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: 2 hours 52 min ago

The Long-Acting D3 Partial Agonist MC-25-41 Attenuates Motivation for Cocaine in Sprague-Dawley Rats.

Tue, 07/28/2020 - 05:06
Related Articles

The Long-Acting D3 Partial Agonist MC-25-41 Attenuates Motivation for Cocaine in Sprague-Dawley Rats.

Biomolecules. 2020 Jul 18;10(7):

Authors: Powell GL, Namba MD, Vannan A, Bonadonna JP, Carlson A, Mendoza R, Chen PJ, Luetdke RR, Blass BE, Neisewander JL

Abstract
The dopamine D3 receptor is a prime target for developing treatments for cocaine use disorders (CUDs). In this study, we conducted a pre-clinical investigation of the therapeutic potential of a long-acting, D3 receptor partial agonist, MC-25-41. Male rats were pre-treated with MC-25-41 (vehicle, 1.0, 3.0, 5.6, or 10 mg/kg, intraperitoneal (IP)) five minutes prior to tests of cocaine or sucrose intake on either a progressive ratio schedule of reinforcement or a variable interval 60 s multiple schedule consisting of 4, 15-min components with sucrose or cocaine available in alternating components. A separate cohort of rats was tested on a within-session, dose-reduction procedure to determine the effects of MC-25-41 on demand for cocaine using a behavioral economics analysis. Finally, rats were tested for effects of MC-25-41 on spontaneous and cocaine-induced locomotion. MC-25-41 failed to alter locomotion, but reduced reinforcement rates for both cocaine and sucrose on the low-effort, multiple schedule. However, on the higher-effort, progressive ratio schedule of cocaine reinforcement, MC-25-41 reduced infusions, and active lever presses at doses that did not alter sucrose intake. The behavioral economics analysis showed that MC-25-41 also increased cocaine demand elasticity compared to vehicle, indicating a reduction in consumption as price increases. Together, these results suggest that similar to other D3-selective antagonists and partial agonists, MC-25-41 reduces motivation for cocaine under conditions of high cost but has the added advantage of a long half-life (>10 h). These findings suggest that MC-25-41 may be a suitable pre-clinical lead compound for development of medications to treat CUDs.

PMID: 32708461 [PubMed - in process]

Work System and Process Designs for Community Pharmacy-Medical Clinic Partnerships to Improve Retention in Care, Antiretroviral Adherence, and Viral Suppression in Persons with HIV.

Tue, 07/28/2020 - 05:06
Related Articles

Work System and Process Designs for Community Pharmacy-Medical Clinic Partnerships to Improve Retention in Care, Antiretroviral Adherence, and Viral Suppression in Persons with HIV.

Pharmacy (Basel). 2020 Jul 22;8(3):

Authors: Schommer JC, Garza OW, Taitel MS, Akinbosoye OE, Suzuki S, Clay PG

Abstract
The objective of this project was to collect and analyze information about work systems and processes that community pharmacy-medical clinic partnerships used for implementing the Patient-Centered HIV Care Model (PCHCM). Paired collaborations of 10 Walgreens community pharmacies and 10 medical clinics were formed in 10 cities located throughout the United States that had relatively high HIV prevalence rates and existing Walgreens HIV Centers of Excellence. Patient service provision data and most significant change stories were collected from key informants at each of the clinic and pharmacy sites over an 8 week period in 2016 and through in-depth phone interviews. Written notes were reviewed by two authors (J.C.S. and O.W.G.) and analyzed using the most significant change technique. The findings showed that half of the partnerships (n = 5) were unable to fully engage in service implementation due to external factors or severe staff turnover during the project period. The other half of the partnerships (n = 5) were able to engage in service implementation, with the most impactful changes being related to strong patient care systems, having a point person at the clinic who served as a connector between sites, and having pharmacists integrated fully into the health care team.

PMID: 32707940 [PubMed]

Mortality association between obesity and pneumonia using a dual restricted cohort model.

Tue, 07/28/2020 - 05:06
Related Articles

Mortality association between obesity and pneumonia using a dual restricted cohort model.

Obes Res Clin Pract. 2019 Nov - Dec;13(6):561-570

Authors: Wang H, Lee CC, Chou EH, Hsu WT, Robinson RD, Su KY, Kirby JJ, Hassani D

Abstract
BACKGROUND: An obesity survival paradox has been reported among obese patients with pneumonia.
AIMS: To determine the impact of obesity on pneumonia outcomes and analyze the correlation between in-hospital all-cause mortality and obesity among patients with pneumonia.
METHODS: The United States Nationwide Readmissions Database (NRD) was retrospectively analyzed for patients with pneumonia from 2013 to 2014. We used a step-wise restricted and propensity score matching cohort model (dual model) to compare mortality rates and other outcomes among pneumonia patients based on BMI. Mortality was calculated by a Cox proportional hazard model, adjusted for potential confounders with propensity score matched analysis.
RESULTS: A total of 70,886,775 patients were registered in NRD during the study period. Of these, 7,786,913 patients (11.0%) were considered obese and 1,652,456 patients (2.3%) were admitted to the hospital with pneumonia. Based on the step-wise restricted cohort model, the hazard ratio comparing the mortality rates among obese pneumonia patients to mortality rates among normal BMI pneumonia patients was 0.75 (95% CI 0.60-0.94). The propensity score matched analysis estimated a hazard rate of 0.84 (95% CI 0.79-0.90) and the hazard ratio estimated from the dual model was 0.82 (95% CI 0.63-1.07).
CONCLUSIONS: With the application of a dual model, there appears to be no significant difference in mortality of obese patients with pneumonia compared to normal BMI patients with pneumonia.

PMID: 31635969 [PubMed - indexed for MEDLINE]

The ADEP Biosynthetic Gene Cluster in Streptomyces hawaiiensis NRRL 15010 Reveals an Accessory clpP Gene as a Novel Antibiotic Resistance Factor.

Tue, 07/28/2020 - 05:06
Related Articles

The ADEP Biosynthetic Gene Cluster in Streptomyces hawaiiensis NRRL 15010 Reveals an Accessory clpP Gene as a Novel Antibiotic Resistance Factor.

Appl Environ Microbiol. 2019 10 15;85(20):

Authors: Thomy D, Culp E, Adamek M, Cheng EY, Ziemert N, Wright GD, Sass P, Brötz-Oesterhelt H

Abstract
The increasing threat posed by multiresistant bacterial pathogens necessitates the discovery of novel antibacterials with unprecedented modes of action. ADEP1, a natural compound produced by Streptomyces hawaiiensis NRRL 15010, is the prototype for a new class of acyldepsipeptide (ADEP) antibiotics. ADEP antibiotics deregulate the proteolytic core ClpP of the bacterial caseinolytic protease, thereby exhibiting potent antibacterial activity against Gram-positive bacteria, including multiresistant pathogens. ADEP1 and derivatives, here collectively called ADEP, have been previously investigated for their antibiotic potency against different species, structure-activity relationship, and mechanism of action; however, knowledge on the biosynthesis of the natural compound and producer self-resistance have remained elusive. In this study, we identified and analyzed the ADEP biosynthetic gene cluster in S. hawaiiensis NRRL 15010, which comprises two NRPSs, genes necessary for the biosynthesis of (4S,2R)-4-methylproline, and a type II polyketide synthase (PKS) for the assembly of highly reduced polyenes. While no resistance factor could be identified within the gene cluster itself, we discovered an additional clpP homologous gene (named clpP ADEP) located further downstream of the biosynthetic genes, separated from the biosynthetic gene cluster by several transposable elements. Heterologous expression of ClpPADEP in three ADEP-sensitive Streptomyces species proved its role in conferring ADEP resistance, thereby revealing a novel type of antibiotic resistance determinant.IMPORTANCE Antibiotic acyldepsipeptides (ADEPs) represent a promising new class of potent antibiotics and, at the same time, are valuable tools to study the molecular functioning of their target, ClpP, the proteolytic core of the bacterial caseinolytic protease. Here, we present a straightforward purification procedure for ADEP1 that yields substantial amounts of the pure compound in a time- and cost-efficient manner, which is a prerequisite to conveniently study the antimicrobial effects of ADEP and the operating mode of bacterial ClpP machineries in diverse bacteria. Identification and characterization of the ADEP biosynthetic gene cluster in Streptomyces hawaiiensis NRRL 15010 enables future bioinformatics screenings for similar gene clusters and/or subclusters to find novel natural compounds with specific substructures. Most strikingly, we identified a cluster-associated clpP homolog (named clpP ADEP) as an ADEP resistance gene. ClpPADEP constitutes a novel bacterial resistance factor that alone is necessary and sufficient to confer high-level ADEP resistance to Streptomyces across species.

PMID: 31399403 [PubMed - indexed for MEDLINE]

Population Pharmacokinetics of Pemetrexed in Adult Non-Small Cell Lung Cancer in Indian Patients.

Tue, 07/28/2020 - 05:06
Related Articles

Population Pharmacokinetics of Pemetrexed in Adult Non-Small Cell Lung Cancer in Indian Patients.

J Clin Pharmacol. 2019 09;59(9):1216-1224

Authors: Srinivasan M, Chaturvedula A, Fossler MJ, Patil A, Gota V, Prabhash K

Abstract
The objective of the study was to develop a population pharmacokinetic model of pemetrexed and identify factors contributing to variability in exposure in Indian patients. Plasma samples were obtained from a cohort of 85 patients following 500 mg/m2 intravenous infusion and population pharmacokinetic analysis was performed using NONMEM (version 7.3.0). The stochastic approximation expectation maximization method was used to estimate parameters. The full covariate model approach was used by specifying clinically meaningful covariates a priori. Credible intervals obtained using Markov chain Monte Carlo Bayesian analysis were used to reduce the full covariate model by eliminating the covariates whose CI included the null. Model qualification was performed using visual predictive check and bootstrap. The final population parameter estimates and relative standard error for clearance (CL) was 3.3 L/h (10.8), central volume of distribution (V1) was 5.2 L (7.8), peripheral volume of distribution (V2) was 5.9 L (14.5) and intercompartmental clearance (Q) was 6.8 L/h (14.3). A large between-subject variability (50%-108% coefficient of variation) was observed in pharmacokinetic parameters. The percent coefficient of variation for the area under the plasma concentration-time curve from time zero to infinity was 72% and for maximum concentration was 68.25%. Diagnostic plots showed no major bias in the model. The final model included V1, V2, and Q scaled to body surface area raised to a fixed exponent of 1. Creatinine clearance and sex on clearance and albumin on V1 were statistically significant covariates based on Bayesian credible interval. However, traditional bootstrap resulted in a 95% confidence interval of the sex effect parameter including null. Given the size and nonsignificant sex effect in traditional bootstrap, it is considered clinically not significant.

PMID: 30973978 [PubMed - indexed for MEDLINE]

Electronic cigarette explosion and burn injuries, US Emergency Departments 2015-2017.

Tue, 07/28/2020 - 05:06
Related Articles

Electronic cigarette explosion and burn injuries, US Emergency Departments 2015-2017.

Tob Control. 2019 07;28(4):472-474

Authors: Rossheim ME, Livingston MD, Soule EK, Zeraye HA, Thombs DL

Abstract
BACKGROUND: Electronic cigarette (e-cigarette) battery failure can result in explosions and burn injuries. Previous attempts to quantify these events has been limited to compilations of case studies, federal agency reports and media reports. Although e-cigarette explosions and burn injuries are thought to be rare, current surveillance methods likely underestimate actual occurrences.
METHODS: Analyses were conducted on cross-sectional data from the US Consumer Product Safety Commission's (CPSC) National Electronic Injury Surveillance System (NEISS). A keyword search of case narrative text was used to identify e-cigarette-related explosion and burn injuries presenting to US emergency departments from 2015 to 2017. Sampling weights were applied to make conservative national incidence estimates.
RESULTS: From 2015 to 2017, there were an estimated 2035 e-cigarette explosion and burn injuries presenting to US hospital emergency departments (95% CI 1107 to 2964).
CONCLUSIONS: There are more e-cigarette explosion and burn injuries in the USA than estimated in the past reports. Improved surveillance of e-cigarette injuries and regulation of e-cigarette devices is urgently needed. NEISS could be a valuable resource for e-cigarette injury surveillance.

PMID: 30219795 [PubMed - indexed for MEDLINE]

Numt identification and removal with RtN!

Mon, 07/27/2020 - 13:46
Related Articles

Numt identification and removal with RtN!

Bioinformatics. 2020 Jul 24;:

Authors: Woerner AE, Cihlar JC, Smart U, Budowle B

Abstract
MOTIVATION: Assays in mitochondrial genomics rely on accurate read mapping and variant calling. However, there are known and unknown nuclear paralogs that have fundamentally different genetic properties than that of the mitochondrial genome. Such paralogs complicate the interpretation of mitochondrial genome data and confound variant calling.
RESULTS: RtN! was developed to categorize reads from massively parallel sequencing data not based on the expected properties and sequence identities of paralogous Numts, but instead using sequence similarity to a large database of publicly available mitochondrial genomes. RtN! removes low-level sequencing noise and mitochondrial paralogs while not impacting variant calling, while competing methods were shown to remove true variants from mitochondrial mixtures.
AVAILABILITY: https://github.com/Ahhgust/RtN.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID: 32706871 [PubMed - as supplied by publisher]

Nuclear factor-kappa beta signaling is required for transforming growth factor Beta-2 induced ocular hypertension.

Mon, 07/27/2020 - 13:46
Related Articles

Nuclear factor-kappa beta signaling is required for transforming growth factor Beta-2 induced ocular hypertension.

Exp Eye Res. 2020 02;191:107920

Authors: Hernandez H, Roberts AL, McDowell CM

Abstract
A major risk for the development of primary open-angle glaucoma (POAG) is elevated intraocular pressure (IOP). Elevated IOP is caused by increased outflow resistance due in part to excessive extracellular matrix (ECM) deposition in the trabecular meshwork (TM). The role of transforming growth factor beta 2 (TGFβ2) in inducing ECM production is well understood. Recent studies suggest that toll-like receptor 4 (TLR4) plays an important role in fibrogenesis. We have previously described a crosstalk between TGFβ2 and TLR4 in the development of ocular hypertension and glaucomatous TM damage. Nuclear factor-kappa beta (NF-κB) is critical for TLR4 signaling. To determine the transactivation of NF-κB, TM cells were stimulated with cellular fibronectin containing the EDA isoform (cFN-EDA), TGFβ2, or lipopolysaccharide (LPS) in combination with a selective TLR4 inhibitor. cFN-EDA, TGFβ2, and LPS all induced transactivation of NF-κB and inhibition of TLR4 blocked the effect of each treatment paradigm. To evaluate the role of NF-κB in IOP regulation, we utilized our inducible mouse model of ocular hypertension by injection of Ad5.TGFβ2 in mice harboring a mutation in NF-κB and wild-type controls. IOP was measured over time and eyes accessed by immunohistochemistry for the ECM protein FN and the specific FN-EDA isoform. Ad5.TGFβ2 induced ocular hypertension and expression of FN and FN-EDA in wild-type mice, but mutation in NF-κB blocked the effect. These data suggest that NF-κB is necessary for TGFβ2-induced ECM production and ocular hypertension and the transactivation of NF-κB is dependent on both TGFβ2 and TLR4.

PMID: 31923415 [PubMed - indexed for MEDLINE]

Laparoscopic bypass reversal for intractable nausea and vomiting using a circular stapler: a video case report.

Mon, 07/27/2020 - 13:46
Related Articles

Laparoscopic bypass reversal for intractable nausea and vomiting using a circular stapler: a video case report.

Surg Obes Relat Dis. 2019 07;15(7):1226-1228

Authors: Roberts J, Vedantam S

PMID: 31427106 [PubMed - indexed for MEDLINE]

RTN4B-mediated suppression of Sirtuin 2 activity ameliorates β-amyloid pathology and cognitive impairment in Alzheimer's disease mouse model.

Fri, 07/24/2020 - 07:55
Related Articles

RTN4B-mediated suppression of Sirtuin 2 activity ameliorates β-amyloid pathology and cognitive impairment in Alzheimer's disease mouse model.

Aging Cell. 2020 Jul 23;:e13194

Authors: Wang Y, Yang JQ, Hong TT, Sun YH, Huang HL, Chen F, Chen XJ, Chen HY, Dong SS, Cui LL, Yang TL

Abstract
Sirtuin 2 (SIRT2) is an NAD+ dependent deacetylase that is the most abundant sirtuin protein in the brain. Accumulating evidence revealed the role of SIRT2 in a wide range of biological processes and age-related diseases. However, the pivotal mechanism of SIRT2 played in Alzheimer's disease (AD) remains unknown. Here, we report that pharmacological inactivation of SIRT2 has a beneficial effect in AD. The deacetylase inhibitor of SIRT2 rescued the cognitive impairment in amyloid precursor protein/presenilin 1 transgenic mouse (APP/PS1 mouse), and the BACE1 cleavage was weakened to reduce the β-amyloid (Aβ) production in the hippocampus. Moreover, we firstly identified that Reticulon 4B (RTN4B) played a crucial role between SIRT2/BACE1 regulation in AD. RTN4B, as a deacetylation substrate for SIRT2, the deacetylation by SIRT2 drived the ubiquitination and degradation of RTN4B and then the disturbed RTN4B interacted with and influenced the expression of BACE1. When we overexpressed RTN4B in neurons of the hippocampus in the AD mouse model, the abnormal Aβ accumulation and cognitive impairment were ameliorated, consistent with the results of SIRT2 inhibition in vivo. Moreover, we showed that the regulatory effect of SIRT2 on BACE1 is dependent on RTN4B. When RTN4B was knocked down, the effects of SIRT2 inhibition on the BACE1 level, Aβ pathology, and AD-liked behaviors were also blocked. Collectively, we provide evidence that SIRT2 may be a potential target for AD; the new found SIRT2/RTN4B/BACE1 pathological pathway is one of the critical mechanisms for the improvement of SIRT2 on AD.

PMID: 32700357 [PubMed - as supplied by publisher]

NT3P75-2 gene-modified bone mesenchymal stem cells improve neurological function recovery in mouse TBI model.

Fri, 07/24/2020 - 07:55
Related Articles

NT3P75-2 gene-modified bone mesenchymal stem cells improve neurological function recovery in mouse TBI model.

Stem Cell Res Ther. 2019 10 24;10(1):311

Authors: Wu K, Huang D, Zhu C, Kasanga EA, Zhang Y, Yu E, Zhang H, Ni Z, Ye S, Zhang C, Hu J, Zhuge Q, Yang J

Abstract
BACKGROUND: The attainment of extensive neurological function recovery remains the key challenge for the treatment of traumatic brain injury (TBI). Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has been shown to improve neurological function recovery after TBI. However, the survival of BMSCs after transplantation in early-stage TBI is limited, and much is unknown about the mechanisms mediating this neurological function recovery. Secretion of neurotrophic factors, including neurotrophin 3 (NT3), is one of the critical factors mediating BMSC neurological function recovery. Gene mutation of NT3 (NT3P75-2) has been shown to enhance the biological function of NT3 via the reduction of the activation of the P75 signal pathway. Thus, we investigated whether NT3P75-2 gene-modified BMSCs could enhance the survival of BMSCs and further improve neurological function recovery after TBI.
METHODS: The ability of NT3P75-2 induction to improve cell growth rate of NSC-34 and PC12 cells in vitro was first determined. BMSCs were then infected with three different lentiviruses (green fluorescent protein (GFP), GFP-NT3, or GFP-NT3P75-2), which stably express GFP, GFP-NT3, or GFP-NT3P75-2. At 24 h post-TBI induction in mice, GFP-labeled BMSCs were locally transplanted into the lesion site. Immunofluorescence and histopathology were performed at 1, 3, and/or 7 days after transplantation to evaluate the survival of BMSCs as well as the lesion volume. A modified neurological severity scoring system and the rotarod test were chosen to evaluate the functional recovery of the mice. Cell growth rate, glial activation, and signaling pathway analyses were performed to determine the potential mechanisms of NT3P75-2 in functional recovery after TBI.
RESULTS: Overall, NT3P75-2 improved cell growth rate of NSC-34 and PC12 cells in vitro. In addition, NT3P75-2 significantly improved the survival of transplanted BMSCs and neurological function recovery after TBI. Overexpression of NT3P75-2 led to a significant reduction in the activation of glial cells, brain water content, and brain lesion volume after TBI. This was associated with a reduced activation of the p75 neurotrophin receptor (P75NTR) and the c-Jun N-terminal kinase (JNK) signal pathway due to the low affinity of NT3P75-2 for the receptor.
CONCLUSIONS: Taken together, our results demonstrate that administration of NT3P75-2 gene-modified BMSCs dramatically improves neurological function recovery after TBI by increasing the survival of BMSCs and ameliorating the inflammatory environment, providing a new promising treatment strategy for TBI.

PMID: 31651375 [PubMed - indexed for MEDLINE]

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

Fri, 07/24/2020 - 07:55
Related Articles

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

Epilepsy Res. 2019 11;157:106193

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

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

PMID: 31520894 [PubMed - indexed for MEDLINE]

What Does Adolescent Substance Use Look Like During the COVID-19 Pandemic? Examining Changes in Frequency, Social Contexts, and Pandemic-Related Predictors.

Thu, 07/23/2020 - 13:34
Related Articles

What Does Adolescent Substance Use Look Like During the COVID-19 Pandemic? Examining Changes in Frequency, Social Contexts, and Pandemic-Related Predictors.

J Adolesc Health. 2020 Jul 18;:

Authors: Dumas TM, Ellis W, Litt DM

Abstract
PURPOSE: The overarching goal of this study was to provide key information on how adolescents' substance use has changed since the corona virus disease (COVID)-19 pandemic, in addition to key contexts and correlates of substance use during social distancing.
METHODS: Canadian adolescents (n = 1,054, Mage = 16.68, standard deviation = .78) completed an online survey, in which they reported on their frequency of alcohol use, binge drinking, cannabis use, and vaping in the 3 weeks before and directly after social distancing practices had taken effect.
RESULTS: For most substances, the percentage of users decreased; however, the frequency of both alcohol and cannabis use increased. Although the greatest percentage of adolescents was engaging in solitary substance use (49.3%), many were still using substances with peers via technology (31.6%) and, shockingly, even face to face (23.6%). Concerns for how social distancing would affect peer reputation was a significant predictor of face-to-face substance use with friends among adolescents with low self-reported popularity, and a significant predictor of solitary substance use among average and high popularity teens. Finally, adjustment predictors, including depression and fear of the infectivity of COVID-19, predicted using solitary substance use during the pandemic.
CONCLUSIONS: Our results provide preliminary evidence that adolescent substance use, including that which occurs face to face with peers, thereby putting adolescents at risk for contracting COVID-19, may be of particular concern during the pandemic. Further, solitary adolescent substance use during the pandemic, which is associated with poorer mental health and coping, may also be a notable concern worthy of further investigation.

PMID: 32693983 [PubMed - as supplied by publisher]

A single episode of early-life status epilepticus impacts neonatal ultrasonic vocalization behavior in the Fmr1 knockout mouse.

Wed, 07/22/2020 - 05:59

A single episode of early-life status epilepticus impacts neonatal ultrasonic vocalization behavior in the Fmr1 knockout mouse.

Epilepsy Behav. 2020 Jul 18;111:107279

Authors: Huebschman JL, Hodges SL, Reynolds CD, Nolan SO, Lugo JN

Abstract
Fragile X syndrome (FXS) is a genetic disorder caused by a trinucleotide (CGG) expansion mutation in the Fmr1 gene located on the X chromosome. It is characterized by hyperactivity, increased anxiety, repetitive-stereotyped behaviors, and impaired language development. Many children diagnosed with FXS also experience seizures during their lifetime. However, the underlying etiology of the relationship between FXS and epilepsy is not fully understood. Ultrasonic vocalizations (UVs) are one tool that may be used to measure early behavioral changes in mouse pups. In the present study, neonatal UVs were analyzed as a measure of communicative behavior in a mouse model of FXS, both with and without early-life seizures (ELSs). On postnatal day (PD) 10, status epilepticus (SE) was induced via intraperitoneal injections of 0.5% kainic acid (2.0 mg/kg) in male Fmr1 knockout (KO) and wild-type (WT) mice. On PD 12, all pups were temporarily isolated from their dam and UVs were recorded. Significant alterations were found in both spectral and temporal measures across genotype and seizure groups. Early-life seizure experience resulted in a significant increase in the quantity of UVs only in WT animals (p < 0.05). We also found that while there was no difference between genotypes in the total number of vocalizations made, calls produced by Fmr1 KO mice were significantly shorter and had a higher peak frequency compared with WT mice. Overall, these findings support the use of vocalization behavior as an early phenotypic marker and highlight the importance of utilizing double-hit models to better understand comorbid disorders.

PMID: 32693376 [PubMed - as supplied by publisher]

Chitin Analog AVR-25 Prevents Experimental Bronchopulmonary Dysplasia.

Tue, 07/21/2020 - 05:46
Related Articles

Chitin Analog AVR-25 Prevents Experimental Bronchopulmonary Dysplasia.

J Pediatr Intensive Care. 2020 Sep;9(3):225-232

Authors: Das P, Acharya S, Shah D, Agarwal B, Prahaladan V, Bhandari V

Abstract
Infants born extremely preterm are at a high risk of developing bronchopulmonary dysplasia (BPD) which is characterized by large, simplified alveoli, increased inflammation, disrupted and dysregulated vasculogenesis, decreased cell proliferation, and increased cell death in the lungs. Due to lack of specific drug treatments to combat this condition, BPD and its long-term complications have taken a significant toll of healthcare resources. AVR-25, a novel immune modulator experimental compound, was able to partially recover the pulmonary phenotype in the hyperoxia-induced experimental mouse model of BPD. We anticipate that AVR-25 will have therapeutic potential for managing human BPD.

PMID: 32685255 [PubMed]

Pancreatic Cancer: An Emphasis on Current Perspectives in Immunotherapy.

Tue, 07/21/2020 - 05:46
Related Articles

Pancreatic Cancer: An Emphasis on Current Perspectives in Immunotherapy.

Crit Rev Oncog. 2019;24(2):105-118

Authors: Patel K, Siraj S, Smith C, Nair M, Vishwanatha JK, Basha R

Abstract
Pancreatic cancer affects both male and female individuals with higher incidences and death rates among the male population. Detection of this malignancy is delayed due to the lack of symptoms in the early-stage cancer, which makes it extremely difficult to treat. Identifying effective strategies has been a challenge for improving the survival rates in pancreatic cancer patients. Resistance to chemotherapy is often developed in pancreatic cancer treatment. Although many strategies are under clinical trials to target certain markers associated with cancer, immunotherapeutic approaches are currently gaining importance. Immunotherapy for pancreatic cancer is in the limelight after preclinical research showed some promise. Immunotherapy approaches were tested along with other treatment options to enhance the treatment effect. Adoptive cell transfer and immune checkpoint inhibitors are currently in clinical trials. The Food and Drug Administration approved pembrolizumab in a fast-tracked review for advanced pancreatic cancer patients. Pembrolizumab blocks the checkpoint protein, programmed cell death protein 1 (PD-1), on T cells to boost the response of the immune system against cancer cells, thereby shrinking tumors. The recent developments in immunotherapy and the early success in other cancers are encouraging to further test immunotherapy in pancreatic cancer. The combination of pembrolizumab and pelareorep, an isolate of human reovirus, is in phase II clinical study in metastatic disease. Depending on the results of current clinical trials and testing, the strategies in the pipeline are expected to increase the use of immunotherapy in the clinical testing setting. Success in immunotherapy is urgently needed to address the side-effects, treating patients with advanced disease and reducing metastasis for increasing the survival rate in pancreatic cancer patients.

PMID: 31679206 [PubMed - indexed for MEDLINE]

Patients and providers' knowledge, attitudes, and beliefs regarding immediate postpartum long-acting reversible contraception: a systematic review.

Tue, 07/21/2020 - 05:46
Related Articles

Patients and providers' knowledge, attitudes, and beliefs regarding immediate postpartum long-acting reversible contraception: a systematic review.

Women Health. 2020 02;60(2):179-196

Authors: Thompson EL, Vamos CA, Logan RG, Bronson EA, Detman LA, Piepenbrink R, Daley EM, Sappenfield WM

Abstract
The American College of Obstetricians and Gynecologists recommends long-acting reversible contraception (LARC) immediately postpartum for preventing unintended pregnancy. This systematic review identified patients' and providers' knowledge, attitudes, and beliefs regarding immediate postpartum LARC use. Web of Science, Embase, PubMed, PsychInfo, and CINHAL databases (from inception to December 2018) were searched using LARC and immediate postpartum as search terms. The inclusion criteria were observational US studies, peer-reviewed, and English language, and the exclusion criterion was published abstracts only. The search yielded 4140 articles, and 18 articles were included in the final sample. Articles focused on women (n = 6) emphasizing patient preferences about the use of postpartum intrauterine devices (IUDs) and comprised samples of postpartum women. Among articles focused on providers (n = 12), knowledge regarding immediate postpartum LARCs varied. Providers reported lack of training and lack of comfort with regard to counseling and insertion as barriers to providing postpartum IUDs. This review identified literature regarding patient and provider perspectives on immediate postpartum LARC. Future work should ascertain patients' and providers' needs and preferences for integrating LARC counseling as a viable contraception option during the immediate postpartum period, ultimately promoting optimal inter-pregnancy intervals and overall health for women and future offspring.

PMID: 31122167 [PubMed - indexed for MEDLINE]

Analysis of mortality risk following receipt of implantable cardioverter defibrillators in patients with and without heart failure.

Mon, 07/20/2020 - 05:30

Analysis of mortality risk following receipt of implantable cardioverter defibrillators in patients with and without heart failure.

J Cardiol. 2020 Jul 15;:

Authors: Caffrey JL, Wu CK, Chang CH, Lin JW

Abstract
BACKGROUND: Patients covered by the Taiwan National Health Insurance (NHI) program are eligible to receive an implantable cardioverter defibrillator (ICD) if diagnosed with heart failure (HF) or were at high risk of sudden cardiac death. The study was designed to evaluate the prognoses for ICD recipients with respect to contributory risks.
METHODS: ICD recipients (N=2138) from Taiwan's NHI database, for the 11-year period 2004-2014 were identified and assigned to no heart failure (NHF, n=978) or heart failure groups (HF, n=1160). The mortality rates were reported and survival trends were compared between groups.
RESULTS: The mean age of these patients was 61.8±15.2 years and 69% were men. The HF group was older (65 vs. 58 years) and had significantly more comorbidities. Pharmaceutical and medical resource utilization was also uniformly higher within the HF group. The 30-day (1.8%) and 1-year (18.4%) mortality rates among the HF patients were 3-4 times higher than in the NHF group (log rank p=0.006 and p<0.001, respectively). A coexistent major diseases score was consistently associated with a progressive mortality risk in ICD recipients overall.
CONCLUSIONS: Of those receiving ICDs, the prognosis for HF patients is poorer than for those in the NHF group which most likely reflects the fact that the HF patients were generally older with more complicated medical conditions as evident by the association between multiple major organ dysfunction and an increased risk of death.

PMID: 32682628 [PubMed - as supplied by publisher]

Prevalence and Impact of Comorbid Widespread Pain in Adults with Chronic Low Back Pain: A Registry-Based Study.

Sat, 07/18/2020 - 07:57
Related Articles

Prevalence and Impact of Comorbid Widespread Pain in Adults with Chronic Low Back Pain: A Registry-Based Study.

J Am Board Fam Med. 2020 Jul-Aug;33(4):541-548

Authors: Licciardone JC, Pandya V

Abstract
INTRODUCTION: Widespread pain (WP) is emerging as a key comorbid condition in patients with chronic low back pain (CLBP). This study measured the prevalence of comorbid WP in adults with CLBP, WP predictors, and impact on patients.
METHODS: Patients with CLBP were recruited from the Pain Registry for Epidemiologic, Clinical, and Interventional Studies and Innovation from 2016 through 2019. They were followed over 12 months to measure annual WP period prevalence rates using an item from the minimum dataset recommended by the National Institutes of Health Task Force on Research Standards for Chronic Low Back Pain. Patients were classified as not having WP, having nonpersistent WP, or having persistent WP. Pain intensity, back-related disability, and quality of life were measured using a numerical rating scale, the Roland-Morris Disability Questionnaire, and the PROMIS-29 instrument, respectively.
RESULTS: A total of 358 patients were studied, including 56 (16%) without WP, 272 (76%) with nonpersistent WP, and 30 (8%) with persistent WP. There were no significant differences among the WP groups with regard to age, sex, or CLBP duration. However, being non-White and having moderate or high levels of pain catastrophizing remained significant predictors of nonpersistent or persistent WP after adjusting for potential confounders. Patients reported greater pain intensity and back-related disability and poorer quality of life over 12 months with increasing levels of WP persistence (P < .001 for each measure).
CONCLUSION: Greater efforts are needed in primary care to help close these gaps in pain intensity, back-related disability, and quality-of-life outcomes associated with WP.

PMID: 32675265 [PubMed - in process]

Cigarette Use Before and After the 2009 Flavored Cigarette Ban.

Sat, 07/18/2020 - 07:57
Related Articles

Cigarette Use Before and After the 2009 Flavored Cigarette Ban.

J Adolesc Health. 2020 Jul 13;:

Authors: Rossheim ME, Livingston MD, Krall JR, Barnett TE, Thombs DL, McDonald KK, Gimm GW

Abstract
PURPOSE: On September 22, 2009, the U.S. Food and Drug Administration's national ban on flavored cigarette products went into effect, barring the sale of flavored cigarettes with the exception of menthol. Flavored cigarettes largely appeal to and were disproportionately used by youth (under age 18 years). However, little research has evaluated the effects of the ban. This study examined past 30-day cigarette use among youth (12-17 years), young adults (18-25 years), adults (26-49 years), and older adults (≥50 years) before and after the implementation of this ban.
METHODS: Analyses were conducted using 2002-2017 National Survey on Drug Use and Health (NSDUH) data (n = 893,226). Regression models-weighted for national representation-were used to examine past 30-day cigarette use before and after the flavored cigarette ban in different age groups, using a quasi-experimental design incorporating elements of interrupted time series and difference-in-differences design. This design was used to examine differences in pre- versus post-ban smoking within age groups and heterogeneous policy effects between age groups, to help adjust for the generally stronger tobacco control environment over time.
RESULTS: The flavor ban was associated with statistically significant immediate increases as well as reductions over time in youth and young adult use of any cigarettes and menthol cigarettes, compared to older adults. In 2017, the predicted probability of youth and young adult cigarette smoking were reduced by 43% and 27%, respectively, compared to the model predicted probability in absence of the ban. No such effect was observed for older adults. The predicted probability of menthol use was reduced by 60% and 55% for youth and young adults, respectively.
CONCLUSIONS: Findings support the effectiveness of flavored cigarette bans at reducing cigarette use among young people and suggest a substitution effect between flavored tobacco products.

PMID: 32674967 [PubMed - as supplied by publisher]

Pages