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: 1 hour 49 min ago

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

Sun, 08/25/2019 - 05:03

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

Neurochem Int. 2019 Aug 21;: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 - as supplied by publisher]

Spatial and temporal patterns of dengue incidence in northeastern Thailand 2006-2016.

Sun, 08/25/2019 - 05:03
Related Articles

Spatial and temporal patterns of dengue incidence in northeastern Thailand 2006-2016.

BMC Infect Dis. 2019 Aug 23;19(1):743

Authors: Phanitchat T, Zhao B, Haque U, Pientong C, Ekalaksananan T, Aromseree S, Thaewnongiew K, Fustec B, Bangs MJ, Alexander N, Overgaard HJ

Abstract
BACKGROUND: Dengue, a viral disease transmitted by Aedes mosquitoes, is an important public health concern throughout Thailand. Climate variables are potential predictors of dengue transmission. Associations between climate variables and dengue have usually been performed on large-scale first-level national administrative divisions, i.e. provinces. Here we analyze data on a finer spatial resolution in one province, which is often more relevant for effective disease control design. The objective of this study was to investigate the effect of seasonal variations, monthly climate variability, and to identify local clusters of symptomatic disease at the sub-district level based on reported dengue cases.
METHODS: Data on dengue cases were retrieved from the national communicable disease surveillance system in Thailand. Between 2006 and 2016, 15,167 cases were recorded in 199 sub-districts of Khon Kaen Province, northeastern Thailand. Descriptive analyses included demographic characteristics and temporal patterns of disease and climate variables. The association between monthly disease incidence and climate variations was analyzed at the sub-district level using Bayesian Poisson spatial regression. A hotspot analysis was used to assess the spatial patterns (clustered/dispersed/random) of dengue incidence.
RESULTS: Dengue was predominant in the 5-14 year-old age group (51.1%). However, over time, dengue incidence in the older age groups (> 15 years) gradually increased and was the most affected group in 2013. Dengue outbreaks coincide with the rainy season. In the spatial regression model, maximum temperature was associated with higher incidence. The hotspot analysis showed clustering of cases around the urbanized area of Khon Kaen city and in rural areas in the southwestern portion of the province.
CONCLUSIONS: There was an increase in the number of reported dengue cases in older age groups over the study period. Dengue incidence was highly seasonal and positively associated with maximum ambient temperature. However, climatic variables did not explain all the spatial variation of dengue in the province. Further analyses are needed to clarify the detailed effects of urbanization and other potential environmental risk factors. These results provide useful information for ongoing prediction modeling and developing of dengue early warning systems to guide vector control operations.

PMID: 31443630 [PubMed - in process]

Underage drinkers' first experience consuming a popular brand of supersized alcopop.

Sat, 08/24/2019 - 07:53
Related Articles

Underage drinkers' first experience consuming a popular brand of supersized alcopop.

Am J Drug Alcohol Abuse. 2019 Aug 23;:1-9

Authors: Rossheim ME, Greene KM, Yurasek AM, Barry AE, Gonzalez-Pons KM, Trangenstein PJ, Cavazos T, Nelson C, Treffers RD, Thombs DL, Jernigan DH

Abstract
Background: Supersized alcopops are sugar sweetened beverages with high alcohol concentration; Four Loko is the most commonly consumed brand among underage drinkers. Objectives: The current study examined the prevalence and correlates of Four Loko consumption, as well as drinking location, beverage source, quantity consumed, and alcohol-related consequences among students who consumed the product before age 21. Methods: Undergraduate drinkers (n = 1,019; 53.5% female) attending public universities in Florida, Montana, and Virginia completed a classroom survey. Multivariable logistic regression models examined first-time Four Loko experiences among students under age 21 at the time of the drinking episode (n = 336). Results: Among drinkers, 46% had consumed Four Loko. The vast majority (93%) drank the product before age 21. During their first Four Loko drinking episode, 57% consumed at least one can and 10% drank two or more cans. Among underage drinkers, being male (AOR = 6.8), paying for the Four Loko (AOR = 3.1), and earlier age of alcohol initiation (AOR = 0.8) were associated with greater odds of drinking at least one can. Among underage drinkers who finished at least one can, 36% blacked out and 21% vomited. The odds of blacking out and vomiting were greater if the participant drank at least one can (AOR = 6.0, AOR = 4.0). Students in states that sold Four Loko with higher alcohol-by-volume were more likely to blackout (AOR = 2.0) and vomit (AOR = 2.5). Conclusions: Delaying the age of first alcohol use may have protective effects on supersized alcopop consumption. Increased enforcement of existing laws is needed to prevent underage access to Four Loko. Further, laws that reduce the alcohol content of Four Loko may reduce negative consequences associated with its consumption.

PMID: 31442085 [PubMed - as supplied by publisher]

Inhibition of Noncanonical Murine Double Minute 2 Homolog Abrogates Ocular Inflammation through NF-κB Suppression.

Sat, 08/24/2019 - 07:53
Related Articles

Inhibition of Noncanonical Murine Double Minute 2 Homolog Abrogates Ocular Inflammation through NF-κB Suppression.

Am J Pathol. 2018 09;188(9):2087-2096

Authors: Fan Y, Zhang W, Ni A, Mahato B, Chavala SH

Abstract
Uveitis is estimated to account for 10% of all cases of blindness in the United States, including 30,000 new cases of legal blindness each year. Intraocular and oral corticosteroids are the effective mainstay treatment, but they carry the risk of serious long-term ocular and systemic morbidity. New noncorticosteroid therapies with a favorable side effect profile are necessary for the treatment of chronic uveitis, given the paucity of existing treatment choices. We have previously demonstrated that Nutlin-3, a small-molecule inhibitor of murine double minute 2 (MDM2) homolog, suppresses pathologic retinal angiogenesis through a p53-dependent mechanism, but the noncanonical p53-independent functions have not been adequately elucidated. Herein, we demonstrate an unanticipated function of MDM2 inhibition, where Nutlin-3 potently abrogates lipopolysaccharide-induced ocular inflammation. Furthermore, we identified a mechanism by which transcription and translation of NF-κB is mediated by MDM2, independent of p53, in ocular inflammation. Small-molecule MDM2 inhibition is a novel noncorticosteroid strategy for inhibiting ocular inflammation, which may potentially benefit patients with chronic uveitis.

PMID: 30126549 [PubMed - indexed for MEDLINE]

Application of a Health Literacy Framework to Explore Patients' Knowledge of the Link between HPV and Cancer.

Fri, 08/23/2019 - 07:44
Related Articles

Application of a Health Literacy Framework to Explore Patients' Knowledge of the Link between HPV and Cancer.

J Health Commun. 2018;23(8):695-702

Authors: Best AL, Logan RG, Vázquez-Otero C, Fung W, Chee V, Thompson EL, Villalona S, Thompson LMA, Gwede CK, Daley EM

Abstract
The human papillomavirus (HPV) is a sexually transmitted infection and causes most oropharyngeal (e.g., throat) and anogenital (e.g., anal, cervical) cancers. Research indicates low knowledge about the link between HPV and cancer among the general population, and similar low knowledge of HPV among individuals diagnosed with HPV-associated cancers. This is important because HPV status can have implications for treatment, prognosis, and future sexual decisions. Using a health literacy framework, this study explored how patients diagnosed with HPV-associated cancers accessed, understood, appraised, and applied HPV information. We conducted 27 in-depth interviews with patients seeking care at a comprehensive cancer center; and data were analyzed using applied thematic analysis. Findings revealed that patients' primary source of HPV information was medical providers (access); and many patients exhibited limited understanding of HPV and its role in their cancer diagnosis (understand). Most patients (17 of 27) did not mention HPV as the cause of their cancer. Many patients displayed difficulty connecting HPV with their lifestyles (appraise); and few discussed plans to engage in HPV prevention practices going forward (apply). Future research should focus on strategies to improve understanding of HPV which could increase vaccine uptake, reduce stigma, and enhance informed decision-making among HPV-associated cancer patients.

PMID: 30153087 [PubMed - indexed for MEDLINE]

Progressive Exercise Training Improves Maximal Aerobic Capacity in Individuals with Well-Healed Burn Injuries.

Thu, 08/22/2019 - 10:38

Progressive Exercise Training Improves Maximal Aerobic Capacity in Individuals with Well-Healed Burn Injuries.

Am J Physiol Regul Integr Comp Physiol. 2019 Aug 21;:

Authors: Romero SA, Moralez G, Jaffery MF, Huang M, Cramer MN, Romain N, Kouda K, Haller RG, Crandall CG

Abstract
Long term rehabilitative strategies are important for individuals with well-healed burn injuries. Such information is particularly critical because patients are routinely surviving severe burn injuries given medical advances in the acute care setting. The purpose of this study was to test the hypothesis that a 6-month community-based exercise training program will increase maximal aerobic capacity (V̇O2max) in subjects with prior burn injuries, with the extent of that increase influenced by the severity of the burn injury (i.e., percent body surface area burned). Maximal aerobic capacity (indirect calorimetry) and skeletal muscle oxidative enzyme activity (biopsy of the vastus lateralis muscle) were measured pre- and post-exercise training in non-injured control subjects (N = 11) and in individuals with well-healed burn injuries (N = 13, moderate body surface area burned; N = 20, high body surface area burned). Exercise training increased V̇O2max in all groups (control 15 ± 5 %; moderate body surface area 11 ± 3 %; high body surface area 11 ± 2 %; P < 0.05), though the magnitude of this improvement did not differ between groups (P = 0.7). Exercise training also increased the activity of the skeletal muscle oxidative enzymes citrate synthase (P < 0.05) and cytochrome C oxidase (P < 0.05), an effect that did not differ between groups (P = 0.2). These data suggest that 6-months of progressive exercise training improves V̇O2max in individuals with burn injuries and that the magnitude of body surface area burned does not lessen this adaptive response.

PMID: 31433672 [PubMed - as supplied by publisher]

Group-Based Trajectory Models to Identify Sociodemographic and Clinical Predictors of Adherence Patterns to Statin Therapy Among Older Adults.

Wed, 08/21/2019 - 07:29
Related Articles

Group-Based Trajectory Models to Identify Sociodemographic and Clinical Predictors of Adherence Patterns to Statin Therapy Among Older Adults.

Am Health Drug Benefits. 2019 Jun-Jul;12(4):202-211

Authors: Vadhariya A, Fleming ML, Johnson ML, Essien EJ, Serna O, Esse T, Choi J, Boklage SH, Abughosh SM

Abstract
Background: The benefits of statins in the prevention of primary and secondary atherosclerotic cardiovascular (CV) disease events have been well documented. Suboptimal adherence is a persistent problem associated with increased CV events and increased healthcare utilization. Proportion of days covered (PDC) is widely used to measure medication adherence, and provides a single value that does not adequately depict different adherence behavior patterns. Group-based trajectory modeling has been used to identify adherence patterns (or trajectories) over time. The identification of characteristics unique to each pattern can help in the early identification of patients who are likely to be poor adherents and can inform the development of interventions.
Objectives: To identify distinct trajectories of statin adherence in patients enrolled in a Medicare Advantage plan and the sociodemographic and clinical predictors associated with each trajectory.
Methods: Patients were included in the study if they were continuously enrolled in a Medicare Advantage plan between 2013 and 2016 and had a statin prescription between January 2015 and June 2015. We observed each patient for 360 days and computed the monthly PDC. The monthly PDC was incorporated into a group-based trajectory model to provide distinct patterns of adherence. Using group-based trajectory modeling, the patients were categorized into groups based on their adherence patterns. Multinomial logistic regression was performed to identify the sociodemographic and clinical factors associated with each group.
Results: A total of 7850 patients were included in the analysis and were categorized into 4 distinct groups based on statin adherence-rapid discontinuation (7.8%), gradual decline (16.8%), gaps in adherence (17.2%), and high or nearly perfect adherence (58.2%). Significant predictors of being placed into one or more of the low-adherence trajectories compared with the high-adherence trajectory included sex, age, low-income subsidy, language, Charlson Comorbidity Index score, statin intensity, and 90-day refills.
Conclusions: The predictors identified in this study provide valuable insight into patient characteristics that increase the risk for statin nonadherence, which has the potential to inform targeted interventions. Identifying patient trajectories can inform the future development of protocols to individualize appropriate interventions for these patients.

PMID: 31428238 [PubMed]

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

Wed, 08/21/2019 - 07:29
Related Articles

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

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

Authors: Roberts J, Vedantam S

PMID: 31427106 [PubMed - in process]

Physical activity intensity of patient's with traumatic brain injury during inpatient rehabilitation.

Wed, 08/21/2019 - 07:29
Related Articles

Physical activity intensity of patient's with traumatic brain injury during inpatient rehabilitation.

Brain Inj. 2018;32(12):1518-1524

Authors: Ramsey J, Driver S, Swank C, Bennett M, Dubiel R

Abstract
OBJECTIVE: Use actigraphy to (1) describe the intensity of physical activity completed by patients with traumatic brain injury (TBI) during inpatient rehabilitation, and (2) examine the association between physical activity intensity and demographic, injury, and programmatic characteristics.
DESIGN: Observational.
METHOD: Fifty individuals with TBI undergoing inpatient rehabilitation wore accelerometers for an average of 8.7 ± 1.8 days to capture physical activity intensity that was summarized using activity counts (ACs). Intensity of activity was described for categories of the participant's day including physical and occupational therapy, non-active therapy, recreation, and sleep. Descriptive statistics, Pearson's correlations, and general linear regression were computed.
RESULTS: Participants average physical activity intensity was considered "inactive" during physical (M = 242.7.7 ± 105.2 AC/min) and occupational therapy (M = 244 ± 105), non-active therapy (M = 142.2 ± 74.1), and recreation (M = 112.8 ± 59.5), and "sedentary" during sleep (M = 26.7 ± 14.8). Significant positive associations were identified between physical activity intensity and categories of the participant's day suggesting that participants who complete more intense activity in therapy also complete more intense activity during non-active therapy and recreation time. General linear regression indicated that age significantly predicted physical activity intensity.
CONCLUSIONS: Findings demonstrate that patients with TBI undergoing inpatient rehabilitation are largely inactive or sedentary. Strategies to promote a safe increase in physical activity intensity are required if cardiovascular conditioning is to be improved during inpatient rehabilitation.

PMID: 30036125 [PubMed - indexed for MEDLINE]

Cholesterol Sulfate Alters Astrocyte Metabolism and Provides Protection Against Oxidative Stress.

Tue, 08/20/2019 - 07:22
Related Articles

Cholesterol Sulfate Alters Astrocyte Metabolism and Provides Protection Against Oxidative Stress.

Brain Res. 2019 Aug 16;:146378

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

Abstract
Cholesterol sulfate (CS) is one of the most important known sterol sulfates in human plasma and it is present as a normal constituent in a variety of human tissues. In both the brain and periphery, CS serves as a substrate for the synthesis of sulfonated adrenal steroids such as pregnenolone sulfate and dehydroepiandrosterone (DHEA) sulfate and as a constituent of many biological membranes including red blood cells where it functions as a stabilizing agent. It also acts as an endogenous regulator of cholesterol synthesis. However, the role of CS in brain metabolism and neurological disorder is unclear. In the current study we investigated the neuroprotective action of CS as well as its role in brain energy metabolism. The neuroprotective effect of CS and its role on cell metabolism were determined in primary astrocyte prepared from the cortex of postnatal day 0-2 C57BL/6 pups and a hippocampal HT-22 cell line using Calcein AM and MTT cell viability assay, flow cytometry, Seahorse extracellular flux analysis, and metabolism assay kits. We found that CS attenuates glutamate and rotenone induced cell death in HT-22 cells, decrease glutamate induced mitochondria membrane potential collapse, and reactive oxygen species production. Additionally, CS activates the Akt/Bcl2 pathway. We observed that CS impacts astrocyte metabolism by increasing mitochondrial phosphorylation, ATP, and glycogen contents. Our study demonstrated that CS modulates brain energy metabolism and its neuroprotective effects might be due to the activation of Akt signaling or its ability to decrease reactive oxygen species production.

PMID: 31425677 [PubMed - as supplied by publisher]

Effects of TAK-639, a novel topical C-type natriuretic peptide analog, on intraocular pressure and aqueous humor dynamics in mice.

Tue, 08/20/2019 - 07:22
Related Articles

Effects of TAK-639, a novel topical C-type natriuretic peptide analog, on intraocular pressure and aqueous humor dynamics in mice.

Exp Eye Res. 2019 Aug 14;:107763

Authors: Millar JC, Savinainen A, Josiah S, Pang IH

Abstract
Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness, and individuals with ocular hypertension are at risk to develop POAG. Currently, the only modifiable risk factor for glaucoma progression is lowering of intraocular pressure (IOP). A novel mechanism for lowering IOP involves activation of the type B natriuretic peptide receptor (NPR-B), the naturally occurring agonist of which is C-type natriuretic peptide (CNP). Being a cyclic peptide of 22 amino acids, CNP does not readily penetrate the cornea and its ocular hypotensive effect requires intraocular injection. TAK-639 is a synthetic, cornea-permeable, 9-amino acid CNP analog has been studied for the treatment of ocular hypertension and POAG. We assessed TAK-639 in a receptor binding profile and the effects of TAK-639 on NPR-B-mediated cyclic GMP production in cultured transformed human trabecular meshwork (TM) cells (GTM-3). We also evaluated the effects of topical ocular administration of TAK-639 on mouse IOP and aqueous humor dynamics. Among 89 non-natriuretic peptide receptors, transporters, and channels evaluated, TAK-639 at 10 μM displaced ligand binding by more than 50% to only two receptors: the type 2 angiotensin receptor (IC50 = 8.2 μM) and the cholecystokinin A receptor (IC50 = 25.8 μM). In vitro, TAK-639 selectively activates NPR-B (EC50 = 61 ± 11 nM; GTM-3 cells) relative to NPR-A (EC50 = 2179 ± 670 nM; 293T cells). In vivo, TAK-639 lowered mouse IOP by three mechanisms: increase in aqueous humor outflow facility (C), reduction in the aqueous humor formation rate (Fin), and reduction in episcleral venous pressure (Pe). The maximum mean IOP decreases from baseline were -12.1%, -21.0%, and -36.1% for 0.1%, 0.3%, and 0.6% doses of TAK-639, respectively. Maximum IOP-lowering effect was seen at 2 h, and the duration of action was >6 h. With TAK-639 0.6%, at 2 h post-dose, aqueous outflow facility (C) increased by 155.8%, Fin decreased by 41.0%, the uveoscleral outflow rate (Fu) decreased by 52.6%, and Pe decreased by 31.5% (all p < 0.05). No ocular adverse effects were observed. TAK-639 is an efficacious IOP-lowering agent, with a unique combination of mechanisms of action on both aqueous formation and aqueous outflow facility. Further study of this mechanism of treatment may optimize pharmacologic outcomes and provide disease management in patients with POAG and ocular hypertension.

PMID: 31421135 [PubMed - as supplied by publisher]

Expression and Function of Transient Receptor Potential Ankyrin 1 Ion Channels in the Caudal Nucleus of the Solitary Tract.

Tue, 08/20/2019 - 07:22
Related Articles

Expression and Function of Transient Receptor Potential Ankyrin 1 Ion Channels in the Caudal Nucleus of the Solitary Tract.

Int J Mol Sci. 2019 Apr 26;20(9):

Authors: Feng L, Uteshev VV, Premkumar LS

Abstract
The nucleus of the solitary tract (NTS) receives visceral information via the solitary tract (ST) that comprises the sensory components of the cranial nerves VII, IX and X. The Transient Receptor Potential Ankyrin 1 (TRPA1) ion channels are non-selective cation channels that are expressed primarily in pain-related sensory neurons and nerve fibers. Thus, TRPA1 expressed in the primary sensory afferents may modulate the function of second order NTS neurons. This hypothesis was tested and confirmed in the present study using acute brainstem slices and caudal NTS neurons by RT-PCR, immunostaining and patch-clamp electrophysiology. The expression of TRPA1 was detected in presynaptic locations, but not the somata of caudal NTS neurons that did not express TRPA1 mRNA or proteins. Moreover, caudal NTS neurons did not show somatodendritic responsiveness to TRPA1 agonists, while TRPA1 immunostaining was detected only in the afferent fibers. Electrophysiological recordings detected activation of presynaptic TRPA1 in glutamatergic terminals synapsing on caudal NTS neurons evidenced by the enhanced glutamatergic synaptic neurotransmission in the presence of TRPA1 agonists. The requirement of TRPA1 for modulation of spontaneous synaptic activity was confirmed using TRPA1 knockout mice where TRPA1 agonists failed to alter synaptic efficacy. Thus, this study provides the first evidence of the TRPA1-dependent modulation of the primary afferent inputs to the caudal NTS. These results suggest that the second order caudal NTS neurons act as a TRPA1-dependent interface for visceral noxious-innocuous integration at the level of the caudal brainstem.

PMID: 31027359 [PubMed - indexed for MEDLINE]

Author Correction: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Sat, 08/17/2019 - 06:53
Related Articles

Author Correction: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Nat Genet. 2019 Aug 15;:

Authors: Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, Boland A, Vronskaya M, van der Lee SJ, Amlie-Wolf A, Bellenguez C, Frizatti A, Chouraki V, Martin ER, Sleegers K, Badarinarayan N, Jakobsdottir J, Hamilton-Nelson KL, Moreno-Grau S, Olaso R, Raybould R, Chen Y, Kuzma AB, Hiltunen M, Morgan T, Ahmad S, Vardarajan BN, Epelbaum J, Hoffmann P, Boada M, Beecham GW, Garnier JG, Harold D, Fitzpatrick AL, Valladares O, Moutet ML, Gerrish A, Smith AV, Qu L, Bacq D, Denning N, Jian X, Zhao Y, Del Zompo M, Fox NC, Choi SH, Mateo I, Hughes JT, Adams HH, Malamon J, Sanchez-Garcia F, Patel Y, Brody JA, Dombroski BA, Naranjo MCD, Daniilidou M, Eiriksdottir G, Mukherjee S, Wallon D, Uphill J, Aspelund T, Cantwell LB, Garzia F, Galimberti D, Hofer E, Butkiewicz M, Fin B, Scarpini E, Sarnowski C, Bush WS, Meslage S, Kornhuber J, White CC, Song Y, Barber RC, Engelborghs S, Sordon S, Voijnovic D, Adams PM, Vandenberghe R, Mayhaus M, Cupples LA, Albert MS, De Deyn PP, Gu W, Himali JJ, Beekly D, Squassina A, Hartmann AM, Orellana A, Blacker D, Rodriguez-Rodriguez E, Lovestone S, Garcia ME, Doody RS, Munoz-Fernadez C, Sussams R, Lin H, Fairchild TJ, Benito YA, Holmes C, Karamujić-Čomić H, Frosch MP, Thonberg H, Maier W, Roshchupkin G, Ghetti B, Giedraitis V, Kawalia A, Li S, Huebinger RM, Kilander L, Moebus S, Hernández I, Kamboh MI, Brundin R, Turton J, Yang Q, Katz MJ, Concari L, Lord J, Beiser AS, Keene CD, Helisalmi S, Kloszewska I, Kukull WA, Koivisto AM, Lynch A, Tarraga L, Larson EB, Haapasalo A, Lawlor B, Mosley TH, Lipton RB, Solfrizzi V, Gill M, Longstreth WT, Montine TJ, Frisardi V, Diez-Fairen M, Rivadeneira F, Petersen RC, Deramecourt V, Alvarez I, Salani F, Ciaramella A, Boerwinkle E, Reiman EM, Fievet N, Rotter JI, Reisch JS, Hanon O, Cupidi C, Uitterlinden AGA, Royall DR, Dufouil C, Maletta RG, de Rojas I, Sano M, Brice A, Cecchetti R, George-Hyslop PS, Ritchie K, Tsolaki M, Tsuang DW, Dubois B, Craig D, Wu CK, Soininen H, Avramidou D, Albin RL, Fratiglioni L, Germanou A, Apostolova LG, Keller L, Koutroumani M, Arnold SE, Panza F, Gkatzima O, Asthana S, Hannequin D, Whitehead P, Atwood CS, Caffarra P, Hampel H, Quintela I, Carracedo Á, Lannfelt L, Rubinsztein DC, Barnes LL, Pasquier F, Frölich L, Barral S, McGuinness B, Beach TG, Johnston JA, Becker JT, Passmore P, Bigio EH, Schott JM, Bird TD, Warren JD, Boeve BF, Lupton MK, Bowen JD, Proitsi P, Boxer A, Powell JF, Burke JR, Kauwe JSK, Burns JM, Mancuso M, Buxbaum JD, Bonuccelli U, Cairns NJ, McQuillin A, Cao C, Livingston G, Carlson CS, Bass NJ, Carlsson CM, Hardy J, Carney RM, Bras J, Carrasquillo MM, Guerreiro R, Allen M, Chui HC, Fisher E, Masullo C, Crocco EA, DeCarli C, Bisceglio G, Dick M, Ma L, Duara R, Graff-Radford NR, Evans DA, Hodges A, Faber KM, Scherer M, Fallon KB, Riemenschneider M, Fardo DW, Heun R, Farlow MR, Kölsch H, Ferris S, Leber M, Foroud TM, Heuser I, Galasko DR, Giegling I, Gearing M, Hüll M, Geschwind DH, Gilbert JR, Morris J, Green RC, Mayo K, Growdon JH, Feulner T, Hamilton RL, Harrell LE, Drichel D, Honig LS, Cushion TD, Huentelman MJ, Hollingworth P, Hulette CM, Hyman BT, Marshall R, Jarvik GP, Meggy A, Abner E, Menzies GE, Jin LW, Leonenko G, Real LM, Jun GR, Baldwin CT, Grozeva D, Karydas A, Russo G, Kaye JA, Kim R, Jessen F, Kowall NW, Vellas B, Kramer JH, Vardy E, LaFerla FM, Jöckel KH, Lah JJ, Dichgans M, Leverenz JB, Mann D, Levey AI, Pickering-Brown S, Lieberman AP, Klopp N, Lunetta KL, Wichmann HE, Lyketsos CG, Morgan K, Marson DC, Brown K, Martiniuk F, Medway C, Mash DC, Nöthen MM, Masliah E, Hooper NM, McCormick WC, Daniele A, McCurry SM, Bayer A, McDavid AN, Gallacher J, McKee AC, van den Bussche H, Mesulam M, Brayne C, Miller BL, Riedel-Heller S, Miller CA, Miller JW, Al-Chalabi A, Morris JC, Shaw CE, Myers AJ, Wiltfang J, O'Bryant S, Olichney JM, Alvarez V, Parisi JE, Singleton AB, Paulson HL, Collinge J, Perry WR, Mead S, Peskind E, Cribbs DH, Rossor M, Pierce A, Ryan NS, Poon WW, Nacmias B, Potter H, Sorbi S, Quinn JF, Sacchinelli E, Raj A, Spalletta G, Raskind M, Caltagirone C, Bossù P, Orfei MD, Reisberg B, Clarke R, Reitz C, Smith AD, Ringman JM, Warden D, Roberson ED, Wilcock G, Rogaeva E, Bruni AC, Rosen HJ, Gallo M, Rosenberg RN, Ben-Shlomo Y, Sager MA, Mecocci P, Saykin AJ, Pastor P, Cuccaro ML, Vance JM, Schneider JA, Schneider LS, Slifer S, Seeley WW, Smith AG, Sonnen JA, Spina S, Stern RA, Swerdlow RH, Tang M, Tanzi RE, Trojanowski JQ, Troncoso JC, Van Deerlin VM, Van Eldik LJ, Vinters HV, Vonsattel JP, Weintraub S, Welsh-Bohmer KA, Wilhelmsen KC, Williamson J, Wingo TS, Woltjer RL, Wright CB, Yu CE, Yu L, Saba Y, Alzheimer Disease Genetics Consortium (ADGC), European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, Polygenic and Environmental Risk for Alzheimer’s Disease Consortium (GERAD/PERADES), Pilotto A, Bullido MJ, Peters O, Crane PK, Bennett D, Bosco P, Coto E, Boccardi V, De Jager PL, Lleo A, Warner N, Lopez OL, Ingelsson M, Deloukas P, Cruchaga C, Graff C, Gwilliam R, Fornage M, Goate AM, Sanchez-Juan P, Kehoe PG, Amin N, Ertekin-Taner N, Berr C, Debette S, Love S, Launer LJ, Younkin SG, Dartigues JF, Corcoran C, Ikram MA, Dickson DW, Nicolas G, Campion D, Tschanz J, Schmidt H, Hakonarson H, Clarimon J, Munger R, Schmidt R, Farrer LA, Van Broeckhoven C, O'Donovan MC, DeStefano AL, Jones L, Haines JL, Deleuze JF, Owen MJ, Gudnason V, Mayeux R, Escott-Price V, Psaty BM, Ramirez A, Wang LS, Ruiz A, van Duijn CM, Holmans PA, Seshadri S, Williams J, Amouyel P, Schellenberg GD, Lambert JC, Pericak-Vance MA

Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PMID: 31417202 [PubMed - as supplied by publisher]

Primary care clinics can be a source of exposure to virulent Clostridium (now Clostridioides) difficile: An environmental screening study of hospitals and clinics in Dallas-Fort Worth region.

Fri, 08/16/2019 - 06:45
Related Articles

Primary care clinics can be a source of exposure to virulent Clostridium (now Clostridioides) difficile: An environmental screening study of hospitals and clinics in Dallas-Fort Worth region.

PLoS One. 2019;14(8):e0220646

Authors: Simecka JW, Fulda KG, Pulse M, Lee JH, Vitucci J, Nguyen P, Taylor P, Filipetto F, Espinoza AM, Sharma S

Abstract
C. difficile is an endospore-forming pathogen, which is becoming a common cause of microbial health-care associated gastrointestinal disease in the United States. Both healthy and symptomatic patients can shed C. difficile spores into the environment, which can survive for long periods, being resistant to desiccation, heat, and disinfectants. In healthcare facilities, environmental contamination with C. difficile is a major concern as a potential source of exposure to this pathogen and risk of disease in susceptible patients. Although hospital-acquired infection is recognized, community-acquired infection is an increasingly recognized health problem. Primary care clinics may be a significant source of exposure to this pathogen; however, there are limited data about presence of environmental C. difficile within clinics. To address the potential for primary care clinics as a source of environmental exposure to virulent C. difficile, we measured the frequency of environmental contamination with spores in clinic examination rooms and hospital rooms in Dallas-Fort Worth (DFW) area of Texas. The ribotypes and presence of toxin genes from some environmental isolates were compared. Our results indicate primary care clinics have higher frequencies of contamination than hospitals. After notification of the presence of C. difficile spores in the clinics and an educational discussion to emphasize the importance of this infection and methods of infection prevention, environmental contamination in clinics was reduced on subsequent sampling to that found in hospitals. Thus, primary care clinics can be a source of exposure to virulent C. difficile, and recognition of this possibility can result in improved infection prevention, potentially reducing community-acquired C. difficile infections and subsequent disease.

PMID: 31415582 [PubMed - in process]

Buffering chronic kidney disease with sodium bicarbonate.

Wed, 08/14/2019 - 06:24
Related Articles

Buffering chronic kidney disease with sodium bicarbonate.

Clin Sci (Lond). 2018 09 14;132(17):1999-2001

Authors: Williams EN, Mathis KW

Abstract
The roles of the kidney are well defined, if there is a progressive loss in renal function, the kidney is no longer able to perform the listed tasks and chronic kidney disease (CKD) persists. In both clinical and experimental studies, NaHCO3 supplementation has been shown to improve glomerular filtration rate (GFR) as well as halt the progression toward end-stage renal disease (ESRD). In an article recently published in Clinical Science (vol 132 (11) 1179-1197), Ray et al. presented an intriguing and timely study, which investigates the mechanisms involved in the protection that follows oral NaHCO3 ingestion. Here we comment on their research findings.

PMID: 30220653 [PubMed - indexed for MEDLINE]

Circulating factors in young blood as potential therapeutic agents for age-related neurodegenerative and neurovascular diseases.

Sun, 08/11/2019 - 05:58

Circulating factors in young blood as potential therapeutic agents for age-related neurodegenerative and neurovascular diseases.

Brain Res Bull. 2019 Aug 07;:

Authors: Ma J, Gao B, Zhang K, Zhang Q, Jia G, Li J, Li C, Yan LJ, Cai Z

Abstract
Recent animal studies on heterochronic parabiosis (a technique combining the blood circulation of two animals) have revealed that young blood has a powerful rejuvenating effect on brain aging. Circulating factors, especially growth differentiation factor 11 (GDF11) and C-C motif chemokine 11 (CCL11), may play a key role in this effect, which inspires hope for novel approaches to treating age-related cerebral diseases in humans, such as neurodegenerative and neurovascular diseases. Recently, attempts have begun to translate these astonishing and exciting findings from mice to humans and from bench to bedside. However, increasing reports have shown contradictory data, questioning the capacity of these circulating factors to reverse age-related brain dysfunction. In this review, we summarize the current research on the role of young blood, as well as the circulating factors GDF11 and CCL11, in the aging brain and age-related cerebral diseases. We highlight recent controversies, discuss related challenges and provide a future outlook.

PMID: 31400495 [PubMed - as supplied by publisher]

The ADEP biosynthetic gene cluster in Streptomyces hawaiiensis NRRL 15010 reveals an accessory clpP gene as a novel antibiotic resistance factor.

Sun, 08/11/2019 - 05:58
Related Articles

The ADEP biosynthetic gene cluster in Streptomyces hawaiiensis NRRL 15010 reveals an accessory clpP gene as a novel antibiotic resistance factor.

Appl Environ Microbiol. 2019 Aug 09;:

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

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

PMID: 31399403 [PubMed - as supplied by publisher]

Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling.

Fri, 08/09/2019 - 07:41
Related Articles

Mechanisms of Sex Disparities in Cardiovascular Function and Remodeling.

Compr Physiol. 2018 12 13;9(1):375-411

Authors: Chaudhari S, Cushen SC, Osikoya O, Jaini PA, Posey R, Mathis KW, Goulopoulou S

Abstract
Epidemiological studies demonstrate disparities between men and women in cardiovascular disease prevalence, clinical symptoms, treatments, and outcomes. Enrollment of women in clinical trials is lower than men, and experimental studies investigating molecular mechanisms and efficacy of certain therapeutics in cardiovascular disease have been primarily conducted in male animals. These practices bias data interpretation and limit the implication of research findings in female clinical populations. This review will focus on the biological origins of sex differences in cardiovascular physiology, health, and disease, with an emphasis on the sex hormones, estrogen and testosterone. First, we will briefly discuss epidemiological evidence of sex disparities in cardiovascular disease prevalence and clinical manifestation. Second, we will describe studies suggesting sexual dimorphism in normal cardiovascular function from fetal life to older age. Third, we will summarize and critically discuss the current literature regarding the molecular mechanisms underlying the effects of estrogens and androgens on cardiac and vascular physiology and the contribution of these hormones to sex differences in cardiovascular disease. Fourth, we will present cardiovascular disease risk factors that are positively associated with the female sex, and thus, contributing to increased cardiovascular risk in women. We conclude that inclusion of both men and women in the investigation of the role of estrogens and androgens in cardiovascular physiology will advance our understanding of the mechanisms underlying sex differences in cardiovascular disease. In addition, investigating the role of sex-specific factors in the development of cardiovascular disease will reduce sex and gender disparities in the treatment and diagnosis of cardiovascular disease. © 2019 American Physiological Society. Compr Physiol 9:375-411, 2019.

PMID: 30549017 [PubMed - indexed for MEDLINE]

Blood Based Biomarkers for Down Syndrome and Alzheimer's Disease: A Systematic Review.

Thu, 08/08/2019 - 07:31
Related Articles

Blood Based Biomarkers for Down Syndrome and Alzheimer's Disease: A Systematic Review.

Dev Neurobiol. 2019 Aug 07;:

Authors: Petersen ME, O'Bryant S

Abstract
Down syndrome (DS) occurs due to triplication of chromosome 21. Individuals with DS face an elevated risk for development of Alzheimer's disease (AD) due to increased amyloid beta (Aβ) resulting from the over-expression of the amyloid precursor protein found on chromosome 21. Diagnosis of AD among individuals with DS poses particular challenges resulting in an increased focus on alternative diagnostic methods such as blood-based biomarkers. The aim of this review was to evaluate the current state of the literature of blood-based biomarkers found in individuals with DS and particularly among those also diagnosed with AD or in prodromal stages (mild cognitive impairment [MCI]). A systematic review was conducted utilizing a comprehensive search strategy. Twenty-four references were identified, of those, 22 fulfilled inclusion criteria and were selected for further analysis with restriction to only plasma-based biomarkers. Studies found Aβ to be consistently higher among individuals with DS; however, the link between Aβ peptides (Aβ 1-42 and Aβ 1-40) and AD among DS was inconsistent. Inflammatory based proteins were more reliably found to be elevated leading to preliminary work focused on an algorithmic approach with predominantly inflammatory based proteins to detect AD and MCI as well as predict risk of incidence among DS. Separate work has also shown remarkable diagnostic accuracy with the use of a single protein (NfL) as compared to combined proteomic profiles. This review serves to outline the current state of the literature and highlight potential plasma-based biomarkers for use in detecting AD and MCI among this at-risk population. This article is protected by copyright. All rights reserved.

PMID: 31389185 [PubMed - as supplied by publisher]

Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands.

Thu, 08/08/2019 - 07:31
Related Articles

Design, synthesis, and evaluation of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamides as selective dopamine D3 receptor ligands.

Bioorg Med Chem Lett. 2019 Jul 11;:

Authors: Chen PJ, Taylor M, Griffin SA, Amani A, Hayatshahi H, Korzekwa K, Ye M, Mach RH, Liu J, Luedtke RR, Gordon JC, Blass BE

Abstract
As part of our on-going effort to explore the role of dopamine receptors in drug addiction and identify potential novel therapies for this condition, we have a identified a series of N-(4-(4-phenyl piperazin-1-yl)butyl)-4-(thiophen-3-yl)benzamide D3 ligands. Members of this class are highly selective for D3 versus D2, and we have identified two compounds (13g and 13r) whose rat in vivo IV pharmacokinetic properties that indicate that they are suitable for assessment in in vivo efficacy models of substance use disorders.

PMID: 31387791 [PubMed - as supplied by publisher]

Pages