Recent Research Articles from UNTHSC

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

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
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CONNECT: Implementation of a School-Based Alcohol Screening and Brief Intervention for Youth in the Cherokee Nation.

Sat, 09/12/2020 - 05:45
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CONNECT: Implementation of a School-Based Alcohol Screening and Brief Intervention for Youth in the Cherokee Nation.

J Sch Health. 2019 11;89(11):874-882

Authors: Garrett BA, Komro KA, Merlo LJ, Livingston BJ, Rentmeester S, Tobler A, Livingston MD, Kominsky TK

Abstract
BACKGROUND: There is growing optimism regarding the use of screening and brief intervention (SBI) to identify and reduce risk behaviors during adolescence. However, understanding successful SBI implementation remains unclear. We previously reported the effects of CONNECT, a school-based SBI, on reducing the primary outcome, the rate of monthly alcohol use among primarily American Indian (AI) and White high school students in the Cherokee Nation. In this paper, we describe the design and implementation process for CONNECT.
METHOD: CONNECT was designed to reduce alcohol use with 2 key strategies: (1) SBI with motivational interviewing (MI), implemented by a school-based CONNECT coach, and (2) a media campaign.
RESULTS: Implementation results indicate that during each semester of the 2-1/2 years, between 73% and 100% of eligible students had at least one 15-minute meeting with a CONNECT coach. Postcards and posters with positive communication tips for parents were displayed in CONNECT communities. No statistically significant differences occurred between the CONNECT and control groups on the hypothesized intermediate outcomes.
CONCLUSIONS: We describe implementation of a universal, school-based, culturally adapted SBI that was effective in reducing alcohol use among youth living in the Cherokee Nation. Schools provide an important context for universal delivery of SBI interventions, such as CONNECT, for diverse adolescent populations, including AI youth.

PMID: 31478206 [PubMed - indexed for MEDLINE]

A novel serum free primary astrocyte culture method that mimic quiescent astrocyte phenotype.

Sat, 09/12/2020 - 05:45
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A novel serum free primary astrocyte culture method that mimic quiescent astrocyte phenotype.

J Neurosci Methods. 2019 05 15;320:50-63

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

Abstract
BACKGROUND: Primary astrocyte cultures have been used for decades to study astrocyte functions in health and disease. The current primary astrocyte cultures are mostly maintained in serum-containing medium which produces astrocytes with a reactive phenotype as compared to in vivo quiescent astrocytes. The aim of this study was to establish a serum-free astrocyte culture medium that maintains primary astrocytes in a quiescent state.
NEW METHOD: Serum free astrocyte base medium (ABM) supplemented with basic fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) (ABM-FGF2-EGF) or serum supplemented DMEM (MD-10%FBS) was used to culture primary astrocytes isolated from cerebral cortex of postnatal day 1 C57BL/6 mice.
RESULTS: Compared to astrocytes cultured in MD-10%FBS medium, astrocytes in ABM-FGF2-EGF had higher process bearing morphologies similar to in vivo astrocytes. Western blot, immunostaining, quantitative polymerase chain reaction and metabolic assays revealed that astrocytes maintained in ABM-FGF2-EGF had enhanced glycolytic metabolism, higher glycogen content, lower GFAP expression, increased glutamine synthase, and glutamate transporter-1 mRNA levels as compared to astrocytes cultured in MD-10% FBS medium.
COMPARISON TO EXISTING METHODS: These observations suggest that astrocytes cultured in ABM-FGF2-EGF media compared to the usual FBS media promote quiescent and biosynthetic phenotype similar to in vivo astrocytes.
CONCLUSION: This media provides a novel method for studying astrocytes functions in vitro under physiological and pathological conditions.

PMID: 30904500 [PubMed - indexed for MEDLINE]

Estrogen receptor involvement in vascular cognitive impairment and vascular dementia pathogenesis and treatment.

Thu, 09/10/2020 - 07:54

Estrogen receptor involvement in vascular cognitive impairment and vascular dementia pathogenesis and treatment.

Geroscience. 2020 Sep 09;:

Authors: Nguyen DH, Cunningham JT, Sumien N

Abstract
Vascular cognitive impairment (VCI) is a term that encompasses a continuum of cognitive disorders with cerebrovascular pathology contribution, ranging from mild cognitive impairment to vascular dementia (VaD). VCI and VaD, thus, represent an interesting intersection between cardiovascular disease and neurodegenerative disorders such as Alzheimer's disease (AD) and a rising area of research in recent years. Although VCI and VaD research has identified various causes and explanations for disease development, many aspects remain unclear, particularly sex differences in VCI (e.g., epidemiology), unlike those available for cardiovascular disease and AD. Despite limited information in the literature, several studies have observed an association of estrogen receptor (ER) polymorphisms and VaD. If further explored, this association could provide valuable insights for novel therapeutic approaches. This review aims to provide a brief epidemiological overview and subsequent discussion exploring concepts of brain aging and involvement of estrogen receptors in potential mechanisms of VCI/VaD pathogenesis and treatment development.

PMID: 32902819 [PubMed - as supplied by publisher]

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

Thu, 09/10/2020 - 07:54
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Predicting Patient Reported Outcomes of Cognitive Function Using Connectome-Based Predictive Modeling in Breast Cancer.

Brain Topogr. 2020 01;33(1):135-142

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

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

PMID: 31745689 [PubMed - indexed for MEDLINE]

Probing the Assembly of HDL Mimetic, Drug Carrying Nanoparticles Using Intrinsic Fluorescence.

Wed, 09/09/2020 - 06:36
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Probing the Assembly of HDL Mimetic, Drug Carrying Nanoparticles Using Intrinsic Fluorescence.

J Pharmacol Exp Ther. 2020 04;373(1):113-121

Authors: Raut S, Garud A, Nagarajan B, Sabnis N, Remaley A, Fudala R, Gryczynski I, Gryczynski Z, Dzyuba SV, Borejdo J, Lacko A

Abstract
Reconstituted high-density lipoprotein (HDL) containing apolipoprotein A-I (Apo A-I) mimics the structure and function of endogenous (human plasma) HDL due to its function and potential therapeutic utility in atherosclerosis, cancer, neurodegenerative diseases, and inflammatory diseases. Recently, a new class of HDL mimetics has emerged, involving peptides with amino acid sequences that simulate the the primary structure of the amphipathic alpha helices within the Apo A-I protein. The findings reported in this communication were obtained using a similar amphiphilic peptide (modified via conjugation of a myristic acid residue at the amino terminal aspartic acid) that self-assembles (by itself) into nanoparticles while retaining the key features of endogenous HDL. The studies presented here involve the macromolecular assembly of the myristic acid conjugated peptide (MYR-5A) into nanomicellar structures and its characterization via steady-state and time-resolved fluorescence spectroscopy. The structural differences between the free peptide (5A) and MYR-5A conjugate were also probed, using tryptophan fluorescence, Fӧrster resonance energy transfer (FRET), dynamic light scattering, and gel exclusion chromatography. To our knowledge, this is the first report of a lipoprotein assembly generated from a single ingredient and without a separate lipid component. The therapeutic utility of these nanoparticles (due to their capablity to incorporate a wide range of drugs into their core region for targeted delivery) was also investigated by probing the role of the scavenger receptor type B1 in this process. SIGNIFICANCE STATEMENT: Although lipoproteins have been considered as effective drug delivery agents, none of these nanoformulations has entered clinical trials to date. A major challenge to advancing lipoprotein-based formulations to the clinic has been the availability of a cost-effective protein or peptide constituent, needed for the assembly of the drug/lipoprotein nanocomplexes. This report of a robust, spontaneously assembling drug transport system from a single component could provide the template for a superior, targeted drug delivery strategy for therapeutics of cancer and other diseases (Counsell and Pohland, 1982).

PMID: 31941718 [PubMed - indexed for MEDLINE]

Glycyrrhizin Protects γ-Irradiated Mice from Gut Bacteria-Associated Infectious Complications by Improving miR-222-Associated Gas5 RNA Reduction in Macrophages of the Bacterial Translocation Site.

Wed, 09/09/2020 - 06:36
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Glycyrrhizin Protects γ-Irradiated Mice from Gut Bacteria-Associated Infectious Complications by Improving miR-222-Associated Gas5 RNA Reduction in Macrophages of the Bacterial Translocation Site.

J Immunol. 2020 03 01;204(5):1255-1262

Authors: Ito I, Loucas BD, Suzuki S, Kobayashi M, Suzuki F

Abstract
Gut bacteria-associated sepsis is a serious concern in patients with gastrointestinal acute radiation syndrome (GIARS). In our previous studies, gut bacteria-associated sepsis caused high mortality rates in mice exposed to 6-9 Gy of γ-rays. IL-12+CD38+ iNOS+ Mϕ (M1Mϕ) located in the bacterial translocation site (mesenteric lymph nodes [MLNs]) of unirradiated mice were characterized as host defense antibacterial effector cells. However, cells isolated from the MLNs of GIARS mice were mostly CCL1+IL-10+LIGHT+miR-27a+ Mϕ (M2bMϕ, inhibitor cells for the M1Mϕ polarization). Reduced long noncoding RNA Gas5 and increased miR-222 expression in MLN-Mϕ influenced by the irradiation were shown to be associated with M2bMϕ polarization. In this study, the mortality of mice exposed to 7 Gy of γ-rays (7 Gy GIARS mice) was completely controlled after the administration of glycyrrhizin (GL), a major active ingredient in licorice root (Glycyrrhiza glabra). Bacterial translocation and subsequent sepsis were minimal in 7 Gy GIARS mice treated with GL. Increased Gas5 RNA level and decreased miR-222 expression were shown in MLN-Mϕ isolated from 7 Gy GIARS mice treated with GL, and these macrophages did not display any properties of M2bMϕ. These results indicate that gut bacteria-associated sepsis in 7 Gy GIARS mice was controlled by the GL through the inhibition of M2bMϕ polarization at the bacteria translocation site. Expression of Ccl1, a gene required for M2bMϕ survival, is silenced in the MLNs of 7 Gy GIARS mice because of Gas5 RNA, which is increased in these cells after the suppression of miR-222 (a Gas5 RNA expression inhibitor) by the GL.

PMID: 31941655 [PubMed - indexed for MEDLINE]

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

Wed, 09/09/2020 - 06:36
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Comparative expression analysis of phospholipid binding protein annexina1 in nephrogenesis and kidney cancer.

J Basic Clin Physiol Pharmacol. 2019 Nov 14;31(4):

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

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

PMID: 31730527 [PubMed - indexed for MEDLINE]

Empirical comparison of approaches for odds ratios to risk ratio transformations in meta-analyses of randomized controlled trials with common outcomes.

Tue, 09/08/2020 - 05:51
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Empirical comparison of approaches for odds ratios to risk ratio transformations in meta-analyses of randomized controlled trials with common outcomes.

Ann Epidemiol. 2020 04;44:57-59.e3

Authors: Chu TC, Ojha RP, VanderWeele TJ

PMID: 32265076 [PubMed - indexed for MEDLINE]

Protective behavioral strategies and alcohol outcomes: Impact of mood and personality disorders.

Sun, 09/06/2020 - 07:06
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Protective behavioral strategies and alcohol outcomes: Impact of mood and personality disorders.

Addict Behav. 2020 Aug 18;112:106615

Authors: Grazioli VS, Studer J, Larimer ME, Lewis MA, Bertholet N, Marmet S, Daeppen JB, Gmel G

Abstract
Although young men or young adults with mental health disorders are at higher risk to engage in problematic drinking, they typically evince stronger associations between protective behavioral strategies (PBS) and fewer alcohol outcomes. This study aimed to contribute to this line of research by examining the moderating effect of depression, bipolar spectrum disorder, borderline personality disorder and social anxiety disorder on the association between PBS and alcohol outcomes. Participants (N = 4,960; mean age = 25.43) were young men participating in the Cohort Study on Substance Use Risk Factors. Measures of PBS use, typical drinks per week, alcohol-related consequences, depression, bipolar spectrum disorder, borderline personality disorder and social anxiety disorder were used from the second follow-up assessment. Main results indicated that the negative association between PBS and alcohol use was stronger in participants with borderline personality disorder than among those without this disorder. Unexpectedly, in participants with depression, PBS were not significantly associated with alcohol use, whereas they were related to fewer drinks among those without the disorder. Similarly, in participants with bipolar spectrum disorder, the association between PBS and alcohol-related consequences was not significant, whereas PBS were associated with fewer consequences in those without the disorder. Finally, findings indicated that social anxiety disorder did not significantly moderate the associations between PBS and alcohol outcomes. If replicated by future research, these findings imply that PBS-intervention may not equally impact young adults with diverse mental health disorders.

PMID: 32889443 [PubMed - as supplied by publisher]

GFR-α1 Expression in Substantia Nigra Increases Bilaterally Following Unilateral Striatal GDNF in Aged Rats and Attenuates Nigral Tyrosine Hydroxylase Loss Following 6-OHDA Nigrostriatal Lesion.

Sat, 09/05/2020 - 06:35
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GFR-α1 Expression in Substantia Nigra Increases Bilaterally Following Unilateral Striatal GDNF in Aged Rats and Attenuates Nigral Tyrosine Hydroxylase Loss Following 6-OHDA Nigrostriatal Lesion.

ACS Chem Neurosci. 2019 10 16;10(10):4237-4249

Authors: Kasanga EA, Owens CL, Cantu MA, Richard AD, Davis RW, McDivitt LM, Blancher B, Pruett BS, Tan C, Gajewski A, Manfredsson FP, Nejtek VA, Salvatore MF

Abstract
Glial cell line-derived neurotrophic factor (GDNF) improved motor function in Parkinson's disease (PD) patients in Phase I clinical trials, and these effects persisted months after GDNF discontinuation. Conversely, phase II clinical trials reported no significant effects on motor improvement vs placebo. The disease duration and the quantity, infusion approach, and duration of GDNF delivery may affect GDNF efficacy in PD treatment. However, identifying mechanisms activated by GDNF that affect nigrostriatal function may reveal additional avenues to partially restore nigrostriatal function. In PD and aging models, GDNF affects tyrosine hydroxylase (TH) expression or phosphorylation in substantia nigra (SN), long after a single GDNF injection in striatum. In aged rats, the GDNF family receptor, GFR-α1, increases TH expression and phosphorylation in SN. To determine if GFR-α1 could be a mechanistic link in long-term GDNF impact, we conducted two studies; first to determine if a single unilateral striatal delivery of GDNF affected GFR-α1 and TH over time (1 day, 1 week, and 4 weeks) in the striatum or SN in aged rats, and second, to determine if soluble GFR-α1 could mitigate TH loss following 6-hydroxydopamine (6-OHDA) lesion. In aged rats, GDNF bilaterally increased ser31 TH phosphorylation and GFR-α1 expression in SN at 1 day and 4 weeks after GDNF, respectively. In striatum, GFR-α1 expression decreased 1 week after GDNF, only on the GDNF-injected side. In 6-OHDA-lesioned rats, recombinant soluble GFR-α1 mitigated nigral, but not striatal, TH protein loss following 6-OHDA. Together, these results show GDNF has immediate and long-term impact on dopamine regulation in the SN, which includes a gradual increase in GFR-α1 expression that may sustain TH expression and dopamine function therein.

PMID: 31538765 [PubMed - indexed for MEDLINE]

Defining Early Life Stress as a Precursor for Autoimmune Disease.

Sat, 09/05/2020 - 06:35
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Defining Early Life Stress as a Precursor for Autoimmune Disease.

Crit Rev Immunol. 2019;39(5):329-342

Authors: Choe JY, Nair M, Basha R, Kim BJ, Jones HP

Abstract
Childhood exposure to traumatic events, termed early life stress (ELS), is now widely recognized for causing long-term negative health effects that may not manifest until adulthood. Allostatic load (AL) describes the cumulative "wear-and-tear" effects of chronic stress on the body that may adversely affect human health by accelerating other disease processes. Recent epidemiological studies have reported higher stress levels in industrialized countries and trends of increasing prevalence in autoimmune diseases during recent decades. To elucidate mechanisms of stress-related immune dysregulation, most animal studies up to now have focused on AL and stress-triggered events occurring in adults but have not explored ELS in the context of autoimmune disorders. We have identified a current gap in understanding the impact of ELS on immune system ontogeny and its potential for priming genetically susceptible individuals who are at increased risk for autoimmune diseases later in life, through mechanisms involving neuroendocrine-immune cross talk. In this review, we highlight the intersection between stress and immune function, with a focus on ELS as consequential for increased autoimmune disorder risks later in life.

PMID: 32422015 [PubMed - indexed for MEDLINE]

Impact of the Microbiome on the Immune System.

Sat, 09/05/2020 - 06:35
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Impact of the Microbiome on the Immune System.

Crit Rev Immunol. 2019;39(5):313-328

Authors: Lambring CB, Siraj S, Patel K, Sankpal UT, Mathew S, Basha R

Abstract
Higher organisms are all born with general immunity as well as with, increasingly, more specific immune systems. All immune mechanisms function with the intent of aiding the body in defense against infection. Internal and external factors alike have varying effects on the immune system, and the immune response is tailored specifically to each one. Accompanying the components of the human innate and adaptive immune systems are the other intermingling systems of the human body. Increasing understanding of the body's immune interactions with other systems has opened new avenues of study, including that of the microbiome. The microbiome has become a highly active area of research over the last 10 to 20 years since the NIH began funding the Human Microbiome Project (HMP), which was established in 2007. Several publications have focused on the characterization, functions, and complex interplay of the microbiome as it relates to the rest of the body. A dysfunction between the microbiome and the host has been linked to various diseases including cancers, metabolic deficiencies, autoimmune disorders, and infectious diseases. Further understanding of the microbiome and its interaction with the host in relation to diseases is needed in order to understand the implications of microbiome dysfunction and the possible use of microbiota in the prevention of disease. In this review, we have summarized information on the immune system, the microbiome, the microbiome's interplay with other systems, and the association of the immune system and the microbiome in diseases such as diabetes and colorectal cancer.

PMID: 32422014 [PubMed - indexed for MEDLINE]

Vagus nerve stimulation as a promising adjunctive treatment for ischemic stroke.

Sat, 09/05/2020 - 03:34
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Vagus nerve stimulation as a promising adjunctive treatment for ischemic stroke.

Neurochem Int. 2019 12;131:104539

Authors: Ma J, Qiao P, Li Q, Wang Y, Zhang L, Yan LJ, Cai Z

Abstract
The Food and Drug Administration has approved vagus-nerve stimulation (VNS) for the treatment of patients with epilepsy, depression, and headache. By targeting diverse neuroprotective and neuroplasticity pathways, VNS has the potential to be expanded as a treatment for ischemic stroke. VNS has been found to attenuate infarct volume, reduce neurological deficits, and improve memory and cognition in rats with stroke injuries. Some pilot studies with small sample sizes suggested that VNS paired with rehabilitation can be a promising approach to improve limb motor function in chronic-stroke patients. In this review, we first provide an overview of the diverse effects of VNS in the post-stroke condition, followed by a thorough discussion of the potential mechanisms responsible for its neuroprotective and neuroplasticity-enhancing properties. We also outline the clinical applications of the recently emerging non-invasive VNS. Finally, we summarize the advantages and adverse effects of the current VNS applications, as well as the future challenges and directions for the clinical implementation of VNS in ischemic stroke. Although more fundamental and clinical research is still required to fully understand its mechanisms of efficacy, we believe that the frequent and successful clinical use of VNS as a treatment for ischemic stroke is well within reach.

PMID: 31445074 [PubMed - indexed for MEDLINE]

Population genetic study of a Peruvian population using human identification STRs.

Thu, 09/03/2020 - 14:41
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Population genetic study of a Peruvian population using human identification STRs.

Int J Legal Med. 2020 Sep 02;:

Authors: Neyra Rivera CD, Delgado Ramos E, Robles Mamani CS, Velasquez Reinoso MRE, Caceres Rey OA, Budowle B

Abstract
In this study, allele frequencies were determined in a Peruvian population for application to human identification. A population of 601 unrelated individuals was analyzed (400 individuals with the GlobalFiler Express kit and 201 individuals with the VeriFiler Express kit). The locus with the highest power of discrimination (PD) was SE33 (0.9851, 31 alleles), while the least polymorphic locus was D22S1045 (0.75810, 11 alleles). The PE in a similar fashion ranged from 0.2421 (D22S1045) to 0.7818 (SE33). Under the assumption of independence, the combined PD was > 0.9999999999 while the combined PE = 0.9999999933. When comparing the population studied with different populations of Latin America, the greatest Fst genetic distance was obtained with a Venezuelan population (0.052), and the shortest distance was with a Bolivian and Peruvian population (0.004).

PMID: 32876758 [PubMed - as supplied by publisher]

Topical dermal steroid-induced retinopathy.

Thu, 09/03/2020 - 14:41
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Topical dermal steroid-induced retinopathy.

JAAD Case Rep. 2020 Sep;6(9):868-870

Authors: Hilton T, DeCrescenzo A, Menter A, Chavala SH

PMID: 32875037 [PubMed]

Examination of physicians' adherence to the 2013 ACC/AHA statin/cholesterol guidelines using a framework of awareness to adherence: A cross-sectional study.

Thu, 09/03/2020 - 14:41
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Examination of physicians' adherence to the 2013 ACC/AHA statin/cholesterol guidelines using a framework of awareness to adherence: A cross-sectional study.

JRSM Cardiovasc Dis. 2020 Jan-Dec;9:2048004020947298

Authors: Fleming ML, Rege S, Johnson ML, Serna O, Esse T, Choi J, Abughosh SM

Abstract
Background: Currently, limited data exists regarding primary care physicians' awareness and implementation of the 2013 cholesterol guidelines.
Objectives: To evaluate primary care physicians' adherence to the 2013 ACC/AHA cholesterol management guidelines using the framework of the awareness-to-adherence model.
Methods: The study was a cross-sectional pre-post survey design based on the constructs of the awareness-to-adherence model to capture physicians' awareness of, agreement with, adoption of, and adherence to the 2013 ACC/AHA guidelines for cholesterol treatment and statin and cholesterol management software applications. Physicians with a Medicare Advantage organization in Texas were surveyed before and after educational interventions.
Results: A total of 170 responses were considered usable (post-survey). A significant difference was observed when physicians were divided into 2 groups (any intervention vs no intervention) (P = .027). Physicians with a higher level of agreement were 4.8 times more likely to be adherent to the guidelines (P = .011), compared with those with a lower level of agreement. Also, physicians practicing in the Rio Grande Valley area were 4.7 times more likely to be adherent to the guidelines (P = .001) compared with those from the Greater Houston area.
Conclusion: A high level of awareness, but a lower level of adherence to the guidelines was reported among responding physicians. The awareness-to-adherence model was useful in examining physicians' level of adherence to the cholesterol guidelines and the utilization of statin and cholesterol management cellular apps and online websites. Future studies are required to examine physicians' adoption and adherence of new guidelines.

PMID: 32874555 [PubMed]

Tofacitinib, the First Oral Janus Kinase Inhibitor Approved for Adult Ulcerative Colitis.

Thu, 09/03/2020 - 14:41
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Tofacitinib, the First Oral Janus Kinase Inhibitor Approved for Adult Ulcerative Colitis.

J Pharm Pract. 2020 Sep 02;:897190020953019

Authors: Palasik BN, Wang H

Abstract
Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) characterized by chronic gastrointestinal inflammation. In most patients, the disease cycles through periods of remission and exacerbations. The complex etiology involves multiple factors including environmental, genetic, and immune causal elements. Janus Kinase (JAK) family is an essential component of a cytokine-signaling cascade partially responsible for the pathogenesis of UC. Treating UC presents difficulties despite various therapeutic options. Medications that block the JAK-signaling pathway can interfere with the inflammatory pathway of UC and possibly reduce symptoms and frequency of exacerbations. Tofacitinib is an oral pan-JAK inhibitor, primarily of JAK1 and JAK3, that was recently approved by the Food and Drug Administration (FDA) for the chronic treatment of UC in 2018. The following review describes the newly approved Janus kinase inhibitor, tofacitinib, including its pharmacokinetic properties, efficacy and safety data, and potential place in therapy.

PMID: 32873116 [PubMed - as supplied by publisher]

Insights into the Gene Expression Profiles of Active and Restricted Red/Green-HIV+ Human Astrocytes: Implications for Shock or Lock Therapies in the Brain.

Thu, 09/03/2020 - 14:41
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Insights into the Gene Expression Profiles of Active and Restricted Red/Green-HIV+ Human Astrocytes: Implications for Shock or Lock Therapies in the Brain.

J Virol. 2020 02 28;94(6):

Authors: Edara VV, Ghorpade A, Borgmann K

Abstract
A significant number of people living with human immunodeficiency virus type 1 (HIV-1) suffer from HIV-associated neurocognitive disorders (HAND). Many previous studies investigating HIV in astrocytes as a heterogenous population have established the relevance of astrocytes to HIV-associated neuropathogenesis. However, these studies were unable to differentiate the state of infection, i.e., active or latent, or to evaluate how this affects astrocyte biology. In this study, the pseudotyped doubly labeled fluorescent reporter red/green (R/G)-HIV-1 was used to identify and enrich restricted and active populations of HIV+ astrocytes based on the viral promoter activity. Here, we report that the majority of human astrocytes restricted R/G-HIV-1 gene expression early during infection and were resistant to reactivation by vorinostat and interleukin 1β. However, actively infected astrocytes were inducible, leading to increased expression of viral proteins upon reactivation. R/G-HIV-1 infection also significantly decreased the cell proliferation and glutamate clearance ability of astrocytes, which may contribute to excitotoxicity. Moreover, transcriptome analyses to compare gene expression patterns of astrocyte harboring active versus restricted long terminal repeats (LTRs) revealed that the gene expression patterns were similar and that the active population demonstrated more widespread and robust changes. Our data suggest that harboring the HIV genome profoundly alters astrocyte biology and that strategies that keep the virus latent (e.g., block and lock) or those that reactivate the latent virus (e.g., shock and kill) would be detrimental to astrocyte function and possibly augment their contributions to HAND.IMPORTANCE More than 36 million people are living with HIV-1 worldwide, and despite antiretroviral therapy, 30 to 50% of the people living with HIV-1 suffer from mild to moderate neurocognitive disorders. HIV-1 reservoirs in the central nervous system (CNS) are challenging to address due to low penetration of antiretroviral drugs, lack of resident T cells, and permanent integration of provirus into neural cells such as microglia and astrocytes. Several studies have shown astrocyte dysfunction during HIV-1 infection. However, little is known about how HIV-1 latency affects their function. The significance of our research is in identifying that the majority of HIV+ astrocytes restrict HIV expression and were resistant to reactivation. Further, simply harboring the HIV genome profoundly altered astrocyte biology, resulting in a proinflammatory phenotype and functional changes. In this context, therapeutic strategies to reactivate or silence astrocyte HIV reservoirs, without excising proviral DNA, will likely lead to detrimental neuropathological outcomes during HIV CNS infection.

PMID: 31896591 [PubMed - indexed for MEDLINE]

Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- and Metallo-β-lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections.

Thu, 09/03/2020 - 14:41
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Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- and Metallo-β-lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections.

J Med Chem. 2020 03 26;63(6):2789-2801

Authors: Liu B, Trout REL, Chu GH, McGarry D, Jackson RW, Hamrick JC, Daigle DM, Cusick SM, Pozzi C, De Luca F, Benvenuti M, Mangani S, Docquier JD, Weiss WJ, Pevear DC, Xerri L, Burns CJ

Abstract
A major resistance mechanism in Gram-negative bacteria is the production of β-lactamase enzymes. Originally recognized for their ability to hydrolyze penicillins, emergent β-lactamases can now confer resistance to other β-lactam drugs, including both cephalosporins and carbapenems. The emergence and global spread of β-lactamase-producing multi-drug-resistant "superbugs" has caused increased alarm within the medical community due to the high mortality rate associated with these difficult-to-treat bacterial infections. To address this unmet medical need, we initiated an iterative program combining medicinal chemistry, structural biology, biochemical testing, and microbiological profiling to identify broad-spectrum inhibitors of both serine- and metallo-β-lactamase enzymes. Lead optimization, beginning with narrower-spectrum, weakly active compounds, provided 20 (VNRX-5133, taniborbactam), a boronic-acid-containing pan-spectrum β-lactamase inhibitor. In vitro and in vivo studies demonstrated that 20 restored the activity of β-lactam antibiotics against carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae. Taniborbactam is the first pan-spectrum β-lactamase inhibitor to enter clinical development.

PMID: 31765155 [PubMed - indexed for MEDLINE]

Impact of a low-cost simulated electronic medical record on perceptions of APPE readiness.

Thu, 09/03/2020 - 14:41
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Impact of a low-cost simulated electronic medical record on perceptions of APPE readiness.

Curr Pharm Teach Learn. 2019 07;11(7):736-741

Authors: Gibson CM, Kwon HI, Tatachar A

Abstract
BACKGROUND: Meaningful use of electronic medical records (EMRs) is critical for providing high-quality, patient-centered care. However, many pharmacy students are not exposed to EMRs until the experiential components of the curriculum.
EDUCATIONAL ACTIVITY AND SETTING: We created a low-cost simulated EMR (SEMR) using Microsoft PowerPoint software (Microsoft, Redmond, WA, Version 16.16) to use in a case-based application course for second-year pharmacy students for two consecutive years.
FINDINGS: Pre- and post-assessment surveys of 162 students indicated that perceived confidence and efficiency navigating EMRs improved after the activity. Students agreed that the activity enhanced learning, improved understanding of how to extract meaningful data from EMRs, benefited their preparation for the fourth professional year, and demonstrated the role of informatics in patient care.
SUMMARY: Incorporation of a SEMR using Microsoft PowerPoint enhances student perceptions of proficiency in navigating the patient medical record. Adoption of similar activities into pharmacy curricula may be an attractive option when adequate financial resources for simulation are unavailable.

PMID: 31227098 [PubMed - indexed for MEDLINE]

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