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Secreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility.

Recent Research Articles from UNTHSC - Thu, 11/05/2020 - 05:16
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Secreted protein acidic and rich in cysteine (SPARC) knockout mice have greater outflow facility.

PLoS One. 2020;15(11):e0241294

Authors: Yu L, Zheng Y, Liu BJ, Kang MH, Millar JC, Rhee DJ

Abstract
PURPOSE: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that regulates intraocular pressure (IOP) by altering extracellular matrix (ECM) homeostasis within the trabecular meshwork (TM). We hypothesized that the lower IOP previously observed in SPARC -/- mice is due to a greater outflow facility.
METHODS: Mouse outflow facility (Clive) was determined by multiple flow rate infusion, and episcleral venous pressure (Pe) was estimated by manometry. The animals were then euthanized, eliminating aqueous formation rate (Fin) and Pe. The C value was determined again (Cdead) while Fin was reduced to zero. Additional mice were euthanized for immunohistochemistry to analyze ECM components of the TM.
RESULTS: The Clive and Cdead of SPARC -/- mice were 0.014 ± 0.002 μL/min/mmHg and 0.015 ± 0.002 μL/min/mmHg, respectively (p = 0.376, N/S). Compared to the Clive = 0.010 ± 0.002 μL/min/mmHg and Cdead = 0.011 ± 0.002 μL/min/mmHg in the WT mice (p = 0.548, N/S), the Clive and Cdead values for the SPARC -/- mice were higher. Pe values were estimated to be 8.0 ± 0.2 mmHg and 8.3 ± 0.7 mmHg in SPARC -/- and WT mice, respectively (p = 0.304, N/S). Uveoscleral outflow (Fu) was 0.019 ± 0.007 μL/min and 0.022 ± 0.006 μL/min for SPARC -/- and WT mice, respectively (p = 0.561, N/S). Fin was 0.114 ± 0.002 μL/min and 0.120 ± 0.016 μL/min for SPARC -/- and WT mice (p = 0.591, N/S). Immunohistochemistry demonstrated decreases of collagen types IV and VI, fibronectin, laminin, PAI-1, and tenascin-C within the TM of SPARC -/- mice (p < 0.05).
CONCLUSIONS: The lower IOP of SPARC -/- mice is due to greater aqueous humor outflow facility through the conventional pathway. Corresponding changes in several matricellular proteins and ECM structural components were noted in the TM of SPARC -/- mice.

PMID: 33147244 [PubMed - as supplied by publisher]

A Computational Modeling Study of COVID-19 in Bangladesh.

Recent Research Articles from UNTHSC - Thu, 11/05/2020 - 05:16
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A Computational Modeling Study of COVID-19 in Bangladesh.

Am J Trop Med Hyg. 2020 Nov 02;:

Authors: Khan IM, Haque U, Kaisar S, Rahman MS

Abstract
The COVID-19 pandemic has spread globally. Only three cases in Bangladesh were reported on March 8, 2020. Here, we aim to predict the epidemic progression for 1 year under different scenarios in Bangladesh. We extracted the number of daily confirmed cases from March 8 to July 20, 2020. We considered the suspected-infected-removed (SIR) model and performed a maximum likelihood-based grid search to determine the removal rate (ɣ). The transmission was modeled as a stochastic random walk process, and sequential Monte Carlo simulation was run 100 times with bootstrap fits to infer the transmission rate (β) and R t. According to the simulation, the (real) peak daily incidence of 3,600 would be followed by a steady decline, reaching below 1,000 in late January 2021. Thus, the model predicted that there would still be more than 300 cases/day even after a year. However, with proper interventions, a much steeper decline would be achieved following the peak. If we apply a combined (0.8β, 1.2ɣ) intervention, there would be less than 100 cases by mid-October, only around five odd cases at the beginning of the year 2021, and zero cases in early March 2021. The predicted total number of deaths (in status quo) after 1 year would be 8,533 which would reduce to 3,577 if combined (0.8β, 1.2ɣ) intervention is applied. We have also predicted the ideal number of tests that Bangladesh should perform and based on that redid the whole simulation. The outcome, though worse, would be manageable with interventions according to the simulation.

PMID: 33146109 [PubMed - as supplied by publisher]

Prevalence of Pulmonary Embolism in COVID-19: a Pooled Analysis.

Recent Research Articles from UNTHSC - Thu, 11/05/2020 - 05:16
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Prevalence of Pulmonary Embolism in COVID-19: a Pooled Analysis.

SN Compr Clin Med. 2020 Oct 28;:1-4

Authors: Desai R, Gandhi Z, Singh S, Sachdeva S, Manaktala P, Savani S, Desai V, Sachdeva R, Kumar G

Abstract
There remains a high risk of thrombosis in patients affected by the SARS-CoV-2 virus and recent reports have shown pulmonary embolism (PE) as a cause of sudden death in these patients. However, the pooled rate of this deadly and frequently underdiagnosed condition among COVID-19 patients remains largely unknown. Given the frequency with which pulmonary embolism has been reported as a fatal complication of severe coronavirus disease, we sought to ascertain the actual prevalence of this event in COVID-19 patients. Using PubMed/Medline, EMBASE, and SCOPUS, a thorough literature search was performed to identify the studies reporting rate of PE among COVID-19. Random effects models were obtained to perform a meta-analysis, and I 2 statistics were used to measure inter-study heterogeneity. Among 3066 COVID-19 patients included from 9 studies, the pooled prevalence of PE was 15.8% (95% CI (6.0-28.8%), I 2 = 98%). The pooled rate in younger cohort (age < 65 years) showed a higher prevalence of 20.5% (95% CI (17.6-24.8%)) as compared to studies including relatively older cohort (age > 65 years) showing 14.3% (95% CI (2.9-30.1%)) (p < 0.05). Single-center studies showed a prevalence of 12.9% (95% CI 1.0-30.2%), while that of multicenter studies was 19.5% (95% CI 14.9-25.2%) (p < 0.05). Pulmonary embolism is a common complication of severe coronavirus disease and a high degree of clinical suspicion for its diagnosis should be maintained in critically ill patients.

PMID: 33145478 [PubMed - as supplied by publisher]

Transformation of nonencapsulated Streptococcus pneumoniae during systemic infection.

Recent Research Articles from UNTHSC - Thu, 11/05/2020 - 05:16
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Transformation of nonencapsulated Streptococcus pneumoniae during systemic infection.

Sci Rep. 2020 Nov 03;10(1):18932

Authors: Bradshaw JL, Rafiqullah IM, Robinson DA, McDaniel LS

Abstract
Streptococcus pneumoniae (pneumococcus) is a principal cause of bacterial middle ear infections, pneumonia, and meningitis. Capsule-targeted pneumococcal vaccines have likely contributed to increased carriage of nonencapsulated S. pneumoniae (NESp). Some NESp lineages are associated with highly efficient DNA uptake and transformation frequencies. However, NESp strains lack capsule that may increase disease severity. We tested the hypothesis that NESp could acquire capsule during systemic infection and transform into more virulent pneumococci. We reveal that NESp strains MNZ67 and MNZ41 are highly transformable and resistant to multiple antibiotics. Natural transformation of NESp when co-administered with heat-killed encapsulated strain WU2 in a murine model of systemic infection resulted in encapsulation of NESp and increased virulence during bacteremia. Functional capsule production increased the pathogenic potential of MNZ67 by significantly decreasing complement deposition on the bacterial surface. However, capsule acquisition did not further decrease complement deposition on the relatively highly pathogenic strain MNZ41. Whole genome sequencing of select transformants demonstrated that recombination of up to 56.7 kbp length occurred at the capsule locus, along with additional recombination occurring at distal sites harboring virulence-associated genes. These findings indicate NESp can compensate for lack of capsule production and rapidly evolve into more virulent strains.

PMID: 33144660 [PubMed - in process]

VU0606170, a Selective Slack Channels Inhibitor, Decreases Calcium Oscillations in Cultured Cortical Neurons.

Recent Research Articles from UNTHSC - Thu, 11/05/2020 - 05:16
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VU0606170, a Selective Slack Channels Inhibitor, Decreases Calcium Oscillations in Cultured Cortical Neurons.

ACS Chem Neurosci. 2020 Nov 04;11(21):3658-3671

Authors: Spitznagel BD, Mishra NM, Qunies AM, Prael FJ, Du Y, Kozek KA, Lazarenko RM, Denton JS, Emmitte KA, Weaver CD

Abstract
Malignant migrating partial seizures of infancy is a rare, devastating form of epilepsy most commonly associated with gain-of-function mutations in the potassium channel, Slack. Not only is this condition almost completely pharmacoresistant, there are not even selective drug-like tools available to evaluate whether inhibition of these overactivated, mutant Slack channels may represent a viable path forward toward new antiepileptic therapies. Therefore, we used a high-throughput thallium flux assay to screen a drug-like, 100 000-compound library in search of inhibitors of both wild-type and a disease-associated mutant Slack channel. Using this approach, we discovered VU0606170, a selective Slack channel inhibitor with low micromolar potency. Critically, VU0606170 also proved effective at significantly decreasing the firing rate in overexcited, spontaneously firing cortical neuron cultures. Taken together, our data provide compelling evidence that selective inhibition of Slack channel activity can be achieved with small molecules and that inhibition of Slack channel activity in neurons produces efficacy consistent with an antiepileptic effect. Thus, the identification of VU0606170 provides a much-needed tool for advancing our understanding of the role of the Slack channel in normal physiology and disease as well as its potential as a target for therapeutic intervention.

PMID: 33143429 [PubMed - in process]

Phylogeography of montane dragons could shed light on the history of forests and diversification processes on Sumatra.

Recent Research Articles from UNTHSC - Thu, 11/05/2020 - 05:16
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Phylogeography of montane dragons could shed light on the history of forests and diversification processes on Sumatra.

Mol Phylogenet Evol. 2020 08;149:106840

Authors: Shaney KJ, Maldonado J, Smart U, Thammachoti P, Fujita M, Hamidy A, Kurniawan N, Harvey MB, Smith EN

Abstract
Biogeographical evidence, both, for and against the "regional endemism paradigm" hypothesis has been uncovered across the Greater Sunda Region (Sundaland) of Southeast Asia. Additionally, there are competing hypotheses regarding how Pleistocene forests may have impacted biological patterns and processes in Sumatra. Using montane agamid lizards from Sumatra, we derived and analyzed a phylogenetic dataset, genetic divergence estimates, and contemporary distributional patterns among species. We tested whether (1) Sumatra's highland Draconinae diversification fits the regional endemism paradigm hypothesis and (2) Draconinae phylogeography provides biological evidence for Pleistocene forest extent at various points in history. Our results suggest in situ diversification was the main driver behind montane Draconinae lizard diversification in Sumatra, rejecting the "regional endemism paradigm". Contemporary distribution of endemic species and their genetic relationships may potentially provide biologicalevidence for determining more precise elevational lower limits of montane forests during the Pleistocene epoch. Our data suggests montane forests did not retreat more than 700-750 m during glacial maxima because lower retreating forests would have become interconnected, allowing for widespread dispersal, exchange of gene flow and sympatric distributions contemporarily. To the contrary, our divergence estimates show that cloud forest dragons have been isolated for millions of years, suggesting there may have been a continuous disconnect between some areas, predating the Pleistocene. There may also be other ecological and evolutionary factors that impacted Draconinae distributions, such as competition, making this an excellent system for testing questions regarding montane biogeography. Additionally, we provide the first phylogeny for a wide range of Sundaland agamid species and identify some biogeographic pressures that may have triggered montane Draconinae diversification in Sumatra.

PMID: 32305510 [PubMed - indexed for MEDLINE]

Muscular architecture of the popliteus muscle and the basic science implications.

Recent Research Articles from UNTHSC - Wed, 11/04/2020 - 06:54
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Muscular architecture of the popliteus muscle and the basic science implications.

Knee. 2020 Mar;27(2):308-314

Authors: Wood A, Boren M, Dodgen T, Wagner R, Patterson RM

Abstract
BACKGROUND: The function of the popliteus muscle is largely treated as a static stabilizer and has a lack of basic muscular architectural data to enable study of its dynamic function. A large volume of literature supports its static function and the essential need for reconstruction in the posterolateral knee when injured to restore knee stability.
HYPOTHESIS/PURPOSE: We hypothesize that the popliteus muscle is more significant as a dynamic presence in the knee.
METHODS: A collection of popliteus architectural data was collected from 28 cadaver specimens (mean (SD) 76 years (11)). Physiological cross-sectional area of the popliteus and semimembranosus muscles were calculated from muscle volume and fiber length to power future muscle force prediction models. Posterior knee muscle trajectories were measured with respect to the longitudinal axis of the tibia. A 2-tailed T test was performed.
RESULTS: Significant differences between males and females were found for both the popliteus (p = 1.1E-05) and semimembranosus (p = 2.0E-05) muscle volumes. Significant differences between males and females were also found in PCSA for the popliteus (p = 0.005) and semimembranosus (p = 4.1E-05) muscles. There were no significant differences in fiber length, overall muscle length (with tendon removed), age, and orientation.
CONCLUSION: Further consideration should be given to include the popliteus muscle as a dynamic entity in the knee given its mechanical properties, trajectory, and prior biomechanical evidence showing when and how it is activated. The present study provides data that may shape future directions of research and treatment with regard to posterolateral corner injuries and ligamentous balancing of the knee.

PMID: 31954610 [PubMed - indexed for MEDLINE]

Response to Pazopanib in Patients With Relapsed Osteosarcoma.

Recent Research Articles from UNTHSC - Wed, 11/04/2020 - 06:54
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Response to Pazopanib in Patients With Relapsed Osteosarcoma.

J Pediatr Hematol Oncol. 2020 05;42(4):e254-e257

Authors: Elete KR, Albritton KH, Akers LJ, Basha R, Ray A

Abstract
Axial skeleton primary tumor, metastatic disease at presentation, incomplete surgical resection, and <90% tumor necrosis have all been known to influence prognosis adversely in osteosarcoma. Relapse of osteosarcoma, typically occurring within the first 18 months of therapy, with an incidence rate of 50% is treated with surgery, chemotherapy, and targeted therapy. Here, we discuss 2 patients treated with pazopanib, a multi-tyrosine kinase inhibitor presently approved to treat renal cell carcinoma and soft tissue sarcomas. Case 1 achieved positive response and remains on pazopanib. Case 2 sustained gastrointestinal toxicity requiring suspension of drug, despite achieving stable disease.

PMID: 30531600 [PubMed - indexed for MEDLINE]

Forensic investigation approaches of searching relatives in DNA databases.

Recent Research Articles from UNTHSC - Tue, 11/03/2020 - 05:27
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Forensic investigation approaches of searching relatives in DNA databases.

J Forensic Sci. 2020 Nov 02;:

Authors: Ge J, Budowle B

Abstract
There are several indirect database searching approaches to identify the potential source of a forensic biological sample. These DNA-based approaches are familial searching, Y-STR database searching, and investigative genetic genealogy (IGG). The first two strategies use forensic DNA databases managed by the government, and the latter uses databases managed by private citizens or companies. Each of these search strategies relies on DNA testing to identify relatives of the donor of the crime scene sample, provided such profiles reside in the DNA database(s). All three approaches have been successfully used to identify the donor of biological evidence, which assisted in solving criminal cases or identifying unknown human remains. This paper describes and compares these approaches in terms of genotyping technologies, searching methods, database structures, searching efficiency, data quality, data security, and costs, and raises some potential privacy and legal considerations for further discussion by stakeholders and scientists. Y-STR database searching and IGG are advantageous since they are able to assist in more cases than familial searching readily identifying distant relatives. In contrast, familial searching can be performed more readily with existing laboratory systems. Every country or state may have its own unique economic, technical, cultural, and legal considerations and should decide the best approach(es) to fit those circumstances. Regardless of the approach, the ultimate goal should be the same: generate investigative leads and solve active and cold criminal cases to public safety, under stringent policies and security practices designed to protect the privacy of its citizenry.

PMID: 33136341 [PubMed - as supplied by publisher]

Correlates of STI Testing Among US Young Adults: Opportunities for Prevention.

Recent Research Articles from UNTHSC - Tue, 11/03/2020 - 05:27
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Correlates of STI Testing Among US Young Adults: Opportunities for Prevention.

Prev Sci. 2020 Nov 02;:

Authors: Thompson EL, Griner SB, Galvin AM, Lowery AD, Lewis MA

Abstract
The purpose of this study was to examine sex cognitions and behavioral strategy correlates for chlamydia, gonorrhea, and HIV testing among a national sample of young adults ages 18-20. Young adults (18-20 years) were recruited nationally (n = 1144). The sample was restricted (n = 817) based on inclusion/exclusion criteria for analysis. The outcome variables were gonorrhea, chlamydia, and HIV testing, respectively, in the last 12 months. Covariates included demographic variables, alcohol use, perceived vulnerability, protective behavioral strategies, and sexual behavior in the last 3 months. Adjusted logistic regression models were estimated in SAS 9.4. Approximately 24% of respondents were tested for chlamydia and gonorrhea, and 21% were tested for HIV in the past year. Women were more likely than men to be tested for chlamydia (OR = 1.67, 95% CI 1.13, 2.46) and gonorrhea (OR = 1.55, 95% CI 1.05, 2.28). Persons who were worried about an STI after a sexual encounter and who engaged in casual sex were more than two times as likely to be tested for all three STIs. Similarly, persons who used more non-condom-related protective behavioral strategies were more likely to be tested. Future studies may consider these correlates as potential intervention points for promoting STI testing among young adults.

PMID: 33135130 [PubMed - as supplied by publisher]

Nationwide Trends in Cardiovascular and Cerebrovascular Diseases and Outcomes Among Young Adults (18-39 years) Hospitalized With Comorbid Depression.

Recent Research Articles from UNTHSC - Tue, 11/03/2020 - 05:27
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Nationwide Trends in Cardiovascular and Cerebrovascular Diseases and Outcomes Among Young Adults (18-39 years) Hospitalized With Comorbid Depression.

Cureus. 2020 Sep 24;12(9):e10640

Authors: Desai R, Valaparla VL, Fong HK, Gandhi ZJ, Varma Y, Varma K, Ali Khan MZ, Dawood B, Desai V, Savani S, Doshi R, Mansuri Z

Abstract
Background Modern-day studies that assess temporal trends in cardiovascular and cerebrovascular events (CCE) and outcomes among the young population in the United States (US) with depression remain limited. Methods We compared baseline demographics, comorbidities, all-cause mortality, acute myocardial infarction (AMI), percutaneous coronary interventions (PCI), arrhythmia, stroke, and venous thromboembolism (VTE) among hospitalized young adults (18-39 years) with vs. without depression using the National Inpatient Sample (NIS) from 2007 to 2014. Results A total of 3,575,275 patients out of 63,020,008 hospitalized young adults had comorbid depression (5.7%; median 31 years, 71.3% females). The depressed cohort more often comprised of older, white, male, and non-electively admitted patients. Higher rates of comorbidities, all-cause mortality, PCI, arrhythmia, VTE, and stroke were observed among the depressed cohort. The rising trend in all-cause mortality was observed among the depressed against a stable trend in the non-depressed. The prevalence of AMI remained stable among depressed with consistent upsurges in arrhythmia and stroke. Those with depression had extended hospital stay, higher hospitalization charges, and were more often transferred to other facilities or discharged against advice. Conclusions Rising trends of inpatient mortality, CCE, and higher resource utilization among young adults with depression are concerning and warrants a multidisciplinary approach to improve quality of life and outcomes.

PMID: 33133810 [PubMed]

Two-stage Bayesian GWAS of 9576 individuals identifies SNP regions that are targeted by miRNAs inversely expressed in Alzheimer's and cancer.

Recent Research Articles from UNTHSC - Sat, 10/31/2020 - 06:14
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Two-stage Bayesian GWAS of 9576 individuals identifies SNP regions that are targeted by miRNAs inversely expressed in Alzheimer's and cancer.

Alzheimers Dement. 2020 01;16(1):162-177

Authors: Pathak GA, Zhou Z, Silzer TK, Barber RC, Phillips NR, Alzheimer's Disease Neuroimaging Initiative, Breast and Prostate Cancer Cohort Consortium, and Alzheimer's Disease Genetics Consortium

Abstract
INTRODUCTION: We compared genetic variants between Alzheimer's disease (AD) and two age-related cancers-breast and prostate -to identify single-nucleotide polymorphisms (SNPs) that are associated with inverse comorbidity of AD and cancer.
METHODS: Bayesian multinomial regression was used to compare sex-stratified cases (AD and cancer) against controls in a two-stage study. A ±500 KB region around each replicated hit was imputed and analyzed after merging individuals from the two stages. The microRNAs (miRNAs) that target the genes involving these SNPs were analyzed for miRNA family enrichment.
RESULTS: We identified 137 variants with inverse odds ratios for AD and cancer located on chromosomes 19, 4, and 5. The mapped miRNAs within the network were enriched for miR-17 and miR-515 families.
DISCUSSION: The identified SNPs were rs4298154 (intergenic), within TOMM40/APOE/APOC1, MARK4, CLPTM1, and near the VDAC1/FSTL4 locus. The miRNAs identified in our network have been previously reported to have inverse expression in AD and cancer.

PMID: 31914222 [PubMed - indexed for MEDLINE]

Hydrogen sulphide ameliorates dopamine-induced astrocytic inflammation and neurodegeneration in minimal hepatic encephalopathy.

Recent Research Articles from UNTHSC - Fri, 10/30/2020 - 07:04
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Hydrogen sulphide ameliorates dopamine-induced astrocytic inflammation and neurodegeneration in minimal hepatic encephalopathy.

J Cell Mol Med. 2020 Oct 28;:

Authors: Zhuge W, Zhuge Q, Wang W, Lu X, You R, Liu L, Yu H, Wang J, Wang X, Ye Y, Ding S

Abstract
It has been demonstrated that the action of dopamine (DA) could enhance the production of tumour necrosis factor-α (TNF-α) by astrocytes and potentiate neuronal apoptosis in minimal hepatic encephalopathy (MHE). Recently, sodium hydrosulfide (NaHS) has been found to have neuroprotective properties. Our study addressed whether NaHS could rescue DA-challenged inflammation and apoptosis in neurons to ameliorate memory impairment in MHE rats and in the neuron and astrocyte coculture system. We found that NaHS suppressed DA-induced p65 acetylation, resulting in reduced TNF-α production in astrocytes both in vitro and in vivo. Furthermore, decreased apoptosis was observed in neurons exposed to conditioned medium from DA + NaHS-challenged astrocytes, which was similar to the results obtained in the neurons exposed to TNF-α + NaHS, suggesting a therapeutic effect of NaHS on the suppression of neuronal apoptosis via the reduction of TNF-α level. DA triggered the inactivation of p70 S6 ribosomal kinase (S6K1) and dephosphorylation of Bad, resulting in the disaggregation of Bclxl and Bak and the release of cytochrome c (Cyt. c), and this process could be reversed by NaHS administration. Our work demonstrated that NaHS attenuated DA-induced astrocytic TNF-α release and ameliorated inflammation-induced neuronal apoptosis in MHE. Further research into this approach may uncover future potential therapeutic strategies for MHE.

PMID: 33118312 [PubMed - as supplied by publisher]

Group-Based Trajectory Modeling to Identify Patterns of Adherence and Its Predictors Among Older Adults on Angiotensin-Converting Enzyme Inhibitors (ACEIs)/Angiotensin Receptor Blockers (ARBs).

Recent Research Articles from UNTHSC - Fri, 10/30/2020 - 07:04
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Group-Based Trajectory Modeling to Identify Patterns of Adherence and Its Predictors Among Older Adults on Angiotensin-Converting Enzyme Inhibitors (ACEIs)/Angiotensin Receptor Blockers (ARBs).

Patient Prefer Adherence. 2020;14:1935-1947

Authors: Paranjpe R, Johnson ML, Essien EJ, Barner JC, Serna O, Gallardo E, Majd Z, Fleming ML, Ordonez N, Holstad MM, Abughosh SM

Abstract
Purpose: Commonly prescribed medications among patients with comorbid diabetes mellitus and hypertension include ARBs and ACEIs. However, these medications are associated with suboptimal adherence leading to inadequately controlled blood pressure. Unlike traditional single estimates of proportion of days covered (PDC), group-based trajectory modeling (GBTM) can graphically display the dynamic nature of adherence. The objective of this study was to evaluate adherence using GBTMs among patients prescribed ACEI/ARBs and identify predictors associated with each adherence trajectory.
Patients and Methods: Patients with an ACEI/ARBs prescription were identified between July 2017 and December 2017 using a Medicare Advantage dataset. PDC was used to measure monthly patient adherence during the one-year follow-up period. The monthly PDC was added to a logistic group-based trajectory model to provide distinct patterns of adherence. Further, a multinomial logistic regression was conducted to determine predictors of each identified adherence trajectory. Predictors included various socio-demographic and clinical patient characteristics.
Results: A total of 22,774 patients were included in the analysis and categorized into 4 distinct adherence trajectories: rapid decline (12.6%); adherent (58.5%); gaps in adherence (12.2%), and gradual decline (16.6%). Significant predictors associated with all lower adherence trajectories included 90 days refill, >2 number of other medications, ≥1 hospitalizations, and prevalent users. Significant predictors associated with the rapid decline trajectory included male sex, comorbidities, and increased CMS risk score. Further, significant predictors associated with the gaps in adherence trajectory included increasing age, and comorbidities. Lastly, significant predictors associated with the gradual decline trajectory included increasing age, no health plan subsidy, comorbidities, and increasing CMS risk score.
Conclusion: Identifying various patient characteristics associated with non-adherent trajectories can guide the development of tailored interventions to enhance adherence to ACEI/ARBs.

PMID: 33116437 [PubMed]

Examining the association between oral health status and dementia: A nationwide nested case-controlled study.

Recent Research Articles from UNTHSC - Fri, 10/30/2020 - 07:04
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Examining the association between oral health status and dementia: A nationwide nested case-controlled study.

Exp Biol Med (Maywood). 2020 02;245(3):231-244

Authors: Lin JW, Chang CH, Caffrey JL

PMID: 32039633 [PubMed - indexed for MEDLINE]

Sniffer cells for the detection of neural Angiotensin II in vitro.

Recent Research Articles from UNTHSC - Thu, 10/29/2020 - 05:38
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Sniffer cells for the detection of neural Angiotensin II in vitro.

Sci Rep. 2019 06 19;9(1):8820

Authors: Farmer GE, Amune A, Bachelor ME, Duong P, Yuan JP, Cunningham JT

Abstract
Neuropeptide release in the brain has traditionally been difficult to observe. Existing methods lack temporal and spatial resolution that is consistent with the function and size of neurons. We use cultured "sniffer cells" to improve the temporal and spatial resolution of observing neuropeptide release. Sniffer cells were created by stably transfecting Chinese Hamster Ovary (CHO) cells with plasmids encoding the rat angiotensin type 1a receptor and a genetically encoded Ca2+ sensor. Isolated, cultured sniffer cells showed dose-dependent increases in fluorescence in response to exogenously applied angiotensin II and III, but not other common neurotransmitters. Sniffer cells placed on the median preoptic nucleus (a presumptive site of angiotensin release) displayed spontaneous activity and evoked responses to either electrical or optogenetic stimulation of the subfornical organ. Stable sniffer cell lines could be a viable method for detecting neuropeptide release in vitro, while still being able to distinguish differences in neuropeptide concentration.

PMID: 31217439 [PubMed - indexed for MEDLINE]

FDA Public Workshop Summary: Advancing Animal Models for Antibacterial Drug Development.

Recent Research Articles from UNTHSC - Wed, 10/28/2020 - 07:14

FDA Public Workshop Summary: Advancing Animal Models for Antibacterial Drug Development.

Antimicrob Agents Chemother. 2020 Oct 26;:

Authors: Byrne JM, Waack U, Weinstein EA, Joshi A, Shurland SM, Iarikov D, Bulitta JB, Diep BA, Guina T, Hope WW, Lawrenz MB, Lepak AJ, Luna BM, Miesel L, Phipps AJ, Walsh TJ, Weiss W, Amini T, Farley JJ

Abstract
The U.S. Food and Drug Administration (FDA) hosted a public workshop entitled "Advancing Animal Models for Antibacterial Drug Development" on March 5, 2020. The workshop mainly focused on models of pneumonia caused by Pseudomonas aeruginosa and Acinetobacter baumannii The program included discussions from academic investigators, industry, and U.S. government scientists. The potential use of mouse, rabbit, and pig models for antibacterial drug development was presented and discussed.

PMID: 33106262 [PubMed - as supplied by publisher]

Cholesterol sulfate alters astrocyte metabolism and provides protection against oxidative stress.

Recent Research Articles from UNTHSC - Wed, 10/28/2020 - 07:14
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Cholesterol sulfate alters astrocyte metabolism and provides protection against oxidative stress.

Brain Res. 2019 11 15;1723:146378

Authors: Prah J, Winters A, Chaudhari K, Hersh J, Liu R, Yang SH

Abstract
Cholesterol sulfate (CS) is one of the most important known sterol sulfates in human plasma and it is present as a normal constituent in a variety of human tissues. In both the brain and periphery, CS serves as a substrate for the synthesis of sulfonated adrenal steroids such as pregnenolone sulfate and dehydroepiandrosterone (DHEA) sulfate and as a constituent of many biological membranes including red blood cells where it functions as a stabilizing agent. It also acts as an endogenous regulator of cholesterol synthesis. However, the role of CS in brain metabolism and neurological disorder is unclear. In the current study we investigated the neuroprotective action of CS as well as its role in brain energy metabolism. The neuroprotective effect of CS and its role on cell metabolism were determined in primary astrocyte prepared from the cortex of postnatal day 0-2 C57BL/6 pups and a hippocampal HT-22 cell line using Calcein AM and MTT cell viability assay, flow cytometry, Seahorse extracellular flux analysis, and metabolism assay kits. We found that CS attenuates glutamate and rotenone induced cell death in HT-22 cells, decrease glutamate induced mitochondria membrane potential collapse, and reactive oxygen species production. Additionally, CS activates the Akt/Bcl2 pathway. We observed that CS impacts astrocyte metabolism by increasing mitochondrial phosphorylation, ATP, and glycogen contents. Our study demonstrated that CS modulates brain energy metabolism and its neuroprotective effects might be due to the activation of Akt signaling or its ability to decrease reactive oxygen species production.

PMID: 31425677 [PubMed - indexed for MEDLINE]

Liposomal mupirocin holds promise for systemic treatment of invasive Staphylococcus aureus infections.

Recent Research Articles from UNTHSC - Tue, 10/27/2020 - 05:31
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Liposomal mupirocin holds promise for systemic treatment of invasive Staphylococcus aureus infections.

J Control Release. 2019 12 28;316:292-301

Authors: Goldmann O, Cern A, Müsken M, Rohde M, Weiss W, Barenholz Y, Medina E

Abstract
Staphylococcus aureus is a major cause of severe invasive infections. The increasing incidence of infections caused by antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA), calls for exploration of new approaches to treat these infections. Mupirocin is an antibiotic with a unique mode of action that is active against MRSA, but its clinical use is restricted to topical administration because of its limited plasma stability and rapid degradation to inactive metabolites. Mupirocin was identified by a machine learning approach to be suitable for nano-liposome encapsulation. The computational predictions were verified experimentally and PEGylated nano-liposomal formulation of mupirocin (Nano-mupirocin) was developed. The aim of this study was to investigate the efficacy of this formulation when administered parenterally for the treatment of S. aureus invasive infections. Nano-mupirocin exhibited prolonged half-life of active antibiotic and displayed superior antimicrobial activity against S. aureus than free mupirocin in the presence of plasma. Parenteral application of Nano-mupirocin in a murine model of S. aureus bloodstream infection resulted in improved antibiotic distribution to infected organs and in a superior therapeutic efficacy than the free drug. Parenterally administered Nano-mupirocin was also more active against MRSA than free mupirocin in a neutropenic murine lung infection model. In addition, Nano-mupirocin was very efficiently taken up by S. aureus-infected macrophages via phagocytosis leading to enhanced delivery of mupirocin in the intracellular niche and to a more efficient elimination of intracellular staphylococci. The outcome of this study highlights the potential of Nano-mupirocin for the treatment of invasive MRSA infections and support the further clinical development of this effective therapeutic approach.

PMID: 31715276 [PubMed - indexed for MEDLINE]

Systematic review of student anxiety and performance during objective structured clinical examinations.

Recent Research Articles from UNTHSC - Sat, 10/24/2020 - 07:39

Systematic review of student anxiety and performance during objective structured clinical examinations.

Curr Pharm Teach Learn. 2020 Dec;12(12):1491-1497

Authors: Martin RD, Naziruddin Z

Abstract
INTRODUCTION: Test anxiety is well studied in higher education, but studies primarily concern traditional assessments, such as written examinations. As use of objective structured clinical examination (OSCE) in pharmacy education increases, a closer examination of non-cognitive factors such as test anxiety is warranted. The purpose of this review was to determine the association between OSCE-associated test anxiety with OSCE performance in health professional students.
METHODS: A literature search was conducted to identify peer-reviewed literature concerning test anxiety in health professional students associated with OSCE. Investigators searched for a combination of OSCE-related terms with anxiety-related terms using PubMed. Articles were included if they assessed OSCE-related anxiety by quantitative or qualitative methods. Data extracted from eligible articles included demographic data, type of the anxiety survey, associations between OSCE-related anxiety and performance, and other student-factors associated with OSCE-related anxiety.
RESULTS: The literature search yielded 339 articles. Nine articles met eligibility criteria and were included in the review. Results included students from medical, pharmacy, dental, and nursing professional programs. Anxiety was assessed via multiple scales. Six out of the eight studies assessing the relationship OSCE-related anxiety and OSCE performance found no association between the two measures. Contrary to literature concerning test anxiety in higher education, female gender was not associated with OSCE-related anxiety.
CONCLUSION: OSCE-related anxiety appears to have minimal to no influence on student performance. Future studies should utilize standardized anxiety assessments and should seek to understand anxiety's effects on student wellbeing and burnout.

PMID: 33092780 [PubMed - in process]

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