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 44 min ago

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

Wed, 09/02/2020 - 07:49
Related Articles

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
Related Articles

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
Related Articles

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
Related Articles

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
Related Articles

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
Related Articles

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
Related Articles

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
Related Articles

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]

Lipoproteins and the Tumor Microenvironment.

Fri, 08/28/2020 - 05:05
Related Articles

Lipoproteins and the Tumor Microenvironment.

Adv Exp Med Biol. 2020;1272:93-116

Authors: Dossou AS, Sabnis N, Nagarajan B, Mathew E, Fudala R, Lacko AG

Abstract
The tumor microenvironment (TME) plays a key role in enhancing the growth of malignant tumors and thus contributing to "aggressive phenotypes," supporting sustained tumor growth and metastasis. The precise interplay between the numerous components of the TME that contribute to the emergence of these aggressive phenotypes is yet to be elucidated and currently under intense investigation. The purpose of this article is to identify specific role(s) for lipoproteins as part of these processes that facilitate (or oppose) malignant growth as they interact with specific components of the TME during tumor development and treatment. Because of the scarcity of literature reports regarding the interaction of lipoproteins with the components of the tumor microenvironment, we were compelled to explore topics that were only tangentially related to this topic, to ensure that we have not missed any important concepts.

PMID: 32845504 [PubMed - in process]

Environment-Wide Association Study on Childhood Obesity in the U.S.

Wed, 08/26/2020 - 06:39
Related Articles

Environment-Wide Association Study on Childhood Obesity in the U.S.

Environ Res. 2020 Aug 22;:110109

Authors: Uche UI, Suzuki S, Fulda KG, Zhou Z

Abstract
BACKGROUND: Childhood obesity is a national public health issue with increasing prevalence. It has been linked to diet, lack of physical activity, and genetic susceptibility, with more recent evidence that it could also result from environmental factors. Studies linking it to environmental factors are limited, unsystematic, incomprehensive, and inconclusive.
OBJECTIVE: To conduct an environment-wide association study (EWAS) to comprehensively investigate all the environmental factors available in a nationally representative sample of children to determine factors associated with childhood obesity.
METHODS: We utilized the 1999-2016 National Health and Nutrition Examination Survey (NHANES) datasets and included all children/adolescents (6-17 years). Obesity was measured using body mass index and waist to height ratio. A multinomial and binary logistic regression were used adjusting for age, sex, race/ethnicity, creatinine, calorie intake, physical activity, screen time, limitation to physical activities, and socioeconomic status. We then controlled for multiple hypothesis testing and validated our findings on a different cohort of children.
RESULTS: We found that metals such as beryllium (OR: 3.305 CI: 1.460-7.479) and platinum (OR: 1.346 CI: 1.107-1.636); vitamins such as gamma-tocopherol (OR: 8.297 CI: 5.683-12.114) and delta-tocopherol (OR: 1.841 CI:1.476-2.297); heterocyclic aromatic amines such as 2-Amino-9H-pyrido (2,3-b) indole (OR: 1.323 CI: 1.083-1.617) and 2-Amino-3-methyl-9H-pyriodo(2,3-b)indole (OR: 2.799 CI: 1.442-5.433); polycyclic aromatic amines such as 9- fluorene (OR: 1.509 CI: 1.230-1.851) and 4-phenanthrene (OR: 2.828 CI: 1.632-4.899); and caffeine metabolites such as 1,3,7-trimethyluric acid (OR: 1.22 CI: 1.029-1.414) and 1,3,7-trimethylxanthine (OR: 1.258 CI: 1.075-1.473) were positively and significantly associated with childhood obesity.
CONCLUSION: Following the unique concept of EWAS, certain environmental factors were associated with childhood obesity. Further studies are required to confirm these associations while investigating their mechanisms of action.

PMID: 32841636 [PubMed - as supplied by publisher]

Comparative analysis of racial differences in breast tumor microbiome.

Wed, 08/26/2020 - 06:39
Related Articles

Comparative analysis of racial differences in breast tumor microbiome.

Sci Rep. 2020 Aug 24;10(1):14116

Authors: Thyagarajan S, Zhang Y, Thapa S, Allen MS, Phillips N, Chaudhary P, Kashyap MV, Vishwanatha JK

Abstract
Studies have demonstrated that environmental, host genetic, and socioeconomic factors influence the breast cancer prevalence landscape with a far-reaching influence on racial disparity to subtypes of breast cancer. To understand whether breast tissue harbors race-specific microbiota, we performed 16S rRNA gene-based sequencing of retrospective tumor and matched normal tissue adjacent to tumor (NAT) samples collected from Black non-Hispanic (BNH) and White non-Hispanic (WNH) women. Analysis of Triple Negative Breast cancer (TNBC) and Triple Positive Breast Cancer (TPBC) tissues for microbiota composition revealed significant differences in relative abundance of specific taxa at both phylum and genus levels between WNH and BNH women cohorts. Our main findings are that microbial diversity as measured by Shannon index was significantly lower in BNH TNBC tumor tissue as compared to matched NAT zone. In contrast, the WNH cohort had an inverse pattern for the Shannon index, when TNBC tumor tissue was compared to the matched NAT. Unweighted Principle Coordinates Analysis (PCoA) revealed a distinct clustering of tumor and NAT microbiota in both BNH and WNH cohorts.

PMID: 32839514 [PubMed - in process]

Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.

Wed, 08/26/2020 - 06:39
Related Articles

Randomized assessment of delayed intensification and two methods for parenteral methotrexate delivery in childhood B-ALL: Children's Oncology Group Studies P9904 and P9905.

Leukemia. 2020 04;34(4):1006-1016

Authors: Winick N, Martin PL, Devidas M, Shuster J, Borowitz MJ, Paul Bowman W, Larsen E, Pullen J, Carroll A, Willman C, Hunger SP, Carroll WL, Camitta BM

Abstract
The delayed intensification (DI) enhanced outcome for patients with acute lymphoblastic leukemia (ALL) treated on BFM 76/79 and CCG 105 after a prednisone-based induction. Childrens Oncology Group protocols P9904/9905 evaluated DI via a post-induction randomization for eligible National Cancer Institute (NCI) standard (SR) and high-risk (HR) patients. A second randomization compared intravenous methotrexate (IV MTX) as a 24- (1 g/m2) vs. 4-h (2 g/m2) infusion. NCI SR patients received a dexamethasone-based three-drug and NCI HR/CNS 3 SR patients a prednisone-based four-drug induction. End induction MRD (minimal residual disease) was obtained but did not impact treatment. DI improved the 10-year continuous complete remission (CCR) rate; 75.5 ± 2.5% vs. 81.8 ± 2.2% p = 0.002, whereas MTX administration did not; 4-h 80.8 ± 1.9%; 24-h 81.4 ± 1.9% (p = 0.7780). Overall survival (OS) at 10 years did not differ with DI: 91.4 ± 1.6% vs. 90.9 ± 1.7% (p = 0.25) without but was higher with the 24-h MTX infusion; 4-h 91.1 ± 1.4%; 24-h 93.9 ± 1.2% (p = 0.0209). MRD predicted outcome; 10-year CCR 87.7 ± 2.2 and 82.1 ± 2.5% when MRD was <0.01% with/without DI (p = 0.007) and 54.3 ± 8% and 44 ± 8% for patients with MRD ≥ 0.01% with/without DI (p = 0.11). DI improved CCR for patients with B-ALL with and without end induction MRD.

PMID: 31728054 [PubMed - indexed for MEDLINE]

Increased expression of Fragile X mental retardation protein in malformative lesions of patients with focal cortical dysplasia.

Tue, 08/25/2020 - 06:12
Related Articles

Increased expression of Fragile X mental retardation protein in malformative lesions of patients with focal cortical dysplasia.

Neuroreport. 2020 Aug 20;:

Authors: Reynolds CD, Nolan SO, Smith GD, Jefferson TS, Hodges SL, Brewster AL, Lugo JN

Abstract
OBJECTIVE: Focal cortical dysplasia (FCD) accounts for nearly half of all cases of medically refractory epilepsy in the pediatric and adult patient populations. This neurological disorder stems from localized malformations in cortical brain tissue due to impaired neuronal proliferation, differentiation, and migration patterns. Recent studies in animal models have highlighted the potential role of the Fragile X mental retardation protein (FMRP) levels in FCD. The purpose of this study was to investigate the status of FMRP activation in cortical brain tissues surgically resected from patients with FCD. In parallel, this study also investigated protein levels within the PI3K/AKT/mTOR and canonical Wnt signaling pathways.
METHODS: Pathologic tissue from malformative lesions of FCD patients with medically refractory epilepsy was compared to relatively normal control non-epileptic tissue from patients with intracranial neoplasms. A series of western blotting assays were performed to assess key proteins in the PI3K/AKT/mTOR, canonical Wnt signaling pathways, and FMRP.
RESULTS: There was suppression of S235/236-phosphorylated S6, GSK3α, and GSK3β protein levels in samples derived from FCD patients, compared to non-epileptic controls. FCD samples also had significantly greater levels of total and S499-phosphorylated FMRP.
CONCLUSION: These findings support our hypothesis that malformative lesions associated with FCD are characterized by high levels of FMRP activation along with dysregulation of both PI3K/AKT/mTOR and canonical Wnt signaling. These novel clinical findings extend previous work in animal models, further suggesting a potential unforeseen role of GSK3α, and GSK3β in the pathophysiology of FCD and refractory epilepsy.

PMID: 32833881 [PubMed - as supplied by publisher]

A positive, growth-based PAM screen identifies noncanonical motifs recognized by the S. pyogenes Cas9.

Tue, 08/25/2020 - 06:12
Related Articles

A positive, growth-based PAM screen identifies noncanonical motifs recognized by the S. pyogenes Cas9.

Sci Adv. 2020 Jul;6(29):eabb4054

Authors: Collias D, Leenay RT, Slotkowski RA, Zuo Z, Collins SP, McGirr BA, Liu J, Beisel CL

Abstract
CRISPR technologies have overwhelmingly relied on the Streptococcus pyogenes Cas9 (SpyCas9), with its consensus NGG and less preferred NAG and NGA protospacer-adjacent motifs (PAMs). Here, we report that SpyCas9 also recognizes sequences within an N(A/C/T)GG motif. These sequences were identified on the basis of preferential enrichment in a growth-based screen in Escherichia coli. DNA binding, cleavage, and editing assays in bacteria and human cells validated recognition, with activities paralleling those for NAG(A/C/T) PAMs and dependent on the first two PAM positions. Molecular-dynamics simulations and plasmid-clearance assays with mismatch-intolerant variants supported induced-fit recognition of an extended PAM by SpyCas9 rather than recognition of NGG with a bulged R-loop. Last, the editing location for SpyCas9-derived base editors could be shifted by one nucleotide by selecting between (C/T)GG and adjacent N(C/T)GG PAMs. SpyCas9 and its enhanced variants thus recognize a larger repertoire of PAMs, with implications for precise editing, off-target predictions, and CRISPR-based immunity.

PMID: 32832642 [PubMed - as supplied by publisher]

Correlates of Nonmedical Prescription Opioid Use Among U.S. Adolescents.

Tue, 08/25/2020 - 06:12
Related Articles

Correlates of Nonmedical Prescription Opioid Use Among U.S. Adolescents.

Am J Prev Med. 2019 11;57(5):e175-e179

Authors: Barnett TE, Thompson EL, Litt DM, Lewis MA

Abstract
INTRODUCTION: The purpose of this study is to assess risk factors, including other substance use, for nonmedical prescription opioid use among U.S. adolescents.
METHODS: A secondary data analysis of the 2017 Youth Risk Behavior Survey was conducted (n=10,175) in 2018. The outcome was nonmedical prescription opioid use. Predictor variables included other substance use, mood, sleep, academic performance, and demographic characteristics. Survey-weighted procedures in SAS, version 9.4 were used, and an adjusted logistic regression model was conducted.
RESULTS: Among the sampled adolescents, 13.8% (95% confidence limit=12.4%, 15.3%) reported nonmedical prescription opioid use. Nonmedical prescription opioid use was more likely among participants aged 15 years (versus 16 years), American Indian/Alaskan Natives, and those who reported being sad or hopeless. All other substance use was significantly associated with increased odds of nonmedical prescription opioid use. Nonmedical prescription opioid use was 1.5 times more likely among electronic vapor users (AOR=1.58, 95% CI=1.34, 1.86), 2 times more likely among cigarette (AOR=2.49, 95% CI=2.16, 2.88) and marijuana users (AOR=2.45, 95% CI=2.05, 2.93), and almost 3 times as likely among alcohol users (AOR=2.98, 95% CI=2.18, 4.07).
CONCLUSIONS: Study findings suggest a need for more interventions for nonmedical prescription opioid use among adolescents in the U.S. Information on nonmedical prescription opioid use should be added to all substance use prevention programs for adolescents. Moreover, future research needs to identify longitudinal predictors of adolescent nonmedical prescription opioid use to inform prevention efforts.

PMID: 31564603 [PubMed - indexed for MEDLINE]

Trunk muscle activity during pressure feedback monitoring among individuals with and without chronic low Back pain.

Mon, 08/24/2020 - 05:23

Trunk muscle activity during pressure feedback monitoring among individuals with and without chronic low Back pain.

BMC Musculoskelet Disord. 2020 Aug 22;21(1):569

Authors: Li X, Lo WLA, Lu SW, Liu H, Lin KY, Lai JY, Li L, Wang CH

Abstract
BACKGROUND: Pressure biofeedback unit (PBU) is a widely used non-invasive device to assist core muscle training by providing pressure feedback. The aim this study was to compare the muscle activities of transverse abdominis (TA) and multifidus (MF) at different target pressures (50, 60 and 70 mmHg) of PBU between individuals with and without cLBP.
METHODS: Twenty-two patients with chronic LBP (cLBP) and 24 age matched healthy individuals were recruited. Electromyography (EMG) signals were recorded from the TA and MF muscles while the TA and MF were contracted to achieve PBU pressure value of 50, 60 and 70 mmHg in random order. The average EMG amplitude (AEMG) of 3 replicate trials was used in the analysis after normalization to %MVIC. %MVIC is defined as the mean of the three AEMG divided by the AEMG of MVIC. Two-way ANOVA was performed to assess the effects of groups (healthy and cLBP) and the three different target pressures of PBU. Independent sample t-test was conducted to compare between the two groups. Spearman's correlation analysis was performed in the cLBP group to determine potential correlations between EMG activity, NPRS and ODI.
RESULTS: The %MVIC of the TA and MF in the cLBP group were higher than the control group at each pressure value (P<0.05). During maximal voluntary isometric contraction (MVIC) of TA and MF, compared with healthy groups, cLBP subjects showed a decrease (TA mean = 47.61 μV; MF mean = 42.40 μV) in EMG amplitudes (P ≤ 0.001). The MVIC of MF was negatively correlated with Numerical Pain Rating Scale (r = - 0.48, P = 0.024) and Oswestry Disability Index (r = - 0.59, P = 0.004).
CONCLUSIONS: We measured the trunk muscles activities at different PBU pressure values, which allows the individual to estimate trunk muscle contraction via PBU. Clinicians may be able to confer the data obtained through EMG recordings to adjust the exercise intensity of PBU training accordingly.

PMID: 32828131 [PubMed - as supplied by publisher]

Hexobarbital Sleep Test for Predicting the Susceptibility or Resistance to Experimental Posttraumatic Stress Disorder.

Sun, 08/23/2020 - 07:00
Related Articles

Hexobarbital Sleep Test for Predicting the Susceptibility or Resistance to Experimental Posttraumatic Stress Disorder.

Int J Mol Sci. 2020 Aug 17;21(16):

Authors: Komelkova M, Manukhina E, Downey HF, Sarapultsev A, Cherkasova O, Kotomtsev V, Platkovskiy P, Fedorov S, Sarapultsev P, Tseilikman O, Tseilikman D, Tseilikman V

Abstract
Hexobarbital sleep test (HST) was performed in male Wistar rats (hexobarbital 60 mg/kg, i.p.) 30 days prior to stress exposure. Based on the duration of hexobarbital-induced sleep, rats were divided into two groups, animals with high intensity (fast metabolizers (FM), sleep duration <15 min) or low intensity of hexobarbital metabolism (slow metabolizers (SM), sleep duration ≥15 min). The SM and FM groups were then divided into two subgroups: unstressed and stressed groups. The stressed subgroups were exposed to predator scent stress for 10 days followed by 15 days of rest. SM and FM rats from the unstressed group exhibited different behavioral and endocrinological patterns. SM showed greater anxiety and higher corticosterone levels. In stressed animals, anxiety-like posttraumatic stress disorder (PTSD) behavior was aggravated only in SM. Corticosterone levels in the stressed FM, PTSD-resistant rats, were lower than in unstressed SM. Thus, HST was able to predict the susceptibility or resistance to experimental PTSD, which was consistent with the changes in glucocorticoid metabolism.

PMID: 32824478 [PubMed - as supplied by publisher]

Effect of functional electrical stimulation plus body weight-supported treadmill training for gait rehabilitation in patients with poststroke: a retrospective case-matched study.

Thu, 08/20/2020 - 07:31
Related Articles

Effect of functional electrical stimulation plus body weight-supported treadmill training for gait rehabilitation in patients with poststroke: a retrospective case-matched study.

Eur J Phys Rehabil Med. 2020 Feb;56(1):34-40

Authors: Bao X, Luo JN, Shao YC, Tang ZQ, Liu HY, Liu H, Tan JW

Abstract
BACKGROUND: Functional electrical stimulation (FES) plus body weight-supported treadmill training (BWSTT) provide effective gait training for poststroke patients with abnormal gait. These features promote a successful active motor relearning of ambulation in stroke survivors.
AIM: This is a retrospective study to assess the effect of FES plus BWSTT for gait rehabilitation in patients poststroke.
DESIGN: A retrospective case-matched study.
SETTING: Participants were recruited from a rehabilitation department in an acute university-affiliated hospital POPULATION: Ninety patients poststroke from Yue Bei People's Hospital underwent BWSTT (A: control group) were compared to an equal number of cross-matched patients who received FES plus BWSTT (B: FES plus BWSTT group).
METHODS: While B group received FES for 45 minutes plus BSWTT for 30 minutes in the program, group A received time-matched BWSTT alone. The walking speed, step length, step cadence, Fugl-Meyer Lower-Limb Scale (LL-FMA), composite spasticity scale (CSS), 10-Meter Walk Test (10MWT), Tinetti Balance Test (TBT) and nerve physiology testing were collected before and after intervention.
RESULTS: One hundred and eighty patients with poststroke abnormal gait were chosen. There were significant differences in walking speed, step length, step cadence, LL-FMA, CSS, TBT, and 10MWT between baseline and postintervention (P<0.05). There were significant differences in walking speed, step length, step cadence, LL-FMA, CSS, TBT, and 10MWT between two groups at the end of the eighth week (P<0.05), but not at baseline (P>0.05). In comparison with group A, the peak of somatosensory evoked potential (SEP) and motor evoked potential (MEP) amplitude increased, the latency was shortened, and the conduction velocity of sensory nerve (SCV) and motor nerve (MCV) was significantly increased in the group B (P<0.05). No adverse events occurred during the study.
CONCLUSIONS: This study suggests that FES plus BWSTT could be more effective than BWSTT alone in the improvement of gait, balance, spasticity, and function of the lower limb in patients poststroke.
CLINICAL REHABILITATION IMPACT: Introduce effective rehabilitation strategies for poststroke patients with abnormal gait.

PMID: 31615194 [PubMed - indexed for MEDLINE]

Understanding perceived usefulness and actual use of protective behavioral strategies: The role of perceived norms for the reasons that young adult drinkers use protective behavioral strategies.

Tue, 08/18/2020 - 06:09

Understanding perceived usefulness and actual use of protective behavioral strategies: The role of perceived norms for the reasons that young adult drinkers use protective behavioral strategies.

Addict Behav. 2020 Jul 31;112:106585

Authors: Fairlie AM, Lewis MA, Waldron KA, Wallace EC, Lee CM

Abstract
INTRODUCTION: The current study examines the norms-behavior link by investigating a novel cognition for protective behavioral strategies (PBS)-descriptive and injunctive norms for close friends' reasons to use PBS (e.g., limit drinking, reduce consequences)-in relation to one's own perception of usefulness and personal use of PBS. Further, we tested whether the association between perceived norms for reasons to use PBS and personal PBS use was mediated by perceived usefulness of PBS.
METHODS: College student drinkers ages 18-24 [N = 301; 53% female, 69% White, mean age = 20.16 years (SD = 1.54)] were recruited for a larger study. Eligible students reported alcohol use 2+ days a week and 1+ occasions of heavy episodic drinking in the last two weeks. Linear regression tested whether descriptive and injunctive norms for reasons to use PBS were associated with perceived usefulness and personal use of PBS; path analysis was used to test mediation. All analyses were conducted by PBS subscale (limiting/stopping, serious harm reduction, manner of drinking).
RESULTS: Descriptive norms for reasons to use PBS (i.e., perceptions that close friends use PBS to reduce drinking/consequences) were positively associated with perceived usefulness and personal PBS use for limiting/stopping and to some extent manner of drinking. For each subscale, the association between descriptive norms for reasons to use PBS and personal PBS use was mediated by perceived usefulness of PBS. Results were not significant for injunctive norms.
CONCLUSIONS: Findings suggest descriptive norms, rather than injunctive norms, for close friends' reasons to use PBS, may be relevant for inclusion in brief interventions.

PMID: 32805540 [PubMed - as supplied by publisher]

Synergistic Effect and Antibiofilm Activity of a Skin and Wound Cleanser.

Tue, 08/18/2020 - 06:09

Synergistic Effect and Antibiofilm Activity of a Skin and Wound Cleanser.

Wounds. 2020 May 07;:

Authors: Salamone AB, Salamone JC, McMahon RE, Poleon S, Bionda N, D'Arpa P

Abstract
INTRODUCTION: Biofilm in chronic wounds impedes the wound healing process. Each biofilm has differing characteristics requiring a multifaceted approach for removal while maintaining a surrounding environment conducive to wound healing.
OBJECTIVE: In this study, 3 of the components in a wound cleanser are tested to determine synergy in eradicating biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in vitro.
MATERIALS AND METHODS: The 3 components assessed for synergy were ethylenediamine tetraacetic acid sodium salts (EDTA), vicinal diols (VD; ethylhexylglycerin and octane-1,2-diol), and polyhexamethylene biguanide (PHMB). Each component was assessed individually and in combination while dissolved in a base solution. The Calgary assay method was used for biofilm growth and treatment. Kull Equation analysis for synergy was conducted using viable count results.
RESULTS: Synergy is defined as the interaction of components to produce a combined effect greater than the sum of their separate effects. The base solution containing all 3 components (EDTA, VD, and PHMB) reduced biofilm viability by more than 5 logs, demonstrating statistically significant synergy. The 3 components tested individually in the base solution resulted in the following: EDTA did not reduce bacteria viability; VD reduced viability by about 1 log; and PHMB reduced P aeruginosa viability by about 2.5 logs and MRSA viability by about 4 logs. Of importance, the MRSA biofilm failed to regrow in the recovery plates after combined treatment, indicating complete elimination of the biofilm bacteria.
CONCLUSIONS: The experimental and calculated results indicate the 3 components (VD, EDTA, and PHMB) when used together act synergistically to eradicate MRSA and P aeruginosa biofilms in vitro.

PMID: 32804659 [PubMed - as supplied by publisher]

Pages