Lower Ankle-Brachial Index Is Related to Worse Cognitive Performance in Old Age

Objective: We aimed to study the associations between peripheral artery disease (PAD) and ankle-brachial index (ABI) and performance in a range of cognitive domains in nondemented elderly persons. Methods: Data were collected within the Lothian Birth Cohort 1921 and 1936 studies. These are two narrow-age cohorts at age 87 (n = 170) and 73 (n = 748) years. ABI was analyzed as a dichotomous (PAD vs. no PAD) and a continuous measure. PAD was defined as having an ABI less than 0.90. Measures of nonverbal reasoning, verbal declarative memory, verbal fluency, working memory, and processing speed were administered. Both samples were screened for dementia. Results: We observed no significant differences in cognitive performance between persons with or without PAD. However, higher ABI was associated with better general cognition (β = .23, p = .02, R(2) change = .05) and processing speed (β = .29, p < .01, R(2) change = .08) in the older cohort and better processing speed (β = .12, p < .01, R(2) change = .01) in the younger cohort. This was after controlling for age, sex, and childhood mental ability and excluding persons with abnormally high ABI (>1.40) and a history of cardiovascular or cerebrovascular disease. Conclusion: Lower ABI is associated with worse cognitive performance in old age, especially in the oldest old (>85 years), possibly because of long-term exposure to atherosclerotic disease. Interventions targeting PAD in persons free of manifest cardiovascular and cerebrovascular disease may reduce the incidence of cognitive impairment and dementia

Transfer of Simple Task Learning is Different in Approach and Withdrawal Contexts

AbstractAcademic achievement, subjective well-being, and effectiveness of training are known to be dependent on motivation. Correspondingly, the utilization of prior knowledge for learning is shown to differ in approach/withdrawal contexts for complex tasks and educational settings. How can this be explained on the level of psychological structures? We assume that approach and withdrawal behaviors are supported by distinct asymmetric domains of individual experience. Hence, we proposed that the transfer-motivation relationship is also valid for simple task learning. Two word discrimination tasks were performed by 58 schoolchildren either to get “reward” or to avoid “punishment” with points. We show that the difference of transfer effect between approach and withdrawal motivational contexts is evident for simple tasks. The implications of these results for an instructional context and normative evaluation are discussed

Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma

Background: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. Patients and methods: Eighty-five mRCC patients received everolimus at Helsinki University Hospital (cohort A). Computed tomography (CT) verified pneumonitis was correlated with outcome using Kaplan-Meier, Cox regression and logistic regression. An independent cohort of 148 everolimus treated mRCC patients (cohort B) at Aarhus University Hospital was assessed for validation. Results: In cohort A, CT-verified pneumonitis (N = 29, 34.1%) was associated with improved overall survival (OS) (24.7 versus 8.5 months; P <0.001), progression-free survival (PFS) (5.5 versus 3.2 months; P = 0.002) and clinical benefit rate (CBR) 57.1% versus 24.1% (P = 0.003). In multivariate analyses pneumonitis was associated with improved OS (hazard ratio [HR], 0.22; 95% confidence interval [CI] 0.12-0.44; P <0.001), PFS (HR 0.37; 95% CI 0.21-0.66; P = 0.001) and CBR (odds ratio [OR] 4.11; 95% CI 1.42-11.95; P = 0.01). In cohort B, CT-verified pneumonitis (N = 29, 19.6%) was associated with improved OS (12.9 versus 6.0 months; P = 0.02), PFS (6.0 versus 2.8 months; P = 0.02) and CBR (79.3% versus 39.5%; P <0.001). In multivariate analyses pneumonitis was associated with improved OS (HR 0.58; 95% CI 0.36-0.94; P = 0.03), PFS (HR 0.61; 95% CI 0.39-0.95; P = 0.03) and CBR (OR 5.65; 95% CI 2.10-15.18; P = 0.001). In a combined multivariate analysis (N = 233), with pneumonitis as a time-dependent covariate, CT-verified pneumonitis was associated with longer OS (HR, 0.67; 95% CI 0.46-0.97; P = 0.03). Furthermore, in a landmark analysis, pneumonitis was associated with longer OS (17.4 versus 7.8 months; P = 0.01). Conclusions: Everolimus-induced pneumonitis is associated with improved outcome in patients with mRCC and may serve as a biomarker of everolimus efficacy. (C) 2017 Elsevier Ltd. All rights reserved.Peer reviewe

Altered high-energy phosphate and membrane metabolism in Pelizaeus-Merzbacher disease using phosphorus magnetic resonance spectroscopy

Pelizaeus-Merzbacher disease is an X-linked recessive leucodystrophy of the central nervous system caused by mutations affecting the major myelin protein, proteolipid protein 1. The extent of the altered in vivo neurochemistry of protein, proteolipid protein 1 duplications, the most common form of Pelizaeus-Merzbacher disease, is, however, poorly understood. Phosphorus magnetic resonance spectroscopy is the only in vivo technique that can assess the biochemistry associated with high-energy phosphate and membrane phospholipid metabolism across different cortical, subcortical and white matter areas. In this cross-sectional study, whole-brain, multi-voxel phosphorus magnetic resonance spectroscopy was acquired at 3 T on 14 patients with Pelizaeus-Merzbacher disease with protein, proteolipid protein 1 duplications and 23 healthy controls (all males). Anabolic and catabolic levels of membrane phospholipids (phosphocholine and phosphoethanolamine, and glycerophosphoethanolamine and glycerophosphocholine, respectively), as well as phosphocreatine, inorganic orthophosphate and adenosine triphosphate levels relative to the total phosphorus magnetic resonance spectroscopy signal from 12 different cortical and subcortical areas were compared between the two groups. Independent of brain area, phosphocholine, glycerophosphoethanolamine and inorganic orthophosphate levels were significantly lower (P = 0.0025, P \u3c 0.0001 and P = 0.0002) and phosphocreatine levels were significantly higher (P \u3c 0.0001) in Pelizaeus-Merzbacher disease patients compared with controls. Additionally, there was a significant group-by-brain area interaction for phosphocreatine with post-hoc analyses demonstrating significantly higher phosphocreatine levels in patients with Pelizaeus-Merzbacher disease compared with controls across multiple brain areas (anterior and posterior white matter, superior parietal lobe, posterior cingulate cortex, hippocampus, occipital cortex, striatum and thalamus; all P ≤ 0.0042). Phosphoethanolamine, glycerophosphoethanolamine and adenosine triphosphate levels were not significantly different between groups. For the first-time, widespread alterations in phosphorus magnetic resonance spectroscopy metabolite levels of Pelizaeus-Merzbacher disease patients are being reported. Specifically, increased high-energy phosphate storage levels of phosphocreatine concomitant with decreased inorganic orthophosphate across multiple areas suggest a widespread reduction in the high-energy phosphate utilization in Pelizaeus-Merzbacher disease, and the membrane phospholipid metabolite deficits suggest a widespread degradation in the neuropil content/maintenance of patients with Pelizaeus-Merzbacher disease which includes axons, dendrites and astrocytes within cortex and the myelin microstructure and oligodendrocytes within white matter. These results provide greater insight into the neuropathology of Pelizaeus-Merzbacher disease both in terms of energy expenditure and membrane phospholipid metabolites. Future longitudinal studies are warranted to investigate the utility of phosphorus magnetic resonance spectroscopy as surrogate biomarkers in monitoring treatment intervention for Pelizaeus-Merzbacher disease

Fumarate drives EMT in renal cancer

Medical Research Counci

Short duration of upper extremity lymphedema correlates with a favorable cytokine response after lymph node transfer surgery

Vascularized lymph node transfer surgery (VLNT) can provide benefit to lymphedema patients. Cytokines mayplaya role in the development oflymphedema and in the regeneration oflymphatic vessels after VLNT. Ourprimary aim was to investigate whether the VLNTpatients have a specific cytokine profile. Our secondary aim was to see whether the preoperative lymphedema or severity affects the postoperative cytokine response. Wound exudate was gathered from 18 patients undergoing VLNT on the first and sixth postoperative day (POD). The concentrations of IL-10, TNF-alpha, TGF-beta 1 and VEGF-C were analyzed using enzyme-inked immune-sorbent assays. A general score was generated to assess the benefit ofthe surgery. The changes in cytokine concentrations (1(st) POD-6th POD) were correlated with the pre- andpostoperative lymphedema related factors. A shorter duration oflymphedema preoperatively correlated with an increase in the concentration of IL-10 and TNF-beta during the first six PODs (IL-10: r=0.495, p=0.051; TNF-alpha: p=0.006) and a decrease in the concentration of 7VF-111 (r= p=0.020). The increase ofthe concentration of TNF-alpha during the first six PODs also correlated with a greater total general score (r=0.775, p=0.005) and hence indicated a better response to the surgery. The patients with a shorter duration oflymphedema preoperatively had a more favorable cytokine response during the first six PODs after VLNT

Low TGF-β1 in Wound Exudate Predicts Surgical Site Infection After Axillary Lymph Node Dissection

PurposeSurgical site infection (SSI) after axillary lymph node dissection (ALND) for breast cancer increases morbidity and delays the onset of adjuvant treatment. Only a few studies have investigated the feasibility of wound exudate analysis in SSI prediction. This study assessed changes in cytokine levels in postsurgical wound exudate after ALND and examined their predictive value for the early diagnosis of SSI.MethodsAn observational prospective pilot study was conducted in 47 patients with breast cancer undergoing ALND. Wound exudate samples were collected on the first and sixth postoperative days (POD). Interleukin (IL)-1α, IL-1β, IL-4, IL-10, IL-13, tumor necrosis factor alpha (TNF-α), transforming growth factor beta1 (TGF-β1) and vascular endothelial growth factor (VEGF) C and D levels were measured by immunoassay. Patients were followed to detect SSI.ResultsSSI was diagnosed in 8/47 (17.0%) patients. Four SSI patients were hospitalized and treated with intravenous antibiotics. The concentration of TGF-β1 in wound exudate was significantly lower on POD#1 in the SSI group compared to the no SSI group (p=0.008). The receiving operator characteristics (ROC) curve for TGF-β1 showed an area under curve of 0.773 (p=0.0149) indicating good diagnostic potential. On POD#6, the concentration of TGF-β1 remained significantly lower (p=0.043) and the concentrations of IL-10 (p=0.000) and IL-1β (0.004) significantly higher in the SSI group compared to the no SSI group.ConclusionTo our knowledge, this is the first study suggesting a predictive role of wound exudate TGF-β1 levels for SSI. Our results suggest that the risk for SSI can be detected already on POD#1 and that the assessment of TGF-β1 levels in the wound exudate after ALND can provide a usefull method for the early detection of SSI. The key findings of this pilot study warrant verification in a larger patient population.</p

Muutos psykiatristen avohoitokäyntien toteutuksessa ja johtajien kokemukset etäasiointia estävistä ja edistävistä tekijöistä COVID-19 aikakaudella

Vertaisarvioitu. English abstract.Peer reviewe

Laugh Like You Mean It:Authenticity Modulates Acoustic, Physiological and Perceptual Properties of Laughter

Several authors have recently presented evidence for perceptual and neural distinctions between genuine and acted expressions of emotion. Here, we describe how differences in authenticity affect the acoustic and perceptual properties of laughter. In an acoustic analysis, we contrasted spontaneous, authentic laughter with volitional, fake laughter, finding that spontaneous laughter was higher in pitch, longer in duration, and had different spectral characteristics from volitional laughter that was produced under full voluntary control. In a behavioral experiment, listeners perceived spontaneous and volitional laughter as distinct in arousal, valence, and authenticity. Multiple regression analyses further revealed that acoustic measures could significantly predict these affective and authenticity judgements, with the notable exception of authenticity ratings for spontaneous laughter. The combination of acoustic predictors differed according to the laughter type, where volitional laughter ratings were uniquely predicted by harmonics-to-noise ratio (HNR). To better understand the role of HNR in terms of the physiological effects on vocal tract configuration as a function of authenticity during laughter production, we ran an additional experiment in which phonetically trained listeners rated each laugh for breathiness, nasality, and mouth opening. Volitional laughter was found to be significantly more nasal than spontaneous laughter, and the item-wise physiological ratings also significantly predicted affective judgements obtained in the first experiment. Our findings suggest that as an alternative to traditional acoustic measures, ratings of phonatory and articulatory features can be useful descriptors of the acoustic qualities of nonverbal emotional vocalizations, and of their perceptual implications