Recent Research Articles from UNTHSC

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

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Updated: 2 hours 7 min ago

Regulatory roles of glutathione-S-transferases and 4-hydroxynonenal in stress-mediated signaling and toxicity.

Wed, 04/04/2018 - 07:48
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Regulatory roles of glutathione-S-transferases and 4-hydroxynonenal in stress-mediated signaling and toxicity.

Free Radic Biol Med. 2017 Oct;111:235-243

Authors: Awasthi YC, Ramana KV, Chaudhary P, Srivastava SK, Awasthi S

Abstract
Glutathione-S-Transferases (GSTs) have primarily been thought to be xenobiotic metabolizing enzymes that protect cells from toxic drugs and environmental electrophiles. However, in last three decades, these enzymes have emerged as the regulators of oxidative stress-induced signaling and toxicity. 4-Hydroxy-trans 2-nonenal (HNE) an end-product of lipid peroxidation, has been shown to be a major determinant of oxidative stress-induced signaling and toxicity. HNE is involved in signaling pathways, including apoptosis, proliferation, modulation of gene expression, activation of transcription factors/repressors, cell cycle arrest, and differentiation. In this article, available evidence for a major role of GSTs in the regulation of HNE-mediated cell signaling processes through modulation of the intracellular levels of HNE is discussed.

PMID: 27794453 [PubMed - indexed for MEDLINE]

Effectiveness of a computerized motivational intervention on treatment initiation and substance use: Results from a randomized trial.

Tue, 04/03/2018 - 07:34
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Effectiveness of a computerized motivational intervention on treatment initiation and substance use: Results from a randomized trial.

J Subst Abuse Treat. 2017 Sep;80:59-66

Authors: Lerch J, Walters ST, Tang L, Taxman FS

Abstract
As many as 80% of the nearly five million adults under community supervision (i.e., probation, parole) are substance involved; however, treatment utilization is low. Using a multi-site randomized controlled trial, we tested the efficacy of in-person motivational interviewing (MI), a motivational computer intervention (MAPIT), or standard probation intake (SAU) to encourage treatment initiation among 316 substance-involved probationers in Dallas, Texas and Baltimore City, Maryland. Ninety-three percent (n=295) of participants completed the 2-month follow-up and 90% (n=285) completed the 6-month follow-up. At 2-months, individuals in the MAPIT condition were more likely to report treatment initiation compared to the SAU condition (OR=2.40, 95% CI=1.06, 5.47) via intent-to-treat analysis, especially among those completing both sessions (RE=0.50, 95% CI=0.05, 0.95) via instrumental variable analysis. At 6-months, MAPIT approached significance for treatment initiation in both analyses. MI did not achieve significance in any model. We did not find any differential impact on substance use. The success of MAPIT suggests that an integrated health-justice computerized intervention as part of a Screening, Brief Intervention, and Referral to Treatment (SBIRT) can be used to address public safety and health issues.

PMID: 28755774 [PubMed - indexed for MEDLINE]

The influence of vitamins E and C and exercise on brain aging.

Tue, 04/03/2018 - 07:34
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The influence of vitamins E and C and exercise on brain aging.

Exp Gerontol. 2017 Aug;94:69-72

Authors: Mock JT, Chaudhari K, Sidhu A, Sumien N

Abstract
Age-related declines in motor and cognitive function have been associated with increases in oxidative stress. Accordingly, interventions capable of reducing the oxidative burden would be capable of preventing or reducing functional declines occurring during aging. Popular interventions such as antioxidant intake and moderate exercise are often recommended to attain healthy aging and have the capacity to alter redox burden. This review is intended to summarize the outcomes of antioxidant supplementation (more specifically of vitamins C and E) and exercise training on motor and cognitive declines during aging, and on measures of oxidative stress. Additionally, we will address whether co-implementation of these two types of interventions can potentially further their individual benefits. Together, these studies highlight the importance of using translationally-relevant parameters for interventions and to study their combined outcomes on healthy brain aging.

PMID: 27939444 [PubMed - indexed for MEDLINE]

Complementing T Regulatory Cells to Combat Hypertension.

Sat, 03/31/2018 - 08:26
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Complementing T Regulatory Cells to Combat Hypertension.

Circ Res. 2018 Mar 30;122(7):911-912

Authors: Mathis KW

PMID: 29599271 [PubMed - in process]

Exfoliative Excrement.

Sat, 03/31/2018 - 08:26
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Exfoliative Excrement.

JAMA Dermatol. 2016 06 01;152(6):701

Authors: Roman J, Reynolds SD

PMID: 27276354 [PubMed - indexed for MEDLINE]

Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC) Inhibitor, in Ischemia Reperfusion in Mouse Eyes.

Fri, 03/30/2018 - 08:51

Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC) Inhibitor, in Ischemia Reperfusion in Mouse Eyes.

Curr Eye Res. 2018 Mar 29;:1-13

Authors: Dibas A, Millar C, Al-Farra A, Yorio T

Abstract
PURPOSE: The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ASIC2 in retinal ganglion cells (RGCs) after retinal ischemia and reperfusion (I/R) injury and to test if inhibition of ASIC1a provides RGC neuroprotection.
METHODS: Transient ischemia was induced in one eye of C57BL/6 mice by raising intraocular pressure to 120 mmHg for 60 min followed by retinal reperfusion by restoring normal pressure. RGC function was measured by Pattern electroretinography (PERG). In addition, retinal ASIC1a and ASIC2 were observed by immunohistochemistry and western blot. Changes in calpain, fodrin, heat shock protein 70 (HSP70), Brn3a, super oxide dismutase-1 (SOD1), catalase, and glutathione perioxidase-4 (GPX4) protein levels were assessed by western blot. RGC numbers were measured by immunohistochemistry on whole retinal flat mounts using anti-RNA binding protein with multiple splicing (RBPMS) antibodies. Intravitreal injection of psalmotoxin-1, a selective ASIC1a blocker, was used to assess the neuroprotective effect of ASIC1a inhibition.
RESULTS: Levels of ASIC1a and ASIC2 after I/R increased in RGCs. Upregulation of ASIC1a but not ASIC2 was attenuated by intravitreal injection of psalmotoxin-1. I/R induced activation of calpain and degradation of fodrin, HSP70, and reduction in Brn3a. In contrast, while psalmotoxin-1 attenuated calpain activation and increased Brn3a levels, it failed to block HSP70 degradation. Unlike SOD1 protein which was reduced, catalase protein levels increased after I/R. Psalmotoxin-1, although not affecting SOD1 and GPX4, increased catalase levels significantly. Psalmotoxin-1 also increased RBPMS-labeled RGCs following I/R as judged by immunohistochemistry of retinal flat mounts. Finally, psalmotoxin-1 enhanced the amplitude of PERG following I/R, suggesting partial rescue of RGC function.
CONCLUSION: Psalmotoxin-1 appears to exert a neuroprotective effect under ischemic insults and targeting inhibition of ASICs may represent a new therapeutic approach in ischemic retinal diseases.

PMID: 29595330 [PubMed - as supplied by publisher]

Why Do Some People Choose Opportunistic Rather Than Organized Cancer Screening? The Korean National Health and Nutrition Examination Survey (KNHANES) 2010-2012.

Fri, 03/30/2018 - 08:51
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Why Do Some People Choose Opportunistic Rather Than Organized Cancer Screening? The Korean National Health and Nutrition Examination Survey (KNHANES) 2010-2012.

Cancer Res Treat. 2017 Jul;49(3):727-738

Authors: Hahm MI, Chen HF, Miller T, O'Neill L, Lee HY

Abstract
PURPOSE: Although the Korean government has implemented a universal screening program for common cancers, some individuals choose to participate in opportunistic screening programs. Therefore, this study was conducted to identify factors contributing to the selection of organized versus opportunistic screening by the Korean general population.
MATERIALS AND METHODS: Data from 11,189 participants aged ≥ 40 yearswho participated in the fifth Korean National Health and Nutrition Examination Survey (2010-2012) were analyzed in this study.
RESULTS: A total of 6,843 of the participants (58.6%) underwent cancer screening, of which 6,019 (51.1%) participated in organized and 824 (7.5%) participated in opportunistic screening programs. Being female, older, highly educated, in the upper quartile of income, an ex-smoker, and a light drinker as well as having supplementary private health insurance and more comorbid conditions and engaging in moderate physical activity 1-4 days per week were related to participation in both types of screening programs. Being at least a high school graduate, in the upper quartile for income, and a light drinker, as well as having more comorbid conditions and engaging in moderate physical activities 1-4 days per week had a stronger effect on those undergoing opportunistic than organized screening.
CONCLUSION: The results of this study suggest that socioeconomic factors such as education and income, as well as health status factors such as health-related quality of life and number of comorbid conditions and health behaviors such as drinking and engaging in moderate physical activity 1-4 days per week had a stronger influence on participation in an opportunistic than in an organized screening program for cancer.

PMID: 27809458 [PubMed - indexed for MEDLINE]

Private sector tuberculosis prevention in the US: Characteristics associated with interferon-gamma release assay or tuberculin skin testing.

Thu, 03/29/2018 - 07:38

Private sector tuberculosis prevention in the US: Characteristics associated with interferon-gamma release assay or tuberculin skin testing.

PLoS One. 2018;13(3):e0193432

Authors: Stockbridge EL, Miller TL, Carlson EK, Ho C

Abstract
OBJECTIVE: To determine whether latent tuberculosis infection risk factors are associated with an increased likelihood of latent tuberculosis infection testing in the US private healthcare sector.
DATA SOURCE: A national sample of medical and pharmacy claims representing services rendered January 2011 through December 2013 for 3,997,986 commercially insured individuals in the US who were 0 to 64 years of age.
STUDY DESIGN: We used multivariable logistic regression models to determine whether TB/LTBI risk factors were associated with an increased likelihood of Interferon-Gamma Release Assay (IGRA) or Tuberculin Skin Test (TST) testing in the private sector.
PRINCIPAL FINDINGS: 4.31% (4.27-4.34%) received at least one TST/IGRA test between 2011 and 2013 while 1.69% (1.67-1.72%) received a TST/IGRA test in 2013. Clinical risk factors associated with a significantly increased likelihood of testing included HIV, immunosuppressive therapy, exposure to tuberculosis, a history of tuberculosis, diabetes, tobacco use, end stage renal disease, and alcohol use disorder. Other significant variables included gender, age, asthma, the state tuberculosis rate, population density, and percent of foreign-born persons in a county.
CONCLUSIONS: Private sector TST/IGRA testing is not uncommon and testing varies with clinical risk indicators. Thus, the private sector can be a powerful resource in the fight against tuberculosis. Analyses of administrative data can inform how best to leverage private sector healthcare toward tuberculosis prevention activities.

PMID: 29590130 [PubMed - in process]

Effect of Intermittent Hypoxia Training for Dizziness: A Randomized Controlled Trial.

Wed, 03/28/2018 - 07:39
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Effect of Intermittent Hypoxia Training for Dizziness: A Randomized Controlled Trial.

J Sport Rehabil. 2018 Mar 27;:1-17

Authors: Bao X, Tan JW, Long Y, Liu H, Liu HY

Abstract
OBJECTIVE: To study the effect of intermittent hypoxia training (IHT) for dizziness.
DESIGN: A single-blind, randomized controlled trial. All participants were recruited from a rehabilitation department in an acute university-affiliated hospital.
INTERVENTION: Participants with dizziness were randomly assigned to two groups (IHT group and control group). The Dizziness Handicap Inventory (DHI), Activities-specific Balance Confidence Scale (ABC), Vertigo Visual Analog Scale (VVAS) were conducted at baseline, end of the 4th week.
RESULTS: Among 52 subjects, eighteen males and thirty four females, ages from 35 to 62 years old (mean ± SD = 46.9 ± 7.93). Time length since onset ranged from 12 months to 34 months (20.2±7.15 months). DHI, ABC, VVAS scores and attack frequencies of dizziness were improved after IH training intervention in the end of 4th week. There were significant differences between IHT group and control group in DHI, ABC, VVAS scores and attack frequencies of dizziness in the end of 4th week (P<0.05). No adverse events occurred during the study.
CONCLUSION: IHT could improve dizziness after intervention in end of 4th week. IHT could be the effective method for releasing dizziness.

PMID: 29584516 [PubMed - as supplied by publisher]

Regulation of Constitutive Tip110 Expression in Human Cord Blood CD34+ Cells Through Selective Usage of the Proximal and Distal Polyadenylation Sites Within the 3'Untranslated Region.

Wed, 03/28/2018 - 07:39
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Regulation of Constitutive Tip110 Expression in Human Cord Blood CD34+ Cells Through Selective Usage of the Proximal and Distal Polyadenylation Sites Within the 3'Untranslated Region.

Stem Cells Dev. 2018 Mar 27;:

Authors: Liu Y, Huang X, Timani KA, Broxmeyer HE, He JJ

Abstract
Tip110 plays important roles for stem cell pluripotency and hematopoiesis. However, little is known about the regulatory mechanisms of Tip110 expression in this process. In this study, we first showed that constitutive Tip110 expression was cell proliferation and differentiation dependent and self-regulated in both human cord blood CD34+ cells. Using a series of molecular techniques, we found that ectopic Tip110 expression led to increased constitutive Tip110 expression through its 3'-untranslated region (3'UTR), specifically through preferential usage of proximal polyadenylation sites within its 3'UTR in cells, including human cord blood CD34+ cells, which indeed led to an increased number of CD34+ cells during differentiation of those cells. Lastly, we showed that Tip110 protein interacted with cleavage stimulation factor 64 (CstF64) protein and that more CstF64 was recruited to the promixal polyadenylation site than the distal polyadenylation site within its 3'UTR. These finding together demonstrates that constitutive Tip110 expression is regulated, at least in part, through its interaction with CstF64, recruitment of CstF64 to, and selective usage of those two polyadenylation sites within its 3'UTR.

PMID: 29583087 [PubMed - as supplied by publisher]

Risk of psychological ill health and methods of organisational downsizing: a cross-sectional survey in four European countries.

Wed, 03/28/2018 - 07:39
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Risk of psychological ill health and methods of organisational downsizing: a cross-sectional survey in four European countries.

BMC Public Health. 2017 Sep 29;17(1):758

Authors: Andreeva E, Brenner MH, Theorell T, Goldberg M

Abstract
BACKGROUND: The manner in which organizational downsizing is implemented can make a substantial difference as to whether the exposed workers will suffer from psychological ill health. Surprisingly, little research has directly investigated this issue. We examined the likelihood of psychological ill health associated with strategic and reactive downsizing.
METHODS: A cross-sectional survey included 1456 respondents from France, Sweden, Hungary and the United Kingdom: 681 employees in stable workplaces (reference group) and 775 workers from downsized companies. Reactive downsizing was exemplified by the exposures to compulsory redundancies of medium to large scale resulting in job loss or surviving a layoff while staying employed in downsized organizations. The workforce exposed to strategic downsizing was represented by surplus employees who were internally redeployed and supported through their career change process within a policy context of "no compulsory redundancy". Symptoms of anxiety, depression and emotional exhaustion were assessed in telephone interviews with brief subscales from Hospital Anxiety Scale (HADS-A), Hopkins Symptom Checklist (SCL-CD6) and Maslach Burnout Inventory (MBI-GS). Data were analyzed using logistic regression.
RESULTS: We observed no increased risk of psychological ill health in the case of strategic downsizing. The number of significant associations with psychological ill health was the largest for the large-scale reactive downsizing: surviving a layoff was consistently associated with all three outcome measures; returning to work after the job loss experience was related to anxiety and depression, while persons still unemployed at interview had elevated odds of anxiety. After reactive medium-scale downsizing, unemployment at interview was the only exposure associated with anxiety and depression.
CONCLUSIONS: The manner in which organizational downsizing is implemented can be important for the psychological wellbeing of workers. If downsizing is unavoidable, it should be achieved strategically. Greater attention is needed to employment and health policies supporting the workers after reactive downsizing.

PMID: 28962605 [PubMed - indexed for MEDLINE]

Combined measurement of plasma cystatin C and low-density lipoprotein cholesterol: A valuable tool for evaluating progressive supranuclear palsy.

Tue, 03/27/2018 - 07:39
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Combined measurement of plasma cystatin C and low-density lipoprotein cholesterol: A valuable tool for evaluating progressive supranuclear palsy.

Parkinsonism Relat Disord. 2018 Mar 19;:

Authors: Weng R, Wei X, Yu B, Zhu S, Yang X, Xie F, Zhang M, Jiang Y, Feng ZP, Sun HS, Xia Y, Jin K, Chan P, Wang Q, Gao X

Abstract
INTRODUCTION: Progressive supranuclear palsy (PSP) was previously thought as a cause of atypical Parkinsonism. Although Cystatin C (Cys C) and low-density cholesterol lipoprotein-C (LDL-C) are known to play critical roles in Parkinsonism, it is unknown whether they can be used as markers to distinguish PSP patients from healthy subjects and to determine disease severity.
METHODS: We conducted a cross-sectional study to determine plasma Cys C/HDL/LDL-C levels of 40 patients with PSP and 40 healthy age-matched controls. An extended battery of motor and neuropsychological tests, including the PSP-Rating Scale (PSPRS), the Non-Motor Symptoms Scale (NMSS), Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE), was used to evaluate the disease severity. Receiver operating characteristic (ROC) curves were adopted to assess the prognostic accuracy of Cys C/LDL-C levels in distinguishing PSP from healthy subjects.
RESULTS: Patients with PSP exhibited significantly higher plasma levels of Cys C and lower LDL-C. The levels of plasma Cys C were positively and inversely correlated with the PSPRS/NMSS and MMSE scores, respectively. The LDL-C/HDL-C ratio was positively associated with PSPRS/NMSS and GDS scores. The ROC curve for the combination of Cys C and LDL-C yielded a better accuracy for distinguishing PSP from healthy subjects than the separate curves for each parameter.
CONCLUSIONS: Plasma Cys C and LDL-C may be valuable screening tools for differentiating PSP from healthy subjects; while they could be useful for the PSP intensifies and severity evaluation. A better understanding of Cys C and LDL-C may yield insights into the pathogenesis of PSP.

PMID: 29574085 [PubMed - as supplied by publisher]

Calcium plus vitamin D supplementation and lung cancer incidence among postmenopausal women in the Women's Health Initiative.

Tue, 03/27/2018 - 07:39
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Calcium plus vitamin D supplementation and lung cancer incidence among postmenopausal women in the Women's Health Initiative.

Lung Cancer. 2017 Aug;110:42-47

Authors: Tao MH, Dai Q, Chen S, Freudenheim JL, Rohan T, Wakelee H, Datta M, Wactawski-Wende J

Abstract
BACKGROUND: Magnesium and calcium are antagonistic in many physiologic processes. However, few studies have investigated the associations of supplemental calcium with lung cancer risk taking this antagonism into account. We evaluated the effect of calcium and vitamin D supplementation on lung cancer incidence and explored whether the ratio of baseline calcium to magnesium (Ca:Mg) intake modifies the association in the Women's Health Initiative (WHI) calcium plus vitamin D supplementation (CaD) trial.
METHODS: The intervention phase of the WHI CaD was a double-blinded, randomized, placebo-controlled trial in 36,382 postmenopausal women aged 50-79 years, recruited at 40U.S. centers. Post-intervention follow-up continued among 29,862 (86%) of the surviving participants. Risk of lung cancer in association with CaD supplementation was evaluated using proportional hazard regression models.
RESULTS: After 11 years' cumulative follow-up, there were 207 lung cancers (incidence 0.11% per year) in the supplement arm and 241 (0.12%) in the placebo arm (hazard ratio (HR) for the intervention, 0.91; 95% confidence interval (CI), 0.71-1.17). Subgroup analyses suggested that the HR for lung cancer varied by baseline Ca:Mg intake ratio among women who were current smokers at enrollment (p=0.04 for interaction).
CONCLUSIONS: Over the entire follow-up period, calcium and vitamin D supplementation did not reduce lung cancer incidence among postmenopausal women. In exploratory analyses, an interaction was found for the baseline Ca:Mg intake ratio on lung cancer among current smokers at the trial entry. This findings need to be further studied for the role of calcium with magnesium in lung carcinogenesis in current smokers.

PMID: 28676217 [PubMed - indexed for MEDLINE]

Surgical management of giant intrapetrous internal carotid aneurysm presenting with coil exposure after endovascular treatment.

Sun, 03/25/2018 - 16:57

Surgical management of giant intrapetrous internal carotid aneurysm presenting with coil exposure after endovascular treatment.

Neurosurg Rev. 2018 Mar 23;:

Authors: Yu LB, Zhang D, Yang SH, Zhao JZ

Abstract
Giant intrapetrous internal carotid aneurysms (petrous ICA aneurysm) are rare. A giant petrous ICA aneurysm presenting with otorrhagia and coil exposure to the external auditory meatus (EAM) after endovascular treatment has never been documented before. The authors report here a case of successful surgical trapping with bypass intervention of a giant petrous ICA aneurysm presenting with coil exposure after endovascular treatment. A 58-year-old man presented with persistent otorrhagia having been admitted to our hospital because of the recurrence of a giant petrous ICA aneurysm after repeated embolization treatments with coils. An electronic otoscope examination demonstrated that a piece of coil escaped into his right EAM. After multidisciplinary consultation, an extracranial-intracranial (EC-IC) bypass with ICA occlusion and coil removal with a closed EAM filling were performed in stages. The patient recovered quickly without any neurological deficits. A digital subtraction angiography confirmed the absence of the aneurysm and patency of the bypass graft.

PMID: 29572579 [PubMed - as supplied by publisher]

Safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in hepatitis C genotype 1 patients including those with decompensated cirrhosis who failed prior treatment with simeprevir/sofosbuvir.

Sat, 03/24/2018 - 07:43

Safety and efficacy of ledipasvir/sofosbuvir with or without ribavirin in hepatitis C genotype 1 patients including those with decompensated cirrhosis who failed prior treatment with simeprevir/sofosbuvir.

Aliment Pharmacol Ther. 2018 Mar 23;:

Authors: Modi AA, Nazario HE, Gonzales GR, Gonzalez SA

Abstract
BACKGROUND: Combination therapy of simeprevir (SIM)/sofosbuvir (SOF) is an approved treatment for hepatitis C genotype (gen) 1 with overall SVR12 rate of 85%-95%. The single tablet fixed-dose combination of ledipasvir (LDV)/SOF is also approved for gen 1 with sustained virologic response at 12 weeks (SVR12) rates ≥95%. No data are available on the efficacy of retreatment with LDV/SOF in patients who failed initial treatment with SIM/SOF.
AIM: Our aim was to evaluate the efficacy of retreatment with LDV/SOF ± ribavirin (RBV) in gen 1 patients who had previously failed treatment with SIM/SOF.
METHODS: Data from a combined treatment cohort of 2 hepatology centres, which included patients previously treated with SIM/SOF ± RBV for 12 weeks but failed to achieve SVR and then underwent retreatment with LDV/SOF ± RBV, were analysed (n = 30). LDV/SOF ± RBV was administered for 12-24 weeks based on the discretion of the treating hepatologist.
RESULTS: Of the 30 patients, 23 (77%) were male, 77% were Caucasian and 26 (87%) were gen 1a. 26 (86%) had cirrhosis, of which 16 (62%) had decompensated, Child's class B or C cirrhosis. Three patients were liver transplant recipients with recurrent hepatitis C. Overall, 27/30 (90%) achieved SVR. Treatment was well tolerated with 37% reporting no adverse events. The most common adverse events were fatigue, headache, insomnia and nausea. Two patients with Child's B cirrhosis required hospitalization during treatment for variceal haemorrhage and abdominal pain respectively. However, no treatment discontinuations or deaths occurred.
CONCLUSION: Single tablet fixed-dose combination LDV/SOF ± RBV is efficacious and well tolerated in patients who previously failed treatment with SIM/SOF, including those with decompensated cirrhosis and recurrent hepatitis C following liver transplantation.

PMID: 29569736 [PubMed - as supplied by publisher]

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

Sat, 03/24/2018 - 07:43

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

CNS Drugs. 2018 Mar 22;:

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 - as supplied by publisher]

Serious mental illness and negative substance use consequences among adults on probation.

Sat, 03/24/2018 - 07:43

Serious mental illness and negative substance use consequences among adults on probation.

Health Justice. 2018 Mar 22;6(1):6

Authors: Rossheim ME, Livingston MD, Lerch JA, Taxman FS, Walters ST

Abstract
BACKGROUND: Adults on probation are at greater risk of both using substances and having a mental disorder compared to the general population. Several theories explain the relationship between substance use and poor mental health. However, the interaction between substance use, mental health, and substance-related consequences is not well understood. A better understanding of this relationship may help treatment programs become more responsive to people with serious mental illness (SMI).
METHOD: The current study used interview data from 313 adults on probation who reported recent substance use. We examined associations between SMI risk, substance use, and substance use consequences.
RESULTS: A substantial proportion of the sample (37.5%) screened at risk of having a SMI. Adjusting for type and amount of substance use, those who screened at risk of having a SMI reported more negative substance use consequences. Significant interaction effects were observed between use of alcohol or opiates and SMI risk. Alcohol use was associated with more negative substance use consequences among those at risk of SMI, while opiate use was associated with more consequences among those not at risk.
CONCLUSIONS: Programs are sorely needed to identify and treat adults with comorbid substance use and mental health symptoms, particularly for adults in the justice system. Clinicians should carefully consider how mental health may interact with substance use to exacerbate consequences.

PMID: 29569076 [PubMed]

Tip110 Deletion Impaired Embryonic and Stem Cell Development Involving Downregulation of Stem Cell Factors Nanog, Oct4, and Sox2.

Sat, 03/24/2018 - 07:43
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Tip110 Deletion Impaired Embryonic and Stem Cell Development Involving Downregulation of Stem Cell Factors Nanog, Oct4, and Sox2.

Stem Cells. 2017 Jul;35(7):1674-1686

Authors: Whitmill A, Liu Y, Timani KA, Niu Y, He JJ

Abstract
HIV-1 Tat-interacting protein of 110 kDa, Tip110, plays important roles in multiple biological processes. In this study, we aimed to characterize the function of Tip110 in embryonic development. Transgenic mice lacking expression of a functional Tip110 gene (Tip110-/- ) died post-implantation, and Tip110-/- embryos exhibited developmental arrest between 8.5 and 9.5 days post coitum. However, in vitro cultures of Tip110-/- embryos showed that Tip110 loss did not impair embryo growth from the zygote to the blastocyst. Extended in vitro cultures of Tip110-/- blastocysts showed that Tip110 loss impaired both blastocyst outgrowth and self-renewal and survival of blastocyst-derived embryonic stem cells. Microarray analysis of Tip110-/- embryonic stem cells revealed that Tip110 loss altered differentiation, pluripotency, and cycling of embryonic stem cells and was associated with downregulation of several major stem cell factors including Nanog, Oct4, and Sox2 through a complex network of signaling pathways. Taken together, these findings document for the first time the lethal effects of complete loss of Tip110 on mammalian embryonic development and suggest that Tip110 is an important regulator of not only embryonic development but also stem cell factors. Stem Cells 2017;35:1674-1686.

PMID: 28436127 [PubMed - indexed for MEDLINE]

Current Strategies for Brain Drug Delivery.

Wed, 03/21/2018 - 07:36

Current Strategies for Brain Drug Delivery.

Theranostics. 2018;8(6):1481-1493

Authors: Dong X

Abstract
The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.

PMID: 29556336 [PubMed - in process]

The Radiographic Prepatellar Fat Thickness Ratio Correlates With Infection Risk After Total Knee Arthroplasty.

Wed, 03/21/2018 - 07:36

The Radiographic Prepatellar Fat Thickness Ratio Correlates With Infection Risk After Total Knee Arthroplasty.

J Arthroplasty. 2018 Feb 15;:

Authors: Wagner RA, Hogan SP, Burge JR, Bates CM, Sanchez HB

Abstract
BACKGROUND: Obesity has been associated with complications after a total knee arthroplasty (TKA). Surgical site infection (SSI) after TKA is one of the feared complications as it increases revision rates, costs, and stress to the patient. There is conflicting evidence in the literature regarding body mass index (BMI) and risk of infection after TKA, and some studies have suggested that site-specific fat distribution may be a better metric for determining risk of postoperative infections. Here, we investigate the correlation of soft tissue distribution about the knee to SSI after TKA.
METHODS: We retrospectively review 572 patients who underwent primary TKA at a single institution from 2006 to 2010. We introduce the prepatellar fat thickness ratio (PFTR) as a radiographic means to quantitatively assess fat distribution about the knee and evaluate this measurement's ability to assess the risk of developing an SSI after TKA.
RESULTS: The PFTR was shown to be a better predictor of SSI than BMI in both the univariate (P = .05) and multivariate (P = .01) analyses.
CONCLUSION: Although BMI cannot fully account for variations in adipose distribution, the PFTR may account for this variability and may be a helpful tool for assessing a patient's preoperative risk of SSI after TKA.

PMID: 29555491 [PubMed - as supplied by publisher]

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