr Serv. 2017 Sep 15;:appips201600351

Authors: Denchev P, Pearson JL, Allen MH, Claassen CA, Currier GW, Zatzick DF, Schoenbaum M

Abstract
OBJECTIVE: This study estimated the expected cost-effectiveness and population impact of outpatient interventions to reduce suicide risk among patients presenting to general hospital emergency departments (EDs), compared with usual care. Several such interventions have been found efficacious, but none is yet widespread, and the cost-effectiveness of population-based implementation is unknown.
METHODS: Modeled cost-effectiveness analysis compared three ED-initiated suicide prevention interventions previously found to be efficacious-follow-up via postcards or caring letters, follow-up via telephone outreach, and suicide-focused cognitive-behavioral therapy (CBT)-with usual care. Primary outcomes were treatment costs, suicides, and life-years saved, evaluated over the year after the index ED visit.
RESULTS: Compared with usual care, adding postcards improved outcomes and reduced costs. Adding telephone outreach and suicide-focused CBT, respectively, improved outcomes at a mean incremental cost of $4,300 and $18,800 per life-year saved, respectively. Monte Carlo simulation (1,000 repetitions) revealed the chance of incremental cost-effectiveness to be a certainty for all three interventions, assuming societal willingness to pay ≥$50,000 per life-year. These main findings were robust to various sensitivity analyses, including conservative assumptions about effect size and incremental costs. Population impact was limited by low sensitivity of detecting ED patients' suicide risk, and health care delivery inefficiencies.
CONCLUSIONS: The highly favorable cost-effectiveness found for each outpatient intervention provides a strong basis for widespread implementation of any or all of the interventions. The estimated population benefits of doing so would be enhanced by increasing the sensitivity of suicide risk detection among individuals presenting to general hospital EDs.

PMID: 28945181 [PubMed - as supplied by publisher]

Serum-based protein profiles of Alzheimer's disease and mild cognitive impairment in elderly Hispanics.

Tue, 09/26/2017 - 07:35
Related Articles

Serum-based protein profiles of Alzheimer's disease and mild cognitive impairment in elderly Hispanics.

Neurodegener Dis Manag. 2016 Jun;6(3):203-13

Authors: Villarreal AE, O'Bryant SE, Edwards M, Grajales S, Britton GB, Panama Aging Research Initiative

Abstract
AIM: To describe the biomarker profiles in elderly Panamanians diagnosed with Alzheimer's disease (AD), mild cognitive impairment (MCI) or no impairment using serum-based biomarkers.
METHODS: Twenty-four proteins were analyzed using an electrochemiluminescence-based multiplex biomarker assay platform. A biomarker profile was generated using random forest analyses.
RESULTS: Two proteins differed among groups: IL-18 and T-lymphocyte-secreted protein I-309. The AD profile was highly accurate and independent of age, gender, education and Apolipoprotein E ε4 status. AD and MCI profiles had substantial overlap among the top markers, suggesting common functions in AD and MCI but differences in their relative importance.
CONCLUSION: Our results underscore the potential influence of genetic and environmental differences within Hispanic populations on the proteomic profile of AD.

PMID: 27229914 [PubMed - indexed for MEDLINE]

The language of change among criminal justice clients: Counselor language, client language, and client substance use outcomes.

Sun, 09/24/2017 - 07:39

The language of change among criminal justice clients: Counselor language, client language, and client substance use outcomes.

J Clin Psychol. 2017 Sep 22;:

Authors: Rodriguez M, Walters ST, Houck JM, Ortiz JA, Taxman FS

Abstract
OBJECTIVE: Counselor and client language have been identified as mechanisms of change in motivational interviewing (MI) counseling sessions. This study evaluated whether language patterns exhibited during MI sessions with substance users in the community would also be found during MI sessions with substance users in the criminal justice system.
METHOD: Forty audio recordings of MI sessions with substance-using probationers were coded and analyzed sequentially using the Motivational Interviewing Skills Code (MISC) 2.5. Analyses examined the relationship between counselor and client language, and the relationship between client language and client substance use after 2 months.
RESULTS: Counselor MI inconsistent language was associated with decreased change talk (lnOR = - 0.76, p < .05) though not with increased sustain talk. Both sustain talk (b = - 4.591, t = - 18.634 p < .001) and MI inconsistent language MIIN (b = - 4.419, t = - 19.886, p < .001) were positively associated with substance use at 2 months. Sustain talk early in the session (i.e., during deciles 1 and 2) was significantly greater among clients who reported using substances at 2 months, compared to clients who did not use substances.
CONCLUSION: These findings are broadly consistent with previous literature documenting the association between counselor language, client language, and client outcome.

PMID: 28940435 [PubMed - as supplied by publisher]

Protein kinase C-eta regulates Mcl-1 level via ERK1.

Sun, 09/24/2017 - 07:39

Protein kinase C-eta regulates Mcl-1 level via ERK1.

Cell Signal. 2017 Sep 19;:

Authors: Pal D, Basu A

Abstract
Protein kinase C (PKC)-eta (PKCη) is a member of the novel category of PKC family. It is overexpressed in breast cancer and was shown to inhibit apoptosis and contribute to chemoresistance. Since the anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance, we investigated if PKCη regulates Mcl-1 level. Silencing of PKCη decreased Mcl-1 in several breast cancer cells, including MCF-7 and T47D cells. PKCη depletion had no effect on MCL1 mRNA but the decrease in Mcl-1 by PKCη knockdown was blocked by proteasomal inhibitors, such as MG132 and lactacystin. Moreover, knockdown of Mule (Mcl-1 ubuiquitin ligase) prevented Mcl-1 downregulation caused by PKCη deficiency. Overexpression of catalytically-active Akt or knockdown of glycogen synthase kinase-3 (GSK3)-β, a substrate for Akt, had little effect on Mcl-1 downregulation caused by PKCη silencing. However, knockdown of PKCη but not PKCα, -δ or -ε caused a significant decrease in ERK (extracellular signal-regulated kinase) phosphorylation. Knockdown of ERK1 but not ERK2 decreased Mcl-1 level, and the decrease in Mcl-1 caused by PKCη knockdown was restored by ERK1 overexpression. These results suggest that PKCη utilizes the ERK signaling pathway to protect against ubiquitin-mediated proteasomal degradation of Mcl-1.

PMID: 28939105 [PubMed - as supplied by publisher]

A feed-forward regulation of endothelin receptors by c-Jun in human non-pigmented ciliary epithelial cells and retinal ganglion cells.

Sat, 09/23/2017 - 07:35

A feed-forward regulation of endothelin receptors by c-Jun in human non-pigmented ciliary epithelial cells and retinal ganglion cells.

PLoS One. 2017;12(9):e0185390

Authors: Wang J, Ma HY, Krishnamoorthy RR, Yorio T, He S

Abstract
c-Jun, c-Jun N-terminal kinase(JNK) and endothelin B (ETB) receptor have been shown to contribute to the pathogenesis of glaucoma. Previously, we reported that an increase of c-Jun and CCAAT/enhancer binding protein β (C/EBPβ) immunohistostaining is associated with upregulation of the ETB receptor within the ganglion cell layer of rats with elevated intraocular pressure (IOP). In addition, both transcription factors regulate the expression of the ETB receptor in human non-pigmented ciliary epithelial cells (HNPE). The current study addressed the mechanisms by which ET-1 produced upregulation of ET receptors in primary rat retinal ganglion cells (RGCs) and HNPE cells. Treatment of ET-1 and ET-3 increased the immunocytochemical staining of c-Jun and C/EBPβ in primary rat RGCs and co-localization of both transcription factors was observed. A marked increase in DNA binding activity of AP-1 and C/EBPβ as well as elevated protein levels of c-Jun and c-Jun-N-terminal kinase (JNK) were detected following ET-1 treatment in HNPE cells. Overexpression of ETA or ETB receptor promoted the upregulation of c-Jun and also elevated its promoter activity. In addition, upregulation of C/EBPβ augmented DNA binding and mRNA expression of c-Jun, and furthermore, the interaction of c-Jun and C/EBPβ was confirmed using co-immunoprecipitation. Apoptosis of HNPE cells was identified following ET-1 treatment, and overexpression of the ETA or ETB receptor produced enhanced apoptosis. ET-1 mediated upregulation of c-Jun and C/EBPβ and their interaction may represent a novel mechanism contributing to the regulation of endothelin receptor expression. Reciprocally, c-Jun was also found to regulate the ET receptors and C/EBPβ appeared to play a regulatory role in promoting expression of c-Jun. Taken together, the data suggests that ET-1 triggers the upregulation of c-Jun through both ETA and ETB receptors, and conversely c-Jun also upregulates endothelin receptor expression, thereby generating a positive feed-forward loop of endothelin receptor activation and expression. This feed-forward regulation may contribute to RGC death and astrocyte proliferation following ET-1 treatment.

PMID: 28938016 [PubMed - in process]

Letter to the Editor. Ventricular catheter tip proximity to choroid plexus is a key factor in shunt failure.

Sat, 09/23/2017 - 07:35

Letter to the Editor. Ventricular catheter tip proximity to choroid plexus is a key factor in shunt failure.

J Neurosurg Pediatr. 2017 Sep 22;:1-3

Authors: Dickerman R, Reynolds A

PMID: 28937314 [PubMed - as supplied by publisher]

Pages