Recent Research Articles from UNTHSC

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

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Intermittent hypoxia improves behavioral and adrenal gland dysfunction induced by posttraumatic stress disorder in rats.

Fri, 11/15/2019 - 05:10
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Intermittent hypoxia improves behavioral and adrenal gland dysfunction induced by posttraumatic stress disorder in rats.

J Appl Physiol (1985). 2018 09 01;125(3):931-937

Authors: Manukhina EB, Tseilikman VE, Tseilikman OB, Komelkova MV, Kondashevskaya MV, Goryacheva AV, Lapshin MS, Platkovskii PO, Alliluev AV, Downey HF

Abstract
Nonpharmacological treatments of stress-induced disorders are promising, since they enhance endogenous stress defense systems, are free of side effects, and have few contraindications. The present study tested the hypothesis that intermittent hypoxia conditioning (IHC) ameliorates behavioral, biochemical, and morphological signs of experimental posttraumatic stress disorder (PTSD) induced in rats with a model of predator stress (10-day exposure to cat urine scent, 15 min daily followed by 14 days of stress-free rest). After the last day of stress exposure, rats were conditioned in an altitude chamber for 14 days at a 1,000-m simulated altitude for 30 min on day 1 with altitude and duration progressively increasing to 4,000 m for 4 h on day 5. PTSD was associated with decreased time spent in open arms and increased time spent in closed arms of the elevated X-maze, increased anxiety index, and increased rate of freezing responses. Functional and structural signs of adrenal cortex degeneration were also observed, including decreased plasma concentration of corticosterone, decreased weight of adrenal glands, reduced thickness of the fasciculate zone, and hydropic degeneration of adrenal gland cells. The thickness of the adrenal fasciculate zone negatively correlated with the anxiety index. IHC alleviated both behavioral signs of PTSD and morphological evidence of adrenal cortex dystrophy. Also, IHC alone exerted an antistress effect, which was evident from the increased time spent in open arms of the elevated X-maze and a lower number of rats displaying freezing responses. Therefore, IHC of rats with experimental PTSD reduced behavioral signs of the condition and damage to the adrenal glands. NEW & NOTEWORTHY Intermittent hypoxia conditioning (IHC) has been shown to be cardio-, vaso-, and neuroprotective. For the first time, in a model of posttraumatic stress disorder (PTSD), this study showed that IHC alleviated both PTSD-induced behavioral disorders and functional and morphological damage to the adrenal glands. Also, IHC alone exerted an antistress effect. These results suggest that IHC may be a promising complementary treatment for PTSD-associated disorders.

PMID: 29927732 [PubMed - indexed for MEDLINE]

Liposomal mupirocin holds promise for systemic treatment of invasive Staphylococcus aureus infections.

Wed, 11/13/2019 - 13:55

Liposomal mupirocin holds promise for systemic treatment of invasive Staphylococcus aureus infections.

J Control Release. 2019 Nov 09;:

Authors: Goldmann O, Cern A, Muesken M, Rohde M, Weiss W, Barenholz Y, Medina E

Abstract
Staphylococcus aureus is a major cause of severe invasive infections. The increasing incidence of infections caused by antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA), calls for exploration of new approaches to treat these infections. Mupirocin is an antibiotic with a unique mode of action that is active against MRSA, but its clinical use is restricted to topical administration because of its limited plasma stability and rapid degradation to inactive metabolites. Mupirocin was identified by a machine learning approach to be suitable for nano-liposome encapsulation. The computational predictions were verified experimentally and PEGylated nano-liposomal formulation of mupirocin (Nano-mupirocin) was developed. The aim of this study was to investigate the efficacy of this formulation when administered parenterally for the treatment of S. aureus invasive infections. Nano-mupirocin exhibited prolonged half-life of active antibiotic and displayed superior antimicrobial activity against S. aureus than free mupirocin in the presence of plasma. Parenteral application of Nano-mupirocin in a murine model of S. aureus bloodstream infection resulted in improved antibiotic distribution to infected organs and in a superior therapeutic efficacy than the free drug. Parenterally administered Nano-mupirocin was also more active against MRSA than free mupirocin in a neutropenic murine lung infection model. In addition, Nano-mupirocin was very efficiently taken up by S. aureus-infected macrophages via phagocytosis leading to enhanced delivery of mupirocin in the intracellular niche and to a more efficient elimination of intracellular staphylococci. The outcome of this study highlights the potential of Nano-mupirocin for the treatment of invasive MRSA infections and support the further clinical development of this effective therapeutic approach.

PMID: 31715276 [PubMed - as supplied by publisher]

Implementation, adoption, and utility of family health history risk assessment in diverse care settings: evaluating implementation processes and impact with an implementation framework.

Wed, 11/13/2019 - 13:55
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Implementation, adoption, and utility of family health history risk assessment in diverse care settings: evaluating implementation processes and impact with an implementation framework.

Genet Med. 2019 02;21(2):331-338

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

Abstract
PURPOSE: This paper describes the implementation outcomes associated with integrating a family health history-based risk assessment and clinical decision support platform within primary care clinics at four diverse healthcare systems.
METHODS: A type III hybrid implementation-effectiveness trial. Uptake and implementation processes were evaluated using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework.
RESULTS: One hundred (58%) primary care providers and 2514 (7.8%) adult patients enrolled. Enrolled patients were 69% female, 22% minority, and 32% Medicare/Medicaid. Compared with their respective clinic's population, patient-participants were more likely to be female (69 vs. 59%), older (mean age 57 vs. 49), and Caucasian (88 vs. 69%) (all p values <0.001). Female (81.3% of females vs. 78.5% of males, p value = 0.018) and Caucasian (Caucasians 90.4% vs. minority 84.1%, p value = 0.02) patient-participants were more likely to complete the study once enrolled. Patient-participant survey responses indicated MeTree was easy to use (95%), and patient-participants would recommend it to family/friends (91%). Minorities and those with less education reported greatest benefit. Enrolled providers reflected demographics of underlying provider population.
CONCLUSION: Family health history-based risk assessment can be effectively implemented in diverse primary care settings and can effectively engage patients and providers. Future research should focus on finding better ways to engage young adults, males, and minorities in preventive healthcare.

PMID: 29875427 [PubMed - indexed for MEDLINE]

Oral bisphosphonate use and lung cancer incidence among postmenopausal women.

Wed, 11/13/2019 - 13:55
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Oral bisphosphonate use and lung cancer incidence among postmenopausal women.

Ann Oncol. 2018 06 01;29(6):1476-1485

Authors: Tao MH, Chen S, Freudenheim JL, Cauley JA, Johnson KC, Mai X, Sarto GE, Wakelee H, Boffetta P, Wactawski-Wende J

Abstract
Background: Bisphosphonates are common medications for the treatment of osteoporosis in older populations. Several studies, including the Women's Health Initiative (WHI), have found inverse associations of bisphosphonate use with risk of breast and endometrial cancer, but little is known about its association with other common malignancies. The objective of this study was to evaluate the association of bisphosphonate use on the incidence of lung cancer in the WHI.
Patients and methods: The association between oral bisphosphonate use and lung cancer risk was examined in 151 432 postmenopausal women enrolled into the WHI in 1993-1998. At baseline and during follow-up, participants completed an inventory of regularly used medications including bisphosphonates.
Results: After a mean follow-up of 13.3 years, 2511 women were diagnosed with incident lung cancer. There was no evidence of a difference in lung cancer incidence between oral bisphosphonate users and never users (adjusted hazard ratio = 0.91; 95% confidence intervals, 0.80-1.04; P = 0.16). However, an inverse association was observed among those who were never smokers (hazard ratio = 0.57, 95% confidence interval, 0.39-0.84; P < 0.01).
Conclusion: In this large prospective cohort of postmenopausal women, oral bisphosphonate use was associated with significantly lower lung cancer risk among never smokers, suggesting bisphosphonates may have a protective effect against lung cancer. Additional studies are needed to confirm our findings.

PMID: 29617712 [PubMed - indexed for MEDLINE]

Acute Lower Leg Hot Water Immersion Protects Macrovascular Dilator Function Following Ischaemia-Reperfusion Injury in Humans.

Mon, 11/11/2019 - 07:34
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Acute Lower Leg Hot Water Immersion Protects Macrovascular Dilator Function Following Ischaemia-Reperfusion Injury in Humans.

Exp Physiol. 2019 Nov 10;:

Authors: Engelland RE, Hemingway HW, Tomasco OG, Olivencia-Yurvati AH, Romero SA

Abstract
NEW FINDINGS: •What is the central question of this study? The effect of lower leg hot water immersion on vascular I/R injury induced in the arm of young healthy humans has not been previously explored. •What is the main finding and its importance? Our findings demonstrate that lower leg hot water immersion successfully protects against vascular I/R injury in humans. This finding raises the possibility that targeted heating of the lower legs may be an alternative therapeutic approach to whole-body heating that is equally efficacious at protecting against vascular I/R injury ABSTRACT: Reperfusion that follows a period of ischaemia paradoxically reduces vasodilator function in humans and contributes to the tissue damage associated with an ischaemic event. Acute whole-body hot water immersion protects against vascular ischaemia-reperfusion (I/R) injury in young healthy humans. However, the effect of acute lower leg heating on I/R injury is unclear. Therefore, the purpose of this study was to test the hypothesis that, compared with thermoneutral control immersion, acute lower leg hot water immersion would prevent the decrease in macro- and microvascular dilator functions following I/R injury in young healthy humans. Ten young healthy subjects (5 female) immersed their lower legs into a circulated water bath for 60 min under two randomized conditions: 1) thermoneutral control immersion (∼33°C); 2) hot water immersion (∼42°C). Macrovascular (brachial artery flow-mediated dilatation) and microvascular (forearm reactive hyperaemia) dilator functions were assessed using Doppler ultrasound at three time points: 1) pre-immersion; 2) 60 min post-immersion; 3) post-I/R (20 min of arm ischaemia followed by 20 min of reperfusion). Ischaemia-reperfusion injury reduced macrovascular dilator function following control immersion (pre-immersion 6.0 ± 2.1 % vs. post-I/R 3.6 ± 2.1 %; P < 0.05), but was well-maintained with prior hot water immersion (pre-immersion 5.8 ± 2.1 % vs. post-I/R 5.3 ± 2.1 %; P = 0.8). Microvascular dilator function did not differ between conditions or across time. Taken together, acute lower leg hot water immersion prevents the decrease in macrovascular dilator function that occurs following I/R injury in young healthy humans. This article is protected by copyright. All rights reserved.

PMID: 31707732 [PubMed - as supplied by publisher]

Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with autism spectrum disorders.

Mon, 11/11/2019 - 07:34
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Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with autism spectrum disorders.

Neurotoxicology. 2019 Nov 05;:

Authors: Quan L, Yi J, Zhao Y, Zhang F, Shi XT, Feng Z, Miller HL

Abstract
OBJECTIVE: The compositions of the gut microbiota and its metabolites were altered in individuals with Autism Spectrum Disorder (ASD). The aim of this study was to assess whether plasma levels of gut-derived metabolite trimethylamine N-oxide (TMAO) were associated with ASD and the degree of symptom severity.
METHODS: From September 2017 to January 2019, a total of three hundred and twenty-eight Chinese children (164 with ASD and 164 their age-sex matched control subjects) aged 3-8 years were included. TMAO levels in plasma were determined using high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS). Logistic regression analysis was used to examine the TMAO-ASD association.
RESULTS: In the study, the median age of the ASD group was 5 years (interquartile range [IQR], 4-6 years) and 129 (78.7%) were boys. The median plasma levels of TMAO in children with ASD and typically-developing (TD) children at admission were 4.2 (IQR, 3.0-5.6) μmol/l and 3.0 (2.0-4.4) μmol/l, respectively (P < 0.001). For each 1 μmol/l increase of plasma TMAO, the unadjusted and adjusted risk of ASD would be increased by 54% (with the odds ratios [OR] of 1.54; 95% confidence intervals [CI]: 1.32-1.78; P < 0.001) and 27% (1.27 [1.10-1.45], P < 0.001), respectively. Symptom severity was classified as mild-to-moderate (CARS < 37) for 66 children with ASD (40.2%). In these children, the plasma levels of TMAO were lower than in the 98 children with ASD (59.8%) whose symptoms were classified as severe (CARS > 36) (3.5[2.5-4.9] μmol/l vs. 4.5(3.7-6.0) μmol/l; P < 0.001). For each 1 μmol/l increase of plasma TMAO, the unadjusted and adjusted risk of severe autism would be increased by 61% (with the OR of 1.61 [95% CI 1.28-2.01], P < 0.001) and 31% (1.31 [1.08-1.49], P < 0.001), respectively.
CONCLUSIONS: Elevated plasma levels of TMAO were associated with ASD and symptom severity.

PMID: 31704102 [PubMed - as supplied by publisher]

Use of the Muddiest Point Technique as an exam review in an integrated pharmacotherapy course.

Sat, 11/09/2019 - 12:53
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Use of the Muddiest Point Technique as an exam review in an integrated pharmacotherapy course.

Curr Pharm Teach Learn. 2018 09;10(9):1295-1302

Authors: Bullock KC, Gibson C, Howard M, Liu J, Tatachar A, Yuet WC

Abstract
BACKGROUND AND PURPOSE: The objective of this study was to evaluate the impact in student pharmacists' exam performance learning outcomes and satisfaction after integrating the Muddiest Point assessment technique into exam reviews.
EDUCATIONAL ACTIVITY AND SETTING: In 2016, the Muddiest Point, a formative assessment tool, was used to develop exam review sessions for second-year student pharmacists in an integrated pharmacotherapy course focused on the cardiovascular system. Performance scores on all four exams were compared between students in the 2015 and 2016 courses. Students' complexity of learning was categorized using a taxonomy of learning structure. A survey was used to evaluate student perceptions of exam reviews and the Muddiest Point technique (MPT).
FINDINGS: Scores were higher on the second exam for the 83 students in the 2016 course (78.0% vs. 86.0%, p<0.001). There was no difference on other exam scores or overall course failures. Muddiest points submitted by students demonstrated a variety of taxonomy of learning levels. Student pharmacists surveyed at the conclusion of the course agreed that exam reviews were helpful for their preparation for exams and that the MPT was a valuable use of class time.
SUMMARY: Incorporating the MPT into exam reviews maintained exam scores and supported evaluation of student learning. In addition, student pharmacists were satisfied with this exam review method.

PMID: 30497634 [PubMed - indexed for MEDLINE]

Tuberculosis Prevention in the Private Sector: Using Claims-Based Methods to Identify and Evaluate Latent Tuberculosis Infection Treatment With Isoniazid Among the Commercially Insured.

Sat, 11/09/2019 - 12:53
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Tuberculosis Prevention in the Private Sector: Using Claims-Based Methods to Identify and Evaluate Latent Tuberculosis Infection Treatment With Isoniazid Among the Commercially Insured.

J Public Health Manag Pract. 2018 Jul/Aug;24(4):E25-E33

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

Abstract
CONTEXT: Targeted identification and treatment of people with latent tuberculosis infection (LTBI) are key components of the US tuberculosis elimination strategy. Because of recent policy changes, some LTBI treatment may shift from public health departments to the private sector.
OBJECTIVES: To (1) develop methodology to estimate initiation and completion of treatment with isoniazid for LTBI using claims data, and (2) estimate treatment completion rates for isoniazid regimens from commercial insurance claims.
METHODS: Medical and pharmacy claims data representing insurance-paid services rendered and prescriptions filled between January 2011 and March 2015 were analyzed.
PARTICIPANTS: Four million commercially insured individuals 0 to 64 years of age.
MAIN OUTCOME MEASURES: Six-month and 9-month treatment completion rates for isoniazid LTBI regimens.
RESULTS: There was an annual isoniazid LTBI treatment initiation rate of 12.5/100 000 insured persons. Of 1074 unique courses of treatment with isoniazid for which treatment completion could be assessed, almost half (46.3%; confidence interval, 43.3-49.3) completed 6 or more months of therapy. Of those, approximately half (48.9%; confidence interval, 44.5-53.3) completed 9 months or more.
CONCLUSIONS: Claims data can be used to identify and evaluate LTBI treatment with isoniazid occurring in the commercial sector. Completion rates were in the range of those found in public health settings. These findings suggest that the commercial sector may be a valuable adjunct to more traditional venues for tuberculosis prevention. In addition, these newly developed claims-based methods offer a means to gain important insights and open new avenues to monitor, evaluate, and coordinate tuberculosis prevention.

PMID: 29084120 [PubMed - indexed for MEDLINE]

Retention in HIV Care Among Participants in the Patient-Centered HIV Care Model: A Collaboration Between Community-Based Pharmacists and Primary Medical Providers.

Fri, 11/08/2019 - 06:39
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Retention in HIV Care Among Participants in the Patient-Centered HIV Care Model: A Collaboration Between Community-Based Pharmacists and Primary Medical Providers.

AIDS Patient Care STDS. 2019 02;33(2):58-66

Authors: Byrd KK, Hardnett F, Clay PG, Delpino A, Hazen R, Shankle MD, Camp NM, Suzuki S, Weidle PJ, Patient-Centered HIV Care Model Team

Abstract
Poor retention in HIV care is associated with higher morbidity and mortality and greater risk of HIV transmission. The Patient-Centered HIV Care Model (PCHCM) integrated community-based pharmacists with medical providers. The model required sharing of patient clinical information and collaborative therapy-related action planning. The proportion of persons retained in care (≥1 medical visit in each 6-month period of a 12-month measurement period with ≥60 days between visits), pre- and post-PCHCM implementation, was modeled using log binomial regression. Factors associated with post-implementation retention were determined using multi-variable regression. Of 765 enrolled persons, the plurality were male (n = 555) and non-Hispanic black (n = 331), with a median age of 48 years (interquartile range = 38-55); 680 and 625 persons were included in the pre- and post-implementation analyses, respectively. Overall, retention improved 12.9% (60.7-68.5%, p = 0.002). The largest improvement was seen among non-Hispanic black persons, 22.6% increase (59.7-73.2%, p < 0.001). Persons who were non-Hispanic black [adjusted risk ratio (ARR) 1.27, 95% confidence interval (CI) 1.08-1.48] received one or more pharmacist-clinic developed action plan (ARR 1.51, 95% CI 1.18-1.93), had three or more pharmacist encounters (ARR 1.17, 95% CI 1.05-1.30), were more likely to be retained post-implementation. In the final multi-variable models, only race/ethnicity [non-Hispanic black (ARR 1.27, 95% CI 1.09-1.48) and "other or unknown" race/ethnicity (ARR 1.36, 95% CI 1.14-1.63)] showed an association with post-implementation retention. PCHCM demonstrated how collaborations between community-based pharmacists and primary medical providers can improve retention in HIV care. This care model may be particularly useful for non-Hispanic black persons who often are less likely to be retained in care.

PMID: 30648888 [PubMed - indexed for MEDLINE]

Letter to the editor.

Thu, 11/07/2019 - 15:30
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Letter to the editor.

J Paediatr Child Health. 2019 Nov;55(11):1407-1408

Authors: Henson R, Collins A, Zia S, Coplin B, Akkad R, Hamby T

PMID: 31691417 [PubMed - in process]

"I'll just pick it up…": Women's Acceptability of Self-Sampling Methods for STI Screening.

Thu, 11/07/2019 - 15:30
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"I'll just pick it up…": Women's Acceptability of Self-Sampling Methods for STI Screening.

Sex Transm Dis. 2019 Oct 30;:

Authors: Griner SB, Vamos CA, Puccio JA, Perrin K, Beckstead J, Daley EM

Abstract
BACKGROUND: Rates of sexually transmitted infection (STI) screening are suboptimal among college women. Self-sampling methods (SSM) may improve STI screening rates, but critical gaps remain regarding the influential characteristics of SSM to prioritize in intervention development. The purpose of this study was to explore intervention characteristics influencing the decision to adopt SSM among college women.
METHODS: In-depth interviews (n=24) were conducted with sexually active college women, age 18-24, to explore preferred intervention characteristics of SSM. Interviews were stratified by screening status (screened or not screened). The instrument was guided by constructs from the Diffusion of Innovation theory and included characteristics of SSM, such as relative advantage, compatibility, complexity, adaptability, and risk and uncertainty.
RESULTS: Overall, women felt that the SSM was not complex and that the instructions were straight-forward. Participants discussed their strong preference for receiving their results via text or email rather than via phone. Additionally, women described their concerns about mailing their sample and described their concern about potential contamination and tampering. The most salient advantage to use of SSM was avoiding an interaction with a healthcare provider.
CONCLUSIONS: This study contributes to an understanding of the salient intervention characteristics influencing the use of SSM for STI screening which can be leveraged to improve the health of students and improve rates of screening. Findings can be used to inform the development of a future innovative, theory-based intervention that promotes the use of SSM to improve STI screening rates, and ultimately decrease the burden of STI-related disease.

PMID: 31688722 [PubMed - as supplied by publisher]

Supplementation with N-Acetyl Cysteine Affects Motor and Cognitive Function in Young but Not Old Mice.

Thu, 11/07/2019 - 15:30
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Supplementation with N-Acetyl Cysteine Affects Motor and Cognitive Function in Young but Not Old Mice.

J Nutr. 2019 03 01;149(3):463-470

Authors: Ikonne US, Vann PH, Wong JM, Forster MJ, Sumien N

Abstract
BACKGROUND: N-acetyl cysteine (NAC) is a thiolic antioxidant that is thought to increase cellular glutathione (GSH) by augmenting the concentration of available cysteine, an essential precursor to GSH production. Manipulating redox status can affect brain function, and NAC intake has been associated with improving brain function in models of neurodegenerative diseases.
OBJECTIVES: The objective of the study was to determine if short-term dietary supplementation with NAC could ameliorate functional impairment associated with aging.
METHODS: C57BL/6J male mice aged 6, 12, or 24 mo were fed a control diet or the control diet supplemented with 0.3% NAC for a total of 12 wk. After 4 wk of dietary supplementation, mice began a series of behavioral tests to measure spontaneous activity (locomotor activity test), psychomotor performance (bridge-walking and coordinated running), and cognitive capacity (Morris water maze and discriminated active avoidance). The performance of the mice on these tests was analyzed through the use of analyses of variance with Age and Diet as factors.
RESULTS: Supplementation of NAC improved peak motor performance in a coordinated running task by 14% (P < 0.05), and increased the time spent around the platform by 24% in a Morris water maze at age 6 mo. However, the supplementation had no to minimal effect on the motor and cognitive functions of 12- and 24-mo-old mice.
CONCLUSIONS: The findings of this preclinical study support the claim that NAC has nootropic properties in 6-mo-old mice, but suggest that it may not be useful for improving motor and cognitive impairments in older mice.

PMID: 30770531 [PubMed - indexed for MEDLINE]

Parental longevity predicts healthy ageing among women.

Thu, 11/07/2019 - 15:30
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Parental longevity predicts healthy ageing among women.

Age Ageing. 2018 11 01;47(6):853-860

Authors: Shadyab AH, Manson JE, Li W, Gass M, Brunner RL, Naughton MJ, Cannell B, Howard BV, LaCroix AZ

Abstract
Objective: to examine the association of parental longevity with healthy survival to age 90 years.
Methods: this was a prospective study among a racially and ethnically diverse cohort of 22,735 postmenopausal women from the Women's Health Initiative recruited from 1993 to 1998 and followed through 2017. Women reported maternal and paternal ages at death and current age of alive parents. Parental survival categories were <70, 70-79 (reference), 80-89 and ≥90 years (longevity). Healthy ageing was defined as reaching age 90 without major chronic conditions (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or physical limitations.
Results: women whose mothers survived to ≥90 years were more likely to attain healthy ageing (OR, 1.25; 95% CI, 1.11-1.42) and less likely to die before age 90 (OR, 0.75; 95% CI, 0.68-0.83). Women whose fathers survived to ≥90 years did not have significantly increased odds of healthy ageing but showed 21% (OR, 0.79; 95% CI, 0.70-0.90) decreased odds of death before age 90. Women whose mother and father both lived to 90 had the strongest odds of healthy ageing (OR, 1.38; 95% CI, 1.09-1.75) and decreased odds of death (OR, 0.68; 95% CI, 0.54-0.85). The proportion of healthy survivors was highest among women whose mother and father lived to 90 (28.6%), followed by those whose mother only lived to 90 (23.2%).
Conclusions: parental longevity predicted healthy ageing in a national cohort of postmenopausal women, supporting the view that genetic, environmental, and behavioral factors transmitted across generations may influence ageing outcomes among offspring.

PMID: 30124748 [PubMed - indexed for MEDLINE]

Different Cutpoints for Transient Elastography Lead to Different Associations With Cirrhosis.

Thu, 11/07/2019 - 15:30
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Different Cutpoints for Transient Elastography Lead to Different Associations With Cirrhosis.

Clin Gastroenterol Hepatol. 2018 08;16(8):1359-1360

Authors: Ojha RP, MacDonald BR, Chu TC, Greenland S

PMID: 29174788 [PubMed - indexed for MEDLINE]

Assessing Neuronal and Astrocyte Derived Exosomes From Individuals With Mild Traumatic Brain Injury for Markers of Neurodegeneration and Cytotoxic Activity.

Tue, 11/05/2019 - 05:58

Assessing Neuronal and Astrocyte Derived Exosomes From Individuals With Mild Traumatic Brain Injury for Markers of Neurodegeneration and Cytotoxic Activity.

Front Neurosci. 2019;13:1005

Authors: Winston CN, Romero HK, Ellisman M, Nauss S, Julovich DA, Conger T, Hall JR, Campana W, O'Bryant SE, Nievergelt CM, Baker DG, Risbrough VB, Rissman RA

Abstract
Mild traumatic brain injury (mTBI) disproportionately affects military service members and is very difficult to diagnose. To-date, there is currently no blood-based, diagnostic biomarker for mTBI cases with persistent post concussive symptoms. To examine the potential of neuronally-derived (NDE) and astrocytic-derived (ADE) exosome cargo proteins as biomarkers of chronic mTBI in younger adults, we examined plasma exosomes from a prospective longitudinal study of combat-related risk and resilience, marine resiliency study II (MRSII). After return from a combat-deployment participants were interviewed to assess TBI exposure while on deployment. Plasma exosomes from military service members with mTBI (mean age, 21.7 years, n = 19, avg. days since injury 151), and age-matched, controls (deployed service members who did not endorse a deployment-related TBI or a pre-deployment history of TBI; mean age, 21.95 years, n = 20) were precipitated and enriched against a neuronal adhesion protein, L1-CAM, and an astrocyte marker, glutamine aspartate transporter (GLAST) using magnetic beads to immunocapture the proteins and subsequently selected by fluorescent activated cell sorting (FACS). Extracted protein cargo from NDE and ADE preparations were quantified for protein levels implicated in TBI neuropathology by standard ELISAs and on the ultra-sensitive single molecule assay (Simoa) platform. Plasma NDE and ADE levels of Aβ42 were significantly higher while plasma NDE and ADE levels of the postsynaptic protein, neurogranin (NRGN) were significantly lower in participants endorsing mTBI exposure compared to controls with no TBI history. Plasma NDE and ADE levels of Aβ40, total tau, and neurofilament light (NFL), P-T181-tau, P-S396-tau were either undetectable or not significantly different between the two groups. In an effort to understand the pathogenetic potential of NDE and ADE cargo proteins, neuron-like cultures were treated with NDE and ADE preparations from TBI and non-TBI groups. Lastly, we determined that plasma NDE but not ADE cargo proteins from mTBI samples were found to be toxic to neuron-like recipient cells in vitro. These data support the presence of markers of neurodegeneration in NDEs of mTBI and suggest that these NDEs can be used as tools to identify pathogenic mechanisms of TBI.

PMID: 31680797 [PubMed]

A Systematic Evaluation of Effect of Adherence Patterns on the Sample Size and Power of a Clinical Study.

Tue, 11/05/2019 - 05:58
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A Systematic Evaluation of Effect of Adherence Patterns on the Sample Size and Power of a Clinical Study.

CPT Pharmacometrics Syst Pharmacol. 2018 12;7(12):818-828

Authors: Mallayasamy S, Chaturvedula A, Blaschke T, Fossler MJ

Abstract
The objective of our study was to evaluate the effect of adherence patterns on the sample size and power of a clinical trial. Simulations from a population pharmacokinetic/pharmacodynamic (PK/PD) model linked to an adherence model were used. Four types of drug characteristics, such as long (~35 hours) and short (~12 hours) half-life in combination with earlier or delayed time to reach steady-state PD end points were studied. Adherence patterns were simulated using Markov chains. Our results clearly demonstrate the significant impact of varying levels and patterns of nonadherence on the sample size and power of a study. For drugs with short half-lives the evidence to support efficacy could be diluted by various patterns of nonadherence that would make its efficacy indistinguishable from the response to placebo. Prospectively utilizing clinical trial simulations with thorough incorporation of various adherence patterns would provide valuable information when designing a trial.

PMID: 30291680 [PubMed - indexed for MEDLINE]

Pancreatic Cancer: An Emphasis on Current Perspectives in Immunotherapy.

Mon, 11/04/2019 - 14:50
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Pancreatic Cancer: An Emphasis on Current Perspectives in Immunotherapy.

Crit Rev Oncog. 2019;24(2):105-118

Authors: Patel K, Siraj S, Smith C, Nair M, Vishwanatha JK, Basha R

Abstract
Pancreatic cancer affects both male and female individuals with higher incidences and death rates among the male population. Detection of this malignancy is delayed due to the lack of symptoms in the early-stage cancer, which makes it extremely difficult to treat. Identifying effective strategies has been a challenge for improving the survival rates in pancreatic cancer patients. Resistance to chemotherapy is often developed in pancreatic cancer treatment. Although many strategies are under clinical trials to target certain markers associated with cancer, immunotherapeutic approaches are currently gaining importance. Immunotherapy for pancreatic cancer is in the limelight after preclinical research showed some promise. Immunotherapy approaches were tested along with other treatment options to enhance the treatment effect. Adoptive cell transfer and immune checkpoint inhibitors are currently in clinical trials. The Food and Drug Administration approved pembrolizumab in a fast-tracked review for advanced pancreatic cancer patients. Pembrolizumab blocks the checkpoint protein, programmed cell death protein 1 (PD-1), on T cells to boost the response of the immune system against cancer cells, thereby shrinking tumors. The recent developments in immunotherapy and the early success in other cancers are encouraging to further test immunotherapy in pancreatic cancer. The combination of pembrolizumab and pelareorep, an isolate of human reovirus, is in phase II clinical study in metastatic disease. Depending on the results of current clinical trials and testing, the strategies in the pipeline are expected to increase the use of immunotherapy in the clinical testing setting. Success in immunotherapy is urgently needed to address the side-effects, treating patients with advanced disease and reducing metastasis for increasing the survival rate in pancreatic cancer patients.

PMID: 31679206 [PubMed - in process]

Proteomics profiling of autologous blood and semen exosomes from HIV-infected and uninfected individuals reveals compositional and functional variabilities.

Mon, 11/04/2019 - 14:50
Related Articles

Proteomics profiling of autologous blood and semen exosomes from HIV-infected and uninfected individuals reveals compositional and functional variabilities.

Mol Cell Proteomics. 2019 Nov 01;:

Authors: Kaddour H, Lyu Y, Welch JL, Paromov V, Mandape SN, Sakhare SS, Pandhare J, Stapleton JT, Pratap S, Dash C, Okeoma CM

Abstract
Blood and semen are important body-fluids that carry exosomes for bioinformation transmission. Therefore, characterization of their proteomes is necessary for understanding body-fluid-specific physiologic and pathophysiologic functions. Using systematic multifactorial proteomic profiling, we characterized the proteomes of exosomes and exosome-free fractions from autologous blood and semen from three HIV-uninfected and three HIV-infected participants (total of 24 samples). We identified exosome-based protein signatures specific to blood and semen along with HIV-induced tissue-dependent proteomic perturbations. We validated our findings with samples from 16 additional donors and showed that unlike blood exosomes (BE), semen exosomes (SE) are enriched in clusterin. SE but not BE promote Protein•Nucleic acid binding and increase cell adhesion irrespective of HIV infection. This is the first comparative study of the proteome of autologous BE and SE. The proteins identified may be developed as biomarkers applicable to different fields of medicine, including reproduction and infectious diseases.

PMID: 31676584 [PubMed - as supplied by publisher]

Caspase Lesions of PVN-Projecting MnPO Neurons Blocks the Sustained Component of CIH-Induced Hypertension in Adult Male Rats.

Sat, 11/02/2019 - 06:26

Caspase Lesions of PVN-Projecting MnPO Neurons Blocks the Sustained Component of CIH-Induced Hypertension in Adult Male Rats.

Am J Physiol Heart Circ Physiol. 2019 Nov 01;:

Authors: Marciante AB, Wang LA, Little JT, Cunningham JT

Abstract
Obstructive Sleep Apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into waking hours. Chronic intermittent hypoxia, which models the hypoxemia associated with sleep apnea, is sufficient to cause a sustained increase in blood pressure that involves the central nervous system. The median preoptic nucleus (MnPO) is an integrative forebrain region that contributes to blood pressure regulation and neurogenic hypertension. The MnPO projects to the paraventricular nucleus (PVN), a pre-autonomic region. We hypothesized that pathway-specific lesions of the projection from the MnPO to the PVN would attenuate the sustained component of chronic intermittent hypoxia -induced hypertension. Adult male Sprague-Dawley rats (250-300g) were anesthetized with isoflurane and stereotaxically injected bilaterally in the PVN with a retrograde Cre-containing AAV (AAV9.CMV.HI.eGFP-Cre.WPRE.SV40) and injected in the MnPO with caspase-3 (AAV5-flex-taCasp3-TEVp) or control virus (AAV5-hSyn-DIO-mCherry). Three weeks after the injections the rats were exposed to a 7-day intermittent hypoxia protocol. During chronic intermittent hypoxia, controls developed a diurnal hypertension that was blunted in rats with caspase lesions. Brain tissue processed for FosB immunohistochemistry showed decreased staining with caspase-induced lesions of MnPO and downstream autonomic-regulating nuclei. Chronic intermittent hypoxia significantly increased plasma advanced oxidative protein products levels in controls but this increase was blocked in caspase-lesioned rats. The results indicate that PVN-projecting MnPO neurons play a significant role in blood pressure regulation in the development of persistent chronic intermittent hypoxia hypertension.

PMID: 31675258 [PubMed - as supplied by publisher]

Social Determinants of Human Papillomavirus Vaccine Uptake: An Assessment of Publicly Available Data.

Sat, 11/02/2019 - 06:26
Related Articles

Social Determinants of Human Papillomavirus Vaccine Uptake: An Assessment of Publicly Available Data.

Public Health Rep. 2019 May/Jun;134(3):264-273

Authors: Maness SB, Thompson EL

Abstract
OBJECTIVES: Despite cancer prevention benefits associated with the human papillomavirus (HPV) vaccine, uptake in the United States is relatively low among males and females. Our objective was to use the Healthy People 2020 social determinants of health framework to determine the availability and characteristics of data on economic, educational, social, health care, and community factors affecting HPV vaccine uptake in the United States.
METHODS: We included the most recent data sets from 6 publicly available, US-based, federally funded surveys that contained at least 1 measure of HPV vaccination among adolescents and young adults. We searched each data set for any social determinants of health measures within the 5 domains of the framework: economic stability, education, social and community context, health and health care, and neighborhood and built environment.
RESULTS: The social determinants of health domains of education, economic stability, and health and health care appeared in all data sets. The domains of social and community context and neighborhood and built environment appeared in only 3 data sets. Even when domains were represented, we discovered gaps in the data sets, in which only limited measures of the social determinants were available.
CONCLUSION: The addition of questions about the social determinants of health to the surveys that generate these data sets, particularly in the domains of social and community context and neighborhood and built environment, would strengthen the ability of public health researchers, policy makers, and professionals to identify associations between the social determinants of health and HPV vaccine uptake.

PMID: 30951641 [PubMed - indexed for MEDLINE]

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