Masked ambiguity – Emotion identification in schizophrenia and major depressive disorder

Both patients with schizophrenia and with a major depressive disorder (MDD) display deficits in identifying facial expressions of emotion during acute phases of their illness. However, specific deficit patterns have not yet been reliably demonstrated. Tasks that employ emotionally ambiguous stimuli have recently shown distinct deficit patterns in patients with schizophrenia compared to other mental disorders as well as healthy controls. We here investigate whether a task which uses an ambiguous Japanese (Noh) mask and a corresponding human stimulus generates distinctive emotion attribution patterns in thirty-two Caucasian patients with schizophrenia, matched MDD patients and healthy controls. Results show that patients with schizophrenia displayed reaction time disadvantages compared to healthy controls while identifying sadness and anger. MDD patients were more likely to label stimuli with basic compared to subtle emotional expressions. Moreover, they showed more difficulties assigning emotions to the human stimulus than to the Noh mask. IQ, age and cognitive functioning did not modulate these results. Because overall group differences were not observed, this task is not suitable for diagnosing patients. However, the subtle differences that did emerge might give therapists handles that can be used in therapy.Action Contro

Acute exposure to simulated nocturnal traffic noise and cardiovascular complications and sleep disturbance : results from a pooled analysis of human field studies

Objectives A series of human field studies demonstrated that acute exposure to simulated nocturnal traffic noise is associated with cardiovascular complications and sleep disturbance, including endothelial dysfunction, increased blood pressure, and impaired sleep quality. A pooled analysis of these results remains to be established and is of tremendous interest to consolidate scientific knowledge. Methods We analyzed data from four randomized crossover studies (published between 2013 to 2021 and conducted at the University Medical Center Mainz, Germany). A total of 275 subjects (40.4% women, mean age 43.03 years) were each exposed to one control scenario (regular background noise) and at least to one traffic noise scenario (60 aircraft or train noise events) in their homes during nighttime. After each night, the subjects visited the study center for comprehensive cardiovascular function assessment, including the measurement of endothelial function and hemodynamic and biochemical parameters, as well as sleep-related variables. Results The pooled analysis revealed a significantly impaired endothelial function when comparing the two different noise sequences (0–60 vs. 60–0 simulated noise events, mean difference in flow-mediated dilation −2.00%, 95% CI −2.32; −1.68, p < 0.0001). In concordance, mean arterial pressure was significantly increased after traffic noise exposure (mean difference 2.50 mmHg, 95% CI 0.54; 4.45, p = 0.013). Self-reported sleep quality, the restfulness of sleep, and feeling in the morning were significantly impaired after traffic noise exposure (all p < 0.0001). Discussion Acute exposure to simulated nocturnal traffic noise is associated with endothelial dysfunction, increased mean arterial pressure, and sleep disturbance

H-Ras Expression in Immortalized Keratinocytes Produces an Invasive Epithelium in Cultured Skin Equivalents

Ras proteins affect both proliferation and expression of collagen-degrading enzymes, two important processes in cancer progression. Normal skin architecture is dependent both on the coordinated proliferation and stratification of keratinocytes, as well as the maintenance of a collagen-rich basement membrane. In the present studies we sought to determine whether expression of H-ras in skin keratinocytes would affect these parameters during the establishment and maintenance of an in vitro skin equivalent.Previously described cdk4 and hTERT immortalized foreskin keratinocytes were engineered to express ectopically introduced H-ras. Skin equivalents, composed of normal fibroblast-contracted collagen gels overlaid with keratinocytes (immortal or immortal expressing H-ras), were prepared and incubated for 3 weeks. Harvested tissues were processed and sectioned for histology and antibody staining. Antigens specific to differentiation (involucrin, keratin-14, p63), basement-membrane formation (collagen IV, laminin-5), and epithelial to mesenchymal transition (EMT; e-cadherin, vimentin) were studied. Results showed that H-ras keratinocytes produced an invasive, disorganized epithelium most apparent in the lower strata while immortalized keratinocytes fully stratified without invasive properties. The superficial strata retained morphologically normal characteristics. Vimentin and p63 co-localization increased with H-ras overexpression, similar to basal wound-healing keratinocytes. In contrast, the cdk4 and hTERT immortalized keratinocytes differentiated similarly to normal unimmortalized keratinocytes.The use of isogenic derivatives of stable immortalized keratinocytes with specified genetic alterations may be helpful in developing more robust in vitro models of cancer progression

The role of tenascin-C in tissue injury and tumorigenesis

The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer

Impact of end-stage renal disease on glucose metabolism-a matched cohort analysis.

Background. Renal function is known to affect glucose metabolism. The aim of this study was to assess glucose metabolism in end-stage renal disease (ESRD) patients and in matched controls with normal renal function and to delineate its underlying pathophysiology. Methods. ESRD patients without diabetes mellitus on the active kidney transplant waiting list of a large European university hospital were metabolically phenotyped by an oral glucose tolerance test (OGTT) and by calculating insulin sensitivity and secretion indices. Matched controls with normal renal function were derived from the TUEF (Tuebingen Family) study cohort, which includes healthy non-diabetic individuals with an increased risk of developing type 2 diabetes. Matches were made for (i) gender, age and body mass index (BMI) (cohort 1) and for (ii) gender, age, BMI, fasting plasma glucose (FPG) and 2-h glucose in OGTT (cohort 2). Results. A total of 107 patients ( 90 on haemodialysis and 17 on peritoneal dialysis) and two cohorts, each comprising 107 matched controls, were investigated. ESRD patients had significantly lower FPG. Additional matching for OGTT glucose concentrations revealed significantly lower insulin sensitivity in ESRD patients than in controls. This finding was abrogated after adjustment for triglyceride levels. Insulin secretion, however, was significantly higher in ESRD patients. Insulin kinetics during OGTT as well as C-peptide levels demonstrate higher insulin secretion to be a compensation for lower insulin sensitivity and not to result from impaired insulin clearance. Conclusion. Our study is the first to provide metabolic phenotyping in patients with ESRD and to compare them with matched controls with normal renal function. Glucose metabolism differs substantially between cohorts, with insulin resistance and a compensatory increase in insulin secretion in ESRD patients

Critical single proximal left arterial descending coronary artery stenosis to mimic chronic myocardial ischemia: a new model induced by minimal invasive technology.

BACKGROUND/AIMS: The present report examines a new pig model for progressive induction of high-grade stenosis, for the study of chronic myocardial ischemia and the dynamics of collateral vessel growth. METHODS: Thirty-nine Landrace pigs were instrumented with a novel experimental stent (GVD stent) in the left anterior descending coronary artery. Eight animals underwent transthoracic echocardiography at rest and under low-dose dobutamine. Seven animals were examined by nuclear PET and SPECT analysis. Epi-, mid- and endocardial fibrosis and the numbers of arterial vessels were examined by histology. RESULTS: Functional analysis showed a significant decrease in global left ventricular ejection fraction (24.5 +/- 1.6%) 3 weeks after implantation. There was a trend to increased left ventricular ejection fraction after low-dose dobutamine stress (36.0 +/- 6.6%) and a significant improvement of the impaired regional anterior wall motion. PET and SPECT imaging documented chronic hibernation. Myocardial fibrosis increased significantly in the ischemic area with a gradient from epi- to endocardial. The number of arterial vessels in the ischemic area increased and coronary angiography showed abundant collateral vessels of Rentrop class 1. CONCLUSION: The presented experimental model mimics the clinical situation of chronic myocardial ischemia secondary to 1-vessel coronary disease

Slow deep breathing modulates cardiac vagal activity but does not affect peripheral glucose metabolism in healthy men.

Parasympathetic nervous system innervates peripheral organs including pancreas, hepatic portal system, and gastrointestinal tract. It thereby contributes to the regulation of whole-body glucose metabolism especially in the postprandial state when it promotes secretion of insulin and enhances its action in major target organs. We now aimed to evaluate the effect of parasympathetic modulation on human&nbsp;glucose metabolism. We used slow deep breathing maneuvers to activate the parasympathetic nervous system and tested for effects on metabolism during an oral glucose tolerance test in a randomized, controlled, cross-over trial in 15 healthy young men. We used projections towards the heart as a readout for parasympathetic activity. When analyzing heart rate variability, there was a significant increase of RMSSD (root mean square of successive differences) when participants performed slow deep breathing compared to the control condition, indicating a modulation of parasympathetic activity. However, no statistically significant effects on peripheral glucose metabolism or energy expenditure after the glucose tolerance test were detected. Of note, we detected a significant association between mean heart rate and serum insulin and C-peptide concentrations. While we did not find major effects of slow deep breathing on glucose metabolism, our correlational results suggest a link between the autonomic nervous system and insulin secretion after oral glucose intake. Future studies need to unravel involved mechanisms and develop potential&nbsp;novel treatment approaches for impaired insulin secretion in diabetes