Recent Research Articles from UNTHSC

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

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Updated: 1 hour 29 min ago

A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease.

Thu, 09/19/2019 - 05:38
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A Precision Medicine Model for Targeted NSAID Therapy in Alzheimer's Disease.

J Alzheimers Dis. 2018;66(1):97-104

Authors: O'Bryant SE, Zhang F, Johnson LA, Hall J, Edwards M, Grammas P, Oh E, Lyketsos CG, Rissman RA

Abstract
BACKGROUND: To date, the therapeutic paradigm for Alzheimer's disease (AD) has focused on a single intervention for all patients. However, a large literature in oncology supports the therapeutic benefits of a precision medicine approach to therapy. Here we test a precision-medicine approach to AD therapy.
OBJECTIVE: To determine if a baseline, blood-based proteomic companion diagnostic predicts response to NSAID therapy.
METHODS: Proteomic assays of plasma from a multicenter, randomized, double-blind, placebo-controlled, parallel group trial, with 1-year exposure to rofecoxib (25 mg once daily), naproxen (220 mg twice-daily) or placebo.
RESULTS: 474 participants with mild-to-moderate AD were screened with 351 enrolled into the trial. Using support vector machine (SVM) analyses, 89% of the subjects randomized to either NSAID treatment arms were correctly classified using a general NSAID companion diagnostic. Drug-specific companion diagnostics yielded 98% theragnostic accuracy in the rofecoxib arm and 97% accuracy in the naproxen arm.
CONCLUSION: Inflammatory-based companion diagnostics have significant potential to identify select patients with AD who have a high likelihood of responding to NSAID therapy. This work provides empirical support for a precision medicine model approach to treating AD.

PMID: 30198872 [PubMed - indexed for MEDLINE]

Atrophied Thymus, a Tumor Reservoir for Harboring Melanoma Cells.

Thu, 09/19/2019 - 05:38
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Atrophied Thymus, a Tumor Reservoir for Harboring Melanoma Cells.

Mol Cancer Res. 2018 11;16(11):1652-1664

Authors: Sizova O, Kuriatnikov D, Liu Y, Su DM

Abstract
Tumor metastatic relapse is the primary cause for cancer-associated mortality. Metastatic relapse is believed to arise from quantities of tumor cells that are below detectable thresholds, which are able to resist radio/chemotherapy by obtaining a dormant state and hiding in certain organs, i.e., tumor reservoirs. The thymus, a central T-cell immune organ, has been suggested to be a premetastatic tumor reservoir for B-lymphoma cells. However, it remains unknown whether the thymus is able to harbor nonlymphoid solid tumor cells, and whether chemotherapy can thoroughly eliminate cancer cells in the thymus. If chemotherapy is not able to eliminate these cells in the thymus, then what processes allow for this? Melanoma cell-inoculated and genotoxic doxorubicin-treated mouse model systems were used to determine that the thymus, particularly the atrophied thymus, was able to harbor blood stream-circulating melanoma cells. In addition, a chemotherapy-induced DNA-damage response triggered p53 activation in nonmalignant thymic cells, which in turn resulted in thymocyte death and thymic epithelial cell senescence to develop an inflammatory thymic microenvironment. This inflammatory condition induced thymic-harbored minimal tumor cells to acquire a chemoresistant state.Implications: Here, the thymus serves as a premetastatic reservoir for nonlymphoid solid tumor cells during chemotherapy, which could be a novel target of minimal residual disease in antitumor therapy, thus preventing tumor metastatic relapse. Mol Cancer Res; 16(11); 1652-64. ©2018 AACR.

PMID: 30006356 [PubMed - indexed for MEDLINE]

Alterations to the Intestinal Microbiome and Metabolome of Pimephales promelas and Mus musculus Following Exposure to Dietary Methylmercury.

Thu, 09/19/2019 - 05:38
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Alterations to the Intestinal Microbiome and Metabolome of Pimephales promelas and Mus musculus Following Exposure to Dietary Methylmercury.

Environ Sci Technol. 2018 08 07;52(15):8774-8784

Authors: Bridges KN, Zhang Y, Curran TE, Magnuson JT, Venables BJ, Durrer KE, Allen MS, Roberts AP

Abstract
Mercury is a global contaminant, which may be microbially transformed into methylmercury (MeHg), which bioaccumulates. This results in potentially toxic body burdens in high trophic level organisms in aquatic ecosystems and maternal transfer to offspring. We previously demonstrated effects on developing fish including hyperactivity, altered time-to-hatch, reduced survival, and dysregulation of the dopaminergic system. A link between gut microbiota and central nervous system function in teleosts has been established with implications for behavior. We sequenced gut microbiomes of fathead minnows exposed to dietary MeHg to determine microbiome effects. Dietary exposures were repeated with adult CD-1 mice. Metabolomics was used to screen for metabolome changes in mouse brain and larval fish, and results indicate effects on lipid metabolism and neurotransmission, supported by microbiome data. Findings suggest environmentally relevant exposure scenarios may cause xenobiotic-mediated dysbiosis of the gut microbiome, contributing to neurotoxicity. Furthermore, small-bodied teleosts may be a useful model species for studying certain types of neurodegenerative diseases, in lieu of higher vertebrates.

PMID: 29943971 [PubMed - indexed for MEDLINE]

A meta-analysis comparing 48-week treatment outcomes of single and multi-tablet antiretroviral regimens for the treatment of people living with HIV.

Tue, 09/17/2019 - 05:17
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A meta-analysis comparing 48-week treatment outcomes of single and multi-tablet antiretroviral regimens for the treatment of people living with HIV.

AIDS Res Ther. 2018 10 30;15(1):17

Authors: Clay PG, Yuet WC, Moecklinghoff CH, Duchesne I, Tronczyński KL, Shah S, Shao D

Abstract
OBJECTIVES: To compare outcomes with single tablet regimens (STR) versus multi-tablet regimens (MTR) for human immunodeficiency virus (HIV) treatment using published data.
DESIGN: Systematic review and random-effects meta-analysis of literature on approved and investigational HIV regimens.
METHODS: The research followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Single or un-blinded studies reporting a direct comparison between STR and MTR were eligible for the meta-analysis. Double-blinded studies were excluded due to lack of difference in pill burden between cohorts. The key outcomes of interest included: adherence rates/proportion meeting target, efficacy, safety/tolerability, non-clinical and economic outcomes.
RESULTS: After screening 63 full-text articles and posters, 14 studies were eligible for the meta-analysis. The analysis showed that patients taking STR had improved outcomes over those taking MTR. Patients were significantly more adherent regardless of daily dosing frequency (odds ratio [OR]: 1.96, p < 0.001) and were more likely to achieve virological suppression (relative risk [RR]: 1.05, p = 0.002). There was a trend toward a lower discontinuation risk in the STR cohort, together with reported higher therapy satisfaction, better symptom control, improved health status, reduced healthcare resource utilization and demonstrated cost-effectiveness compared to MTR. There were no differences in CD4 cell count increase (at 48 weeks) or safety outcomes.
CONCLUSIONS: The findings of this study confirm previously reported preliminary findings of the advantages of STR over MTR for HIV treatment in adherence, therapy continuation, viral suppression, tolerability, quality of life improvement, cost-effectiveness and healthcare resource utilization.

PMID: 30373620 [PubMed - indexed for MEDLINE]

Safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in hepatitis C genotype 1 patients including those with decompensated cirrhosis who failed prior treatment with simeprevir/sofosbuvir.

Tue, 09/17/2019 - 05:17
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Safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in hepatitis C genotype 1 patients including those with decompensated cirrhosis who failed prior treatment with simeprevir/sofosbuvir.

Aliment Pharmacol Ther. 2018 05;47(10):1409-1415

Authors: Modi AA, Nazario HE, Gonzales GR, Gonzalez SA

Abstract
BACKGROUND: Combination therapy of simeprevir (SIM)/sofosbuvir (SOF) is an approved treatment for hepatitis C genotype (gen) 1 with overall SVR12 rate of 85%-95%. The single tablet fixed-dose combination of ledipasvir (LDV)/SOF is also approved for gen 1 with sustained virologic response at 12 weeks (SVR12) rates ≥95%. No data are available on the efficacy of retreatment with LDV/SOF in patients who failed initial treatment with SIM/SOF.
AIM: To evaluate the efficacy of retreatment with LDV/SOF ± ribavirin (RBV) in gen 1 patients who had previously failed treatment with SIM/SOF.
METHODS: Data from a combined treatment cohort of 2 hepatology centres, which included patients previously treated with SIM/SOF ± RBV for 12 weeks but failed to achieve SVR and then underwent retreatment with LDV/SOF ± RBV, were analysed (n = 30). LDV/SOF ± RBV was administered for 12-24 weeks based on the discretion of the treating hepatologist.
RESULTS: Of the 30 patients, 23 (77%) were male, 77% were Caucasian and 26 (87%) were gen 1a. 26 (86%) had cirrhosis, of which 16 (62%) had decompensated, Child's class B or C cirrhosis. Three patients were liver transplant recipients with recurrent hepatitis C. Overall, 27/30 (90%) achieved SVR. Treatment was well tolerated with 37% reporting no adverse events. The most common adverse events were fatigue, headache, insomnia and nausea. Two patients with Child's B cirrhosis required hospitalization during treatment for variceal haemorrhage and abdominal pain respectively. However, no treatment discontinuations or deaths occurred.
CONCLUSION: Single tablet fixed-dose combination LDV/SOF ± RBV is efficacious and well tolerated in patients who previously failed treatment with SIM/SOF, including those with decompensated cirrhosis and recurrent hepatitis C following liver transplantation.

PMID: 29569736 [PubMed - indexed for MEDLINE]

A single early-life seizure results in long-term behavioral changes in the adult Fmr1 knockout mouse.

Sun, 09/15/2019 - 07:56
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A single early-life seizure results in long-term behavioral changes in the adult Fmr1 knockout mouse.

Epilepsy Res. 2019 Aug 29;157:106193

Authors: Hodges SL, Reynolds CD, Nolan SO, Huebschman JL, Okoh JT, Binder MS, Lugo JN

Abstract
Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability and a significant genetic contributor to Autism spectrum disorder. In addition to autistic-like phenotypes, individuals with FXS are subject to developing numerous comorbidities, one of the most prevalent being seizures. In the present study, we investigated how a single early-life seizure superimposed on a genetic condition impacts the autistic-like behavioral phenotype of the mouse. We induced status epilepticus (SE) on postnatal day (PD) 10 in Fmr1 wild type (WT) and knockout (KO) mice. We then tested the mice in a battery of behavioral tests during adulthood (PD90) to examine the long-term impact of an early-life seizure. Our findings replicated prior work that reported a single instance of SE results in behavioral deficits, including increases in repetitive behavior, enhanced hippocampal-dependent learning, and reduced sociability and prepulse inhibition (p <  0.05). We also observed genotypic differences characteristic of the FXS phenotype in Fmr1 KO mice, such as enhanced prepulse inhibition and repetitive behavior, hyperactivity, and reduced startle responses (p <  0.05). Superimposing a seizure on deletion of Fmr1 significantly impacted repetitive behavior in a nosepoke task. Specifically, a single early-life seizure increased consecutive nose poking behavior in the task in WT mice (p <  0.05), yet seizures did not exacerbate the elevated stereotypy observed in Fmr1 KO mice (p >  0.05). Overall, these findings help to elucidate how seizures in a critical period of development can impact long-term behavioral manifestations caused by underlying gene mutations in Fmr1. Utilizing double-hit models, such as superimposing seizures on the Fmr1 mutation, can help to enhance our understanding of comorbidities in disease models.

PMID: 31520894 [PubMed - as supplied by publisher]

Glucagon-like peptide-1 receptor pathway inhibits extracellular matrix production by mesangial cells through store-operated Ca2+ channel.

Fri, 09/13/2019 - 07:39
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Glucagon-like peptide-1 receptor pathway inhibits extracellular matrix production by mesangial cells through store-operated Ca2+ channel.

Exp Biol Med (Maywood). 2019 Sep 11;:1535370219876531

Authors: Huang L, Ma R, Lin T, Chaudhari S, Shotorbani PY, Yang L, Wu P

PMID: 31510798 [PubMed - as supplied by publisher]

Incidence of Endemic Human Cutaneous Leishmaniasis in the United States.

Fri, 09/13/2019 - 07:39
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Incidence of Endemic Human Cutaneous Leishmaniasis in the United States.

JAMA Dermatol. 2018 09 01;154(9):1032-1039

Authors: McIlwee BE, Weis SE, Hosler GA

Abstract
Importance: Leishmaniasis is recognized as an endemic human disease in Africa, the Middle East, Asia, and South America. Yet despite case reports of endemic human leishmaniasis in the United States, and well-documented occurrences of disease in various animal vectors and reservoirs, the endemicity of leishmaniasis in North America has not yet been established. Moreover, leishmaniasis is not a federally reportable disease in the United States. Clinical awareness of endemic disease therefore remains low, with North American physicians considering leishmaniasis a tropical disease.
Objective: To assess the endemicity of human leishmaniasis in the United States.
Design, Setting, and Participants: This cross-sectional multicenter observational study reviewed cases of human leishmaniasis occurring in the United States from 2007 through 2017. Previously diagnosed, deidentified cases of leishmaniasis were reported by the institutions of the authors and acknowledged contributors, as well as the Texas Department of State Health Services. Cases of leishmaniasis were identified by searching by disease name (leishmaniasis) or International Classification of Diseases, 9th and 10th Revisions diagnosis codes in the respective laboratory information systems.
Exposures: Via examination of deidentified demographics, cases of leishmaniasis were classified as one of the following: (1) documentation of no history of travel outside of the United States within 10 years; (2) positive history of travel outside of the United States within 10 years; or (3) unknown or no documentation of travel history.
Main Outcomes and Measures: Cases of leishmaniasis were considered endemic if identified in patients with documentation of no travel history outside of the United States within 10 years.
Results: Of the 69 novel cases of human cutaneous leishmaniasis identified in this study, 41 (59%) were endemic; the median age at diagnosis was 61 years (range, 3-89 years), and 28 (68%) of the endemic cases occurred in female patients. Twenty-two (32%) cases had documentation of Leishmania speciation performed by polymerase chain reaction, and in 100% of these cases the infectious organism was identified as Leishmania mexicana.
Conclusions and Relevance: Human cutaneous leishmaniasis is endemic in the United States, and, at least regionally, is acquired endemically more frequently than it is via travel. Our data argue in favor of making leishmaniasis a federally reportable disease and may have substantial implications on North American public health initiatives, with climate models predicting the number of citizens exposed to leishmaniasis will double by 2080.

PMID: 30046836 [PubMed - indexed for MEDLINE]

Human Papillomavirus Vaccine Initiation for Adolescents Following Rhode Island's School-Entry Requirement, 2010-2016.

Thu, 09/12/2019 - 07:31
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Human Papillomavirus Vaccine Initiation for Adolescents Following Rhode Island's School-Entry Requirement, 2010-2016.

Am J Public Health. 2018 10;108(10):1421-1423

Authors: Thompson EL, Livingston MD, Daley EM, Zimet GD

Abstract
OBJECTIVES: To assess changes in human papillomavirus (HPV) vaccine initiation for adolescent girls and boys in Rhode Island compared with all other states.
METHODS: We estimated the gender-specific effects of Rhode Island's school-entry HPV vaccination policy on self-reported HPV vaccination initiation by using a difference-in-differences design with the National Immunization Survey-Teen from 2010 through 2016.
RESULTS: Compared with boys in other states, boys in Rhode Island increased their HPV vaccine initiation rate by 11% (b = 0.11; 95% confidence interval [CI] = 0.05, 0.18) after enactment of the requirement. No difference was seen in the probability of HPV vaccine initiation among girls in Rhode Island compared with girls in the multistate control (b = -0.01; 95% CI = -0.08, 0.05).
CONCLUSIONS: Our analysis identified an 11% increase in HPV vaccine initiation rate among boys in Rhode Island after the school-entry requirement was enacted, whereas no significant change was observed for girls. Public Health Implications. Given suboptimal vaccine uptake rates in the United States, continued pursuit of state-level public policy to improve HPV vaccination is needed. School-entry requirements for HPV vaccination may be a strategy for closing the gap in HPV vaccine uptake for boys and girls.

PMID: 30024803 [PubMed - indexed for MEDLINE]

Trajectories of Relative Performance with 2 Measures of Global Cognitive Function.

Thu, 09/12/2019 - 07:31
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Trajectories of Relative Performance with 2 Measures of Global Cognitive Function.

J Am Geriatr Soc. 2018 08;66(8):1575-1580

Authors: Espeland MA, Chen JC, Weitlauf J, Hayden KM, Rapp SR, Resnick SM, Garcia L, Cannell B, Baker LD, Sachs BC, Tindle HA, Wallace R, Casanova R, Women's Health Initiative Memory Study Magnetic Resonance Imaging Study Group

Abstract
OBJECTIVES: To examine whether trajectories of global cognitive function over time in studies that change assessment protocols may be modeled based on an individual's performance relative to others in the study cohort.
DESIGN: Extended follow-up of a cohort originally enrolled in a clinical trial of postmenopausal hormone therapy.
SETTING: The Women's Health Initiative Memory Study switched from an in-person interview with the Modified Mini-Mental State Examination to a telephone-based interview with the modified Telephone Interview for Cognitive Status to assess global cognitive function over long-term follow-up.
PARTICIPANTS: Women aged 75 to 92 (N=2,561).
MEASUREMENTS: Annual cognitive assessments from participants, ranked according to age-, race- and ethnicity-adjusted performance levels, were used to identify distinct trajectories. Participants assigned to the resulting trajectories were compared for selected risk factor profiles.
RESULTS: Our approach grouped participants into five trajectories according to relative cognitive performance over time. These groups differed significantly according to 3 known risk factors for cognitive decline-education level, apolipoprotein E-ϵ4 genotype, and type 2 diabetes mellitus-and a biomarker based on brain structure that has been linked to cognitive decline and Alzheimer's disease. Participants with consistently low relative levels of cognitive function over time and those whose relative performance over time declined to these levels tended to have poorer risk factor profiles.
CONCLUSION: Longitudinal measures of an individual's relative performance on different assessment protocols for global cognitive function can be used to identify trajectories of change over time that appear to have internal validity with respect to known risk factors.

PMID: 29972592 [PubMed - indexed for MEDLINE]

Challenges in the development of dopamine D2- and D3-selective radiotracers for PET imaging studies.

Thu, 09/12/2019 - 07:31
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Challenges in the development of dopamine D2- and D3-selective radiotracers for PET imaging studies.

J Labelled Comp Radiopharm. 2018 03;61(3):291-298

Authors: Mach RH, Luedtke RR

Abstract
The dopamine D2-like receptors (ie, D2/3 receptors) have been the most extensively studied CNS receptor with Positron Emission Tomography (PET). The 3 different radiotracers that have been used in these studies are [11 C]raclopride, [18 F]fallypride, and [11 C]PHNO. Because these radiotracers have a high affinity for both dopamine D2 and D3 receptors, the density of dopamine receptors in the CNS is reported as the D2/3 binding potential, which reflects a measure of the density of both receptor subtypes. Although the development of D2- and D3-selective PET radiotracers has been an active area of research for many years, this by and large presents an unmet need in the area of translational PET imaging studies. This article discusses some of the challenges that have inhibited progress in this area of research and the current status of the development of subtype selective radiotracers for imaging D3 and D2 dopamine receptors with PET.

PMID: 28857231 [PubMed - indexed for MEDLINE]

Post-Traumatic Stress Disorder Chronification via Monoaminooxidase and Cortisol Metabolism.

Wed, 09/11/2019 - 07:26

Post-Traumatic Stress Disorder Chronification via Monoaminooxidase and Cortisol Metabolism.

Horm Metab Res. 2019 Sep;51(9):618-622

Authors: Tseilikman V, Dremencov E, Maslennikova E, Ishmatova A, Manukhina E, Downey HF, Klebanov I, Tseilikman O, Komelkova M, Lapshin MS, Vasilyeva MV, Bornstein SR, Perry SW, Wong ML, Licinio J, Yehuda R, Ullmann E

PMID: 31505706 [PubMed - in process]

Models of poststroke depression and assessments of core depressive symptoms in rodents: How to choose?

Wed, 09/11/2019 - 07:26

Models of poststroke depression and assessments of core depressive symptoms in rodents: How to choose?

Exp Neurol. 2019 Sep 07;:113060

Authors: Tao X, Yang W, Zhu S, Que R, Liu C, Fan T, Wang J, Mo D, Zhang Z, Tan J, Jin K, Yenarih MA, Song T, Wang Q

Abstract
Our previous studies have indicated that depression and declined cognition have been involved in some neurodegenerative diseases including Stroke, Parkinson's diseases and Vascular Parkinsonism. Post-stroke depression (PSD) is the most common psychiatric disorder following a stroke and has high morbidity and mortality. Studies on PSD are increasingly common, but the specific mechanisms remain unknown. Current research mainly includes clinical and animal aspects. Questionnaires and peripheral blood examination are two of the most common methods used to study clinical PSD. The results of questionnaires are influenced by multiple factors such as disease history, education background, occupation, economic status, family relationships and social support. There are certain limitations to blood sample testing; for example, it is influenced by cerebrovascular diseases and some other disruptions of the internal environment. It is difficult for either method to fully clarify the pathophysiological mechanism of PSD. Animal models provide alternative methods to further understand the pathophysiological mechanisms of PSD, such as the involvement of neuronal circuits and cytokines. More than ten animal models of PSD have been developed, and new models are constantly being introduced. Therefore, it is important to choose the appropriate model for any given study. In this paper, we will discuss the characteristics of the different models of PSD and comment on the advantages and disadvantages of each model, drawing from research on model innovation. Finally, we briefly describe the current assessment methods for the core symptoms of PSD models, point out the shortcomings, and present the improved sucrose preference test as a rational evaluation of anhedonia.

PMID: 31505162 [PubMed - as supplied by publisher]

Pharmacist-Led Chronic Care Management Services.

Wed, 09/11/2019 - 07:26
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Pharmacist-Led Chronic Care Management Services.

Ann Fam Med. 2019 Sep;17(5):465

Authors: Yuet WC, Gardea J, Ebert D, Martin RD

PMID: 31501211 [PubMed - in process]

Characteristics and Outcomes of Psychology Referrals in a Palliative Care Department.

Wed, 09/11/2019 - 07:26
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Characteristics and Outcomes of Psychology Referrals in a Palliative Care Department.

J Pain Symptom Manage. 2018 09;56(3):344-351

Authors: Ann-Yi S, Bruera E, Wu J, Liu DD, Agosta M, Williams JL, Balankari VR, Carmack CL

Abstract
CONTEXT: Psychologists can provide unique contributions to interdisciplinary palliative care. Despite research indicating high distress in palliative care cancer patients, little has been reported regarding the feasibility and practice of psychology in this setting.
OBJECTIVES: To review the integration of clinical psychology practice in a palliative care department at a major comprehensive cancer center.
METHODS: Retrospective chart review of 1940 unique cancer patients (6451 total patient contacts) referred for psychology services provided by clinical psychologists in palliative care from September 1, 2013 to February 29, 2016.
RESULTS: Psychologists provided services to 1644 inpatients (24% of palliative care inpatients) and 296 outpatients (19% of palliative care outpatients). Most of them (85%) received services in the inpatient setting. Most patients were females (57%) and white (68%) with a variety of cancer diagnoses. Adjustment disorders were the most prevalent in both settings with significant differences in other Diagnostic and Statistical Manual of Mental Disorders (5th Edition) diagnoses by service location (P < 0.0001). Psychological assessment (86%) and supportive expressive counseling (79%) were the most frequent services provided in the initial consult. Duration of initial visit was significantly longer in outpatient (median 60 minutes) compared with inpatient setting (median 40 minutes) (P < 0.0001). No significant differences were noted between settings regarding the median number of counseling sessions per patient; however, most (70%) only received one or two sessions. Over time, total patient encounters increased in the inpatient setting (P < 0.0001), whereas session lengths in both settings significantly decreased (P < 0.0001).
CONCLUSION: Palliative care psychology services successfully integrated into an interdisciplinary palliative care department and rapidly grew in both inpatient and outpatient settings.

PMID: 29885458 [PubMed - indexed for MEDLINE]

Utility of the Ion S5™ and MiSeq FGx™ sequencing platforms to characterize challenging human remains.

Tue, 09/10/2019 - 07:20
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Utility of the Ion S5™ and MiSeq FGx™ sequencing platforms to characterize challenging human remains.

Leg Med (Tokyo). 2019 Aug 14;41:101623

Authors: Elwick K, Bus MM, King JL, Chang J, Hughes-Stamm S, Budowle B

Abstract
Often in missing persons' and mass disaster cases, the samples remaining for analysis are hard tissues such as bones, teeth, nails, and hair. These remains may have been exposed to harsh environmental conditions, which pose challenges for downstream genotyping. Short tandem repeat analysis (STR) via capillary electrophoresis (CE) is still the gold standard for DNA typing; however, a newer technology known as massively parallel sequencing (MPS) could improve upon our current techniques by typing different and more markers in a single analysis, and consequently improving the power of discrimination. In this study, bone and tooth samples exposed to a variety of DNA insults (cremation, embalming, decomposition, thermal degradation, and fire) were assessed and sequenced using the Precision ID chemistry and a custom AmpliSeq™ STR and iiSNP panel on the Ion S5™ System, and the ForenSeq DNA Signature Prep Kit on the MiSeq FGx™ system, as well as the GlobalFiler™ PCR Amplification Kit on the 3500™ Genetic Analyzer. The results demonstrated that using traditional CE-based genotyping performed as expected, producing a partial or full DNA profile for all samples, and that both sequencing chemistries and platforms were able to recover sufficient STR and SNP information from a majority of the same challenging samples. Run metrics including profile completeness and mean read depth produced good results with each system, considering the degree of damage of some samples. Most sample insults (except decomposed) produced similar numbers of alleles for both MPS systems. Comparable markers produced full concordance between the two platforms.

PMID: 31499459 [PubMed - as supplied by publisher]

Do physical activity levels differ by number of children at home in women aged 25-44 in the general population?

Tue, 09/10/2019 - 07:20
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Do physical activity levels differ by number of children at home in women aged 25-44 in the general population?

Womens Health (Lond). 2019 Jan-Dec;15:1745506519871186

Authors: Abell LP, Tanase KA, Gilmore ML, Winnicki AE, Holmes VL, Hartos JL

Abstract
OBJECTIVES: While physical activity is important for health, many women do not meet recommended levels, particularly mothers. The purpose of this study was to assess whether physical activity levels differ by number of children at home in women aged 25-44 in the general US population.
METHODS: This cross-sectional analysis used 2017 Behavioral Risk Factor Surveillance System data for females aged 25-44 (N = 6266) from California, Colorado, New York, Texas, and Utah. Ordered logistic regression analysis assessed the relationship between physical activity levels and number of children at home while controlling for state and demographic, socioeconomic, and health-related factors.
RESULTS: About half of participants reported "inactive" or "insufficiently active" physical activity levels and about two-thirds reported having one or more children at home. The results of adjusted analysis indicated that physical activity level was significantly related to having one child (adjusted odds ratio = 0.75, 95% confidence interval = 0.63, 0.89), two children (adjusted odds ratio = 0.79; 95% confidence interval = 0.67, 0.93), and three or more children (adjusted odds ratio = 0.80, 95% confidence interval = 0.67, 0.94) at home.
CONCLUSION: Overall, physical activity levels were significantly related to presence of children at home for women aged 25-44, but increasing number of children at home did not impact effect size. For women aged 25-44 in a primary care setting, a moderate prevalence of inactive or insufficiently active physical activity may be expected. Providers should address physical activity with all patients in this target population during well-visits, but particularly for women with children at home; educate patients about the health benefits of regular physical activity; and provide resources that will help them integrate physical activity into their daily lifestyles.

PMID: 31495288 [PubMed - in process]

Associations Between Race, Perceived Psychological Stress, and the Gut Microbiota in a Sample of Generally Healthy Black and White Women: A Pilot Study on the Role of Race and Perceived Psychological Stress.

Tue, 09/10/2019 - 07:20
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Associations Between Race, Perceived Psychological Stress, and the Gut Microbiota in a Sample of Generally Healthy Black and White Women: A Pilot Study on the Role of Race and Perceived Psychological Stress.

Psychosom Med. 2018 09;80(7):640-648

Authors: Carson TL, Wang F, Cui X, Jackson BE, Van Der Pol WJ, Lefkowitz EJ, Morrow C, Baskin ML

Abstract
OBJECTIVE: Racial health disparities persist among black and white women for colorectal cancer. Understanding racial differences in the gut microbiota and related covariates (e.g., stress) may yield new insight into unexplained colorectal cancer disparities.
METHODS: Healthy non-Hispanic black or white women (age ≥19 years) provided survey data, anthropometrics, and stool samples. Fecal DNA was collected and isolated from a wipe. Polymerase chain reaction was used to amplify the V4 region of the 16SrRNA gene and 250 bases were sequenced using the MiSeq platform. Microbiome data were analyzed using QIIME. Operational taxonomic unit data were log transformed and normalized. Analyses were conducted using linear models in R Package "limma."
RESULTS: Fecal samples were analyzed for 80 women (M (SD) age = 39.9 (14.0) years, 47 black, 33 white). Blacks had greater average body mass index (33.3 versus 27.5 kg/m, p < .01) and waist circumference (98.3 versus 86.6 cm, p = .003) than whites. Whites reported more stressful life events (p = .026) and greater distress (p = .052) than blacks. Final models accounted for these differences. There were no significant differences in dietary variables. Unadjusted comparisons revealed no racial differences in alpha diversity. Racial differences were observed in beta diversity and abundance of top 10 operational taxonomic units. Blacks had higher abundances than whites of Faecalibacterium (p = .034) and Bacteroides (p = .038). Stress was associated with abundances of Bifidobacterium. The association between race and Bacteroides (logFC = 1.72, 0 = 0.020) persisted in fully adjusted models.
CONCLUSIONS: Racial differences in the gut microbiota were observed including higher Bacteroides among blacks. Efforts to cultivate an "ideal" gut microbiota may help reduce colorectal cancer risk.

PMID: 29901485 [PubMed - indexed for MEDLINE]

Participation and retention can be high in randomized controlled trials targeting underserved populations: a systematic review and meta-analysis.

Tue, 09/10/2019 - 07:20
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Participation and retention can be high in randomized controlled trials targeting underserved populations: a systematic review and meta-analysis.

J Clin Epidemiol. 2018 06;98:154-157

Authors: Ojha RP, Jackson BE, Lu Y, Burton M, Blair SE, MacDonald BR, Chu TC, Teigen KJ, Acosta M

PMID: 29183689 [PubMed - indexed for MEDLINE]

Transitioning from acute to chronic pain: a simulation study of trajectories of low back pain.

Sun, 09/08/2019 - 07:01
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Transitioning from acute to chronic pain: a simulation study of trajectories of low back pain.

J Transl Med. 2019 Sep 06;17(1):306

Authors: Su J, Du Y, Bevers K, Xiao P, Licciardone J, Brotto M, Gatchel RJ

Abstract
BACKGROUND: Identifying how pain transitions from acute to chronic is critical in designing effective prevention and management techniques for patients' well-being, physically, psychosocially, and financially. There is an increasingly pressing need for a quantitative and predictive method to evaluate how low back pain trajectories are classified and, subsequently, how we can more effectively intervene during these progression stages.
METHODS: In order to better understand pain mechanisms, we investigated, using computational modeling, how best to describe pain trajectories by developing a platform by which we studied the transition of acute chronic pain.
RESULTS: The present study uses a computational neuroscience-based method to conduct such trajectory research, motivated by the use of hypothalamic-pituitary-adrenal (HPA) axis activity-history over a time-period as a way to mimic pain trajectories. A numerical simulation study is presented as a "proof of concept" for this modeling approach.
CONCLUSIONS: This model and its simulation results have highlighted the feasibility and the potential of developing such a broader model for patient evaluations.

PMID: 31492167 [PubMed - in process]

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