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]
Updated: 2 hours 29 min ago

Neuroprotection of Cyperus esculentus L. orientin against cerebral ischemia/reperfusion induced brain injury.

Wed, 10/02/2019 - 07:53

Neuroprotection of Cyperus esculentus L. orientin against cerebral ischemia/reperfusion induced brain injury.

Neural Regen Res. 2020 Mar;15(3):548-556

Authors: Jing SQ, Wang SS, Zhong RM, Zhang JY, Wu JZ, Tu YX, Pu Y, Yan LJ

Abstract
Orientin is a flavonoid monomer. In recent years, its importance as a source of pharmacological active substance is growing rapidly due to its properties such as anti-myocardial ischemia, anti-apoptosis, anti-radiation, anti-tumor, and anti-aging. However, the neuroprotective effects of Orientin on stroke injury have not been comprehensively evaluated. The aim of the present study was thus to investigate the neuroprotective capacity and the potential mechanisms of Cyperus esculentus L. orientin (CLO) from Cyperus esculentus L. leaves against ischemia/reperfusion (I/R) injury using standard orientin as control. For in vitro studies, we treated HT22 cells with CoCl2 as an in vitro ischemic injury model. HT22 cells in the control group were treated with CoCl2. For in vivo studies, we used rat models of middle cerebral artery occlusion, and animals that received sham surgery were used as controls. We found that CLO protected CoCl2-induced HT22 cells against ischemia/reperfusion injury by lowering lipid peroxidation and reactive oxygen species formation as well as decreasing protein oxidation. However, CLO did not reduce the release of lactate dehydrogenase nor increase the activity of superoxide dismutase. Results showed that CLO could decrease neurological deficit score, attenuate brain water content, and reduce cerebral infarct volume, leading to neuroprotection during cerebral ischemia-reperfusion injury. Our studies indicate that CLO flavonoids can be taken as a natural antioxidant and bacteriostastic substance in food and pharmaceutical industry. The molecular mechanisms of CLO could be at least partially attributed to the antioxidant properties and subsequently inhibiting activation of casepase-3. All experimental procedures and protocols were approved on May 16, 2016 by the Experimental Animal Ethics Committee of Xinjiang Medical University of China (approval No. IACUC20160516-57).

PMID: 31571667 [PubMed]

Hypoxia compounds exercise-induced free radical formation in humans; partitioning contributions from the cerebral and femoral circulation.

Wed, 10/02/2019 - 07:53
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Hypoxia compounds exercise-induced free radical formation in humans; partitioning contributions from the cerebral and femoral circulation.

Free Radic Biol Med. 2018 08 20;124:104-113

Authors: Bailey DM, Rasmussen P, Evans KA, Bohm AM, Zaar M, Nielsen HB, Brassard P, Nordsborg NB, Homann PH, Raven PB, McEneny J, Young IS, McCord JM, Secher NH

Abstract
This study examined to what extent the human cerebral and femoral circulation contribute to free radical formation during basal and exercise-induced responses to hypoxia. Healthy participants (5♂, 5♀) were randomly assigned single-blinded to normoxic (21% O2) and hypoxic (10% O2) trials with measurements taken at rest and 30 min after cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled from the brachial artery (a), internal jugular and femoral veins (v) for non-enzymatic antioxidants (HPLC), ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH) and low density lipoprotein (LDL) oxidation (spectrophotometry). Cerebral and femoral venous blood flow was evaluated by transcranial Doppler ultrasound (CBF) and constant infusion thermodilution (FBF). With 3 participants lost to follow up (final n = 4♂, 3♀), hypoxia increased CBF and FBF (P = 0.041 vs. normoxia) with further elevations in FBF during exercise (P = 0.002 vs. rest). Cerebral and femoral ascorbate and α-tocopherol consumption (v < a) was accompanied by A•-/LOOH formation (v > a) and increased LDL oxidation during hypoxia (P < 0.043-0.049 vs. normoxia) implying free radical-mediated lipid peroxidation subsequent to inadequate antioxidant defense. This was pronounced during exercise across the femoral circulation in proportion to the increase in local O2 uptake (r = -0.397 to -0.459, P = 0.037-0.045) but unrelated to any reduction in PO2. These findings highlight considerable regional heterogeneity in the oxidative stress response to hypoxia that may be more attributable to local differences in O2 flux than to O2 tension.

PMID: 29859345 [PubMed - indexed for MEDLINE]

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

Tue, 10/01/2019 - 07:41
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Correlates of Nonmedical Prescription Opioid Use Among U.S. Adolescents.

Am J Prev Med. 2019 Sep 26;:

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 - as supplied by publisher]

Letter to the Editor. Reversal of low prealbumin with oral branched-chain amino acids: a simple solution to an expensive problem.

Tue, 10/01/2019 - 07:41
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Letter to the Editor. Reversal of low prealbumin with oral branched-chain amino acids: a simple solution to an expensive problem.

J Neurosurg Spine. 2018 10 26;30(1):146-147

Authors: Dickerman R, Williamson J, Bennett M

PMID: 30485191 [PubMed - indexed for MEDLINE]

Dopamine D3 receptor partial agonist LS-3-134 attenuates cocaine-motivated behaviors.

Tue, 10/01/2019 - 07:41
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Dopamine D3 receptor partial agonist LS-3-134 attenuates cocaine-motivated behaviors.

Pharmacol Biochem Behav. 2018 12;175:123-129

Authors: Powell GL, Bonadonna JP, Vannan A, Xu K, Mach RH, Luedtke RR, Neisewander JL

Abstract
AIMS: The dopamine D3 receptor (D3R) is a pharmacotherapeutic target for drug dependence. We have successfully imaged human D3Rs using radiolabeled LS-3-134, an arylamide phenylpiperazine with moderate selectivity for the D3R over D2R and low efficacy at the D2 and D3R. In this study, we screened for effects of LS-3-134 as a potential anti-cocaine therapeutic.
METHODS: Male rats were pretreated with LS-3-134 (0, 1.0, 3.2, or 5.6 mg/kg, IP) 15 min prior to tests for its effects on spontaneous and cocaine-induced locomotion. We next investigated the effects of LS-3-134 (0, 1.0, 3.2, 5.6, or 10.0 mg/kg, IP) on operant responding on a multiple variable-interval (VI) 60-second schedule with alternating cocaine (0.375 mg/kg, IV) and sucrose (45 mg) reinforcer components. Additionally, we tested LS-3-134 (5.6 mg/kg, IP) effects on a progressive ratio (PR) schedule of cocaine reinforcement, on extinction of cocaine-seeking behavior, and on reinstatement of extinguished cocaine-seeking behavior by cocaine-associated light/tone cues.
RESULTS: LS-3-134 did not alter spontaneous locomotion, but reduced cocaine-induced locomotion, break points on the high-effort progressive ratio schedule of reinforcement, and responding during extinction and cue reinstatement. In contrast, LS-3-134 did not alter cocaine or sucrose reinforcement on the low-effort multiple VI 60-second schedule.
CONCLUSIONS: The effects of LS-3-134 are similar to other dopamine D3 low efficacy partial agonists and antagonists in attenuating cocaine intake under high effort schedules of reinforcement and in attenuating cocaine-seeking behavior elicited by cocaine-associated cues. These findings are consistent with the anti-craving profile of other dopamine D3 drugs.

PMID: 30308214 [PubMed - indexed for MEDLINE]

High salt loading increases brain derived neurotrophic factor in supraoptic vasopressin neurones.

Tue, 10/01/2019 - 07:41
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High salt loading increases brain derived neurotrophic factor in supraoptic vasopressin neurones.

J Neuroendocrinol. 2018 11;30(11):e12639

Authors: Balapattabi K, Little JT, Farmer GE, Cunningham JT

Abstract
High salt loading (SL) is associated with inappropriate arginine vasopressin (AVP) release and increased mean arterial pressure. Previous work has shown that chronic high salt intake impairs baroreceptor inhibition of rat AVP neurones through brain-derived neurotrophic factor (BDNF) dependent activation of tyrosine receptor kinase B (TrkB) and down-regulation of K+/Cl- co-transporter KCC2. This mechanism diminishes the GABAA inhibition of AVP neurones in the supraoptic nucleus (SON) by increasing intracellular chloride. However, the source of BDNF leading to this ionic plasticity is unknown. In the present study, we used adeno-associated viral vectors with short hairpin RNA against BDNF to test whether SON is the source of BDNF contributing to increased AVP release and elevated mean arterial pressure in high salt loaded rats. Virally mediated BDNF knockdown (shBDNF) in the SON of salt loaded rats significantly blocked the increases in BDNF mRNA and AVP heterogeneous RNA expression. The observed increase in the activation of TrkB receptor during salt loading is consistent with previous studies. Western blot analysis of SON punches revealed that tyrosine phosphorylation of TrkB (pTrkBY515) was significantly decreased in salt shBDNF rats compared to the salt scrambled (SCR) rats. Injections of shBDNF in the SON also significantly prevented the increase in plasma AVP concentration associated with salt loading. However, the salt loading induced increase in mean arterial pressure was not decreased with BDNF knockdown in the SON. Average daily fluid intake and urine output were significantly elevated in both salt SCR and salt shBDNF rats compared to the euhydrated controls. Daily average urine sodium concentration was significantly higher in shBDNF injected salt rats than the other groups. These findings indicate that BDNF produced in the SON contributes to the increased AVP secretion during high salt loading but not with respect to the subsequent increase in mean arterial pressure.

PMID: 30129982 [PubMed - indexed for MEDLINE]

Neuronal subset-specific deletion of Pten results in aberrant Wnt signaling and memory impairments.

Tue, 10/01/2019 - 07:41
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Neuronal subset-specific deletion of Pten results in aberrant Wnt signaling and memory impairments.

Brain Res. 2018 11 15;1699:100-106

Authors: Hodges SL, Reynolds CD, Smith GD, Jefferson TS, Gao N, Morrison JB, White J, Nolan SO, Lugo JN

Abstract
The canonical Wnt and PI3K/Akt/mTOR pathways both play critical roles in brain development early in life. There is extensive evidence of how each pathway is involved in neuronal and synaptic maturation, however, how these molecular networks interact requires further investigation. The present study examines the effect of neuronal subset-specific deletion of phosphatase and tensin homolog (Pten) in mice on Wnt signaling protein levels and associated cognitive impairments. PTEN functions as a negative regulator of the PI3K/Akt/mTOR pathway, and mutations in Pten can result in cognitive and behavioral impairments. We found that deletion of Pten resulted in elevated Dvl2, Wnt5a/b, and Naked2, along with decreased GSK3β hippocampal synaptosome protein expression compared to wild type mice. Aberrations in the canonical Wnt pathway were associated with learning and memory deficits in Pten knockout mice, specifically in novel object recognition and the Lashley maze. This study demonstrates that deletion of Pten not only significantly impacts PI3K/Akt/mTOR signaling, but affects proper functioning of the Wnt signaling pathway. Overall, these findings will help elucidate how the PI3K/Akt/mTOR pathway intersects with Wnt signaling to result in cognitive impairments, specifically in memory.

PMID: 30086265 [PubMed - indexed for MEDLINE]

Antibiotic-Induced Dysbiosis Predicts Mortality in an Animal Model of Clostridium difficile Infection.

Tue, 10/01/2019 - 07:41
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Antibiotic-Induced Dysbiosis Predicts Mortality in an Animal Model of Clostridium difficile Infection.

Antimicrob Agents Chemother. 2018 10;62(10):

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

Abstract
Antibiotic disruption of the intestinal microbiota favors colonization by Clostridium difficile Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrations in feces and the intensity of dysbiosis and quantified the link between this intensity and mortality. We administered either moxifloxacin (n = 70) or clindamycin (n = 60) to hamsters by subcutaneous injection from day 1 (D1) to D5 and challenged them with a C. difficile toxigenic strain at D3 Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D0 and D3 using diversity indices determined from 16S rRNA gene profiling. Survival was monitored until D16 We analyzed the relationship between fecal antibiotic concentrations and dysbiosis at the time of C. difficile challenge and studied their capacity to predict subsequent death of the animals. Increasing doses of DAV131A reduced fecal concentrations of both antibiotics, lowered dysbiosis, and increased survival from 0% to 100%. Mortality was related to the level of dysbiosis (P < 10-5 for the change of Shannon index in moxifloxacin-treated animals and P < 10-9 in clindamycin-treated animals). The Shannon diversity index and unweighted UniFrac distance best predicted death, with areas under the receiver operating curve (ROC) of 0.89 (95% confidence interval [CI], 0.82, 0.95) and 0.95 (0.90, 0.98), respectively. Altogether, moxifloxacin and clindamycin disrupted the diversity of the intestinal microbiota with a dependency on the DAV131A dose; mortality after C. difficile challenge was related to the intensity of dysbiosis in similar manners with the two antibiotics.

PMID: 30061286 [PubMed - indexed for MEDLINE]

Ovarian cancer: Current status and strategies for improving therapeutic outcomes.

Sat, 09/28/2019 - 16:18

Ovarian cancer: Current status and strategies for improving therapeutic outcomes.

Cancer Med. 2019 Sep 27;:

Authors: Chandra A, Pius C, Nabeel M, Nair M, Vishwanatha JK, Ahmad S, Basha R

Abstract
Of all the gynecologic tumors, ovarian cancer (OC) is known to be the deadliest. Advanced-stages of OC are linked with high morbidity and low survival rates despite the immense amount of research in the field. Shortage of promising screening tools for early-stage detection is one of the major challenges linked with the poor survival rate for patients with OC. In OC, therapeutic management is used with multidisciplinary approaches that includes debulking surgery, chemotherapy, and (rarely) radiotherapy. Recently, there is an increasing interest in using immunomodulation for treating OC. Relapse rates are high in this malignancy and averages around every 2-years. Further treatments after the relapse are more intense, increasing the toxicity, resistance to chemotherapy drugs, and financial burden to patients with poor quality-of-life. A procedure that has been studied to help reduce the morbidity rate involves pre-sensitizing cancer cells with standard therapy in order to produce optimal results with minimum dosage. Utilizing such an approach, platinum-based agents are effective due to their increased response to platinum-based chemotherapy in relapsed cases. These chemo-drugs also help address the issue of drug resistance. After conducting an extensive search with available literature and the resources for clinical trials, information is precisely documented on current research, biomarkers, options for treatment and clinical trials. Several schemes for enhancing the therapeutic responses for OC are discussed systematically in this review with an attempt in summarizing the recent developments in this exciting field of translational/clinical research.

PMID: 31560828 [PubMed - as supplied by publisher]

Reduced Cerebrovascular and Cardioventilatory Responses to Intermittent Hypoxia in Elderly.

Fri, 09/27/2019 - 07:04
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Reduced Cerebrovascular and Cardioventilatory Responses to Intermittent Hypoxia in Elderly.

Respir Physiol Neurobiol. 2019 Sep 23;:103306

Authors: Liu X, Chen X, Kline G, Ross SE, Hall JR, Ding Y, Mallet RT, Shi X

Abstract
BACKGROUND: The impact of aging on cerebrovascular function and tissue oxygenation during graded hypoxemia is incompletely known. This study compared the age effect on these variables during cyclic hypoxemia-reoxygenation.
METHODS: Hypoxia-induced changes in arterial (SaO2) and cerebral tissue (ScO2) O2 saturation, middle cerebral arterial flow velocity (VMCA), estimated cerebral vascular conductance (CVC), heart rate (HR) and ventilation were compared between 12 elderly (71 ± 2 yr, 7 women) and 13 young (24 ± 3 yr, 5 women) adults during the first and fifth 5-min exposures to 10% O2.
RESULTS: Although pre-hypoxia SaO2 did not differ between the groups, ScO2 was lower (P < 0.05) in the elderly (68.4 ± 1.2%) than young (73.8 ± 0.9%) adults, commensurate with a lower resting VMCA (P < 0.05). SaO2 fell less sharply (P < 0.05) in the elderly subjects during the first and fifth hypoxia exposures. Moreover, the responses of ScO2, VMCA, CVC, HR and breathing frequency to hypoxia were attenuated in the elderly subjects. Systolic and diastolic arterial pressures fell by 2-6 mmHg during hypoxia in both young and elderly. Thus, hypoxemia developed more gradually in elderly than young adults during normobaric hypoxia, concordant with a reduced metabolic demand in the elderly.
CONCLUSIONS: The elderly adults safely tolerated cyclic, moderate hypoxemia which lowered SaO2 by 2025%, despite dampening of cerebrovascular and cardiac responses to hypoxemia.

PMID: 31557538 [PubMed - as supplied by publisher]

Inducible Rodent Models of Glaucoma.

Fri, 09/27/2019 - 07:04
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Inducible Rodent Models of Glaucoma.

Prog Retin Eye Res. 2019 Sep 23;:100799

Authors: Pang IH, Clark AF

Abstract
Glaucoma is one of the leading causes of vision impairment worldwide. In order to further understand the molecular pathobiology of this disease and to develop better therapies, clinically relevant animal models are necessary. In recent years, both the rat and mouse have become popular models in glaucoma research. Key reasons are: many important biological similarities shared among rodent eyes and the human eye; development of improved methods to induce glaucoma and to evaluate glaucomatous damage; availability of genetic tools in the mouse; as well as the relatively low cost of rodent studies. Commonly studied rat and mouse glaucoma models include intraocular pressure (IOP)-dependent and pressure-independent models. The pressure-dependent models address the most important risk factor of elevated IOP, whereas the pressure-independent models assess "normal tension" glaucoma and other "non-IOP" related factors associated with glaucomatous damage. The current article provides descriptions of these models, their characterizations, specific techniques to induce glaucoma, mechanisms of injury, advantages, and limitations.

PMID: 31557521 [PubMed - as supplied by publisher]

Enhancing Statin Adherence Using a Motivational Interviewing Intervention and Past Adherence Trajectories in Patients with Suboptimal Adherence.

Fri, 09/27/2019 - 07:04
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Enhancing Statin Adherence Using a Motivational Interviewing Intervention and Past Adherence Trajectories in Patients with Suboptimal Adherence.

J Manag Care Spec Pharm. 2019 Oct;25(10):1053-1062

Authors: Abughosh SM, Vadhariya A, Johnson ML, Essien EJ, Esse TW, Serna O, Gallardo E, Boklage SH, Choi J, Holstad MM, Fleming ML

Abstract
BACKGROUND: Statins have been shown to be effective in reducing the occurrence of cardiovascular (CV) events and are widely prescribed for the risk reduction of CV diseases and recurrent CV events. However, poor adherence prevents some patients from receiving the maximum benefit of the therapy. Motivational interviewing (MoI) is a patient-centered collaborative approach that can be used to improve medication adherence. Group-based trajectory modeling depicts patterns of adherence over time and may help tailor the MoI intervention to further enhance adherence.
OBJECTIVE: To assess the effect of a phone-based MoI intervention tailored by patients' past adherence trajectory in improving adherence to statins among patients in a Medicare Advantage prescription drug plan (MAPD).
METHODS: Patients continuously enrolled in an MAPD from 2013 to 2017 with a statin prescription between January and June 2015 to allow 2 years of pre-index period and 1 year of follow-up were included in the study. Adherence to statins was measured monthly during the 1-year follow-up as proportion of days covered (PDC) and incorporated into a group-based trajectory model to provide 4 distinct patterns of adherence: adherent, rapid decline, gradual decline, and gaps in adherence. Patients in the 3 nonadherent groups were randomized to either control or intervention. The intervention was an initial counseling call and up to 2 monthly follow-up calls by pharmacy students trained in MoI, providing education consistent with a previously identified pattern of use. Refill data at 6 months post-intervention were evaluated to examine the intervention's effect on PDC, as continuous and dichotomized as PDC ≥ 0.8, as well as discontinuation. Multivariable regression adjusted for baseline demographics, clinical characteristics, and past adherence trajectory.
RESULTS: There were 152 patients included in the analysis who received MoI phone calls and 304 randomly selected controls. Mean PDC for the intervention group (0.67 ± 0.3) was significantly higher than the control (0.55 ± 0.4; P < 0.001). The intervention group was also less likely to discontinue (OR = 0.38; 95% CI = 0.19-0.76) and more likely to be adherent in the linear regression model (β = 12.4; P < 0.001) as well as in the logistic regression model (OR = 1.87; 95% CI = 1.18-2.95). Previous adherence trajectories were significantly associated with adherence in the follow-up.
CONCLUSIONS: Patients who received the MoI intervention were more likely to be adherent and less likely to discontinue the statin in the 6 months follow-up compared with controls. Future research can identify other approaches to tailor interventions and expand the intervention to other languages. This intervention may also prove valuable to improve adherence to other medications for chronic and asymptomatic diseases.
DISCLOSURES: This study was funded by Regeneron Pharmaceuticals, which provided critical input during study design, implementation, and manuscript preparation. Abughosh reports grants from Sanofi, BMS/Pfizer, and Valeant Pharmaceuticals, unrelated to this study. Vadhariya reports a past internship at Regeneron Pharmaceuticals, unrelated to this study. Esse, Serna, and Gallardo are employees of CareAllies, a Cigna subsidiary. Boklage is an employee of Regeneron Pharmaceuticals. Choi was an employee of Sanofi during this study. Johnson, Essien, Fleming, and Holstad have nothing to disclose. A poster based on this study was presented at AMCP Nexus 2018; October 22-25, 2018; Orlando, FL.

PMID: 31556824 [PubMed - in process]

Prospective Risk for Incapacitated Rape among Sexual Minority Women: Hookups and Drinking.

Fri, 09/27/2019 - 07:04
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Prospective Risk for Incapacitated Rape among Sexual Minority Women: Hookups and Drinking.

J Sex Res. 2019 Sep 26;:1-12

Authors: Jaffe AE, Blayney JA, Lewis MA, Kaysen D

Abstract
Sexual minority women (SMW), including lesbian and bisexual women, are at greater risk for heavy drinking and sexual victimization than heterosexual women. Risk factors for alcohol-related sexual victimization, such as incapacitated rape (IR), include frequent heavy drinking and hookups among heterosexual women, but it is less clear whether these risk factors extend to SMW. This current study was designed to address this gap. In a national sample of SMW (N = 1,057), logistic regressions were used to test whether heavy drinking and hookups in the first year of the study were risk factors for IR during the second year. After controlling for history of prior sexual victimization, subsequent IR was predicted by an interaction between heavy drinking and the number of male hookup partners. Specifically, more frequent heavy drinking was associated with increased risk for subsequent IR, but only among SMW who reported more than one male hookup partner, indicating exposure to more potential perpetrators. When examined separately, this finding held for bisexual women, but was not significant for lesbian women, likely because they reported fewer male hookup partners. Overall, findings from this longitudinal study highlight that in combination, heavy drinking and hookups with multiple men elevate risk for IR.

PMID: 31556751 [PubMed - as supplied by publisher]

The Emerging Roles of mTORC1 in Macromanaging Autophagy.

Fri, 09/27/2019 - 07:04
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The Emerging Roles of mTORC1 in Macromanaging Autophagy.

Cancers (Basel). 2019 Sep 24;11(10):

Authors: Dossou AS, Basu A

Abstract
Autophagy is a process of self-degradation that enables the cell to survive when faced with starvation or stressful conditions. The mechanistic target of rapamycin (mTOR), also known as the mammalian target of rapamycin, plays a critical role in maintaining a balance between cellular anabolism and catabolism. mTOR complex 1 (mTORC1) was unveiled as a master regulator of autophagy since inhibition of mTORC1 was required to initiate the autophagy process. Evidence has emerged in recent years to indicate that mTORC1 also directly regulates the subsequent steps of the autophagy process, including the nucleation, autophagosome elongation, autophagosome maturation and termination. By phosphorylating select protein targets of the autophagy core machinery and/or their regulators, mTORC1 can alter their functions, increase their proteasomal degradation or modulate their acetylation status, which is a key switch of the autophagy process. Moreover, it phosphorylates and alters the subcellular localization of transcription factors to suppress the expression of genes needed for autophagosome formation and lysosome biogenesis. The purpose of this review article is to critically analyze current literatures to provide an integrated view of how mTORC1 regulates various steps of the autophagy process.

PMID: 31554253 [PubMed]

An investigation of the Plasmodium falciparum malaria epidemic in Kavango and Zambezi regions of Namibia in 2016.

Fri, 09/27/2019 - 07:04
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An investigation of the Plasmodium falciparum malaria epidemic in Kavango and Zambezi regions of Namibia in 2016.

Trans R Soc Trop Med Hyg. 2018 Dec 01;112(12):546-554

Authors: Chanda E, Arshad M, Khaloua A, Zhang W, Namboze J, Uusiku P, Angula AH, Gausi K, Tiruneh D, Islam QM, Kolivras K, Haque U

Abstract
Background: Namibia is one of the countries among the eight that are targeting malaria elimination in southern Africa. However, the country has encountered malaria epidemics in recent years. The objective of this study was to investigate malaria epidemics and to contribute to strengthening malaria surveillance and control in an effort to move Namibia toward eliminating malaria.
Method: Malaria epidemiology data for 2014-2015 were collected from the weekly surveillance system. All consenting household members within a 100-m radius of index households were screened in 2016 using a Carestart malaria HRP2/pLDH combined rapid diagnostic test after epidemics. All houses within this radius were sprayed in 2016 with the pyrethroid deltamethrin and K-Othrine WG 250. Anopheles mosquito-positive breeding sites were identified and treated with the organophosphate larvicide temephos. Insecticide susceptibility and bioassay tests were conducted.
Results: During the epidemic response period in 2016, 56 parasitologically confirmed Plasmodium falciparum malaria cases in the Zambezi region were detected from active screening. The majority of those cases (83%) were asymptomatic infections. In the Kavango region, the malaria epidemic persisted, with 228 P. falciparum malaria cases recorded, but only 97 were investigated. In Namibia, malaria vector susceptibility was detected to 4% dichlorodiphenyltrichloroethane. Indoor residual spraying was conducted in 377 (90%) of the targeted households along with community awareness through health education of 1499 people and distribution of more than 2000 information, education and communication materials. The P. falciparum malaria cases in the Zambezi decreased from 122 in week 9 to 97 after week 15.
Conclusions: Malaria epidemics along with the persistence of asymptomatic reservoir infections pose a serious challenge in Namibia's elimination effort. The country needs to ensure sustainable interventions to target asymptomatic reservoir infections and prevent epidemics in order to successfully achieve its goal of eliminating malaria.

PMID: 30252108 [PubMed - indexed for MEDLINE]

Alcohol retail sales licenses and sexually transmitted infections in Texas counties, 2008-2015.

Fri, 09/27/2019 - 07:04
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Alcohol retail sales licenses and sexually transmitted infections in Texas counties, 2008-2015.

Am J Drug Alcohol Abuse. 2018;44(6):678-685

Authors: Rossheim ME, Krall JR, Painter JE, Thombs DL, Stephenson CJ, Suzuki S, Cannell MB, Livingston MD, Gonzalez-Pons KM, Wagenaar AC

Abstract
BACKGROUND: Research suggests that reduced retail alcohol outlet density may be associated with lower prevalence of HIV and other sexually transmitted infections (STIs). On-premise sale of alcohol for immediate consumption is theorized as increasing social interactions that can lead to sexual encounters.
OBJECTIVE: We examined associations between on- and off-premise retail alcohol sales licenses and number of newly diagnosed HIV and STI cases in Texas counties.
METHODS: Retail alcohol sales license data were obtained from the Texas Alcoholic Beverage Commission. HIV and bacterial STI data were obtained from the Texas Department of State Health Services. Associations between retail alcohol sales licenses and STIs were estimated using spatial linear models and Poisson mixed effects models for over-dispersed count data.
RESULTS: Adjusting for county-specific confounders, there was no evidence of residual spatial correlation. In Poisson models, each additional on-premise (e.g., bar and restaurant) alcohol license per 10,000 population in a county was associated with a 1.5% increase (95% CI: 0.4%, 2.6%) in the rate of HIV and a 2.4% increase (95% CI: 1.9%, 3.0%) in the rate of bacterial STIs, adjusting for potential confounders. In contrast, number of off-premise licenses (e.g., take-out stores) was inversely associated with the incidence of STI and HIV, although the association with HIV was not statistically significant.
CONCLUSIONS: This study adds to the limited literature on the association between retail alcohol availability and STIs. Additional research is needed on the role of alcohol availability (and policies affecting availability) in the spread of HIV and other STIs.

PMID: 29863903 [PubMed - indexed for MEDLINE]

Growing Up, Hooking Up, and Drinking: A Review of Uncommitted Sexual Behavior and Its Association With Alcohol Use and Related Consequences Among Adolescents and Young Adults in the United States.

Thu, 09/26/2019 - 06:52
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Growing Up, Hooking Up, and Drinking: A Review of Uncommitted Sexual Behavior and Its Association With Alcohol Use and Related Consequences Among Adolescents and Young Adults in the United States.

Front Psychol. 2019;10:1872

Authors: Garcia TA, Litt DM, Davis KC, Norris J, Kaysen D, Lewis MA

Abstract
Hookups are uncommitted sexual encounters that range from kissing to intercourse and occur between individuals in whom there is no current dating relationship and no expressed or acknowledged expectations of a relationship following the hookup. Research over the last decade has begun to focus on hooking up among adolescents and young adults with significant research demonstrating how alcohol is often involved in hooking up. Given alcohol's involvement with hooking up behavior, the array of health consequences associated with this relationship, as well as its increasing prevalence from adolescence to young adulthood, it is important to determine the predictors and consequences associated with alcohol-related hooking up. The current review extends prior reviews by adding more recent research, including both qualitative and experimental studies (i.e., expanding to review more diverse methods), research that focuses on the use of technology in alcohol-related hookups (i.e., emerging issues), further develops prevention and intervention potentials and directions, and also offers a broader discussion of hooking up outside of college student populations (i.e., expanding generalization). This article will review the operationalization and ambiguity of the phrase hooking up, the relationship between hooking up and alcohol use at both the global and event levels, predictors of alcohol-related hooking up, and both positive and negative consequences, including sexual victimization, associated with alcohol-related hookups. Throughout, commentary is provided on the methodological issues present in the field, as well as limitations of the existing research. Future directions for research that could significantly advance our understanding of hookups and alcohol use are provided.

PMID: 31551844 [PubMed]

Comparative effectiveness of 8- and 12-week ledipasvir/sofosbuvir regimens for HCV infection.

Thu, 09/26/2019 - 06:52
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Comparative effectiveness of 8- and 12-week ledipasvir/sofosbuvir regimens for HCV infection.

Antivir Ther. 2018;23(7):585-592

Authors: Ojha RP, MacDonald BR, Chu TC, Fasanmi EO, Moore JD, Stewart RA

Abstract
BACKGROUND: Real-world studies have aimed to compare the effects of 8- and 12-week ledipasvir/sofosbuvir regimens on sustained virological response (SVR) among HCV infection genotype-1 (HCV-1) treatment-naive patients. Nevertheless, real-world comparative effectiveness studies pose unique challenges, such as confounding by indication, that were not adequately addressed in prior studies. We thus aimed to address limitations in prior studies and compare overall- and subgroup-specific effectiveness of 8- and 12-week ledipasvir/sofosbuvir regimens among HCV-1 treatment-naive patients.
METHODS: Patients eligible for our study were aged ≥18 years and initiated 8- or 12-week ledipasvir/sofosbuvir regimens for treatment-naive HCV-1 at an urban public hospital network. We excluded patients with HIV or cirrhosis. We used marginal structural models to estimate overall and subgroup-specific risk ratios (RRs) and 95% confidence limits (CL) comparing the effect of 8- and 12-week ledipasvir/sofosbuvir regimens on 12-week SVR.
RESULTS: Our study population comprised 191 patients. Among both regimens, the majority were aged >50 years, non-Hispanic White and uninsured. The overall risk of SVR was comparable between the 8- and 12-week regimens (RR=1.01, 95% CL: 0.92, 1.11). The risk of SVR did not vary by race/ethnicity (non-Hispanic Black: RR=1.01, 95% CL: 0.84, 1.21; non-Hispanic White: RR=1.01, 95% CL: 0.89, 1.04).
CONCLUSIONS: Our real-world results suggest that 8- and 12-week ledipasvir/sofosbuvir have comparable effects on SVR among HCV-1 patients without cirrhosis or HIV. In addition, the comparable effectiveness of 8- and 12-week regimens among non-Hispanic Black individuals adds to the growing body of evidence that supports the removal of race-based treatment guidelines.

PMID: 29969099 [PubMed - indexed for MEDLINE]

College Students' Underestimation of Blood Alcohol Concentration from Hypothetical Consumption of Supersized Alcopops: Results from a Cluster-Randomized Classroom Study.

Thu, 09/26/2019 - 06:52
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College Students' Underestimation of Blood Alcohol Concentration from Hypothetical Consumption of Supersized Alcopops: Results from a Cluster-Randomized Classroom Study.

Alcohol Clin Exp Res. 2018 07;42(7):1271-1280

Authors: Rossheim ME, Thombs DL, Krall JR, Jernigan DH

Abstract
BACKGROUND: Supersized alcopops are a class of single-serving beverages popular among underage drinkers. These products contain large quantities of alcohol. This study examines the extent to which young adults recognize how intoxicated they would become from consuming these products.
METHODS: The study sample included 309 undergraduates who had consumed alcohol within the past year. Thirty-two sections of a college English course were randomized to 1 of 2 survey conditions, based on hypothetical consumption of supersized alcopops or beer of comparable liquid volume. Students were provided an empty can of 1 of the 2 beverages to help them answer the survey questions. Equation-calculated blood alcohol concentrations (BACs)-based on body weight and sex-were compared to the students' self-estimated BACs for consuming 1, 2, and 3 cans of the beverage provided to them.
RESULTS: In adjusted regression models, students randomized to the supersized alcopop group greatly underestimated their BAC, whereas students randomized to the beer group overestimated it. The supersized alcopop group underestimated their BAC by 0.04 (95% confidence interval [CI]: 0.034, 0.053), 0.09 (95% CI: 0.067, 0.107), and 0.13 g/dl (95% CI: 0.097, 0.163) compared to the beer group. When asked how much alcohol they could consume before it would be unsafe to drive, students in the supersized alcopop group had 7 times the odds of estimating consumption that would generate a calculated BAC of at least 0.08 g/dl, compared to those making estimates based on beer consumption (95% CI: 3.734, 13.025).
CONCLUSIONS: Students underestimated the intoxication they would experience from consuming supersized alcopops. Revised product warning labels are urgently needed to clearly identify the number of standard drinks contained in a supersized alcopop can. Moreover, regulations are needed to limit alcohol content of single-serving products.

PMID: 29846956 [PubMed - indexed for MEDLINE]

Perceptions of Zika Virus Prevention Among College Students in Florida.

Thu, 09/26/2019 - 06:52
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Perceptions of Zika Virus Prevention Among College Students in Florida.

J Community Health. 2018 08;43(4):673-679

Authors: Thompson EL, Vamos CA, Jones J, Liggett LG, Griner SB, G Logan R, Daley EM

Abstract
Zika virus in Florida prompted a strong public health response, due to its causal association with birth defects. While primarily spread by mosquitos, Zika can be transmitted sexually. The spread of Zika may influence reproductive behaviors among sexually active persons in Florida. This study examined factors associated with willingness to change birth control method use in response to Zika virus among college women and men in Florida. Women and men ages 18-44 at a Florida university (N = 328) were surveyed about Zika knowledge, beliefs about Zika, use of contraceptives and condoms, and socio-demographics between November 2016-April 2017. The outcome variable was willingness to change birth control method were Zika in their area. Logistic regression models in SAS 9.4 were used. Most participants were women (80%), and 47% were 20-22 years old. Only 27% of participants said they would change their birth control method if Zika were in their area. Participants who knew that Zika was sexually transmitted were more likely to be willing to change their birth control method (aOR = 1.71, 95%CI 1.01-2.91). Participants who agreed or strongly agreed that they were fearful of being infected with Zika virus were more likely to be willing to change their birth control methods (aOR = 1.98, 95%CI 1.07-3.67). This study found that, among Florida college students, Zika beliefs and knowledge were associated with a willingness to change birth control method in response to Zika. Understanding the factors that motivate individuals to change reproductive behaviors during an emerging health issue can help tailor preventative messages.

PMID: 29380211 [PubMed - indexed for MEDLINE]

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