Recent Research Articles from UNTHSC

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

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Updated: 44 min 34 sec ago

Children with Autism Spectrum Disorder, Developmental Coordination Disorder, and typical development differ in characteristics of dynamic postural control: A preliminary study.

Wed, 03/20/2019 - 06:50
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Children with Autism Spectrum Disorder, Developmental Coordination Disorder, and typical development differ in characteristics of dynamic postural control: A preliminary study.

Gait Posture. 2019 01;67:9-11

Authors: Miller HL, Caçola PM, Sherrod GM, Patterson RM, Bugnariu NL

Abstract
BACKGROUND: Autism Spectrum Disorder (ASD) and Developmental Coordination Disorder (DCD) are developmental disorders with distinct definitions and symptoms. However, both conditions share difficulties with motor skills, including impairments in postural control. While studies have explored postural sway variables in children with DCD and ASD as compared to typical development (TD), few have used kinematic data to assess the magnitude of differences between these two neurodevelopmental conditions. There are few sensitive and specific measures available to assess balance impairment severity in these populations.
RESEARCH QUESTION: Do individuals with ASD, DCD, and TD differ in dynamic postural control?
METHODS: We quantified postural control differences between ASD, DCD, and TD during a dynamic balance task. 10 ASD, 10 DCD, and 8 TD agematched children completed a dynamic postural control task in a virtual environment. They leaned to shift their center of pressure (CoP) to match a user-controlled object to an oscillating target (0.1 Hz-0.8 Hz).
RESULTS: The DCD group had higher CoP accelerations compared to ASD or TD. While the DCD and TD groups did not differ in their medial-lateral velocity, the ASD group had low medial-lateral velocity and acceleration as compared to DCD and TD. ASD group velocity and acceleration did not differ from that of the TD group in the anterior-posterior direction. Higher accelerations in the DCD group reflected non-fluid movements; by contrast, the ASD group had slower, more fluid movements. Results may reflect differences in how children with ASD and DCD plan, execute, and modify motor actions.
SIGNIFICANCE: This study demonstrates the potential utility of CoP acceleration and velocity as a sensitive and specific means of differentiating between ASD, DCD, and TD. Results indicating group differences between ASD and DCD in velocity and acceleration profiles represent an important step toward understanding how these populations modify motor plans during dynamic tasks.

PMID: 30245240 [PubMed - indexed for MEDLINE]

Lipoproteins for therapeutic delivery: recent advances and future opportunities.

Wed, 03/20/2019 - 06:50
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Lipoproteins for therapeutic delivery: recent advances and future opportunities.

Ther Deliv. 2018 03 01;9(4):257-268

Authors: Raut S, Dasseux JL, Sabnis NA, Mooberry L, Lacko A

Abstract
The physiological role(s) of mammalian plasma lipoproteins is to transport hydrophobic molecules (primarily cholesterol and triacylglycerols) to their respective destinations. Lipoproteins have also been studied as drug-delivery agents due to their advantageous payload capacity, long residence time in the circulation and biocompatibility. The purpose of this review is to briefly discuss current findings with the focus on each type of formulation's potential for clinical applications. Regarding utilizing lipoprotein type formulation for cancer therapeutics, their potential for tumor-selective delivery is also discussed.

PMID: 29495929 [PubMed - indexed for MEDLINE]

Cannabinoid-like effects of five novel carboxamide synthetic cannabinoids.

Tue, 03/19/2019 - 06:43
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Cannabinoid-like effects of five novel carboxamide synthetic cannabinoids.

Neurotoxicology. 2019 01;70:72-79

Authors: Gatch MB, Forster MJ

Abstract
A new generation of novel cannabinoid compounds have been developed as marijuana substitutes to avoid drug control laws and cannabinoid blood tests. 5F-MDMB-PINACA (also known as 5F-ADB, 5F-ADB-PINACA), MDMB-CHIMICA, MDMB-FUBINACA, ADB-FUBINACA, and AMB-FUBINACA (also known as FUB-AMB, MMB-FUBINACA) were tested for in vivo cannabinoid-like effects to assess their abuse liability. Locomotor activity in mice was tested to screen for locomotor depressant effects and to identify behaviorally-active dose ranges and times of peak effect. Discriminative stimulus effects were tested in rats trained to discriminate Δ9-tetrahydrocannabinol (3 mg/kg, 30-min pretreatment). 5F-MDMB-PINACA (ED50 = 1.1 mg/kg) and MDMB-CHIMICA (ED50 = 0.024 mg/kg) produced short-acting (30 min) depression of locomotor activity. ADB-FUBINACA (ED50 = 0.19 mg/kg), and AMB- FUBINACA (ED50 = 0.19 mg/kg) depressed locomotor activity for 60-90 min; whereas MDMB-FUBINACA (ED50 = 0.04 mg/kg) depressed locomotor activity for 150 min. AMB-FUBINACA produced tremors at the highest dose tested. 5F-MDMB-PINACA (ED50 = 0.07), MDMB-CHIMICA (ED50 = 0.01 mg/kg), MDMB-FUBINACA (ED50 = 0.051 mg/kg), ADB-FUBINACA (ED50 = 0.075 mg/kg) and AMB-FUBINACA (ED50 = 0.029) fully substituted for the discriminative stimulus effects of Δ9-THC following 15-min pretreatment. All 5 compounds decreased locomotor activity and produced discriminative stimulus effects similar to those of Δ9-THC, which suggests they may have abuse liability similar to that of Δ9-THC. AMB-FUBINACA may have an increased risk of toxicities in recreational users.

PMID: 30439379 [PubMed - indexed for MEDLINE]

CRISPR deletion of MIEN1 in breast cancer cells.

Tue, 03/19/2019 - 06:43
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CRISPR deletion of MIEN1 in breast cancer cells.

PLoS One. 2018;13(10):e0204976

Authors: Van Treuren T, Vishwanatha JK

Abstract
Migration and Invasion Enhancer (MIEN1) is an oncogene which is involved in facilitating motility of cancer cells through actin dynamics and gene expression. Increased MIEN1 expression in many types of tumors leads to disease progression and metastatic propensity. It is unclear precisely how MIEN1 is involved in this process and more studies are required to tease out the mechanisms. Here we show that Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) genome editing effectively produced specific genomic deletions in the MIEN1 gene which led to the abrogation of its expression in breast cancer cells. The single guide RNAs (sgRNAs) mediated targeting of MIEN1 was specific and none of the clones screened for off-target cleavage revealed any insertions or deletions (indels). Additionally, disruption of the MIEN1 gene did not alter the cell morphology, growth, proliferation or survival. Knocking out MIEN1 in these breast cancer cells will allow future studies to determine the exact role MIEN1 plays in breast tumor metastasis, which might lead to production of novel therapeutics to treat this and other cancers.

PMID: 30286132 [PubMed - indexed for MEDLINE]

Plasma pentraxin 3 and glucose kinetics following acute high-intensity interval exercise versus continuous moderate-intensity exercise in healthy men.

Tue, 03/19/2019 - 06:43
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Plasma pentraxin 3 and glucose kinetics following acute high-intensity interval exercise versus continuous moderate-intensity exercise in healthy men.

Appl Physiol Nutr Metab. 2018 Dec;43(12):1233-1238

Authors: Slusher AL, Whitehurst M, Maharaj A, Dodge KM, Fico BG, Mock JT, Huang CJ

Abstract
Pentraxin 3 (PTX3) is mainly synthesized and released by neutrophils to help regulate innate immunity. While plasma PTX3 concentrations are associated with improved glucose metabolism and overall metabolic health, there is evidence that significant elevations in plasma glucose downregulate circulating levels of PTX3. To examine whether this relationship would be altered in response to exercise, this study investigated the kinetics of the plasma glucose and PTX3 responses following high-intensity interval exercise (HIIE) and continuous moderate-intensity exercise (CMIE). It was hypothesized that the increased concentrations of plasma glucose following HIIE compared with CMIE would be associated with an attenuated plasma PTX3 response. Eight healthy male subjects participated in both HIIE and CMIE protocols administered as a randomized, counterbalanced design. Linear mixed models for repeated measures revealed that the overall plasma glucose response was greater following HIIE compared with CMIE (protocol × time effect: p = 0.037). Although the plasma PTX3 response was higher only at 19 min into HIIE compared with CMIE (protocol × time effect: p = 0.013), no relationships were observed between plasma glucose and PTX3 either at baseline or in response to both exercise protocols, as indicated by the area under the curve "with respect to increase" analysis. Our results indicate that exercise-mediated plasma PTX3 concentrations are independent of the plasma glucose response. In addition, the present study suggests that the neutrophil-mediated innate immune response, as indicated by plasma PTX3 response, may be activated earlier during HIIE compared with CMIE.

PMID: 29738271 [PubMed - indexed for MEDLINE]

Sinus Histiocytosis With Massive Lymphadenopathy (Rosai Dorfman Disease): Diagnostic and Treatment Modalities for this Rare Entity Revisited.

Tue, 03/19/2019 - 06:43
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Sinus Histiocytosis With Massive Lymphadenopathy (Rosai Dorfman Disease): Diagnostic and Treatment Modalities for this Rare Entity Revisited.

J Pediatr Hematol Oncol. 2018 05;40(4):e198-e202

Authors: Averitt AW, Heym K, Akers L, Castro-Silva F, Ray A

Abstract
Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy is a rare non-Langerhans' cell histiocytic disease resulting from the proliferation and accumulation of sinus histiocytes within lymph nodes. Extranodal involvement frequently occurs, which increases the morbidity and mortality of the disease. There is no clear consensus with regard to the most effective diagnostic and treatment modalities. This report will focus on the diagnostic imaging, treatment, and outcomes for 3 cases of Rosai-Dorfman disease. Imaging has typically utilized computed tomography (CT)/magnetic resonance imaging to detect extranodal involvement. However, the addition of fluorodeoxyglucose positron emission tomography/CT scans has shown value in identifying lesions unidentified or ambiguous on other modalities. Fluorodeoxyglucose positron emission tomography/CT detected disease involvement in 2 instances either not reported or not felt to be significant on correlative CT imaging. Areas of involvement included the stomach/liver in case 1, and the paranasal sinus in case 3. In addition, previously utilized chemotherapy regimens have not consistently displayed regression of the disease, which lends credence to the pursuit of more successful treatment. Notably, Clofarabine has shown promise in its use against histiocytic disorders. Our study concluded that Clofarabine demonstrates the ability to decrease lesion size and should be considered as an effective chemotherapeutic treatment method.

PMID: 29200169 [PubMed - indexed for MEDLINE]

Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases.

Tue, 03/19/2019 - 06:43
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Hybrid Nitric Oxide Donor and its Carrier for the Treatment of Peripheral Arterial Diseases.

Sci Rep. 2017 08 18;7(1):8692

Authors: Le DQ, Kuriakose AE, Nguyen DX, Nguyen KT, Acharya S

Abstract
Nitric oxide (NO) has been known to promote physiological angiogenesis to treat peripheral arterial diseases (PAD) by increasing the vascular endothelial growth factor (VEGF) level in endothelial cells (ECs) and preventing platelet adherence and leukocyte chemotaxis. However, the ongoing ischemic event during peripheral ischemia produces superoxide and diminishes the NO bioavailability by forming toxic peroxynitrite anion. Here we disclose an efficacious hybrid molecule 4-(5-Amino-1,2,3-oxadiazol-3-yl)-2,2,6,6-tetramethyl-1-piperidinol (SA-2) containing both antioxidant and NO donor functionalities that provide a therapeutic level of NO necessary to promote angiogenesis and to protect ECs against hydrogen peroxide-induced oxidative stress. Compound SA-2 scavenged reactive oxygen species, inhibited proliferation and migration of smooth muscle cells (SMCs) and promoted the tube formation from ECs. Copolymer poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with SA-2 provided a sustained release of NO over days, improved aqueous stability in serum, protected ECs against oxidative stress, and enhanced angiogenesis under stress conditions as compared to that of the control in the in vitro matrigel tube formation assay. These results indicated the potential use of SA-2 nanoparticles as an alternative therapy to treat PAD.

PMID: 28821752 [PubMed - indexed for MEDLINE]

Human papillomavirus risk perceptions and relationship status: a barrier to HPV vaccination?

Mon, 03/18/2019 - 06:34
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Human papillomavirus risk perceptions and relationship status: a barrier to HPV vaccination?

J Behav Med. 2019 Mar 16;:

Authors: Thompson EL, Vamos CA, Piepenbrink R, Kadono M, Vázquez-Otero C, Matthes S, Daley EM

Abstract
The purpose of this study was to assess the association between relationship status and perceived risk for human papillomavirus (HPV) among young adults. College adults, aged 18-26 years, completed an online survey from November 2016-April 2017 (n = 385). The survey assessed HPV vaccination status, perceived HPV risk, and current relationship status. Logistic regression models estimated the odds of perceived high risk for HPV, stratified by vaccination status. Among unvaccinated women, relationship status and HPV risk perception were significantly associated, with dating women more likely (OR = 5.33, 95%CI 1.16-24.50) to perceive a high risk for HPV compared to women in a committed relationship. Women in relationships were less likely to perceive themselves at high risk for HPV, even though HPV infection is prevalent among young adults. This association is not present for vaccinated women, suggesting that relationship status and risk perceptions may represent barriers to HPV vaccine uptake.

PMID: 30879225 [PubMed - as supplied by publisher]

Amyand hernia repair with mesh and appendectomy.

Sun, 03/17/2019 - 06:24
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Amyand hernia repair with mesh and appendectomy.

Surg Case Rep. 2019 Mar 15;5(1):42

Authors: Holmes K, Guinn JE

Abstract
BACKGROUND: Amyand hernias have been described in case reports in the literature and are a rare occurrence in the career of a surgeon. Their management is even less well described and often poses problems in the management of repair due to concerns with contamination associated with appendectomy. Here, we describe a patient with an Amyand hernia seen on CT imaging preoperatively, who underwent appendectomy along with a lightweight mesh plug repair of his hernia.
CASE PRESENTATION: An 88-year-old male presented with a right groin bulge and underwent preoperative imaging which indicated the presence of his appendix within his hernia. He was taken to the operating room electively where an appendectomy was performed due to significant chronic inflammatory changes. A lightweight mesh plug was used to repair the hernia to prevent recurrence. He did well post operatively without any complications.
CONCLUSIONS: A review of the literature supports the use of mesh repair in these of hernias even with appendectomy at the time of the hernia repair. This will guide surgeons who encounter this clinical rarity in their practice.

PMID: 30877403 [PubMed]

Calpain inhibitor MDL28170 improves the transplantation-mediated therapeutic effect of bone marrow-derived mesenchymal stem cells following traumatic brain injury.

Sun, 03/17/2019 - 06:24
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Calpain inhibitor MDL28170 improves the transplantation-mediated therapeutic effect of bone marrow-derived mesenchymal stem cells following traumatic brain injury.

Stem Cell Res Ther. 2019 Mar 15;10(1):96

Authors: Hu J, Chen L, Huang X, Wu K, Ding S, Wang W, Wang B, Smith C, Ren C, Ni H, ZhuGe Q, Yang J

Abstract
BACKGROUND: Studies have shown that transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) protects against brain damage. However, the low survival number of transplanted BMSCs remains a pertinent challenge and can be attributed to the unfavorable microenvironment of the injured brain. It is well known that calpain activation plays a critical role in traumatic brain injury (TBI)-mediated inflammation and cell death; previous studies showed that inhibiting calpain activation is neuroprotective after TBI. Thus, we investigated whether preconditioning with the calpain inhibitor, MDL28170, could enhance the survival of BMSCs transplanted at 24 h post TBI to improve neurological function.
METHODS: TBI rat model was induced by the weight-drop method, using the gravitational forces of a free falling weight to produce a focal brain injury. MDL28170 was injected intracranially at the lesion site at 30 min post TBI, and the secretion levels of neuroinflammatory factors were assessed 24 h later. BMSCs labeled with green fluorescent protein (GFP) were locally administrated into the lesion site of TBI rat brains at 24 h post TBI. Immunofluorescence and histopathology were performed to evaluate the BMSC survival and the TBI lesion volume. Modified neurological severity scores were chosen to evaluate the functional recovery. The potential mechanisms by which MDL28170 is involved in the regulation of inflammation signaling pathway and cell apoptosis were determined by western blot and immunofluorescence staining.
RESULTS: Overall, we found that a single dose of MDL28170 at acute phase of TBI improved the microenvironment by inhibiting the inflammation, facilitated the survival of grafted GFP-BMSCs, and reduced the grafted cell apoptosis, leading to the reduction of lesion cavity. Furthermore, a significant neurological function improvement was observed when BMSCs were transplanted into a MDL28170-preconditioned TBI brains compared with the one without MDL28170-precondition group.
CONCLUSIONS: Taken together, our data suggest that MDL28170 improves BMSC transplantation microenvironment and enhances the neurological function restoration after TBI via increased survival rate of BMSCs. We suggest that the calpain inhibitor, MDL28170, could be pursued as a new combination therapeutic strategy to advance the effects of transplanted BMSCs in cell-based regenerative medicine.

PMID: 30876457 [PubMed - in process]

#drunktwitter: Examining the relations between alcohol-related Twitter content and alcohol willingness and use among underage young adults.

Sat, 03/16/2019 - 06:09
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#drunktwitter: Examining the relations between alcohol-related Twitter content and alcohol willingness and use among underage young adults.

Drug Alcohol Depend. 2018 12 01;193:75-82

Authors: Litt DM, Lewis MA, Spiro ES, Aulck L, Waldron KA, Head-Corliss MK, Swanson A

Abstract
PURPOSE: Despite the importance of social networking sites on young adult alcohol use, few studies have examined Twitter as a conduit for sharing drinking behavior. However, this work generally uses random samples of tweets and thus cannot determine the extent to which Tweets correspond with self-reported drinking cognitions or behaviors. The primary aims of the present study were to (1) document basic patterns of alcohol-related Twitter activity in a subsample of young adult drinkers, and (2) examine whether willingness to drink, alcohol use, and negative consequences are associated with alcohol-related tweeting behavior.
METHODS: 186 young adults age 18-20 completed an online survey and provided Twitter handle information. From these participants, a random sample of 5000 Tweets was coded by a trained team to determine whether tweets were related to alcohol use or not. Ordinary least squares regression analyses were conducted to determine whether the proportion of alcohol-related Tweets is associated with self-reported alcohol use willingness, behaviors, and negative consequences.
RESULTS: Results indicated that not only are alcohol-related tweets common among young adults, but that the proportion of one's overall tweets that are related to alcohol is significantly associated with willingness to drink, alcohol use, and negative consequences.
CONCLUSIONS: The results of this study are an important step to understanding how digital behavior (e.g., posting about alcohol on Twitter) is related to an individual's self-reported drinking cognitions, alcohol use, and negative consequences and has implications for the way Twitter data can be used for public health surveillance and interventions.

PMID: 30343237 [PubMed - indexed for MEDLINE]

Effect of Sociodemographic Factors on Uptake of a Patient-Facing Information Technology Family Health History Risk Assessment Platform.

Thu, 03/14/2019 - 05:53

Effect of Sociodemographic Factors on Uptake of a Patient-Facing Information Technology Family Health History Risk Assessment Platform.

Appl Clin Inform. 2019 Mar;10(2):180-188

Authors: Wu RR, Myers RA, Buchanan AH, Dimmock D, Fulda KG, Haller IV, Haga SB, Harry ML, McCarty C, Neuner J, Rakhra-Burris T, Sperber N, Voils CI, Ginsburg GS, Orlando LA

Abstract
OBJECTIVE:  Investigate sociodemographic differences in the use of a patient-facing family health history (FHH)-based risk assessment platform.
METHODS:  In this large multisite trial with a diverse patient population, we evaluated the relationship between sociodemographic factors and FHH health risk assessment uptake using an information technology (IT) platform. The entire study was administered online, including consent, baseline survey, and risk assessment completion. We used multivariate logistic regression to model effect of sociodemographic factors on study progression. Quality of FHH data entered as defined as relatives: (1) with age of onset reported on relevant conditions; (2) if deceased, with cause of death and (3) age of death reported; and (4) percentage of relatives with medical history marked as unknown was analyzed using grouped logistic fixed effect regression.
RESULTS:  A total of 2,514 participants consented with a mean age of 57 and 10.4% minority. Multivariate modeling showed that progression through study stages was more likely for younger (p-value = 0.005), more educated (p-value = 0.004), non-Asian (p-value = 0.009), and female (p-value = 0.005) participants. Those with lower health literacy or information-seeking confidence were also less likely to complete the study. Most significant drop-out occurred during the risk assessment completion phase. Overall, quality of FHH data entered was high with condition's age of onset reported 87.85%, relative's cause of death 85.55% and age of death 93.76%, and relative's medical history marked as unknown 19.75% of the time.
CONCLUSION:  A demographically diverse population was able to complete an IT-based risk assessment but there were differences in attrition by sociodemographic factors. More attention should be given to ensure end-user functionality of health IT and leverage electronic medical records to lessen patient burden.

PMID: 30866001 [PubMed - in process]

In vivo imaging and biodistribution of near infrared dye loaded brain-metastatic-breast-cancer-cell-membrane coated polymeric nanoparticles.

Thu, 03/14/2019 - 05:53

In vivo imaging and biodistribution of near infrared dye loaded brain-metastatic-breast-cancer-cell-membrane coated polymeric nanoparticles.

Nanotechnology. 2019 Mar 13;:

Authors: Kumar P, Treuren TV, Ranjan A, Chaudhary P, Vishwanatha JK

Abstract
Brain-metastatic-breast cancer is challenging to treat due to the presence of the blood-brain barrier (BBB) and a lack of ability to precisely target. Most drugs fail to cross the BBB limiting their effectiveness. To combat this problem, a brain metastatic breast cancer cell (MDA-MB-831) membrane-coated polymeric nanoparticle (CCNP) was synthesized. The small size (~70 nm) and anionic surface charge (-20 mV) achieved during formulation allowed for high penetration and retention in the brain when compared to the PEGylated polymeric nanoparticle alone (mPEG-PLGA or NP). Doxorubicin-loaded CCNP showed high preferential cytotoxicity in vitro. Live (4 h-120 h) and ex-vivo near-infrared imaging in nude mice showed extended circulation and retention of CCNP compared to uncoated nanoparticles. These data indicate that drug/dye-loaded CCNPs demonstrate excellent potential for cancer theranostics of brain-metastatic breast tumors.

PMID: 30865940 [PubMed - as supplied by publisher]

Neuronal deletion of Pten results in cerebellar motor learning dysfunction and alterations in intracellular signaling.

Thu, 03/14/2019 - 05:53

Neuronal deletion of Pten results in cerebellar motor learning dysfunction and alterations in intracellular signaling.

CNS Neurol Disord Drug Targets. 2019 Mar 12;:

Authors: Nolan SO, Jefferson TS, Reynolds CD, Smith GD, Holley AJ, Hodges SL, Lugo JN

Abstract
BACKGROUND: Loss of the Pten (phosphatase and tensin homolog) gene has been demonstrated to result in hyperactivation of the mammalian target of rapamycin (mTOR) pathway, a signaling pathway common to many disease etiologies, including tuberous sclerosis complex, Fragile X syndrome, and schizophrenia. Previous studies have focused on the impact of hyperactivation of the mTOR pathway in hippocampus and cortex and behaviors among those structures, but little is known about the relationship of Pten and mTOR signaling in the development and function of the cerebellum.
OBJECTIVE: The purpose of this investigation was to examine cerebellar levels of several molecular signaling pathways, including PI3K/AKT/mTOR signaling and markers of neuronal migration, following loss of Pten in a subset of neurons, as well as the accompanying behavior phenotype.
METHODS: Motor coordination and learning was measured by the sticker removal task, the accelerating rotarod, and spontaneous activity in a cylinder. Western blots were conducted on cerebellar tissue samples.
RESULTS: We demonstrated that neuron-specific deletion of Pten (NS-Pten) in mice led to deficits in motor coordination. These changes were accompanied by alterations in many different proteins, including the PI3K/AKT/mTOR signaling pathway, FMRP, glutamate receptors and neuronal migration markers.
CONCLUSIONS: These data firstly support a role for hyperactivation of mTOR in the cerebellum following loss of Pten, accompanied by behavioral deficits. Moreover, the results of the current study support a broader role for Pten signaling in early neuronal migration and organization of the cerebellum, and point to a putative role for Pten for many neuropsychiatric conditions.

PMID: 30864513 [PubMed - as supplied by publisher]

Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans.

Wed, 03/13/2019 - 05:45

Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans.

PLoS One. 2019;14(3):e0213527

Authors: Silzer T, Barber R, Sun J, Pathak G, Johnson L, O'Bryant S, Phillips N

Abstract
Mitochondrial function has been implicated and studied in numerous complex age-related diseases. Understanding the potential role of mitochondria in disease pathophysiology is of importance due to the rise in prevalence of complex age-related diseases, such as type 2 diabetes (T2D) and Alzheimer's disease (AD). These two diseases specifically share common pathophysiological characteristics which potentially point to a common root cause or factors for disease exacerbation. Studying the shared phenomena in Mexican Americans is of particular importance due to the disproportionate prevalence of both T2D and AD in this population. Here, we assessed the potential role of mitochondria in T2D and cognitive impairment (CI) in a Mexican American cohort by analyzing blood-based indices of mitochondrial DNA copy number (mtDNACN) and cell-free mitochondrial DNA (CFmtDNA). These mitochondrial metrics were also analyzed for correlation with relevant neuropsychological variables and physiological data collected as indicators of disease and/or disease progression. We found mtDNACN to be significantly decreased in individuals with CI, while CFmtDNA was significantly elevated in T2D; further, CFmtDNA elevation was significantly exacerbated in individuals with both diseases. MtDNACN was found to negatively correlate with age and fatty acid binding protein concentration, while positively correlating with CFmtDNA as well as CERAD total recall score. Candidate gene SNP-set analysis was performed on genes previously implicated in maintenance and control of mitochondrial dynamics to determine if nuclear variants may account for variability in mtDNACN. The results point to a single significant locus, in the LRRK2/MUC19 region, encoding leucine rich repeat kinase 2 and mucin 19. This locus has been previously implicated in Parkinson's disease, among others; rs7302859 was the driver SNP. These combined findings further indicate that mitochondrial dysfunction (as assessed by proxy via mtDNACN) is intimately linked to both T2D and CI phenotypes as well as aging.

PMID: 30861027 [PubMed - in process]

Vitamin B3 in Health and Disease: Toward the Second Century of Discovery.

Wed, 03/13/2019 - 05:45
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Vitamin B3 in Health and Disease: Toward the Second Century of Discovery.

Methods Mol Biol. 2018;1813:3-8

Authors: Jacobson MK, Jacobson EL

Abstract
This introductory chapter briefly reviews the history, chemistry, and biochemistry of NAD (the term NAD as it is used here refers to both oxidized and reduced forms of the molecule) consuming ADP-ribose transfer enzymes as components of the involvement of vitamin B3 in health and disease.

PMID: 30097857 [PubMed - indexed for MEDLINE]

Antihypertensive Treatment Fails to Control Blood Pressure During Exercise.

Tue, 03/12/2019 - 05:27
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Antihypertensive Treatment Fails to Control Blood Pressure During Exercise.

Hypertension. 2018 07;72(1):63-64

Authors: Raven PB

PMID: 29895531 [PubMed - indexed for MEDLINE]

Long-Acting Injectable Second-Generation Antipsychotics: An Update and Comparison Between Agents.

Tue, 03/12/2019 - 05:27
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Long-Acting Injectable Second-Generation Antipsychotics: An Update and Comparison Between Agents.

CNS Drugs. 2018 03;32(3):241-257

Authors: Jann MW, Penzak SR

Abstract
Schizophrenia is a chronic medical condition with periods of remission and relapses over a patient's lifetime. Antipsychotic medications represent the mainstay of treatment for this disease. Long-acting injectable (LAI) formulations of antipsychotics are an attractive alternative to their oral counterparts, as they enhance patient adherence. A number of second-generation antipsychotics (SGAs) are available in LAI formulations. These include paliperidone, aripiprazole, olanzapine, and risperidone. This article reviews the most recently developed and approved of these formulations-aripiprazole monohydrate, aripiprazole lauroxil, and paliperidone palmitate. While all were initially available as once-monthly formulations, a paliperidone palmitate 3-monthly injection formulation has been approved and is the first LAI agent to extend the dosing administration beyond the typical monthly time period. In addition, aripiprazole lauroxil every 6-week and 8-week administration preparations have been developed. LAI preparations of the SGAs have all demonstrated superiority over placebo and are comparable to their oral counterparts in terms of safety and tolerability, if injection site reactions are not taken into account. First-generation antipsychotic LAI preparations (e.g., haloperidol decanoate) have recently been compared with SGA LAI agents, and both formulations demonstrated comparable efficacy with the expected adverse events seen with each drug. Despite their availability, barriers to the use of LAIs remain. Education of both patients and clinicians on the use of LAI formulations and the continued development of these agents are important steps in ensuring these medications are available to the patients they would be most likely to benefit.

PMID: 29569082 [PubMed - indexed for MEDLINE]

Global genetic variation of select opiate metabolism genes in self-reported healthy individuals.

Tue, 03/12/2019 - 05:27
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Global genetic variation of select opiate metabolism genes in self-reported healthy individuals.

Pharmacogenomics J. 2018 04;18(2):281-294

Authors: Wendt FR, Pathak G, Sajantila A, Chakraborty R, Budowle B

Abstract
CYP2D6 is a key pharmacogene encoding an enzyme impacting poor, intermediate, extensive and ultrarapid phase I metabolism of many marketed drugs. The pharmacogenetics of opiate drug metabolism is particularly interesting due to the relatively high incidence of addiction and overdose. Recently, trans-acting opiate metabolism and analgesic response enzymes (UGT2B7, ABCB1, OPRM1 and COMT) have been incorporated into pharmacogenetic studies to generate more comprehensive metabolic profiles of patients. With use of massively parallel sequencing, it is possible to identify additional polymorphisms that fine tune, or redefine, previous pharmacogenetic findings, which typically rely on targeted approaches. The 1000 Genomes Project data were analyzed to describe population genetic variation and statistics for these five genes in self-reported healthy individuals in five global super- and 26 sub-populations. Findings on the variation of these genes in various populations expand baseline understanding of pharmacogenetically relevant polymorphisms for future studies of affected cohorts.

PMID: 28398354 [PubMed - indexed for MEDLINE]

Examining the association between prescription opioid misuse and suicidal behaviors among adolescent high school students in the United States.

Mon, 03/11/2019 - 05:09

Examining the association between prescription opioid misuse and suicidal behaviors among adolescent high school students in the United States.

J Psychiatr Res. 2019 Mar 01;112:44-51

Authors: Baiden P, Graaf G, Zaami M, Acolatse CK, Adeku Y

Abstract
Although some studies have examined the association between prescription opioid misuse and mental health outcomes, few studies have examined the effects of prescription opioid misuse on suicidal behaviors among adolescents. The objective of this study was to examine the association between prescription opioid misuse and suicidal ideation, suicide plan, and suicide attempt among adolescents. Data for this study came from the 2017 Youth Risk Behavior Surveillance System. A sample of 8830 adolescents aged 14-18 years (50.9% female) were analyzed using logistic regression with suicidal ideation, suicide plan, and suicide attempt as outcome variables and prescription opioid misuse as the main explanatory variable. Of the 8830 adolescents, 13.3% ever misused prescription opioids; 17.7% experienced suicidal ideation, 13.3% made a suicide plan, and 6.5% attempted suicide during the past 12 months. In the multivariate logistic regression models, adolescent students who misused prescription opioids were 1.50 times more likely to have experienced suicidal ideation, 1.44 times more likely to have made a suicide plan, and 1.58 times more likely to have attempted suicide during the past 12 months when compared to their counterparts who did not misuse prescription opioids. Other significant predictors of suicidal behaviors include sexual minority, history of sexual assault, traditional bullying and cyberbullying victimization, feeling sad or hopeless, cigarette smoking, and illicit drug use. The findings of the present study demonstrate the harmful effects of prescription opioid misuse and its association with suicidal behaviors among adolescents.

PMID: 30852426 [PubMed - as supplied by publisher]

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