Recent Research Articles from UNTHSC

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

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Effects of elastic band exercise on the frailty states in pre-frail elderly people.

6 hours 7 min ago
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Effects of elastic band exercise on the frailty states in pre-frail elderly people.

Physiother Theory Pract. 2020 Sep;36(9):1000-1008

Authors: Chen R, Wu Q, Wang D, Li Z, Liu H, Liu G, Cui Y, Song L

Abstract
OBJECTIVE: To discuss the effects of elastic band exercise on the frailty states in pre-frail elderly people.
METHODS: This study was a randomized controlled trial. Trial registration number is ChiCTR-IOC-17012579. Seventy pre-frail elderly people were randomly divided into elastic band group (n = 35) and control group (n = 35). Elastic band exercise was applied to elastic band group, 45-60 min per time for 8 weeks by 3 days a week; no exercise was applied to the control group. The frailty states, grip strength (female/male), walking speed, and physical activity were measured by the Fried frailty phenotype at pre-intervention, 4, and 8 weeks after intervention to assess the effects of exercise.
RESULTS: The elastic band group showed significant improvements in the frailty states, grip strength (female) and walking speed both after 4-week and 8-week intervention (P< 0.001), and significant improvements in grip strength (male) and physical activity after 8-week intervention (P< 0.05). Within-group analysis (pre-intervention vs. after 4-week, after 4-week vs after 8-week, pre-intervention vs after 8-week) showed significant improvements (P< 0.001) in grip strength (female/male) and walking speed in the elastic band group over time, while no significant differences in the control group (P > 0.05).
CONCLUSION: Elastic band exercise can improve frailty states in pre-frail elderly people, make them broke away from pre-frailty and restore them to non-frailty through improving the grip strength, walking speed and physical activity, and the effects after 8 weeks are better than those after 4 weeks.

PMID: 30741081 [PubMed - indexed for MEDLINE]

Teaching About Racism in Medical Education: A Mixed-Method Analysis of a Train-the-Trainer Faculty Development Workshop.

Thu, 01/21/2021 - 06:16
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Teaching About Racism in Medical Education: A Mixed-Method Analysis of a Train-the-Trainer Faculty Development Workshop.

Fam Med. 2021 Jan;53(1):23-31

Authors: Edgoose J, Brown Speights J, White-Davis T, Guh J, Bullock K, Roberson K, De Leon J, Ferguson W, Saba GW

Abstract
BACKGROUND AND OBJECTIVES: Curriculum addressing racism as a driver of inequities is lacking at most health professional programs. We describe and evaluate a faculty development workshop on teaching about racism to facilitate curriculum development at home institutions.
METHODS: Following development of a curricular toolkit, a train-the-trainer workshop was delivered at the 2017 Society of Teachers of Family Medicine Annual Spring Conference. Preconference evaluation and a needs assessment collected demographic data of participants, their learning communities, and experience in teaching about racism. Post-conference evaluations were completed at 2- and 6-month intervals querying participants' experiences with teaching about racism, including barriers; commitment to change expressed at the workshop; and development of the workshop-delivered curriculum. We analyzed quantitative data using Statistical Package for the Social Sciences (SPSS) software and qualitative data, through open thematic coding and content analysis.
RESULTS: Forty-nine people consented to participate. The needs assessment revealed anxiety but also an interest in obtaining skills to teach about racism. The most reported barriers to developing curriculum were institutional and educator related. The majority of respondents at 2 months (61%, n=14/23) and 6 months (70%, n=14/20) had used the toolkit. Respondents ranked all 10 components as useful. The three highest-ranked components were (1) definitions and developing common language; (2) facilitation training, exploring implicit bias, privilege, intersectionality and microaggressions, and videos/podcasts; and (3) Theater of the Oppressed and articles/books.
CONCLUSIONS: Faculty development training, such as this day-long workshop and accompanying toolkit, can advance skills and increase confidence in teaching about racism.

PMID: 33471919 [PubMed - as supplied by publisher]

Combating COVID-19 With Mesenchymal Stem/Stromal Cell Therapy: Promise and Challenges.

Thu, 01/21/2021 - 06:16
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Combating COVID-19 With Mesenchymal Stem/Stromal Cell Therapy: Promise and Challenges.

Front Cell Dev Biol. 2020;8:627414

Authors: Wang SH, Shetty AK, Jin K, Chunhua Zhao R

PMID: 33469541 [PubMed]

Association of Home Food Availability with Prediabetes and Diabetes among Adults in the United States.

Thu, 01/21/2021 - 06:16
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Association of Home Food Availability with Prediabetes and Diabetes among Adults in the United States.

Nutrients. 2020 Apr 25;12(5):

Authors: McAtee JR, Tao MH, King C, Chai W

Abstract
This study examined associations of home food availabilities with prediabetes and diabetes among 8929 adults (20-70 years) participating in 2007-2010 National Health and Nutrition Examination Surveys. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression. Relative to non-diabetic participants (individuals without diabetes or prediabetes), prediabetes participants were associated with lower availabilities of green vegetables (OR = 0.82; 95% CI = 0.73-0.91; p = 0.0006) and fat-free/low-fat milk (OR = 0.80, 95% CI = 0.65-0.89; p = 0.001) and higher sugary drink availability (OR = 1.24, 95% CI = 1.04-1.48; p = 0.02), adjusting for age, sex, and ethnicity (Model 1). The associations remained significant for vegetables (p = 0.005) and fat-free/low-fat milk (p = 0.02) adjusting for additional confounders (body mass index, education, Model 2). Adjusting for dietary components did not change the above results (in model 2) significantly. Participants with high healthy food availability scores had approximately 31% reduction (p = 0.003) in odds of prediabetes compared to those with low scores in Model 1. No associations were detected for diabetes except for fat-free/low-fat milk availability, for which an inverse association was observed in Model 1 (OR = 0.80, 95% CI = 0.65-0.99; p = 0.04). The results show prediabetes participants had lower availability of healthy foods and higher availability of unhealthy foods, suggesting the need to improve healthy food availability at home for this population.

PMID: 32344821 [PubMed - indexed for MEDLINE]

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

Thu, 01/21/2021 - 06:16
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Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with autism spectrum disorders.

Neurotoxicology. 2020 01;76:93-98

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 - indexed for MEDLINE]

Piezo1 plays a role in optic nerve head astrocyte reactivity.

Wed, 01/20/2021 - 08:10
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Piezo1 plays a role in optic nerve head astrocyte reactivity.

Exp Eye Res. 2021 Jan 16;:108445

Authors: Liu J, Yang Y, Liu Y

Abstract
Piezo1 (also known as Fam38A) is a mechanosensing channel required for mechanotransduction in various cell types. In astrocytes, Piezo1 activation is associated with the pathogenesis of central nervous system neurodegeneration. Expression of Piezo1 has been detected in mouse optic nerve head astrocytes, however, the functional role of Piezo1 has not been identified. In this study, we investigated the role of Piezo1 in optic nerve head astrocyte reactivity. Primary mouse optic nerve head astrocytes were cultured and subject to mechanical stretch. The expression level of Piezo1 was determined by quantitative PCR and immunocytochemistry staining. Astrocytes were further treated with Yoda1, a specific Piezo1 agonist. The intracellular calcium concentration and expression of F-actin and fibronectin were determined in Yoda1 treated cells. We found that mechanical stretch activated Piezo1 in optic nerve head astrocytes. Yoda1 induced robust Ca2+ responses in a dose dependent manner. In addition, Yoda1 treated cells showed a redistribution of F-actin cytoskeleton and an increased expression of fibronectin which indicated astrocyte reactivity. Our results suggest that Piezo1 responses to mechanical stimulation and plays a role in astrocyte reactivity. This study provides new insights into optic nerve head astrocyte mechanotransduction.

PMID: 33465396 [PubMed - as supplied by publisher]

Antipsychotic medication adherence and preventive diabetes screening in Medicaid enrollees with serious mental illness: an analysis of real-world administrative data.

Wed, 01/20/2021 - 08:10
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Antipsychotic medication adherence and preventive diabetes screening in Medicaid enrollees with serious mental illness: an analysis of real-world administrative data.

BMC Health Serv Res. 2021 Jan 18;21(1):69

Authors: Stockbridge EL, Webb NJ, Dhakal E, Garg M, Loethen AD, Miller TL, Nandy K

Abstract
BACKGROUND: There is excess amenable mortality risk and evidence of healthcare quality deficits for persons with serious mental illness (SMI). We sought to identify sociodemographic and clinical characteristics associated with variations in two 2015 Healthcare Effectiveness Data and Information Set (HEDIS) measures, antipsychotic medication adherence and preventive diabetes screening, among Medicaid enrollees with serious mental illness (SMI).
METHODS: We retrospectively analyzed claims data from September 2014 to December 2015 from enrollees in a Medicaid specialty health plan in Florida. All plan enrollees had SMI; analyses included continuously enrolled adults with antipsychotic medication prescriptions and schizophrenia or bipolar disorder. Associations were identified using mixed effects logistic regression models.
RESULTS: Data for 5502 enrollees were analyzed. Substance use disorders, depression, and having both schizophrenia and bipolar disorder diagnoses were associated with both HEDIS measures but the direction of the associations differed; each was significantly associated with antipsychotic medication non-adherence (a marker of suboptimal care quality) but an increased likelihood of diabetes screening (a marker of quality care). Compared to whites, blacks and Hispanics had a significantly greater risk of medication non-adherence. Increasing age was significantly associated with increasing medication adherence, but the association between age and diabetes screening varied by sex. Other characteristics significantly associated with quality variations according to one or both measures were education (associated with antipsychotic medication adherence), urbanization (relative to urban locales, residing in suburban areas was associated with both adherence and diabetes screening), obesity (associated with both adherence and diabetes screening), language (non-English speakers had a greater likelihood of diabetes screening), and anxiety, asthma, and hypertension (each positively associated with diabetes screening).
CONCLUSIONS: The characteristics associated with variations in the quality of care provided to Medicaid enrollees with SMI as gauged by two HEDIS measures often differed, and at times associations were directionally opposite. The variations in the quality of healthcare received by persons with SMI that were identified in this study can guide quality improvement and delivery system reform efforts; however, given the sociodemographic and clinical characteristics' differing associations with different measures of care quality, multidimensional approaches are warranted.

PMID: 33461561 [PubMed - in process]

Adult Cancer Survivors' Engagement and Interest in Patient-Centered Research.

Wed, 01/20/2021 - 08:10
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Adult Cancer Survivors' Engagement and Interest in Patient-Centered Research.

Cancer Epidemiol Biomarkers Prev. 2020 02;29(2):329-335

Authors: Lubas MM, Lu Y, Gehr AW, Ghabach B, Tanna B, Narra K, Brinkman TM, Ojha RP

Abstract
BACKGROUND: Limited information is available about the representativeness of survivors engaging in patient-centered research, despite the potential for threats to generalizability. We thus aimed to assess the representativeness of survivors engaged or interested in research development.
METHODS: We used data from the Health Information National Trends Survey, a nationally representative survey, to identify survivors of adult cancers. Our outcomes of interest were based on responses to questions about engagement or interest in developing patient-centered research. We estimated the ratio of relative frequencies (RRF) and corresponding 95% confidence limits (CL) of sociodemographic and survivorship characteristics between survivors engaged or interested in patient-centered research and the overall survivor population.
RESULTS: Our study population comprised 934 survivors, of whom 5% reported being engaged in patient-centered research and 26% reported an interest in participating. Relative frequencies of characteristics were discordant for engaged survivors but largely similar for interested survivors compared with all survivors. In particular, engaged survivors had a higher relative frequency of individuals ages 50 to 64 years (RRF = 1.7; 95% CL, 1.1-2.5), Hispanic (RRF = 2.9; 95% CL, 1.2-6.9), non-Hispanic Black (RRF = 2.9; 95% CL, 1.1-2.5), and unemployment (RRF = 4.7; 95% CL, 1.4-16).
CONCLUSIONS: We observed several meaningful differences in the characteristics of survivors engaged in patient-centered research compared with all survivors, which raises concerns about the generalizability of findings from such studies.
IMPACT: Patient-centered research may not benefit the broader survivor community if survivors engaging in research development are not representative of all survivors. Greater attention to recruiting mechanisms is necessary to avoid creating disparities.

PMID: 31740520 [PubMed - indexed for MEDLINE]

The impact of comorbid depression-diabetes on proteomic outcomes among community-dwelling Mexican Americans with mild cognitive impairment.

Wed, 01/20/2021 - 08:10
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The impact of comorbid depression-diabetes on proteomic outcomes among community-dwelling Mexican Americans with mild cognitive impairment.

Int Psychogeriatr. 2020 01;32(1):17-23

Authors: Johnson LA, Zhang F, Large S, Hall J, O'Bryant SE

Abstract
BACKGROUND: Mexican Americans suffer from a disproportionate burden of modifiable risk factors, which may contribute to the health disparities in mild cognitive impairment (MCI) and Alzheimer's disease (AD).
OBJECTIVE: The purpose of this study was to elucidate the impact of comorbid depression and diabetes on proteomic outcomes among community-dwelling Mexican American adults and elders.
METHODS: Data from participants enrolled in the Health and Aging Brain among Latino Elders study was utilized. Participants were 50 or older and identified as Mexican American (N = 514). Cognition was assessed via neuropsychological test battery and diagnoses of MCI and AD adjudicated by consensus review. The sample was stratified into four groups: Depression only, Neither depression nor diabetes, Diabetes only, and Comorbid depression and diabetes. Proteomic profiles were created via support vector machine analyses.
RESULTS: In Mexican Americans, the proteomic profile of MCI may change based upon the presence of diabetes. The profile has a strong inflammatory component and diabetes increases metabolic markers in the profile.
CONCLUSION: Medical comorbidities may impact the proteomics of MCI and AD, which lend support for a precision medicine approach to treating this disease.

PMID: 31658917 [PubMed - indexed for MEDLINE]

Mitochondrial DNA analysis of the putative skeletal remains of Sieur de Marle: Genetic support for anthropological assessment of biogeographic ancestry.

Wed, 01/20/2021 - 05:09
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Mitochondrial DNA analysis of the putative skeletal remains of Sieur de Marle: Genetic support for anthropological assessment of biogeographic ancestry.

Forensic Sci Int. 2021 Jan 08;320:110682

Authors: Ambers A, Elwick K, Cropper ER, Brandhagen MD, Jones B, Durst J, Gilmore KK, Bruseth JE, Gill-King H

Abstract
In 1932, seven burials were discovered on a Texas plantation that was originally the site of a 17th-century Caddo Indian village. Of the seven excavated graves, one set of remains (an adult male) was notably buried in a manner inconsistent with traditional Caddoan burial practices and has long been purported to be the remains of Sieur de Marle (a member of the French explorer La Salle's last expedition). Diary accounts of La Salle's expedition scribe report that Sieur de Marle died along a river near an Indian village during a trek to Canada to find help for colonists left behind at the ill-fated Fort St. Louis. Additionally, two lead projectiles recovered from the grave were ballistically analyzed and determined to be consistent with ammunition used in 17th-century weaponry. In the 1980s, anthropologists requested access to the remains for study, but the skull was missing. Cranial measurements recorded in 1940 and 1962 (by two independent anthropologists) were used to investigate the ancestry of this individual; and the Giles-Elliot (G-E) discriminant function was calculated to be 18.1, within the Anglo-European range. Dietary isotope testing on non-cranial skeletal elements determined that this unknown male's diet was rich in animal/marine protein sources, which differs appreciably from Caddo Indian populations of that time period. In order to genetically assess this individual's biogeographic ancestry and to provide further support that this individual is of European descent, mitochondrial DNA (mtDNA) sequencing was performed using the Applied Biosystems™ Precision ID mtDNA Whole Genome Panel. mtDNA sequencing of multiple sections from two different long bones yielded compiled results consistent with either Haplogroup H or R, both predominantly European mtDNA haplogroups. Further anthropological calculations were conducted using cranial measurements, FORDISC™ software, and discriminant function analysis. Two-way, four-way, and multigroup discriminant function analyses further classify this set of unidentified remains as being White (European) in origin, with posterior probabilities of 0.999, 0.881 and 0.986, respectively. Combined with historical records of Sieur de Marle's death, as well as overlays of historical and contemporary maps which demonstrate that the plantation site aligns with Joutel's diary accounts of de Marle's burial, these collective results support that these remains are of a European male and may possibly belong to this prominent member of La Salle's expedition team.

PMID: 33461005 [PubMed - as supplied by publisher]

Proteomics Profiling of Autologous Blood and Semen Exosomes from HIV-infected and Uninfected Individuals Reveals Compositional and Functional Variabilities.

Sun, 01/17/2021 - 07:26
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Proteomics Profiling of Autologous Blood and Semen Exosomes from HIV-infected and Uninfected Individuals Reveals Compositional and Functional Variabilities.

Mol Cell Proteomics. 2020 Jan;19(1):78-100

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: 33451560 [PubMed - as supplied by publisher]

49,000 Avocado Cutting Injuries.

Sat, 01/16/2021 - 05:10
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49,000 Avocado Cutting Injuries.

Am J Health Behav. 2020 01 01;44(1):13-17

Authors: Rossheim ME, Ninh EQ, Livingston MD, Thombs DL

Abstract
Objectives: In the United States (US), avocado consumption has increased dramatically since the year 2000. Despite media attention concerning injuries resulting from cutting or pitting avocados, such injuries have not been monitored systematically. The current study is the first to estimate the number of people with avocado cutting injuries presenting to US hospital emergency departments. Methods: We utilized cross-sectional data from the US Consumer Product Safety Commission's (CPSC) National Electronic Injury Surveillance System (NEISS). We used keyword searches of case narrative text to identify avocado cutting and pitting injuries from 2000 to 2017. Sampling weights were applied to generate national estimates of avocado cutting injuries. Results: From 2000 to 2017, there were an estimated 49,331 avocado cutting injuries presenting to US emergency departments (95% CI 34,178-64,483). The increase in these injuries appears to coincide with increases in per capita avocado consumption. Avocado cutting injuries now constitute nearly 2% of knife-related injuries presenting to US hospital emergency departments. Conclusions: Due to the increase in avocado cutting injuries and the severity of these injuries, more systematic surveillance is needed as well as improved safety measures.

PMID: 31783928 [PubMed - indexed for MEDLINE]

Cardiovascular Risk Factors, Cognitive Dysfunction, and Mild Cognitive Impairment.

Fri, 01/15/2021 - 07:03
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Cardiovascular Risk Factors, Cognitive Dysfunction, and Mild Cognitive Impairment.

Dement Geriatr Cogn Dis Extra. 2020 Sep-Dec;10(3):154-162

Authors: Vintimilla R, Balasubramanian K, Hall J, Johnson L, O'Bryant S

Abstract
Objectives: The present study sought to evaluate the contribution of cardiovascular risk factors to cognitive functioning in a sample of Mexican Americans diagnosed with mild cognitive impairment (MCI).
Methods: Hypertension, diabetes, dyslipidemia, and obesity were diagnosed based on self-report and/or standardized procedures. Cognitive function was measured with MMSE, Logical Memory I and II, Trail A & B, FAS, animal naming, and digit span tests. Independent samples t tests and two-way ANOVAs were conducted for analyses, adjusting for relevant covariates. We studied 100 Mexican Americans (65 female) with MCI, ages 50-86, from a longitudinal study of cognitive aging conducted at the University of North Texas Health Science Center.
Results: A difference between subjects with and without obesity and memory scores was shown by t tests. Two-way ANOVAs detected an association between the coexistence of hypertension and diabetes with language measures, diabetes and dyslipidemia with executive function, and diabetes and obesity with memory and language measures.
Conclusions: This study provides additional evidence about the link between cardiovascular risk factors and cognitive dysfunction in MCI subjects, and also demonstrated that comorbid risk factors increased the degree of cognitive deficit in many areas, which may indicate a higher risk of developing dementia.

PMID: 33442392 [PubMed]

Prediction of dengue outbreak in Selangor Malaysia using machine learning techniques.

Fri, 01/15/2021 - 07:03
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Prediction of dengue outbreak in Selangor Malaysia using machine learning techniques.

Sci Rep. 2021 Jan 13;11(1):939

Authors: Salim NAM, Wah YB, Reeves C, Smith M, Yaacob WFW, Mudin RN, Dapari R, Sapri NNFF, Haque U

Abstract
Dengue fever is a mosquito-borne disease that affects nearly 3.9 billion people globally. Dengue remains endemic in Malaysia since its outbreak in the 1980's, with its highest concentration of cases in the state of Selangor. Predictors of dengue fever outbreaks could provide timely information for health officials to implement preventative actions. In this study, five districts in Selangor, Malaysia, that demonstrated the highest incidence of dengue fever from 2013 to 2017 were evaluated for the best machine learning model to predict Dengue outbreaks. Climate variables such as temperature, wind speed, humidity and rainfall were used in each model. Based on results, the SVM (linear kernel) exhibited the best prediction performance (Accuracy = 70%, Sensitivity = 14%, Specificity = 95%, Precision = 56%). However, the sensitivity for SVM (linear) for the testing sample increased up to 63.54% compared to 14.4% for imbalanced data (original data). The week-of-the-year was the most important predictor in the SVM model. This study exemplifies that machine learning has respectable potential for the prediction of dengue outbreaks. Future research should consider boosting, or using, nature inspired algorithms to develop a dengue prediction model.

PMID: 33441678 [PubMed - in process]

On the possibility of direct triplet state excitation of indole.

Fri, 01/15/2021 - 07:03
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On the possibility of direct triplet state excitation of indole.

J Photochem Photobiol B. 2020 Jul;208:111897

Authors: Chavez J, Ceresa L, Kitchner E, Kimball J, Shtoyko T, Fudala R, Borejdo J, Gryczynski Z, Gryczynski I

Abstract
We studied the luminescence properties of indole in poly (vinyl alcohol) (PVA) film. The indole molecules are effectively immobilized in this polymer film and display both fluorescence and phosphorescence emission at room temperature. We noticed that the phosphorescence of indole in PVA film can be effectively excited at a longer wavelength than its typical singlet to triplet population route involving intersystem crossing. The maximum of the phosphorescence excitation is about 410 nm which corresponds to the energy of indole's triplet state. Interestingly, the phosphorescence anisotropy excited with the longer wavelength (405 nm) is positive and reaches a value of about 0.25 in contrast to the phosphorescence anisotropy excited within the indole singlet absorption spectrum (290 nm), which is negative. Very different temperature dependences have been observed for fluorescence and phosphorescence of indole in PVA film. While fluorescence depends minimally, the phosphorescence decreases with temperature dramatically. The fluorescence lifetime was measured to be a single component 4.78 ns while the intensity weighted average phosphorescence lifetime with 290 nm and 405 nm excitations were 6.57 and 5.62 ms, respectively. We believe that the possibility of the excitation of indole phosphorescence in the blue region of visible light and its high anisotropy opens a new avenue for future protein studies.

PMID: 32447191 [PubMed - indexed for MEDLINE]

Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease.

Thu, 01/14/2021 - 05:28
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Novel pharmacotherapy: NNI-362, an allosteric p70S6 kinase stimulator, reverses cognitive and neural regenerative deficits in models of aging and disease.

Stem Cell Res Ther. 2021 Jan 13;12(1):59

Authors: Sumien N, Wells MS, Sidhu A, Wong JM, Forster MJ, Zheng QX, Kelleher-Andersson JA

Abstract
Aging is known to slow the neurogenic capacity of the hippocampus, one of only two mammalian adult neurogenic niches. The reduction of adult-born neurons with age may initiate cognitive decline progression which is exacerbated in chronic neurodegenerative disorders, e.g., Alzheimer's disease (AD). With physiologic neurogenesis diminished, but still viable in aging, non-invasive therapeutic modulation of this neuron regeneration process remains possible. The discovery of truly novel neuron regenerative therapies could be identified through phenotypic screening of small molecules that promote adult-born neurons from human neural progenitor cells (hNPCs). By identifying neuron-generating therapeutics and potentially novel mechanism of actions, therapeutic benefit could be confirmed through in vivo proof-of-concept studies. The key aging and longevity mTOR/p70S6 kinase axis, a commonly targeted pathway, is substrate for potential selective kinase modulators to promote new hippocampal neurons from NPCs. The highly regulated downstream substrate of mTOR, p70S6 kinase, directly controls pleiotropic cellular activities, including translation and cell growth. Stimulating this kinase, selectively in an adult neurogenic niche, should promote NPC proliferation, and cell growth and survival in the hippocampus. Studies of kinase profiling and immunocytochemistry of human progenitor neurogenesis suggest that the novel small molecule NNI-362 stimulates p70S6 kinase phosphorylation, which, in turn, promotes proliferation and differentiation of NPCs to neurons. NNI-362 promoted the associative reversal of age- and disease-related cognitive deficits in aged mice and Down syndrome-modeled mice. This oral, allosteric modulator may ultimately be beneficial for age-related neurodegenerative disorders involving hippocampal-dependent cognitive impairment, specifically AD, by promoting endogenous hippocampal regeneration.

PMID: 33436007 [PubMed - in process]

Modeling the cornea in 3-dimensions: Current and future perspectives.

Thu, 01/14/2021 - 05:28
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Modeling the cornea in 3-dimensions: Current and future perspectives.

Exp Eye Res. 2020 08;197:108127

Authors: McKay TB, Hutcheon AEK, Guo X, Zieske JD, Karamichos D

Abstract
The cornea is an avascular, transparent ocular tissue that serves as a refractive and protective structure for the eye. Over 90% of the cornea is composed of a collagenous-rich extracellular matrix within the stroma with the other 10% composed by the corneal epithelium and endothelium layers and their corresponding supporting collagen layers (e.g., Bowman's and Descemet's membranes) at the anterior and posterior cornea, respectively. Due to its prominent role in corneal structure, tissue engineering approaches to model the human cornea in vitro have focused heavily on the cellular and functional properties of the corneal stroma. In this review, we discuss model development in the context of culture dimensionality (e.g., 2-dimensional versus 3-dimensional) and expand on the optical, biomechanical, and cellular functions promoted by the culture microenvironment. We describe current methods to model the human cornea with focus on organotypic approaches, compressed collagen, bioprinting, and self-assembled stromal models. We also expand on co-culture applications with the inclusion of relevant corneal cell types, such as epithelial, stromal keratocyte or fibroblast, endothelial, and neuronal cells. Further advancements in corneal tissue model development will markedly improve our current understanding of corneal wound healing and regeneration.

PMID: 32619578 [PubMed - indexed for MEDLINE]

Isolation and characterization of human optic nerve head astrocytes and lamina cribrosa cells.

Thu, 01/14/2021 - 05:28
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Isolation and characterization of human optic nerve head astrocytes and lamina cribrosa cells.

Exp Eye Res. 2020 08;197:108103

Authors: Lopez NN, Clark AF, Tovar-Vidales T

Abstract
The lamina cribrosa is the initial site of glaucomatous injury. Pathological changes to the lamina cribrosa include posterior displacement of the lamina cribrosa, loss of trophic support, and remodeling of the extracellular matrix. Optic nerve head (ONH) astrocytes and lamina cribrosa cells synthesize extracellular matrix proteins to support and maintain the lamina cribrosa under physiological conditions. During glaucoma, these cells respond to mechanical strain and other stimuli, which leads to pathological remodeling of the ONH. Although ONH astrocytes and lamina cribrosa cells have been previously cultured, there is no well-accepted, straightforward technique to isolate both cell types from a single dissected human ONH. To better understand the pathophysiology of glaucoma, we obtained and cultured lamina cribrosa explants from human donor eyes. Initially, cells that grew out from the explant were ONH astrocytes and lamina cribrosa cells. Using a specialized medium, we isolated pure populations of lamina cribrosa cells and ONH astrocytes. ONH astrocytes expressed glial fibrillary acidic protein (GFAP). Lamina cribrosa cells expressed alpha-smooth muscle actin (α-SMA), but were negative for GFAP. This method of ONH cell isolation and cell-culture will provide a technique to better understand the molecular and cell-specific changes in glaucomatous damage to the ONH.

PMID: 32522476 [PubMed - indexed for MEDLINE]

Motivational Interviewing to Encourage Quit Attempts Among Smokers Not Ready to Quit: A Trial-Based Economic Analysis.

Wed, 01/13/2021 - 07:39
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Motivational Interviewing to Encourage Quit Attempts Among Smokers Not Ready to Quit: A Trial-Based Economic Analysis.

Nicotine Tob Res. 2020 08 24;22(9):1515-1523

Authors: Rasu RS, Thelen J, Agbor Bawa W, Goggin K, Bradley-Ewing A, Catley D

Abstract
INTRODUCTION: This study used data from a randomized controlled trial evaluating the efficacy of motivational interviewing (MI) relative to health education (HE) and brief advice (BA) to encourage quit attempts and cessation in order to determine their relative cost-effectiveness.
AIMS AND METHODS: Urban community residents (n = 255) with low desire to quit smoking were randomized to MI, HE, or BA which differed in communication style and/or number of treatment sessions. Incremental cost-effectiveness ratios were used to compare the intensive interventions (MI and HE) to BA for facilitating quit attempts and smoking cessation. Costs were calculated from the perspective of an agency that might engage in program delivery. Sensitivity analysis examined different assumptions for MI training and pharmacotherapy costs.
RESULTS: Total intervention delivery time costs per participant for MI, HE, and BA were $46.63, $42.87, and $2.4, respectively. Cost-effectiveness ratios per quit attempt at 24 weeks were $380 for MI, $272 for HE, and $209 for BA. The cost per additional quit attempt for MI and HE relative to BA was $508 and $301, respectively. The cost per additional quit for MI and HE relative to BA was $2030 and $752, respectively. Four separate sensitivity analyses conducted in our study did not change the conclusion the HE had a lower Incremental Cost-Effectiveness Ratio for both quit attempts and cessation.
CONCLUSIONS: HE was the most cost-effective of the three types of smoking cessation induction therapies and therefore may be preferable for smokers who are less motivated to quit. Providing valuable cost information in choosing different clinical methods for motivating smokers to quit.
IMPLICATIONS: All direct costs and activity-based time costs associated with delivering the intervention were analyzed from the perspective of an agency that may wish to replicate these strategies. A randomized controlled trial evaluating the efficacy of MI relative to HE and BA to encourage quit attempts and cessation determined their relative cost-effectiveness. HE was the most cost-effective of the three types of smoking cessation induction therapies and therefore may be preferable. Despite guideline recommendations, MI may not be the best approach to encourage quit attempts in diverse populations. Rather, a structured, intensive HE intervention might be the most cost-effective alternative.

PMID: 31820002 [PubMed - indexed for MEDLINE]

Fixed-dose gabapentin augmentation in the treatment of alcohol withdrawal syndrome: a retrospective, open-label study.

Wed, 01/13/2021 - 07:39
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Fixed-dose gabapentin augmentation in the treatment of alcohol withdrawal syndrome: a retrospective, open-label study.

Am J Drug Alcohol Abuse. 2020;46(1):49-57

Authors: Andaluz A, DeMoss D, Claassen C, Blair S, Hsu J, Bakre S, Khan M, Atem F, Rush AJ

Abstract
Background: Lorazepam use in the treatment of alcohol withdrawal syndrome (AWS) is not without risk.Objective: This study compares AWS outcomes using a standard, symptom-triggered lorazepam dosing protocol (control group) and symptom-triggered lorazepam dosing augmented with a gabapentin loading dose and taper (GABA group).Methods: Consecutive, non-randomized adults (n = 982; 64.0% male) undergoing treatment for AWS were included in this retrospective, open-label study. Symptom-triggered lorazepam dosing was informed by scores on the Clinical Institute Withdrawal Assessment-Alcohol, revised (CIWA-Ar). Gabapentin augmentation utilized an initial loading dose (900 mg) and a three-day taper. Outcomes included average symptom severity per treatment hour and average lorazepam dose per treatment hour. Average time in the protocol by group, stratified by highest CIWA-Ar score, was examined as a secondary outcome. A priori group differences were controlled statistically.Results: GABA patients were older and exhibited somewhat more severe withdrawal symptoms than controls. After controlling for confounders, gabapentin augmentation did not significantly lower average lorazepam dosing per treatment hour or withdrawal symptom severity per treatment hour. Compared to controls, overall withdrawal symptoms diminished somewhat more rapidly for GABA patients experiencing low or moderate-level withdrawal symptoms; however, severe withdrawal symptoms remitted more slowly in the GABA group. Results should be interpreted in light of the uncontrolled nature of group assignment and other confounders.Conclusions: Compared to symptom-triggered lorazepam dosing alone, gabapentin augmentation did not produce better outcomes during treatment of acute AWS. These results do not support the use of scheduled gabapentin as an augmentation to benzodiazepines during inpatient treatment of AWS.

PMID: 31490712 [PubMed - indexed for MEDLINE]

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