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

Improved Y-STR typing for disaster victim identification, missing persons investigations, and historical human skeletal remains.

Thu, 11/01/2018 - 05:20
Related Articles

Improved Y-STR typing for disaster victim identification, missing persons investigations, and historical human skeletal remains.

Int J Legal Med. 2018 Nov;132(6):1545-1553

Authors: Ambers A, Votrubova J, Vanek D, Sajantila A, Budowle B

Abstract
Bones are a valuable source of DNA in forensic, anthropological, and archaeological investigations. There are a number of scenarios in which the only samples available for testing are highly degraded and/or skeletonized. Often it is necessary to perform more than one type of marker analysis on such samples in order to compile sufficient data for identification. Lineage markers, such as Y-STRs and mitochondrial DNA (mtDNA), represent important systems to complement autosomal DNA markers and anthropological metadata in making associations between unidentified remains and living relatives or for characterization of the remains for historical and archaeological studies. In this comparative study, Y-STR typing with both Yfiler™ and Yfiler™ Plus (Thermo Fisher Scientific, Waltham, MA, USA) was performed on a variety of human skeletal remains, including samples from the American Civil War (1861-1865), the late nineteenth century gold rush era in Deadwood, SD, USA (1874-1877), the Seven Years' War (1756-1763), a seventeenth-century archaeological site in Raspenava, Bohemia (Czech Republic), and World War II (1939-1945). The skeletal remains used for this study were recovered from a wide range of environmental conditions and were extracted using several common methods. Regardless of the DNA extraction method used and the age/condition of the remains, 22 out of 24 bone samples yielded a greater number of alleles using the Yfiler™ Plus kit compared to the Yfiler™ kit using the same quantity of input DNA. There was no discernable correlation with the degradation index values for these samples. Overall, the efficacy of the Yfiler™ Plus assay was demonstrated on degraded DNA from skeletal remains. Yfiler™ Plus increases the discriminatory power over the previous generation multiplex due to the larger set of Y-STR markers available for analysis and buffer modifications with the newer version kit. Increased haplotype resolution is provided to infer or refute putative genetic relationships.

PMID: 29476237 [PubMed - indexed for MEDLINE]

Comparison of faculty assessment and students' self-assessment of performance during clinical case discussions in a pharmacotherapy capstone course.

Thu, 11/01/2018 - 05:20
Related Articles

Comparison of faculty assessment and students' self-assessment of performance during clinical case discussions in a pharmacotherapy capstone course.

Med Teach. 2018 02;40(2):193-198

Authors: Wettergreen SA, Brunner J, Linnebur SA, Borgelt LM, Saseen JJ

Abstract
OBJECTIVES: The primary objective of this study was to compare faculty assessment and third year students' self-assessment of performance in clinical case discussions. The secondary objective was to evaluate if student characteristics influence self-assessments.
METHODS: This retrospective analysis compared faculty and student self-assessment scores for two clinical case discussions using Spearman's correlation and Wilcoxon's signed ranks test. Chi-squared test was used to compare frequency of faculty and student self-assessments indicating the highest possible rating for the pooled score and for each individual component. The pooled score included three individual components: level of engagement, quality of contribution, and professionalism.
RESULTS: Pooled faculty and student self-assessments correlated for both the first (r = 0.41, p < 0.001) and second (r = 0.35; p < 0.001) clinical case discussions. The frequency that faculty and student self-assessment ratings were the highest possible pooled score was similar for both the first (51.3% vs. 44.7%, respectively, p = 0.25) and second (58.6% vs. 47.4%, p = 0.05) clinical case discussions. Student characteristics (age, gender, and grade point average at graduation) did not influence self-assessments.
CONCLUSIONS: Students' self-assessment correlated with faculty assessment of performance during clinical case discussions. Increased use of self-assessments for professional development in pharmacy and other healthcare professional curricula should be considered.

PMID: 29117750 [PubMed - indexed for MEDLINE]

Osteopathic Manipulative Treatment Alters Gastric Myoelectric Activity in Healthy Subjects.

Wed, 10/31/2018 - 05:16

Osteopathic Manipulative Treatment Alters Gastric Myoelectric Activity in Healthy Subjects.

J Altern Complement Med. 2018 Oct 30;:

Authors: Shadiack E, Jouett N, van den Raadt A, Liganor R, Watters J, Hensel K, Smith M

Abstract
OBJECTIVES: It is unclear whether osteopathic manipulative treatment (OMT) affects gastric myoelectric activity (GMA), an index of gastric motility. We hypothesized that OMT significantly alters power spectral density (PSD) analyses of electrogastrography (EGG) recordings, an index of GMA, compared with time control OMT.
DESIGN: GMA data were obtained from nine subjects before and after OMT and time control on separate days in a cross-over design. Fifteen-minute EGG recordings were obtained before and after each intervention and after a water challenge (WC). Percent power in the normogastric range (PPN) was estimated from PSD analyses. Absolute percent change of PPN and dominant frequency (DF) from baseline to postintervention and baseline to post-WC was computed and compared using two-way repeated-measures ANOVA.
RESULTS: OMT altered PPN versus time control (time control: 5.3% ± 1.2%; OMT: 24.5% ± 4.5%; p = 0.015). WC altered PPN compared with time control (post-time control ΔPPN: 5.3% ± 1.2%; post-drink ΔPPN: 30.3% ± 7.2%; p < 0.01). However, WC did not alter PPN with prior OMT treatment (post-OMT ΔPPN: 24.5% ± 4.5%; post-WC ΔPPN: 19.4% ± 5.6%; p = 0.47). Nevertheless, OMT reduced the rate of change for DF compared with time control (WC post-time control: 37.9% ± 7.4%; WC post-OMT: 20.0% ± 5.9%; p = 0.02).
CONCLUSIONS: We conclude that (1) OMT significantly alters GMA compared with time control and that (2) OMT reduces the rate of change in the frequency response to WC within the normal frequency range of 2-4 cycles per minute, indicating a physiological effect.

PMID: 30376351 [PubMed - as supplied by publisher]

Clinical Outcomes for Diabetic Foot Ulcers Treated with Clostridial Collagenase Ointment or with a Product Containing Silver.

Wed, 10/31/2018 - 05:16
Related Articles

Clinical Outcomes for Diabetic Foot Ulcers Treated with Clostridial Collagenase Ointment or with a Product Containing Silver.

Adv Wound Care (New Rochelle). 2018 Oct 01;7(10):339-348

Authors: Motley TA, Caporusso JM, Lange DL, Eichelkraut RA, Cargill DI, Dickerson JE

Abstract
Objective: To compare outcomes of diabetic foot ulcers (DFUs) treated with clostridial collagenase ointment (CCO) or silver-containing products, both in combination with sharp debridement as needed. Approach: One hundred two subjects with qualifying DFUs were randomized to daily treatment with either CCO or a silver-containing product for 6 weeks followed by a 4 -week follow-up period. The primary outcome was the mean percent reduction in DFU area. A secondary outcome was the incidence of ulcer infections between groups. Results: At the end of treatment, the mean percent reduction in area from baseline of DFUs treated with CCO was 62% (p < 0.0001) and with silver was 40% (p < 0.0001). The difference between groups-22%-was not statistically significant (p = 0.071). Among ulcers closed by the end of treatment, the mean time to closure was 31.1 ± 9.0 days versus 37.1 ± 7.7 days, respectively (not statistically significant). There was a numerically greater incidence of target ulcer infections in the silver group (11, 21.6%) than in the CCO group (5, 9.8%; p = 0.208). No clinically relevant safety signals were identified in either group. Innovation: CCO treatment can progress a wound toward closure. Ulcer infection prophylaxis may not be sacrificed when treating DFU with CCO in lieu of silver-containing products. Conclusion: Both CCO and silver-containing products promote significant reduction in DFU area over 6 weeks of treatment with no clinically relevant safety concerns. Mean percent reduction in lesion area was numerically (22%) but not significantly greater with CCO compared to silver, as was time to ulcer closure, with an incidence of ulcer infection at least as low as for silver-containing products.

PMID: 30374419 [PubMed]

Reconstituted HDL: Drug Delivery Platform for Overcoming Biological Barriers to Cancer Therapy.

Wed, 10/31/2018 - 05:16
Related Articles

Reconstituted HDL: Drug Delivery Platform for Overcoming Biological Barriers to Cancer Therapy.

Front Pharmacol. 2018;9:1154

Authors: Raut S, Mooberry L, Sabnis N, Garud A, Dossou AS, Lacko A

Abstract
Drug delivery to malignant tumors is limited by several factors, including off-target toxicities and suboptimal benefits to cancer patient. Major research efforts have been directed toward developing novel technologies involving nanoparticles (NPs) to overcome these challenges. Major obstacles, however, including, opsonization, transport across cancer cell membranes, multidrug-resistant proteins, and endosomal sequestration of the therapeutic agent continue to limit the efficiency of cancer chemotherapy. Lipoprotein-based drug delivery technology, "nature's drug delivery system," while exhibits highly desirable characteristics, it still needs substantial investment from private/government stakeholders to promote its eventual advance to the bedside. Consequently, this review focuses specifically on the synthetic (reconstituted) high-density lipoprotein rHDL NPs, evaluating their potential to overcome specific biological barriers and the challenges of translation toward clinical utilization and commercialization. This highly robust drug transport system provides site-specific, tumor-selective delivery of anti-cancer agents while reducing harmful off-target effects. Utilizing rHDL NPs for anti-cancer therapeutics and tumor imaging revolutionizes the future strategy for the management of a broad range of cancers and other diseases.

PMID: 30374303 [PubMed]

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

Wed, 10/31/2018 - 05:16
Related Articles

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 Oct 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 - in process]

Cataract Preventive Role of Isolated Phytoconstituents: Findings from a Decade of Research.

Wed, 10/31/2018 - 05:16
Related Articles

Cataract Preventive Role of Isolated Phytoconstituents: Findings from a Decade of Research.

Nutrients. 2018 Oct 26;10(11):

Authors: Lim V, Schneider E, Wu H, Pang IH

Abstract
Cataract is an eye disease with clouding of the eye lens leading to disrupted vision, which often develops slowly and causes blurriness of the eyesight. Although the restoration of the vision in people with cataract is conducted through surgery, the costs and risks remain an issue. Botanical drugs have been evaluated for their potential efficacies in reducing cataract formation decades ago and major active phytoconstituents were isolated from the plant extracts. The aim of this review is to find effective phytoconstituents in cataract treatments in vitro, ex vivo, and in vivo. A literature search was synthesized from the databases of Pubmed, Science Direct, Google Scholar, Web of Science, and Scopus using different combinations of keywords. Selection of all manuscripts were based on inclusion and exclusion criteria together with analysis of publication year, plant species, isolated phytoconstituents, and evaluated cataract activities. Scientists have focused their attention not only for anti-cataract activity in vitro, but also in ex vivo and in vivo from the review of active phytoconstituents in medicinal plants. In our present review, we identified 58 active phytoconstituents with strong anti-cataract effects at in vitro and ex vivo with lack of in vivo studies. Considering the benefits of anti-cataract activities require critical evaluation, more in vivo and clinical trials need to be conducted to increase our understanding on the possible mechanisms of action and the therapeutic effects.

PMID: 30373159 [PubMed - in process]

An In Vitro Oxygen-Glucose Deprivation Model for Studying Ischemia-Reperfusion Injury of Neuronal Cells.

Wed, 10/31/2018 - 05:16
Related Articles

An In Vitro Oxygen-Glucose Deprivation Model for Studying Ischemia-Reperfusion Injury of Neuronal Cells.

Methods Mol Biol. 2018;1717:229-235

Authors: Ryou MG, Mallet RT

Abstract
Ischemia-reperfusion syndromes of the heart and brain are the leading cause of death and long-term disability worldwide. Development of effective treatments for myocardial infarction, stroke, cardiac arrest and their sequelae requires preclinical models that replicate specific features of ischemia-reperfusion. The complexities of intact animals, including the integrated function of organ systems, autonomic innervation and endocrine factors, often preclude detailed study of specific components of ischemia-reperfusion injury cascades. Ischemia represents the interruption of metabolic fuel and oxygen delivery to support cellular oxidative metabolism; reintroduction of oxygen upon reperfusion of ischemic tissue triggers oxidative stress which initiates the reperfusion injury cascade culminating in injury and death of cells and tissues. Thus, cultured cells subjected to hypoxia, fuel deprivation and reoxygenation replicate the cardinal features of ischemia-reperfusion, while accommodating interventions such as siRNA suppression of specific genes and pharmacological activation or inhibition of signaling cascades that are not feasible in more complex preparations, especially intact animals. This chapter describes an in vitro OGD-reoxygenation cell culture model, an excellent preparation to examine the cellular mechanisms mediating ischemia-reperfusion injury and/or cytoprotection.

PMID: 29468596 [PubMed - indexed for MEDLINE]

Sex-related differences in oxidative stress and neurodegeneration.

Wed, 10/31/2018 - 05:16
Related Articles

Sex-related differences in oxidative stress and neurodegeneration.

Steroids. 2018 05;133:21-27

Authors: Tenkorang MA, Snyder B, Cunningham RL

Abstract
Oxidative stress has been implicated in a number of neurodegenerative diseases spanning various fields of research. Reactive oxygen species can be beneficial or harmful, depending on their concentration. High levels of reactive oxygen species can lead to oxidative stress, which is an imbalance between free radicals and antioxidants. Increased oxidative stress can result in cell loss. Interestingly, sex differences have been observed in oxidative stress generation, which may underlie sex differences observed in neurodegenerative disorders. An enhanced knowledge of the role of sex hormones on oxidative stress signaling and cell loss can yield valuable information, leading to sex-based mechanistic approaches to neurodegeneration.

PMID: 29274405 [PubMed - indexed for MEDLINE]

Sex differences in sleep apnea and comorbid neurodegenerative diseases.

Wed, 10/31/2018 - 05:16
Related Articles

Sex differences in sleep apnea and comorbid neurodegenerative diseases.

Steroids. 2018 05;133:28-33

Authors: Snyder B, Cunningham RL

Abstract
Sleep apnea is a disorder, which increasingly affects people worldwide. Whether the associated hypoxic events during sleep are central or obstructive in origin, the end result is excessive daytime sleepiness and an increased risk for several comorbidities, such as cardiovascular and neurodegenerative disorders. Sleep apnea is diagnosed more frequently in men than women, suggesting a role of sex hormones in the pathology of the disease. Furthermore, there are sex differences in the development and progression of comorbid diseases associated with sleep apnea. Therefore, treatment of sleep apnea may be clinically relevant for prevention of subsequent sex-specific comorbid disorders. While the impact sleep apnea has on cardiovascular events has been the subject of many research studies, the role of sleep apnea in neurodegeneration is less established. Here we review known risk factors for sleep apnea and the implications of the observed sex differences in this disease. We also summarize the evidence and mechanisms for how sleep apnea may contribute to the onset of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease.

PMID: 29258810 [PubMed - indexed for MEDLINE]

N-terminal truncations in sex steroid receptors and rapid steroid actions.

Wed, 10/31/2018 - 05:16
Related Articles

N-terminal truncations in sex steroid receptors and rapid steroid actions.

Steroids. 2018 05;133:15-20

Authors: Schreihofer DA, Duong P, Cunningham RL

Abstract
Sex steroid receptors act as ligand activated nuclear transcription factors throughout the body, including the brain. However, post-translational modification of these receptors can direct them to extranuclear sites, including the plasma membrane, where they are able to initiate rapid signaling. Because of the conserved domain structure of these receptors, alternative exon splicing can result in proteins with altered nuclear and extranuclear actions. Although much attention has focused on internal and C-terminal splice variants, both estrogen and androgen receptors undergo N-terminal truncations, as well. These truncated proteins not only influence the transcriptional activity of the full-length receptors, but also associate with caveolin and initiate signaling at the plasma membrane. Such actions may have important physiological consequences in neuronal, endothelial, and cancer signaling and cell survival.

PMID: 29104096 [PubMed - indexed for MEDLINE]

The "Warm Zone" Cases: Environmental Monitoring Immediately Outside the Fire Incident Response Arena by Firefighters.

Tue, 10/30/2018 - 05:13
Related Articles

The "Warm Zone" Cases: Environmental Monitoring Immediately Outside the Fire Incident Response Arena by Firefighters.

Saf Health Work. 2018 Sep;9(3):352-355

Authors: Caban-Martinez AJ, Kropa B, Niemczyk N, Moore KJ, Baum J, Solle NS, Sterling DA, Kobetz EN

Abstract
Hazardous work zones (i.e., hot, warm, and cold) are typically established by emergency response teams during hazardous materials (HAZMAT) calls but less consistently for fire responses to segment personnel and response activities in the immediate geographic area around the fire. Despite national guidelines, studies have documented the inconsistent use of respiratory protective equipment by firefighters at the fire scene. In this case-series report, we describe warm zone gas levels using multigas detectors across five independent fire incident responses all occurring in a large South Florida fire department. Multigas detector data collected at each fire response indicate the presence of sustained levels of volatile organic compounds in the "warm zone" of each fire event. These cases suggest that firefighters should not only implement strategies for multigas detector use within the warm zone but also include respiratory protection to provide adequate safety from toxic exposures in the warm zone.

PMID: 30370169 [PubMed]

Using a composite adherence tool to assess ART response and risk factors of poor adherence in pregnant and breastfeeding HIV-positive Cameroonian women at 6 and 12 months after initiating option B.

Fri, 10/26/2018 - 07:56
Related Articles

Using a composite adherence tool to assess ART response and risk factors of poor adherence in pregnant and breastfeeding HIV-positive Cameroonian women at 6 and 12 months after initiating option B.

BMC Pregnancy Childbirth. 2018 Oct 25;18(1):418

Authors: Atanga PN, Ndetan HT, Fon PN, Meriki HD, Muffih TP, Achidi EA, Hoelscher M, Kroidl A

Abstract
BACKGROUND: Antiretroviral therapy (ART) adherence in preventing HIV mother-to-child transmission in association with virological suppression and risk factors of low adherence in the Cameroon's Option B+ programme are poorly understood. We used a composite adherence score (CAS) to determine adherence and risk factors of poor adherence in association with virological treatment response in HIV-positive pregnant and breastfeeding women who remained in care at 6 and 12 months after initiating ART.
METHODS: We prospectively enrolled 268 women after ART initiation between October 2013 and December 2015 from five facilities within the Kumba health district. Adherence at 6 and 12 months were measured using a CAS comprising of a 6-month medication refill record review, a four-item self-reported questionnaires and a 30-day visual analogue scale. Adherence was defined as the sum scores of the three measures and classified as high, moderate and low. Measured adherence levels were compared to virological suppression rates at month 12 and risk factors of poor adherence were determined.
RESULTS: At 6 and 12 months, 217 (81.0%) and 185 (69.0%) women were available for adherence evaluation. Respectively. Of those, 128 (59.0%) and 68 (31.4%) had high or moderate adherence as per the CAS tool at month 6, and 116 (62.7%) and 48 (24.9%) at month 12, respectively. Viral loads were assessed in 165 women at months 12, and 92.7% had viral suppression (< 1000 copies/mL). Viral suppression was seen in 100% of women with high, 89.5% with moderate, and 52.9% with low adherence using the CAS tool. Virological treatment failure was significantly associated with low adherence [OR 7.6, (95%CI, 1.8-30.8)]. Risk factors for low adherence were younger age [aOR 3.8, (95%CI, 1.4-10.6)], primary as compared to higher levels of education [aOR 2.7, (95%CI, 1.4-5.2)] and employment in the informal sector compared to unemployment [aOR 1.9, (95%CI,1.0-3.6)].
CONCLUSIONS: During the first year of Option B+ implementation in Cameroon our novel CAS adherence tool was feasible, and useful to discriminate ART adherence levels which correlated with viral suppression. Younger age, less educated and informal sector employed women may need more attention for optimal adherence to reduce the risk of virological failure.

PMID: 30359239 [PubMed - in process]

Variations of the lung microbiome and immune response in mechanically ventilated surgical patients.

Fri, 10/26/2018 - 07:56
Related Articles

Variations of the lung microbiome and immune response in mechanically ventilated surgical patients.

PLoS One. 2018;13(10):e0205788

Authors: Huebinger RM, Smith AD, Zhang Y, Monson NL, Ireland SJ, Barber RC, Kubasiak JC, Minshall CT, Minei JP, Wolf SE, Allen MS

Abstract
Mechanically ventilated surgical patients have a variety of bacterial flora that are often undetectable by traditional culture methods. The source of infection in many of these patients remains unclear. To address this clinical problem, the microbiome profile and host inflammatory response in bronchoalveolar lavage samples from the surgical intensive care unit were examined relative to clinical pathology diagnoses. The hypothesis was tested that clinical diagnosis of respiratory tract flora were similar to culture positive lavage samples in both microbiome and inflammatory profile. Bronchoalveolar lavage samples were collected in the surgical intensive care unit as standard of care for intubated individuals with a clinical pulmonary infection score of >6 or who were expected to be intubated for >48 hours. Cytokine analysis was conducted with the Bioplex Pro Human Th17 cytokine panel. The microbiome of the samples was sequenced for the 16S rRNA region using the Ion Torrent. Microbiome diversity analysis showed the culture-positive samples had the lowest levels of diversity and culture negative with the highest based upon the Shannon-Wiener index (culture positive: 0.77 ± 0.36, respiratory tract flora: 2.06 ± 0.73, culture negative: 3.97 ± 0.65). Culture-negative samples were not dominated by a single bacterial genera. Lavages classified as respiratory tract flora were more similar to the culture-positive in the microbiome profile. A comparison of cytokine expression between groups showed increased levels of cytokines (IFN-g, IL-17F, IL-1B, IL-31, TNF-a) in culture-positive and respiratory tract flora groups. Culture-positive samples exhibited a more robust immune response and reduced diversity of bacterial genera. Lower cytokine levels in culture-negative samples, despite a greater number of bacterial species, suggest a resident nonpathogenic bacterial community may be indicative of a normal pulmonary environment. Respiratory tract flora samples were most similar to the culture-positive samples and may warrant classification as culture-positive when considering clinical treatment.

PMID: 30356313 [PubMed - in process]

CRHR2 (Corticotropin-Releasing Hormone Receptor 2) in the Nucleus of the Solitary Tract Contributes to Intermittent Hypoxia-Induced Hypertension.

Fri, 10/26/2018 - 07:56
Related Articles

CRHR2 (Corticotropin-Releasing Hormone Receptor 2) in the Nucleus of the Solitary Tract Contributes to Intermittent Hypoxia-Induced Hypertension.

Hypertension. 2018 Oct;72(4):994-1001

Authors: Wang LA, Nguyen DH, Mifflin SW

Abstract
This study tested the hypothesis that CRHRs (corticotropin-releasing hormone receptors) in the nucleus of the solitary tract (NTS) contribute to the hypertension induced by intermittent hypoxia (IH) exposure in rats. Initial studies using in situ hybridization revealed low mRNA level of CRHR1 (CRH type 1 receptor) but high mRNA level of CRHR2 (CRH type 2 receptor) in the NTS. Calcium imaging studies on NTS slice preparations using Fura-2-acetoxymethyl ester demonstrated that CRH induced a transient increase of intracellular calcium level. The CRH-induced calcium response was reproduced in the presence of TTX (tetrodotoxin) but was abolished by depletion of extracellular calcium or by the L-type calcium channel blocker Nifedipine. The CRH-induced calcium influx was attenuated by the CRHR2 antagonist K41498 but not by the CRHR1 antagonist NBI-35 965. Calcium influx can be induced by the CRHR2 agonist Urocortin II but not by the CRHR1 agonist Stressin 1. IH exposure did not affect CRHR1 mRNA level but significantly decreased CRHR2 mRNA level and the CRH-induced calcium influx in the NTS. Further in vivo studies showed that intra-fourth ventricle infusion of K41498 did not affect the basal blood pressure but significantly attenuated the IH-induced hypertension; intra-fourth ventricle infusion of Urocortin II significantly increased basal blood pressure and exacerbated the IH-induced hypertension. Collectively, these results suggest that CRHR2 in the NTS contributes to the IH-induced hypertension; downregulation of CRHR2 and CRHR2-mediated calcium influx in the NTS may serve as an adaptive response to protect against the IH-induced hypertension.

PMID: 30354709 [PubMed - in process]

2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) in systemic lupus erythematosus and cancer.

Tue, 10/23/2018 - 07:45
Related Articles

2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) in systemic lupus erythematosus and cancer.

Clin Immunol. 2018 Oct 19;:

Authors: Malaer JD, Marrufo AM, Mathew PA

Abstract
Signaling Lymphocyte Activation Molecule (SLAM) family receptors are expressed on different types of hematopoietic cells and play important role in immune regulation in health and disease. 2B4 (CD244, SLAMF4) and CS1 (CD319, CRACC, SLAMF7) were originally identified as NK cell receptors regulating NK cell cytolytic activity. 2B4 is expressed on all NK cells, a subpopulation of T cells, monocytes and basophils. Unlike other activating and inhibitory receptors, 2B4 (CD244) interaction with its ligand CD48 has been shown to mediate both activating and inhibitory functions. Defective signaling via 2B4 due to mutations in signaling adaptor SAP contributes to X-linked lymphoproliferative Disease (XLP). Expression of 2B4 and CS1 are altered in systemic lupus erythematosus (SLE). CS1 is overexpressed in multiple myeloma (MM) and anti-CS1 mab (Elotuzumab/Empliciti) has been approved by FDA as a breakthrough drug for treatment for MM patients. CAR -T cells or CAR- NK cells containing full length CS1 or the signaling domain of 2B4 with TCR-ζ have shown promising results to treat cancer and autoimmune diseases.

PMID: 30347240 [PubMed - as supplied by publisher]

Predicted activity of UGT2B7, ABCB1, OPRM1, and COMT using full-gene haplotypes and their association with the CYP2D6-inferred metabolizer phenotype.

Tue, 10/23/2018 - 07:45
Related Articles

Predicted activity of UGT2B7, ABCB1, OPRM1, and COMT using full-gene haplotypes and their association with the CYP2D6-inferred metabolizer phenotype.

Forensic Sci Int Genet. 2018 03;33:48-58

Authors: Wendt FR, Sajantila A, Budowle B

Abstract
The pharmacogene, CYP2D6, is commonly used to infer metabolizer phenotype of many marketed drugs and endogenous toxins in ante- and post-mortem patients but only represents the efficiency of phase 1 metabolism. Downstream metabolic enzymes encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable individual response to drugs due to their activity at different stages of the tramadol ADME (absorption, distribution, metabolism, and excretion) process. While commonly studied as single genes using targeted genotyping approaches, a more comprehensive tramadol metabolism profile has not been evaluated. 1000 Genomes Project data for UGT2B7, ABCB1, OPRM1, and COMT were used to characterize full-gene haplotypes and their effect on protein function using in-house excel-based workbooks, PopART, and TreeView. Population genetic summary statistics and intergenic analyses associated these haplotypes with full-gene CYP2D6-inferred metabolizer phenotype. The findings suggest that UGT2B7, ABCB1, OPRM1, and COMT may contribute to predicted metabolizer phenotype as opposed to relying solely on CYP2D6.

PMID: 29190510 [PubMed - indexed for MEDLINE]

#drunktwitter: Examining the relations between alcohol-related Twitter content and alcohol willingness and use among underage young adults.

Mon, 10/22/2018 - 07:40
Related Articles

#drunktwitter: Examining the relations between alcohol-related Twitter content and alcohol willingness and use among underage young adults.

Drug Alcohol Depend. 2018 Oct 04;193:75-82

Authors: Litt DM, Lewis MA, Spiro ES, Aulck L, Waldron KA, Head-Corliss MK, Swanson A

Abstract
PURPOSE: Despite the importance of social networking sites on young adult alcohol use, few studies have examined Twitter as a conduit for sharing drinking behavior. However, this work generally uses random samples of tweets and thus cannot determine the extent to which Tweets correspond with self-reported drinking cognitions or behaviors. The primary aims of the present study were to (1) document basic patterns of alcohol-related Twitter activity in a subsample of young adult drinkers, and (2) examine whether willingness to drink, alcohol use, and negative consequences are associated with alcohol-related tweeting behavior.
METHODS: 186 young adults age 18-20 completed an online survey and provided Twitter handle information. From these participants, a random sample of 5000 Tweets was coded by a trained team to determine whether tweets were related to alcohol use or not. Ordinary least squares regression analyses were conducted to determine whether the proportion of alcohol-related Tweets is associated with self-reported alcohol use willingness, behaviors, and negative consequences.
RESULTS: Results indicated that not only are alcohol-related tweets common among young adults, but that the proportion of one's overall tweets that are related to alcohol is significantly associated with willingness to drink, alcohol use, and negative consequences.
CONCLUSIONS: The results of this study are an important step to understanding how digital behavior (e.g., posting about alcohol on Twitter) is related to an individual's self-reported drinking cognitions, alcohol use, and negative consequences and has implications for the way Twitter data can be used for public health surveillance and interventions.

PMID: 30343237 [PubMed - as supplied by publisher]

Assessment of impact of DNA extraction methods on analysis of human remain samples on massively parallel sequencing success.

Sun, 10/21/2018 - 07:36
Related Articles

Assessment of impact of DNA extraction methods on analysis of human remain samples on massively parallel sequencing success.

Int J Legal Med. 2018 Oct 19;:

Authors: Zeng X, Elwick K, Mayes C, Takahashi M, King JL, Gangitano D, Budowle B, Hughes-Stamm S

Abstract
Skeletal remains recovered from missing persons' cases are often exposed to harsh environmental conditions resulting in the DNA being damaged, degraded, and/or the samples containing PCR inhibitors. In this study, the efficacy of common extraction methods was evaluated to remove high levels of PCR inhibitors commonly encountered with human remains, and their downstream compatibility with the two leading sequencing chemistries and platforms for human identification purposes. Blood, hair, and bone samples were spiked with high levels of inhibitors commonly identified in each particular substrate in order to test the efficiency of various DNA extraction methods prior to sequencing. Samples were extracted using three commercial extraction kits (DNA IQ™, DNA Investigator, and PrepFiler® BTA), organic (blood and hair only), and two total demineralization protocols (bone only)). Massively parallel sequencing (MPS) was performed using two different systems: 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™. The overall results showed that all DNA extraction methods were efficient and are fully compatible with both MPS systems. Key performance indicators such as STR and SNP reportable alleles, read depth, and heterozygote balance were comparable for each extraction method. In samples where CE-based STRs yielded partial profiles (bone), MPS-based STRs generated more complete or full profiles. Moreover, MPS panels contain more STR loci than current CE-based STR kits and also include SNPs, which can further increase the power of discrimination obtained from these samples, making MPS a desirable choice for the forensic analysis of such challenging samples.

PMID: 30341454 [PubMed - as supplied by publisher]

Vive la résistance! The Role of Inspiratory Resistance Breathing on Cerebral Blood Flow.

Sat, 10/20/2018 - 07:30
Related Articles

Vive la résistance! The Role of Inspiratory Resistance Breathing on Cerebral Blood Flow.

Respir Physiol Neurobiol. 2018 Oct 16;:

Authors: Rickards CA

Abstract
Prolonging the therapeutic window for treatment is imperative for survival from a multitude of life-threatening events such as hemorrhage, cardiac arrest, and stroke. Inspiratory resistance breathing is a therapeutic approach that augments the reduction in intrathoracic and intracranial pressure during inspiration, facilitating improvements in vital organ perfusion under conditions of ischemia, such as blood loss and cardiac arrest. In this review a series of studies will be presented assessing the role of inspiratory resistance breathing on responses of cerebral blood flow and cerebral tissue oxygenation under conditions of cardiac arrest and blood loss in animal models, and simulated hemorrhage in humans. Knowledge gaps in this field of investigation will be presented, and future research directions will be discussed.

PMID: 30340016 [PubMed - as supplied by publisher]

Pages