Recent Research Articles from UNTHSC

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

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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: 2 hours 33 min ago

The Road to a Hypoglycemic Care Model.

Tue, 11/26/2019 - 07:38
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The Road to a Hypoglycemic Care Model.

Cureus. 2019 Oct 08;11(10):e5865

Authors: Moore M, Alzghari SK

Abstract
Hypoglycemia is a modifiable condition that causes mortality and readmission rates to increase in a hospital setting. The condition is worsened by its complications, quick onset, and an absence of a protocol mapped out by hospitals. This complication does not come from one origin, but rather from a range of barriers. Research from a variety of sources, such as those found from the American Diabetes Association, have shown great promises in ways to treat and prevent hypoglycemia that are of importance to highlight for practitioners in the inpatient setting.

PMID: 31763088 [PubMed]

Successful Remediation of an Advanced Pharmacy Practice Experience for an At-risk Student.

Tue, 11/26/2019 - 07:38
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Successful Remediation of an Advanced Pharmacy Practice Experience for an At-risk Student.

Am J Pharm Educ. 2018 11;82(9):6762

Authors: Martin RD, Wheeler E, White A, Killam-Worrall LJ

Abstract
Objective. To describe a successful remediation for an Acute Care Medicine advanced pharmacy practice experience (APPE) in a student with multiple learning deficits. Methods. A literature review of pharmacy and medical experiential remediation was conducted to identify best practices to implement prior to designing the remediation for our student case. Based on this search and experience as preceptors, a three-phase remediation was designed: one week for assessment, two weeks for development of learning skills and strategies and six weeks for an on-campus APPE. Success of the remediation was determined by student performance, as defined by the APPE preceptor, in all relevant 2013 Center for the Advancement of Pharmacy Education (CAPE) educational outcomes. Results. Baseline assessment indicated that the student was below minimal competency in six of 13 relevant 2013 CAPE educational outcomes. Upon completion of the three-part remediation, the student repeated the Acute Care Medicine APPE, achieving better than minimal competency in all 13 outcomes. The student demonstrated significant improvement in nine of 13 CAPE educational outcomes. Conclusion. This student case provides a novel and successful blueprint for remediation of APPE. However, more evidence-based literature is needed to guide educators in experiential remediation.

PMID: 30559502 [PubMed - indexed for MEDLINE]

Human Papillomavirus Vaccination and School Entry Requirements: Politically Challenging, but Not Impossible.

Tue, 11/26/2019 - 07:38
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Human Papillomavirus Vaccination and School Entry Requirements: Politically Challenging, but Not Impossible.

JAMA Pediatr. 2019 01 01;173(1):6-7

Authors: Daley E, Thompson E, Zimet G

PMID: 30398530 [PubMed - indexed for MEDLINE]

Doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) as an HIV/neuroAIDS model.

Tue, 11/26/2019 - 07:38
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Doxycycline-inducible and astrocyte-specific HIV-1 Tat transgenic mice (iTat) as an HIV/neuroAIDS model.

J Neurovirol. 2018 04;24(2):168-179

Authors: Langford D, Oh Kim B, Zou W, Fan Y, Rahimain P, Liu Y, He JJ

Abstract
HIV-1 Tat is known to be neurotoxic and important for HIV/neuroAIDS pathogenesis. However, the overwhelming majority of the studies involved use of recombinant Tat protein. To understand the contributions of Tat protein to HIV/neuroAIDS and the underlying molecular mechanisms of HIV-1 Tat neurotoxicity in the context of a whole organism and independently of HIV-1 infection, a doxycycline-inducible astrocyte-specific HIV-1 Tat transgenic mouse (iTat) was created. Tat expression in the brains of iTat mice was determined to be in the range of 1-5 ng/ml and led to astrocytosis, loss of neuronal dendrites, and neuroinflammation. iTat mice have allowed us to define the direct effects of Tat on astrocytes and the molecular mechanisms of Tat-induced GFAP expression/astrocytosis, astrocyte-mediated Tat neurotoxicity, Tat-impaired neurogenesis, Tat-induced loss of neuronal integrity, and exosome-associated Tat release and uptake. In this review, we will provide an overview about the creation and characterization of this model and its utilities for our understanding of Tat neurotoxicity and the underlying molecular mechanisms.

PMID: 29143286 [PubMed - indexed for MEDLINE]

Comparison of Dietary Micronutrient Intakes by Body Weight Status among Mexican-American and Non-Hispanic Black Women Aged 19-39 Years: An Analysis of NHANES 2003-2014.

Sun, 11/24/2019 - 07:14
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Comparison of Dietary Micronutrient Intakes by Body Weight Status among Mexican-American and Non-Hispanic Black Women Aged 19-39 Years: An Analysis of NHANES 2003-2014.

Nutrients. 2019 Nov 20;11(12):

Authors: Liu J, Zhu X, Fulda KG, Chen S, Tao MH

Abstract
The objective of the current study was to examine micronutrient intake from foods in women of childbearing age and to better understand potential nutritional problems varied by body weight status in minority women. A sample of women aged 19-39 years from the National Health and Nutrition Examination Surveys (NHANES) 2003-2014 was analyzed. Dietary intakes of 13 micronutrients were estimated using the National Cancer Institute method. Mexican-American and non-Hispanic Black women were categorized into normal/under-weight, overweight, or obese groups according to their body mass index (BMI). Mexican-American and non-Hispanic Black women had lower dietary intakes for vitamins A, B2, B6, B12, and D, folate, calcium, and magnesium than non-Hispanic Whites. Among Mexican-Americans, obese women had the lowest dietary intake of vitamins A, B2, C and D. Obese non-Hispanic Black women had significantly lower dietary intakes of iron and zinc than their normal/under-weight counterparts. Comparable percentages (>30%) of Mexican-American and non-Hispanic Black women had dietary intake less than the Estimated Average Requirements (EARs) for several key nutrients including vitamin A, C and D, folate, calcium and magnesium, and the percentages varied by body weight status. These results indicate micronutrient inadequacies persist among and within racial/ethnic and body weight groups.

PMID: 31757075 [PubMed - in process]

Recent changes in cervical cancer screening guidelines: U.S. women's willingness for HPV testing instead of Pap testing.

Sat, 11/23/2019 - 06:46
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Recent changes in cervical cancer screening guidelines: U.S. women's willingness for HPV testing instead of Pap testing.

Prev Med. 2019 Nov 19;:105928

Authors: Thompson EL, Galvin AM, Daley EM, Tatar O, Zimet GD, Rosberger Z

Abstract
Cervical cancer screening guidelines in the United States were revised in 2018 to include the option of primary human papillomavirus (HPV) testing. The transition to this screening method may face difficulties as Pap testing has been the primary screening modality in the United States. The objective of this study is to assess information, motivation, and behavioral skills associated with willingness to receive an HPV test instead of a Pap test among women. The sample included U.S. 812 women, ages 30 to 65 years. Participants completed an online survey in 2018. The Information, Motivation, and Behavioral Skills (IMB) model was used to measure predictors of willingness for HPV testing. The outcome variables were willingness to receive the HPV test instead of the Pap test, with and without time interval details. Logistic regression modeling was used with SAS 9.4. Over half of the sample (55%) were willing to receive the HPV test. For the information domain, HPV knowledge was significantly associated with willingness for HPV testing (OR = 1.08, 95%CI 1.04-1.13). Significant motivating factors included: positive attitudes, social norms, perceived benefits, worry about cervical cancer, and worry about abnormal HPV tests. For behavioral skills, women were significantly more willing to get the HPV test if a provider recommended it (OR = 2.43, 95%CI 1.53-3.87) and currently up-to-date on cervical cancer screening guidelines (OR = 1.52, 95%CI 1.52-2.26). Addressing barriers and facilitators to willingness to transition to primary HPV testing over Pap testing is needed as the United States has updated guidelines for cervical cancer screening.

PMID: 31756351 [PubMed - as supplied by publisher]

Sex-dependent mechanisms of glucocorticoid regulation of the mouse hypothalamic corticotropin-releasing hormone gene.

Sat, 11/23/2019 - 06:46
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Sex-dependent mechanisms of glucocorticoid regulation of the mouse hypothalamic corticotropin-releasing hormone gene.

Endocrinology. 2019 Nov 22;:

Authors: Heck AL, Thompson MK, Uht RM, Handa RJ

Abstract
To limit excessive glucocorticoid secretion following hypothalamic pituitary adrenal (HPA) axis stimulation, circulating glucocorticoids inhibit corticotropin-releasing hormone (CRH) expression in paraventricular nucleus (PVN) neurons. As HPA function differs between sexes and depends on circulating estradiol (E2) levels in females, we investigated sex/estrous stage-dependent glucocorticoid regulation of PVN Crh. Using NanoString nCounter technology, we first demonstrated that adrenalectomized (ADX'd) diestrous female (low E2), but not male or proestrous female (high E2), mice exhibited a robust decrease in PVN CRH mRNA following two-day treatment with the glucocorticoid receptor (GR) agonist RU28362. Immunohistochemical analysis of PVN CRH neurons in Crh-IRES-cre;Ai14 mice, where TdTomato fluorescence permanently tags CRH-expressing neurons, showed similarly abundant co-expression of GR-immunoreactivity in males, diestrous females, and proestrous females. However, we identified sex/estrous stage-related glucocorticoid regulation or expression of GR transcriptional co-regulators. Out of 17 co-regulator genes examined using nCounter multiplex analysis, mRNAs decreased by RU28362 in ADX'd mice in a sex/ estrous stage-dependent fashion included: GR (males = diestrous females > proestrous females), STAT3 (males < diestrous = proestrous), and HDAC1 (males < diestrous > proestrous). SRC-3, NCoR1, hnrnpu, CBP and CRTC2 mRNAs were lower in ADX'd diestrous and proestrous females versus males. Additionally, most PVN CRH neurons co-expressed MeCP2-immunoreactivity in diestrous female and male Crh-IRES-Cre;Ai14 mice. Our findings collectively suggest that GR's sex-dependent regulation of PVN Crh may depend upon differences in the GR transcriptional machinery and an underlying influence of E2 levels in females.

PMID: 31754709 [PubMed - as supplied by publisher]

A Novel Prodrug Approach for Central Nervous System-Selective Estrogen Therapy.

Sat, 11/23/2019 - 06:46
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A Novel Prodrug Approach for Central Nervous System-Selective Estrogen Therapy.

Molecules. 2019 Nov 19;24(22):

Authors: Prokai-Tatrai K, Prokai L

Abstract
Beneficial effects of estrogens in the central nervous system (CNS) results from the synergistic combination of their well-orchestrated genomic and non-genomic actions, making them potential broad-spectrum neurotherapeutic agents. However, owing to unwanted peripheral hormonal burdens by any currently known non-invasive drug administrations, the development of estrogens as safe pharmacotherapeutic modalities cannot be realized until they are confined specifically and selectively to the site of action. We have developed small-molecule bioprecursor prodrugs carrying the para-quinol scaffold on the steroidal A-ring that are preferentially metabolized in the CNS to the corresponding estrogens. Here, we give an overview of our discovery of these prodrugs. Selected examples are shown to illustrate that, independently of the route of administrations and duration of treatments, these agents produce high concentration of estrogens only in the CNS without peripheral hormonal liability. 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) has been the best-studied representative of this novel type of prodrugs for brain and retina health. Specific applications in preclinical animal models of centrally-regulated and estrogen-responsive human diseases, including neurodegeneration, menopausal symptoms, cognitive decline and depression, are discussed to demonstrate the translational potential of our prodrug approach for CNS-selective and gender-independent estrogen therapy with inherent therapeutic safety.

PMID: 31752337 [PubMed - in process]

Behavioral health conditions and potentially preventable diabetes-related hospitalizations in the United States: Findings from a national sample of commercial claims data.

Sat, 11/23/2019 - 06:46
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Behavioral health conditions and potentially preventable diabetes-related hospitalizations in the United States: Findings from a national sample of commercial claims data.

PLoS One. 2019;14(2):e0212955

Authors: Stockbridge EL, Chhetri S, Polcar LE, Loethen AD, Carney CP

Abstract
OBJECTIVE: To characterize the relationship between potentially preventable hospitalizations (PPHs) for diabetes and behavioral health conditions in commercially insured working-age persons with diabetes in the United States.
RESEARCH DESIGN AND METHODS: We retrospectively analyzed medical and pharmacy claims from services rendered between 2011 and 2013 for 229,039 adults with diabetes. Diabetes PPHs were identified using the Agency for Healthcare Research and Quality's Prevention Quality Indicators v6.0 logic. We used negative binomial-logit hurdle regression models to explore the adjusted relationships between diabetes PPHs and schizophrenia, bipolar, depression, anxiety, adjustment disorder, alcohol use disorder, and drug use disorder.
RESULTS: A total of 4,521 diabetes PPHs were experienced by 3,246 of the persons in the sample. The 20.83% of persons with one or more behavioral health conditions experienced 43.62% (1,972/4,521; 95% CI 42.18%-45.07%) of all diabetes PPHs, and the 7.14% of persons with more than one diagnosed behavioral health condition experienced 24.77% (1,120/4,521; 95% CI 23.54%-26.05%) of all diabetes PPHs. After adjusting for sociodemographic and physical health covariates, patients with depression, schizophrenia, drug or alcohol use disorders, or multiple behavioral health conditions were at significantly increased risk of experiencing at least one diabetes PPH, while patients with depression, drug use disorder, or multiple behavioral health conditions were at significantly increased risk of experiencing recurring diabetes PPHs over time.
CONCLUSIONS: A number of behavioral health conditions are associated with diabetes PPHs, which are often preventable with timely, high-quality outpatient care. The results of this study will enable clinicians, payers, and policy-makers to better focus outpatient care interventions and resources within the population of persons with diabetes.

PMID: 30818377 [PubMed - indexed for MEDLINE]

Liquid Biopsy for Cancer: Review and Implications for the Radiologist.

Thu, 11/21/2019 - 06:26

Liquid Biopsy for Cancer: Review and Implications for the Radiologist.

Radiology. 2019 Nov 19;:182584

Authors: Underwood JJ, Quadri RS, Kalva SP, Shah H, Sanjeeviah AR, Beg MS, Sutphin PD

Abstract
Imaging and image-guided procedures play an imperative role in the screening, diagnosis, and surveillance of cancer. Although emerging imaging techniques now enable more precise molecular characterization of tumors, multigenetic tumor profiling for targeted therapeutic selection remains limited to direct tissue acquisition. Even in the context of targeted therapy, tumors adapt to acquire resistance. This necessitates serial monitoring, traditionally through tissue acquisition, to identify the molecular mechanism of resistance and to guide second-line therapy. An alternative to tissue acquisition is the collection of circulating tumor markers such as cell-free nucleic acids and circulating tumor cells in the peripheral blood. This noninvasive diagnostic approach is referred to as the liquid biopsy. The liquid biopsy is currently used clinically for therapeutic guidance when tissue acquisition is impossible or when the specimen is inadequate. It is also being studied in the context of screening, diagnosis, and surveillance. As cancer treatment continues to move toward a focus on precision medicine, this developing technology may alter and/or augment the role of imaging in the management of cancer. This review aims to outline the use of liquid biopsy in cancer and its potential impact on diagnostic imaging and image-guided procedures.

PMID: 31746691 [PubMed - as supplied by publisher]

Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer.

Thu, 11/21/2019 - 06:26
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Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer.

Brain Topogr. 2019 Nov 19;:

Authors: Henneghan AM, Gibbons C, Harrison RA, Edwards ML, Rao V, Blayney DW, Palesh O, Kesler SR

Abstract
Being able to predict who will likely experience cancer related cognitive impairment (CRCI) could enhance patient care and potentially reduce economic and human costs associated with this adverse event. We aimed to determine if post-treatment patient reported CRCI could also be predicted from baseline resting state fMRI in patients with breast cancer. 76 newly diagnosed patients (n = 42 planned for chemotherapy; n = 34 not planned for chemotherapy) and 50 healthy female controls were assessed at 3 times points [T1 (prior to treatment); T2 (1 month post chemotherapy); T3 (1 year after T2)], and at yoked intervals for controls. Data collection included self-reported executive dysfunction, memory function, and psychological distress and resting state fMRI data converted to connectome matrices for each participant. Statistical analyses included linear mixed modeling, independent t tests, and connectome-based predictive modeling (CPM). Executive dysfunction increased over time in the chemotherapy group and was stable in the other two groups (p < 0.001). Memory function decreased over time in both patient groups compared to controls (p < 0.001). CPM models successfully predicted executive dysfunction and memory function scores (r > 0.31, p < 0.002). Support vector regression with a radial basis function (SVR RBF) showed the highest performance for executive dysfunction and memory function (r = 0.68; r = 0.44, p's < 0.001). Baseline neuroimaging may be useful for predicting patient reported cognitive outcomes which could assist in identifying patients in need of surveillance and/or early intervention for treatment-related cognitive effects.

PMID: 31745689 [PubMed - as supplied by publisher]

Racial Disparities in Menu-Labeling Usage: Analysis of the 2012 Behavioral Risk Factor Surveillance System (BRFSS) Sugar-Sweetened Beverage and Menu-Labeling Module.

Thu, 11/21/2019 - 06:26
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Racial Disparities in Menu-Labeling Usage: Analysis of the 2012 Behavioral Risk Factor Surveillance System (BRFSS) Sugar-Sweetened Beverage and Menu-Labeling Module.

J Racial Ethn Health Disparities. 2018 06;5(3):514-521

Authors: Shikdar S, Suzuki S

Abstract
OBJECTIVES: Race/ethnic disparities in obesity are widely reported and are often attributed to diet-related factors, such as menu-labeling usage. We aimed to determine whether racial difference exists in menu-labeling usage.
METHODS: Data from the 2012 Behavioral Risk Factor Surveillance System were used. Menu labeling was measured from the Sugar-Sweetened Beverages and Menu Labeling module administered in 18 states. We stratified the population into four race/ethnic categories: non-Hispanic whites (reference, n = 66,019, 63%), non-Hispanic blacks (n = 13,623, 13%), Hispanics (n = 14,671, 14%), and others (n = 7336, 7%). Logistic regression was used to examine the racial/ethnic differences in menu-labeling usage. Analyses were conducted adjusting for sociodemographic characteristics, sugar-sweetened beverage intake, and exercise.
RESULTS: The prevalence of menu-labeling usage was approximately 55% overall. Hispanics (adjusted odds ratio [AOR], 1.35; 95% confidence interval [CI], 1.14-1.60) and other race/ethnic groups (AOR, 1.39; 95% CI, 1.18-1.64) used menu labeling more compared to non-Hispanic whites. After stratification by race/ethnicity, menu-labeling usage was not associated with exercise or soda consumption among Hispanics, but significant associations were observed among the other three race/ethnic groups.
CONCLUSIONS: The findings suggest that participation in healthy behaviors was associated with the higher usage of menu labeling across all racial/ethnic groups except Hispanics. Future studies are needed to explore this mechanism among individuals engaging in unhealthier behavior as well as how it affects Hispanics.

PMID: 28646355 [PubMed - indexed for MEDLINE]

Approaches to Whole Mitochondrial Genome Sequencing on the Oxford Nanopore MinION.

Wed, 11/20/2019 - 06:17

Approaches to Whole Mitochondrial Genome Sequencing on the Oxford Nanopore MinION.

Curr Protoc Hum Genet. 2019 Dec;104(1):e94

Authors: Zascavage RR, Hall CL, Thorson K, Mahmoud M, Sedlazeck FJ, Planz JV

Abstract
Traditional approaches for interrogating the mitochondrial genome often involve laborious extraction and enrichment protocols followed by Sanger sequencing. Although preparation techniques are still demanding, the advent of next-generation or massively parallel sequencing has made it possible to routinely obtain nucleotide-level data with relative ease. These short-read sequencing platforms offer deep coverage with unparalleled read accuracy in high-complexity genomic regions but encounter numerous difficulties in the low-complexity homopolymeric sequences characteristic of the mitochondrial genome. The inability to discern identical units within monomeric repeats and resolve copy-number variations for heteroplasmy detection results in suboptimal genome assemblies that ultimately complicate downstream data analysis and interpretation of biological significance. Oxford Nanopore Technologies offers the ability to generate long-read sequencing data on a pocket-sized device known as the MinION. Nanopore-based sequencing is scalable, portable, and theoretically capable of sequencing the entire mitochondrial genome in a single contig. Furthermore, the recent development of a nanopore protein with dual reader heads allows for clear identification of nucleotides within homopolymeric stretches, significantly increasing resolution throughout these regions. The unrestricted read lengths, superior homopolymeric resolution, and affordability of the MinION device make it an attractive alternative to the labor-intensive, time-consuming, and costly mainstay deep-sequencing platforms. This article describes three approaches to extract, prepare, and sequence mitochondrial DNA on the Oxford Nanopore MinION device. Two of the workflows include enrichment of mitochondrial DNA prior to sequencing, whereas the other relies on direct sequencing of native genomic DNA to allow for simultaneous assessment of the nuclear and mitochondrial genomes. © 2019 by John Wiley & Sons, Inc. Basic Protocol: Enrichment-free mitochondrial DNA sequencing Alternate Protocol 1: Mitochondrial DNA sequencing following enrichment with polymerase chain reaction (PCR) Alternate Protocol 2: Mitochondrial DNA sequencing following enrichment with PCR-free hybridization capture Support Protocol 1: DNA quantification and quality assessment using the Agilent 4200 TapeStation System Support Protocol 2: AMPure XP bead clean-up Support Protocol 3: Suggested data analysis pipeline.

PMID: 31743587 [PubMed - in process]

Inline flow sensor for ventriculoperitoneal shunts: Experimental evaluation in swine.

Wed, 11/20/2019 - 06:17
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Inline flow sensor for ventriculoperitoneal shunts: Experimental evaluation in swine.

Med Eng Phys. 2019 05;67:66-72

Authors: Qin C, Olivencia-Yurvati AH, Williams AG, Eskildsen D, Mallet RT, Dasgupta PK

Abstract
Shunts are commonly employed to treat hydrocephalus, a severe central nervous disease caused by the buildup of cerebrospinal fluid in the brain. These shunts divert excessive cerebrospinal fluid from brain ventricles to other body cavities, thereby relieving the symptoms. However, these shunts are highly prone to failure due to obstruction from cellular debris, leading to cerebrospinal fluid accumulation in the brain and exacerbation of neurological symptoms. Therefore, there is a clinical need for a reliable, non-invasive method of monitoring shunt performance. Recently, a simple inline flow sensor was reported for monitoring ventriculoperitoneal shunting of cerebrospinal fluid in hydrocephalus treatment. The present work aimed to evaluate performance of the device in an animal model of hydrocephalus. Sensor-equipped shunt tubes were placed in anesthetized, juvenile swine. The flows reported by the sensor were compared with gravimetric flow measurements. Robust correlations (r ≈ 0.87-0.96) between the gravimetric and sensor-reported flows were obtained in 4 of the 6 experiments. The mean slope of the linear relationship of the gravimetrically determined vs. sensor flow rates was 0.98 ± 0.09 in the 6 experiments, indicating the sensor accurately reported shunt flows up to 35 ml/h. The sensor responded immediately to abrupt flow changes following cerebroventricular fluid injections. Minor hardware problems were identified and corrected. These experiments provide practical guidance for future preclinical testing of the device.

PMID: 30922842 [PubMed - indexed for MEDLINE]

Impact of environmental stressors on tolerance to hemorrhage in humans.

Wed, 11/20/2019 - 06:17
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Impact of environmental stressors on tolerance to hemorrhage in humans.

Am J Physiol Regul Integr Comp Physiol. 2019 02 01;316(2):R88-R100

Authors: Crandall CG, Rickards CA, Johnson BD

Abstract
Hemorrhage is a leading cause of death in military and civilian settings, and ~85% of potentially survivable battlefield deaths are hemorrhage-related. Soldiers and civilians are exposed to a number of environmental and physiological conditions that have the potential to alter tolerance to a hemorrhagic insult. The objective of this review is to summarize the known impact of commonly encountered environmental and physiological conditions on tolerance to hemorrhagic insult, primarily in humans. The majority of the studies used lower body negative pressure (LBNP) to simulate a hemorrhagic insult, although some studies employed incremental blood withdrawal. This review addresses, first, the use of LBNP as a model of hemorrhage-induced central hypovolemia and, then, the effects of the following conditions on tolerance to LBNP: passive and exercise-induced heat stress with and without hypohydration/dehydration, exposure to hypothermia, and exposure to altitude/hypoxia. An understanding of the effects of these environmental and physiological conditions on responses to a hemorrhagic challenge, including tolerance, can enable development and implementation of targeted strategies and interventions to reduce the impact of such conditions on tolerance to a hemorrhagic insult and, ultimately, improve survival from blood loss injuries.

PMID: 30517019 [PubMed - indexed for MEDLINE]

Research Agenda for the Prevention of Pain and Its Impact: Report of the Work Group on the Prevention of Acute and Chronic Pain of the Federal Pain Research Strategy.

Wed, 11/20/2019 - 06:17
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Research Agenda for the Prevention of Pain and Its Impact: Report of the Work Group on the Prevention of Acute and Chronic Pain of the Federal Pain Research Strategy.

J Pain. 2018 08;19(8):837-851

Authors: Gatchel RJ, Reuben DB, Dagenais S, Turk DC, Chou R, Hershey AD, Hicks GE, Licciardone JC, Horn SD

Abstract
After the 2011 Institute of Medicine report on chronic pain, the Interagency Pain Research Coordinating Committee (IPRCC) was created to enhance research efforts among federal agencies. The IPRCC and Office of Pain Policy at the National Institutes of Health collaborated to identify gaps in knowledge and address them via a Federal Pain Research Strategy (FPRS). Interdisciplinary work groups (WGs) were established to make research recommendations in 5 areas: prevention of acute and chronic pain, acute pain and acute pain management, transition from acute to chronic pain, chronic pain and chronic pain management, and disparities in pain and pain care; cross-cutting issues were also considered. The objective was to provide guidance on current research and to make recommendations about addressing identified gaps. Findings from the Prevention of Acute and Chronic Pain WG are summarized in this article. The WG created subgroups to develop recommendations on specific aspects of prevention of acute and chronic pain, including: public education, primary prevention, secondary prevention, tertiary prevention, transition from acute to chronic pain, and cross-cutting mediators. No formal literature review was conducted; however, external advisors were available and consulted as needed. Seven key research priorities were identified. The one deemed "greatest near-term value" was to optimize public health strategies to educate patients on managing pain; that deemed "most impactful" was to determine an association between patient and intervention factors. Other recommendations were related to the epidemiology of acute pain from health care procedures, the epidemiology of acute pain from work-related injuries, safety and effectiveness of management of pain associated with health care procedures, optimizing approaches to acute postsurgical pain, and safety and effectiveness of early interventions for tertiary prevention. Stakeholders, including federally sponsored research programs, researchers, health care providers, policy makers, patients, and others should work together to implement recommendations and address important gaps.
PERSPECTIVE: The FPRS Steering Committee created 5 WGs to identify research needs and make recommendations in key areas of research. This article reports the results of one-the Prevention of Acute and Chronic Pain group. Several research priorities emerged, and recommendations made to fill existing knowledge gaps.

PMID: 29578089 [PubMed - indexed for MEDLINE]

Comparative expression analysis of phospholipid binding protein annexina1 in nephrogenesis and kidney cancer.

Sat, 11/16/2019 - 05:23

Comparative expression analysis of phospholipid binding protein annexina1 in nephrogenesis and kidney cancer.

J Basic Clin Physiol Pharmacol. 2019 Nov 14;:

Authors: Sadashiv R, Bannur BM, Shetty P, Dinesh US, K Vishwanatha J, Deshpande SK, Bargale A, E S, Ruikar K

Abstract
Background The expression in the glomerular mesangial cells, papillary, and collecting duct cells demonstrated annexin A1 (AnxA1)'s role in specific renal functions. With varying concentrations of calcium (Ca2+), it is considered to regulate cellular processes such as cell proliferation, apoptosis, and clearance of apoptotic cells by forming ceramides, a key lipid mediator of apoptosis. It also participates in tumorigenesis based on its location. On account of these features, we investigated the expression of this apoptosis-associated protein in fetal kidneys at different gestational periods, mature kidneys and in kidney cancer tissues in order to localize and possibly characterize its role during nephrogenesis and renal tumors. Methods AnxA1 expression was evaluated by an immunohistochemistry technique in "paraffin-embedded" renal tissue sections from autopsied fetuses at different gestational ages, in mature kidneys and renal cancer tissues. Results The current study data demonstrated that AnxA1 is expressed in the mesangial cells and podocytes of maturing glomeruli in the developing renal cortex of fetal kidneys at 14 to 19 weeks of gestation. The expression in the mesangial cells declined in later weeks of gestation and persisted into adulthood. AnxA1 expression increased with the progression of clear cell renal cell carcinoma (CCRCC) and also in other cancer types indicating a potential role of the protein in tumorigenesis. Conclusions We presume that AnxA1 in the podocytes and mesangial cells play important roles in various signaling pathways in the functioning of the glomerulus. These results and concepts provide a framework to further dissect its biological properties and thereby develop diagnostic, prognostic, and therapeutic strategies targeting the molecule in various renal pathologies.

PMID: 31730527 [PubMed - as supplied by publisher]

Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.

Sat, 11/16/2019 - 05:23
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Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.

Leukemia. 2019 Nov 14;:

Authors: Winick N, Martin PL, Devidas M, Shuster J, Borowitz MJ, Paul Bowman W, Larsen E, Pullen J, Carroll A, Willman C, Hunger SP, Carroll WL, Camitta BM

Abstract
The delayed intensification (DI) enhanced outcome for patients with acute lymphoblastic leukemia (ALL) treated on BFM 76/79 and CCG 105 after a prednisone-based induction. Childrens Oncology Group protocols P9904/9905 evaluated DI via a post-induction randomization for eligible National Cancer Institute (NCI) standard (SR) and high-risk (HR) patients. A second randomization compared intravenous methotrexate (IV MTX) as a 24- (1 g/m2) vs. 4-h (2 g/m2) infusion. NCI SR patients received a dexamethasone-based three-drug and NCI HR/CNS 3 SR patients a prednisone-based four-drug induction. End induction MRD (minimal residual disease) was obtained but did not impact treatment. DI improved the 10-year continuous complete remission (CCR) rate; 75.5 ± 2.5% vs. 81.8 ± 2.2% p = 0.002, whereas MTX administration did not; 4-h 80.8 ± 1.9%; 24-h 81.4 ± 1.9% (p = 0.7780). Overall survival (OS) at 10 years did not differ with DI: 91.4 ± 1.6% vs. 90.9 ± 1.7% (p = 0.25) without but was higher with the 24-h MTX infusion; 4-h 91.1 ± 1.4%; 24-h 93.9 ± 1.2% (p = 0.0209). MRD predicted outcome; 10-year CCR 87.7 ± 2.2 and 82.1 ± 2.5% when MRD was <0.01% with/without DI (p = 0.007) and 54.3 ± 8% and 44 ± 8% for patients with MRD ≥ 0.01% with/without DI (p = 0.11). DI improved CCR for patients with B-ALL with and without end induction MRD.

PMID: 31728054 [PubMed - as supplied by publisher]

Cannulated Screws.

Sat, 11/16/2019 - 05:23
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Cannulated Screws.

J Foot Ankle Surg. 2019 Mar;58(2):333-336

Authors: Carpenter B, Bohay D, Early JS, Jennings M, Pomeroy G, Schuberth JM, Wukich DK

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