Recent Research Articles from UNTHSC

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

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Updated: 2 hours 8 min ago

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]

Protective behavioral strategies are more helpful for avoiding alcohol-related problems for college drinkers who drink less.

Wed, 09/02/2020 - 07:49
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Protective behavioral strategies are more helpful for avoiding alcohol-related problems for college drinkers who drink less.

J Am Coll Health. 2020 Sep 01;:1-7

Authors: Li X, Clarke N, Kim SY, Ray AE, Walters ST, Mun EY

Abstract
OBJECTIVE: To examine race, gender, and alcohol use level as moderators of the association between protective behavioral strategies (PBS) and alcohol-related problems. Participants: A sample of 12,011 participants who reported recent drinking (87.7% White, 61% Women) from Project INTEGRATE, a study that combined individual participant data (IPD) from 24 brief motivational intervention trials for college students. Methods: Hierarchical regressions were conducted to determine whether there was a moderated effect of PBS on alcohol problems across alcohol use levels, and whether the moderated protective effect of PBS by alcohol use differed by gender and race. Results: The protective association between PBS and alcohol-related problems was greater for those who drank less. This moderated effect did not differ across men and women or across racial groups. Conclusions: College drinking prevention programs should ensure that students are aware of the limits of PBS as a mitigator of alcohol problems.

PMID: 32870746 [PubMed - as supplied by publisher]

Targeted Molecular Therapeutic Options for Hepatocellular Carcinoma.

Tue, 09/01/2020 - 07:01
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Targeted Molecular Therapeutic Options for Hepatocellular Carcinoma.

Crit Rev Oncog. 2020;25(1):47-55

Authors: Sridhar S, Sharma I, Sankpal UT, Ghabach B, Narra K, Neerukonda L, Basha R

Abstract
Liver cancer is the 6th leading cause of cancer related deaths in the US even though it ranks 14th in incidence. More men are diagnosed with liver cancer than women, and the number of projected deaths among men (20,020) is almost double that among women (10,140) in the US. Infections like hepatitis and metabolic conditions like obesity are believed to be major risk factors for the onset of liver cancer. Hepatocellular carcinoma (HCC), the most common type of liver cancer, accounts for 75% of all cases. Chemotherapy has not been effective in treating HCC. Targeted therapies are being used in advanced HCC patients due to a better survival and less side effects when compared to traditional chemotherapy. Therapeutic agents targeting the regulators of growth factor signaling pathways and the mediators of downstream signaling-for example, inhibitors of the tyrosine kinase receptor-are used as targeted molecular therapies. Kinase inhibitors that modulate growth signals, such as sorafenib and lenvatinib, are commonly employed in targeted molecular therapy for HCC patients. This review covers these agents, highlighting modes of action and providing details on clinical trials.

PMID: 32865910 [PubMed - as supplied by publisher]

Current Perspectives in Immunotherapy for Liver Cancer.

Tue, 09/01/2020 - 07:01
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Current Perspectives in Immunotherapy for Liver Cancer.

Crit Rev Oncog. 2020;25(1):31-46

Authors: Lambring CB, Ghabach B, Narra K, Basha R

Abstract
Liver cancer is a particularly aggressive group of malignancies with historically low survival rates. Despite advancements in cancer treatments in general in the last few decades, incidence and mortality have not changed. Even though some phase 1 and 2 studies have shown promising results, many medication have failed to reach a sustainable level of efficacy to move into the clinical setting. Immunotherapy drugs have shown impressive results in the treatment of specific immunogenic cancers, prompting the possibility of their use in liver cancers. Immunotherapy medications approved for other cancers have received FDA accelerated approval for treatment of hepatocellular carcinoma. But, these approvals are contingent upon verification and description of clinical benefit in confirmatory trials. With more treatments in development involving cancer vaccines and natural killer cell-mediated therapy, liver cancer treatment is being reinvigorated with a broad array of new treatment angles. In this review article, we discuss these treatments, focusing on mechanism of action and clinical trials. Much needed advancements in treating late- and early-stage liver cancers will require new and innovative immunotherapeutic treatments.

PMID: 32865909 [PubMed - as supplied by publisher]

DAV131A Protects Hamsters from Lethal Clostridioides difficile Infection Induced by Fluoroquinolones.

Tue, 09/01/2020 - 07:01
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DAV131A Protects Hamsters from Lethal Clostridioides difficile Infection Induced by Fluoroquinolones.

Antimicrob Agents Chemother. 2019 12 20;64(1):

Authors: Saint-Lu N, Burdet C, Sablier-Gallis F, Corbel T, Nevière A, Sayah-Jeanne S, Pulse M, Weiss W, Ferreira S, Andremont A, Mentré F, de Gunzburg J

Abstract
Fluoroquinolone treatments induce dysbiosis of the intestinal microbiota, resulting in loss of resistance to colonization by exogenous bacteria such as Clostridioides difficile that may cause severe diarrhea in humans and lethal infection in hamsters. We show here that DAV131A, a charcoal-based adsorbent, decreases the intestinal levels of the fluoroquinolone antibiotics levofloxacin and ciprofloxacin in hamsters, protects their intestinal microbiota, and prevents lethal infection by C. difficile.

PMID: 31636067 [PubMed - indexed for MEDLINE]

Price of Four Loko in Large U.S. Cities, 2018.

Tue, 09/01/2020 - 07:01
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Price of Four Loko in Large U.S. Cities, 2018.

Alcohol Clin Exp Res. 2019 07;43(7):1585-1590

Authors: Rossheim ME, Thombs DL, Treffers RD, Trangenstein PJ, McDonald KK, Ahmad R, Siklo SS, Gonzalez-Pons KM, Suzuki S, Jernigan DH

Abstract
BACKGROUND: Supersized alcopops are flavored alcoholic beverages that contain up to 5.5 standard alcoholic drinks in a single can. Limited research suggests Four Loko-the most commonly consumed supersized alcopop by underage drinkers-is among the least expensive ready-to-drink alcohol products on the U.S. market. This is a public health concern because alcohol prices are inversely associated with consumption and related harms, particularly among youth. This study investigated Four Loko's retail price per volume of alcohol in large U.S. cities.
METHODS: This study used multistage random sampling to collect data in the largest city of each state and Washington, DC. A simple random sample of 5 ZIP codes from each city was selected and entered into Four Loko's website product locator. Within ZIP codes, up to 4 stores were randomly selected and contacted by telephone. Retailers were interviewed about Four Loko in regard to: availability, volume, alcohol by volume (abv), price for 1 can, and discounts for purchasing more than 1 can.
RESULTS: The sample included 344 retail stores with Four Loko in stock. Average price per standard alcoholic drink (i.e., 14 g of absolute alcohol) was $0.54 for Four Loko products. Taking into account volume, price, and discounts, an average of 17 standard alcoholic drinks could be purchased via Four Loko with $10. Adjusted analysis using linear regression showed that availability of bulk price discounts and higher abv (14% vs. 12%) were associated with lower price per drink.
CONCLUSION: This study verifies that Four Loko is among the least expensive ready-to-drink alcohol available for purchase in the United States. Given that consuming a single supersized alcopop constitutes binge drinking and is therefore unsafe, regulatory agencies should consider a variety of steps to reduce the availability and abv of these products and increase their retail price in order to reduce and prevent unsafe alcohol consumption.

PMID: 31066910 [PubMed - indexed for MEDLINE]

Risk Factors for Failure of Splenic Angioembolization: A Multicenter Study of Level I Trauma Centers.

Sun, 08/30/2020 - 06:48
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Risk Factors for Failure of Splenic Angioembolization: A Multicenter Study of Level I Trauma Centers.

J Surg Res. 2020 Aug 26;257:227-231

Authors: Bankhead-Kendall B, Teixeira P, Musonza T, Donahue T, Regner J, Harrell K, Brown CVR, Texas Trauma Study Group

Abstract
BACKGROUND: Angioembolization (AE) is an adjunct to nonoperative management (NOM) of splenic injuries. We hypothesize that failure of AE is associated with blood transfusion, grade of injury, and technique of AE.
METHODS: We performed a retrospective (2010-2017) multicenter study (nine Level I trauma centers) of adult trauma patients with splenic injuries who underwent splenic AE. Variables included patient physiology, injury grade, transfusion requirement, and embolization technique. The primary outcome was NOM failure requiring splenectomy. Secondary outcomes were mortality, complications, and length of stay.
RESULTS: A total of 409 patients met inclusion criteria; only 33 patients (8%) required delayed splenectomy. Patients who failed received more blood in the first 24 h (P = 0.009) and more often received massive transfusion (P = 0.01). There was no difference in failure rates for grade of injury, contrast blush on computed tomography, and branch embolized. After logistic regression, transfusion in the first 24 h was independently associated with failure of NOM (P = 0.02). Patients who failed NOM had more complications (P = 0.002) and spent more days in the intensive care unit (P < 0.0001), on the ventilator (P = 0.0001), and in the hospital (P < 0.0001). Patients who failed NOM had a higher mortality (15% versus 3%, P = 0.007), and delayed splenectomy was independently associated with mortality (odds ratio, 4.2; 95% confidence interval, 1.2-14.7; P = 0.03).
CONCLUSIONS: AE for splenic injury leads to effective NOM in 92% of patients. Transfusion in the first 24 h is independently associated with failure of NOM. Patients who required a delayed splenectomy suffered more complications and had higher hospital length of stay. Failure of NOM is independently associated with a fourfold increase in mortality.

PMID: 32861100 [PubMed - as supplied by publisher]

Distribution pattern of invasion-related bio-markers in head Marjolin's ulcer.

Sat, 08/29/2020 - 05:51
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Distribution pattern of invasion-related bio-markers in head Marjolin's ulcer.

Exp Ther Med. 2020 Oct;20(4):3316-3323

Authors: Ni Z, Zheng Z, Yu E, Zu C, Huang D, Wu K, Hu J, Ye S, Zhuge Q, Yang J, Ruan L

Abstract
Marjolin's ulcer (MU) is a rare and aggressive cutaneous malignancy that typically presented in an area of traumatized or chronically inflamed skin and particularly in burn scars. Among them, the MU in the scalp with extensive invasion of the skull is exceptional and severe. The principle of management for MU is to obtain an early diagnosis and perform prompt surgical interventions. The invasive capacity of MU may vary among different sites of the scalp, which may require different therapeutic strategies for surgical excision. However, no clear evidence has been provided to determine the invasion ability of MU at different regions of the lesion as a surgical guidance. In present study, a 41-year-old female with a 40-year history of scalp ulceration has been examined. After resection of the MU lesion, hematoxylin and eosin (H&E) staining was performed to confirm the pathology of the cutaneous malignancy after surgical excision. Furthermore, reverse transcription-quantitative PCR experiment was performed out to determine the expression levels of invasion-associated biomarkers at different sites of the scalp affected by MU. Pathological analysis with H&E staining indicated a differentiated squamous cell carcinoma with invasion of the skull. The invasion-associated biomarkers were highly expressed in the core region compared to the middle region as well as the edge of MU tissue. Taken together, the present study suggests that the expression pattern of invasion-associated biomarkers varies between different regions of the MU lesion. High expression levels in the core region of MU indicates that the resection of the center area may be critical for the successful surgical treatment of MU.

PMID: 32855703 [PubMed]

CNS axonal degeneration and transport deficits at the optic nerve head precede structural and functional loss of retinal ganglion cells in a mouse model of glaucoma.

Sat, 08/29/2020 - 05:51
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CNS axonal degeneration and transport deficits at the optic nerve head precede structural and functional loss of retinal ganglion cells in a mouse model of glaucoma.

Mol Neurodegener. 2020 Aug 27;15(1):48

Authors: Maddineni P, Kasetti RB, Patel PD, Millar JC, Kiehlbauch C, Clark AF, Zode GS

Abstract
BACKGROUND: Glaucoma is a leading neurodegenerative disease affecting over 70 million individuals worldwide. Early pathological events of axonal degeneration and retinopathy in response to elevated intraocular pressure (IOP) are limited and not well-defined due to the lack of appropriate animal models that faithfully replicate all the phenotypes of primary open angle glaucoma (POAG), the most common form of glaucoma. Glucocorticoid (GC)-induced ocular hypertension (OHT) and its associated iatrogenic open-angle glaucoma share many features with POAG. Here, we characterized a novel mouse model of GC-induced OHT for glaucomatous neurodegeneration and further explored early pathological events of axonal degeneration in response to elevated IOP.
METHODS: C57BL/6 J mice were periocularly injected with either vehicle or the potent GC, dexamethasone 21-acetate (Dex) once a week for 10 weeks. Glaucoma phenotypes including IOP, outflow facility, structural and functional loss of retinal ganglion cells (RGCs), optic nerve (ON) degeneration, gliosis, and anterograde axonal transport deficits were examined at various stages of OHT.
RESULTS: Prolonged treatment with Dex leads to glaucoma in mice similar to POAG patients including IOP elevation due to reduced outflow facility and dysfunction of trabecular meshwork, progressive ON degeneration and structural and functional loss of RGCs. Lowering of IOP rescued Dex-induced ON degeneration and RGC loss, suggesting that glaucomatous neurodegeneration is IOP dependent. Also, Dex-induced neurodegeneration was associated with activation of astrocytes, axonal transport deficits, ON demyelination, mitochondrial accumulation and immune cell infiltration in the optic nerve head (ONH) region. Our studies further show that ON degeneration precedes structural and functional loss of RGCs in Dex-treated mice. Axonal damage and transport deficits initiate at the ONH and progress toward the distal end of ON and target regions in the brain (i.e. superior colliculus). Most of anterograde transport was preserved during initial stages of axonal degeneration (30% loss) and complete transport deficits were only observed at the ONH during later stages of severe axonal degeneration (50% loss).
CONCLUSIONS: These findings indicate that ON degeneration and transport deficits at the ONH precede RGC structural and functional loss and provide a new potential therapeutic window for rescuing neuronal loss and restoring health of damaged axons in glaucoma.

PMID: 32854767 [PubMed - in process]

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