Social contact, social support, and cognitive health in a population-based study of middle-aged and older men and women in rural South Africa

BACKGROUND: Several theories seek to explain how social connections and cognitive function are interconnected in older age. These include that social interaction protects against cognitive decline, that cognitive decline leads to shedding of social connections and that cognitive decline leads to increased instrumental support. We investigated how patterns of social contact, social support and cognitive health in rural South Africa fit with these three theories. METHOD: We used data from the baseline of "Health and Aging in Africa: a Longitudinal Study of an INDEPTH community in South Africa" (HAALSI), a population-based study of 5059 individuals aged ≥ 40 years. We evaluated how a range of egocentric social connectedness measures varied by respondents' cognitive function. RESULTS: We found that respondents with lower cognitive function had smaller, denser social networks that were more local and more kin-based than their peers. Lower cognitive function was associated with receipt of less social support generally, but this difference was stronger for emotional and informational support than for financial and physical support. Impairment was associated with greater differences among those aged 40-59 and those with any (versus no) educational attainment. CONCLUSIONS: The patterns we found suggest that cognitively impaired older adults in this setting rely on their core social networks for support, and that theories relating to social connectedness and cognitive function developed in higher-income and higher-education settings may also apply in lower-resource settings elsewhere

Subjective social position and cognitive function in a longitudinal cohort of older, rural South African adults, 2014–2019

BACKGROUND: The relationship between subjective social position (SSP) and cognitive ageing unclear, especially in low-income settings. We aimed to investigate the relationship between SSP and cognitive function over time among older adults in rural South Africa. METHODS: Data were from 3771 adults aged ≥40 in the population-representative 'Health and Ageing in Africa: A Longitudinal Study of an INDEPTH Community in South Africa' from 2014/2015 (baseline) to 2018/2019 (follow-up). SSP was assessed at baseline with the 10-rung MacArthur Network social position ladder. Outcomes were composite orientation and episodic memory scores at baseline and follow-up (range: 0-24). Mortality- and attrition-weighted linear regression estimated the associations between baseline SSP with cognitive scores at each of the baseline and follow-up. Models were adjusted for age, age2, sex, country of birth, father's occupation, education, employment, household assets, literacy, marital status and health-related covariates. RESULTS: SSP responses ranged from 0 (bottom ladder rung/lowest social position) to 10 (top ladder rung/highest social position), with a mean of 6.6 (SD: 2.3). SSP was positively associated with baseline cognitive score (adjusted β=0.198 points per ladder rung increase; 95% CI 0.145 to 0.253) and follow-up cognitive score (adjusted β=0.078 points per ladder rung increase; 95% CI 0.021 to 0.136). CONCLUSION: Independent of objective socioeconomic position measures, SSP is associated with orientation and episodic memory scores over two time points approximately 3 years apart among older rural South Africans. Future research is needed to establish the causality of the observed relationships, whether they persist over longer follow-up periods and their consistency in other populations

Standardized volumetric 3D-analysis of SPECT/CT imaging in orthopaedics: overcoming the limitations of qualitative 2D analysis

<p>Abstract</p> <p>Background</p> <p>SPECT/CT combines high resolution anatomical 3D computerized tomography (CT) and single photon emission computerized tomography (SPECT) as functional imaging, which provides 3D information about biological processes into a single imaging modality. The clinical utility of SPECT/CT imaging has been recognized in a variety of medical fields and most recently in orthopaedics; however, clinical adoption has been limited due to shortcomings of analytical tools available. Specifically, SPECT analyses are mainly qualitative due to variation in overall metabolic uptake among patients. Furthermore, most analyses are done in 2D, although rich 3D data are available. Consequently, it is difficult to quantitatively compare the position, size, and intensity of SPECT uptake regions among patients, and therefore difficult to draw meaningful clinical conclusions.</p> <p>Methods</p> <p>We propose a method for normalizing orthopaedic SPECT/CT data that enables standardised 3D volumetric quantitative measurements and comparison among patients. Our method is based on 3D localisation using clinically relevant anatomical landmarks and frames of reference, along with intensity value normalisation using clinically relevant reference regions. Using the normalised data, we describe a thresholding technique to distinguish clinically relevant hot spots from background activity.</p> <p>Results</p> <p>Using an exemplar comparison of two patients, we demonstrate how the normalised, 3D-rendered data can provide a richer source of clinical information and allow quantitative comparison of SPECT/CT measurements across patients. Specifically, we demonstrate how non-normalized SPECT/CT analysis can lead to different clinical conclusions than the normalized SPECT/CT analysis, and that normalized quantitative analysis can be a more accurate indicator of pathology.</p> <p>Conclusions</p> <p>Conventional orthopaedic frames of reference, 3D volumetric data analysis and thresholding are used to distinguish clinically relevant hot spots from background activity. Our goal is to facilitate a standardised approach to quantitative data collection and comparison of clinical studies using SPECT/CT, enabling more widespread clinical use of this powerful imaging tool.</p

Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

Managing fatigue in sarcoidosis – a systematic review of the evidence

Fatigue is a common manifestation of sarcoidosis, often persisting without evidence of disease activity. First-line therapies for sarcoidosis have limited effect on fatigue. This review aimed to assess the treatment options targeting sarcoidosis-associated fatigue. Medline and Web of Science were searched in November 2015; the bibliographies of these papers, and relevant review papers, were also searched. Studies were included if they reported on the efficacy of interventions (both pharmacological and non-pharmacological) on fatigue scores in sarcoidosis patients. Eight studies were identified that fulfilled the inclusion criteria. These studies evaluated six different interventions (infliximab, adalimumab, ARA 290, methylphenidate, armodafinil and exercise programmes). There is evidence to support a treatment effect of anti-tumour necrosis factor (TNF)-αtherapies (adalimumab and infliximab) and neurostimulants (methylphenidate and armodafinil), but within five of the studies, the risk of bias was high within most domains and the remaining three studies included only small numbers of participants and were short in duration. Trial evidence for treating fatigue as a manifestation of sarcoidosis is limited and requires further investigation. Anti-TNF-α therapies may be beneficial in patients with organ-threatening disease. Neurostimulants have some trial evidence supporting improvements in fatigue but further investigation is needed before they can be recommended

PPARβ activation inhibits melanoma cell proliferation involving repression of the Wilms’ tumour suppressor WT1

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that strongly influence molecular signalling in normal and cancer cells. Although increasing evidence suggests a role of PPARs in skin carcinogenesis, only expression of PPARγ has been investigated in human melanoma tissues. Activation of PPARα has been shown to inhibit the metastatic potential, whereas stimulation of PPARγ decreased melanoma cell proliferation. We show here that the third member of the PPAR family, PPARβ/δ is expressed in human melanoma samples. Specific pharmacological activation of PPARβ using GW0742 or GW501516 in low concentrations inhibits proliferation of human and murine melanoma cells. Inhibition of proliferation is accompanied by decreased expression of the Wilms’ tumour suppressor 1 (WT1), which is implicated in melanoma proliferation. We demonstrate that PPARβ directly represses WT1 as (1) PPARβ activation represses WT1 promoter activity; (2) in chromatin immunoprecipitation and electrophoretic mobility shift assays, we identified a binding element for PPARβ in the WT1 promoter; (3) deletion of this binding element abolishes repression by PPARβ and (4) the WT1 downstream molecules nestin and zyxin are down-regulated upon PPARβ activation. Our findings elucidate a novel mechanism of signalling by ligands of PPARβ, which leads to suppression of melanoma cell growth through direct repression of WT1

Short- and long-term effects of a quality improvement collaborative on diabetes management

Introduction: This study examined the short- and long-term effects of a quality improvement collaborative on patient outcomes, professional performance, and structural aspects of chronic care management of type 2 diabetes in an integrated care setting.Methods: Controlled pre- and post-intervention study assessing patient outcomes (hemoglobin A1c, cholesterol, blood pressure, weight, blood lipid levels, and smoking status), professional performance (guideline adherence), and structural aspects of chronic care management from baseline up to 24 months. Analyses were based on 1,861 patients with diabetes in six intervention and nine control regions representing 37 general practices and 13 outpatient clinics.Results: Modest but significant improvement was seen in mean systolic blood pressure (decrease by 4.0 mm Hg versus 1.6 mm Hg) and mean high density lipoprotein levels (increase by 0.12 versus 0.03 points) at two-year follow up. Positive but insignificant differences were found in hemoglobin A1c (0.3%), cholesterol, and blood lipid levels. The intervention group showed significant improvement in the percentage of patients receiving advice and instruction to examine feet, and smaller reductions in the percentage of patients receiving instruction to monitor blood glucose and visiting a dietician annually. Structural aspects of self-management and decision support also improved significantly.Conclusions: At a time of heightened national attention toward diabetes care, our results demonstrate a modest benefit of participation in a multi-institutional quality improvement collaborative focusing on integrated, patient-centered care. The effects persisted for at least 12 months after the intervention was completed.Trial number: http://clinicaltrials.gov Identifier: NCT 00160017

Do red deer stags (Cervus elaphus) use roar fundamental frequency (F0) to assess rivals?

It is well established that in humans, male voices are disproportionately lower pitched than female voices, and recent studies suggest that this dimorphism in fundamental frequency (F0) results from both intrasexual (male competition) and intersexual (female mate choice) selection for lower pitched voices in men. However, comparative investigations indicate that sexual dimorphism in F0 is not universal in terrestrial mammals. In the highly polygynous and sexually dimorphic Scottish red deer Cervus elaphus scoticus, more successful males give sexually-selected calls (roars) with higher minimum F0s, suggesting that high, rather than low F0s advertise quality in this subspecies. While playback experiments demonstrated that oestrous females prefer higher pitched roars, the potential role of roar F0 in male competition remains untested. Here we examined the response of rutting red deer stags to playbacks of re-synthesized male roars with different median F0s. Our results show that stags’ responses (latencies and durations of attention, vocal and approach responses) were not affected by the F0 of the roar. This suggests that intrasexual selection is unlikely to strongly influence the evolution of roar F0 in Scottish red deer stags, and illustrates how the F0 of terrestrial mammal vocal sexual signals may be subject to different selection pressures across species. Further investigations on species characterized by different F0 profiles are needed to provide a comparative background for evolutionary interpretations of sex differences in mammalian vocalizations

Estimation of the solubility parameters of model plant surfaces and agrochemicals: a valuable tool for understanding plant surface interactions

Background Most aerial plant parts are covered with a hydrophobic lipid-rich cuticle, which is the interface between the plant organs and the surrounding environment. Plant surfaces may have a high degree of hydrophobicity because of the combined effects of surface chemistry and roughness. The physical and chemical complexity of the plant cuticle limits the development of models that explain its internal structure and interactions with surface-applied agrochemicals. In this article we introduce a thermodynamic method for estimating the solubilities of model plant surface constituents and relating them to the effects of agrochemicals. Results Following the van Krevelen and Hoftyzer method, we calculated the solubility parameters of three model plant species and eight compounds that differ in hydrophobicity and polarity. In addition, intact tissues were examined by scanning electron microscopy and the surface free energy, polarity, solubility parameter and work of adhesion of each were calculated from contact angle measurements of three liquids with different polarities. By comparing the affinities between plant surface constituents and agrochemicals derived from (a) theoretical calculations and (b) contact angle measurements we were able to distinguish the physical effect of surface roughness from the effect of the chemical nature of the epicuticular waxes. A solubility parameter model for plant surfaces is proposed on the basis of an increasing gradient from the cuticular surface towards the underlying cell wall. Conclusions The procedure enabled us to predict the interactions among agrochemicals, plant surfaces, and cuticular and cell wall components, and promises to be a useful tool for improving our understanding of biological surface interactions

Validity of the Clock Drawing Test in predicting reports of driving problems in the elderly

BACKGROUND: This study examined the use of the Folstein Mini Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) in predicting retrospective reports of driving problems among the elderly. The utility of existing scoring systems for the CDT was also examined. METHODS: Archival chart records of 325 patients of a geriatric outpatient clinic were reviewed, of which 162 had CDT results (including original clock drawings). T-test, correlation, and regression procedures were used to analyze the data. RESULTS: Both CDT and MMSE scores were significantly worse among non-drivers than individuals who were currently or recently driving. Among current or recent drivers, scores on both instruments correlated significantly with the total number of reported accidents or near misses, although the magnitude of the respective correlations was small. Only MMSE scores, however, significantly predicted whether or not any accidents or near misses were reported at all. Neither MMSE nor CDT scores predicted unique variance in the regressions. CONCLUSIONS: The overall results suggest that both the MMSE and CDT have limited utility as potential indicators of driving problems in the elderly. The demonstrated predictive power for these instruments appears to be redundant, such that both appear to assess general cognitive function versus more specific abilities. Furthermore, the lack of robust prediction suggests that neither are sufficient to serve as stand-alone instruments on which to solely base decisions of driving capacity. Rather, individuals who evidence impairment should be provided a more thorough and comprehensive assessment than can be obtained through screening tools