Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization

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Education modifies the effect of apolipoprotein epsilon 4 on cognitive decline

OBJECTIVES: To assess the influence of education on the association between apolipoprotein E and cognitive change. DESIGN: Prospective cohort. PARTICIPANTS: HMO-based sample of 2168 non-demented community-dwelling elderly followed over 6 years. MEASUREMENTS: Generalized estimating equations were used with the difference between baseline and follow-up cognitive abilities screening instrument (CASI) as the outcome variable. RESULTS: At follow-up, 6% of the sample had a decline of 1.5 S.D. or greater on the CASI. Compared to individuals without an APOE4 allele, individuals with a single APOE4 allele did not have greater CASI decline. By contrast, individuals with two APOE4 alleles experienced greater decline in cognitive performance and the magnitude of that decline decreased as years of educational attainment increased. These relationships held after adjusting for age, gender, ethnicity, depression, diabetes, and history of vascular disease. CONCLUSION: Lower education was associated with steep 4-year cognitive decline for APOE4 homozygotes but not for APOE4 heterozygotes. Potentially modifiable host factors such as education could influence the association of high-risk genotypes and cognitive decline.     

Association of natural tooth loss with genetic variation at the human matrix Gla protein locus in elderly women

Natural tooth loss represents a major medical issue within the elderly population, since it impairs masticatory function critical for oral intake of essential nutrition. Contribution of genetic factors has been implicated in the determination of natural tooth loss; degree of reduction in number of natural teeth remaining intact (NTI) varies among individuals; thus, heterogeneity in NTI might reflect genetic variation within the population. One candidate gene, the matrix Gla protein gene (MGP), has been implicated in the pathogenesis of bone loss through a repression of bone/tooth formation. We have investigated a possible association between the CA repeat polymorphism at the human MGP gene locus and the NTI in 458 elderly Japanese women. In 916 chromosomes tested, ten alleles of the polymorphic nucleotide repeat were observed (designated A1–A10), among which five alleles were regarded as major alleles to be tested for the association. Twenty-seven women who possessed an A6 allele (164 bp) had significantly higher NTI than the remaining participants (n=431), who did not carry an allele of that size (mean: 10.0 teeth vs 5.6 teeth; P=0.007, Mann-Whitney test). An eight-year longitudinal follow-up study of NTI suggested that the genetic variations at the MGP locus did not affect the rate of tooth loss in the elderly period. These results suggest that genetic variation at the MGP gene locus is associated with some determinants for tooth loss in elderly women.     

Two dinucleotide repeat polymorphisms at the D8S1442 and D8S1443 loci

Two polymorphic dinucleotide (CA) repeat clones were isolated from cosmids, cCI8-1121 and cCI8-1199, mapped to chromosome 8p11.2-p12.     

The dorsal facial area of the medulla in cats: inhibitory action of serotonin on glutamate release in regulating common carotid blood flow

Whether glutamate and serotonin would release and interact in the dorsal facial area (DFA) of cat medulla to regulate common carotid arterial (CCA) blood flow was explored by placing a microdialysis probe in DFA and employing high performance liquid chromatographic technique. Glutamate concentration was dose-dependently decreased by perfusion with serotonin, or alaproclate, a serotonin reuptake inhibitor. Serotonin and glutamate concentrations were increased by perfusion with KC1, a depolarizing agent. Furthermore, CCA blood flow was decreased when glutamate concentration was reduced by serotonin or alaproclate perfusion, and conversely increased when glutamate concentration was increased by KC1 perfusion. In conclusion, glutamate and serotonin releases in DFA that involve regulation of CCA blood flow are tonically mediated by nerve terminals. The glutamate release is depressed by the serotonin release.     

Orexin A mediation of time spent moving in rats: Neural mechanisms

The brain regulates energy balance and spontaneous physical activity, including both small- and large-motor activities. Neural mediators of spontaneous physical activity are currently undefined, although the amount of time spent in sedentary positions versus standing and ambulating may be important in the energetics of human obesity. Orexin A, a neuropeptide produced in caudal hypothalamic areas and projecting throughout the neuraxis, enhances arousal and spontaneous physical activity. To test the hypothesis that orexin A affects the amount of time spent moving, we injected orexin A (0–1000 pmol) into three orexin projection sites in male Sprague–Dawley rats: hypothalamic paraventricular nucleus, rostral lateral hypothalamic area and substantia nigra pars compacta, and measured spontaneous physical activity. Orexin A affects local GABA release and we co-injected orexin A with a GABA agonist, muscimol, in each brain site. Dopamine signaling is important to substantia nigra function and so we also co-injected a dopamine 1 receptor antagonist (SCH 23390) in the substantia nigra pars compacta. In all brain sites orexin A significantly increased time spent vertical and ambulating. Muscimol significantly and dose-dependently inhibited orexin A effects on time spent moving only when administered to the rostral lateral hypothalamic area. In the substantia nigra pars compacta, SCH 23390 completely blocked orexin A–induced ambulation. These data indicate that orexin A influences time spent moving, in three brain sites utilizing separate signaling mechanisms. That orexin A modulation of spontaneous physical activity occurs in brain areas with multiple roles indicates generalization across brain site, and may reflect a fundamental mechanism for enhancing activity levels. This potential for conferring physical activity stimulation may be useful for inducing shifts in time spent moving, which has important implications for obesity.     

Reference Values and Psychometric Properties of the Quality of Life After Traumatic Brain Injury-Overall Scale in Italy,The Netherlands,and the United Kingdom

ObjectivesThe Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS) is a short screening instrument for assessing disease-specific health-related quality of life (HRQoL) after traumatic brain injury. To date, no reference values are available for the QOLIBRI-OS in general populations. Thus, this study aimed to establish reference values for the QOLIBRI-OS in general population samples from Italy, The Netherlands, and the United Kingdom.MethodsData were collected using an online survey. The total sample comprised 11759 participants, consisting of 3549 Italian, 3564 Dutch, and 4646 British subjects. In this sample, 49% of the total sample did not report any health complaints, whereas 51% had at least 1 chronic health condition. Reference values were deduced for the QOLIBRI-OS for health-condition–related samples and total general population samples per country. To ensure the comparability of these values, measurement invariance was assessed using a multigroup confirmatory factor analysis. Covariates characterizing the reference values were selected with the help of regression analyses.ResultsThe confirmatory factor analysis confirmed that the QOLIBRI-OS scores measured the same traumatic brain injury–specific HRQoL construct across the 3 countries. Healthy individuals reported significantly higher HRQoL than individuals with at least 1 chronic health condition. Older age and higher education levels were significantly associated with higher HRQoL.ConclusionsBecause the reference values displayed differences in terms of age and education level across the 3 countries, we recommend using country-specific reference values stratified by sociodemographic and health status in research and clinical practice.     

Machine Learning Algorithms to Predict Mortality and Allocate Palliative Care for Older Patients With Hip Fracture

ObjectivesTo evaluate a machine learning model designed to predict mortality for Medicare beneficiaries aged >65 years treated for hip fracture in Inpatient Rehabilitation Facilities (IRFs).DesignRetrospective design/cohort analysis of Centers for Medicare & Medicaid Services Inpatient Rehabilitation Facility–Patient Assessment Instrument data.Setting and ParticipantsA total of 17,140 persons admitted to Medicare-certified IRFs in 2015 following hospitalization for hip fracture.MeasuresPatient characteristics include sociodemographic (age, gender, race, and social support) and clinical factors (functional status at admission, chronic conditions) and IRF length of stay. Outcomes were 30-day and 1-year all-cause mortality. We trained and evaluated 2 classification models, logistic regression and a multilayer perceptron (MLP), to predict the probability of 30-day and 1-year mortality and evaluated the calibration, discrimination, and precision of the models.ResultsFor 30-day mortality, MLP performed well [acc = 0.74, area under the receiver operating characteristic curve (AUROC) = 0.76, avg prec = 0.10, slope = 1.14] as did logistic regression (acc = 0.78, AUROC = 0.76, avg prec = 0.09, slope = 1.20). For 1-year mortality, the performances were similar for both MLP (acc = 0.68, AUROC = 0.75, avg prec = 0.32, slope = 0.96) and logistic regression (acc = 0.68, AUROC = 0.75, avg prec = 0.32, slope = 0.95).Conclusion and ImplicationsA scoring system based on logistic regression may be more feasible to run in current electronic medical records. But MLP models may reduce cognitive burden and increase ability to calibrate to local data, yielding clinical specificity in mortality prediction so that palliative care resources may be allocated more effectively.     

Testing the Implementation of Function-focused Care in Assisted Living Settings

ObjectivesThe purpose of this study was to evaluate the Function-Focused Care for Assisted Living Using the Evidence Integration Triangle (FFC-AL-EIT) intervention.DesignFFC-AL-EIT was a randomized controlled pragmatic trial including 85 sites and 794 residents.InterventionFFC-AL-EIT was implemented by a Research Nurse Facilitator working with a facility champion and stakeholder team for 12 months to increase function and physical activity among residents. FFC-AL-EIT included (Step I) Environment and Policy Assessments; (Step II) Education; (Step III) Establishing Resident Function-Focused Care Service Plans; and (Step IV) Mentoring and Motivating.Setting and ParticipantsThe age of participants was 89.48 years [standard deviation (SD) = 7.43], and the majority were female (n = 561; 71%) and white (n = 771; 97%).MethodsResident measures, obtained at baseline, 4, and 12 months, included function, physical activity, and performance of function-focused care. Setting outcomes, obtained at baseline and 12 months, included environment and policy assessments and service plans.ResultsReach was based on 85 of 90 sites that volunteered (94%) participating. Effectiveness was based on less decline in function (P < .001), more function-focused care (P = .012) and better environment (P = .032) and policy (P = .003) support for function-focused care in treatment sites. Adoption was supported with 10.00 (SD = 2.00) monthly meetings held, 77% of settings engaged in study activities as or more than expected, and direct care workers providing function-focused care (63% to 68% at 4 months and 90% at 12 months). The intervention was implemented as intended, and education was received based on a mean knowledge test score of 88% correct. Evidence of maintenance from 12 to 18 months was noted in treatment site environments (P = .35) and policies continuing to support function-focused care (P = .28)].Conclusions and ImplicationsThe Evidence Integration Triangle is an effective implementation approach for assisted living. Future work should continue to consider innovative approaches for measuring RE-AIM outcomes.