Impaired wake-promoting mechanisms in ghrelin receptor-deficient mice

Ghrelin receptors are expressed by key components of the arousal system. Exogenous ghrelin induces behavioral activation, promotes wakefulness and stimulates eating. We hypothesized that ghrelin-sensitive mechanisms play a role in the arousal system. To test this, we investigated the responsiveness of ghrelin receptor knockout (KO) mice to two natural wake-promoting stimuli. Additionally, we assessed the integrity of their homeostatic sleep-promoting system using sleep deprivation. There was no significant difference in the spontaneous sleep-wake activity between ghrelin receptor KO and wild-type (WT) mice. WT mice mounted robust arousal responses to a novel environment and food deprivation. Wakefulness increased for 6 h after cage change accompanied by increases in body temperature and locomotor activity. Ghrelin receptor KO mice completely lacked the wake and body temperature responses to new environment. When subjected to 48 h food deprivation, WT mice showed marked increases in their waking time during the dark periods of both days. Ghrelin receptor KO mice failed to mount an arousal response on the first night and wake increases were attenuated on the second day. The responsiveness to sleep deprivation did not differ between the two genotypes. These results indicate that the ghrelin-receptive mechanisms play an essential role in the function of the arousal system but not in homeostatic sleep-promoting mechanisms.     

Combination of pharmacotherapy and psychotherapy in the treatment of chronic depression: A systematic review and meta-analysis

ABSTRACT: BACKGROUND: Chronic depression represents a substantial portion of depressive disorders and is associated with severe consequences. This review examined whether the combination of pharmacological treatments and psychotherapy is associated with higher effectiveness than pharmacotherapy alone via meta-analysis; and identified possible treatment effect modifiers via meta-regression-analysis. METHODS: A systematic search was conducted in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ISI Web of Science, BIOSIS, PsycINFO, and CINAHL. Primary efficacy outcome was a response to treatment; primary acceptance outcome was dropping out of the study. Only randomized controlled trials were considered. RESULTS: We identified 8 studies with a total of 9 relevant comparisons. Our analysis revealed small, but statistically not significant effects of combined therapies on outcomes directly related to depression (BR=1.20) with substantial heterogeneity between studies (I^2=67%). Three treatment effect modifiers were identified: target disorders, the type of psychotherapy and the type of pharmacotherapy. Small but statistically significant effects of combined therapies on quality of life (SMD=0.18) were revealed. No differences in acceptance rates and the long-term effects between combined treatments and pure pharmacological interventions were observed. CONCLUSIONS: This systematic review could not provide clear evidence for the combination of pharmacotherapy and psychotherapy. However, due to the small amount of primary studies further research is needed for a conclusive decision.     

Response to an Online Version of a PRAMS-like Survey in South Dakota

Objectives Increasing response rates for research surveys is challenging, especially in minority populations. A unique minority group in South Dakota is the American Indian (AI) representing about 9 % of the state’s population and 15 % of the births. The purpose of this study was to determine race differences among White, AI, and Other Races (OR) in contact, participation, and response rates in the South Dakota Pregnancy Risk Assessment Monitoring System (SDPRAMS). We determined response rates of an online version and evaluated demographic characteristics associated with online response. Methods The SDPRAMS was sent to 1814 mothers randomly sampled from 2014 birth certificate files. Results The weighted response rate was 71.3 %, and varied significantly among the three races: 79.1 % for White race, 48.6 % for AI race, and 60.6 % for OR (p < 0.01). A higher percent of White mothers responded online than AI and OR (35, 25 and 26 %, respectively; p = 0.001); no difference between AI and OR. Online responders were more likely to be married, educated beyond high school and having annual incomes ≥$25,000 (p ≤ 0.01 for all), but only education (p < 0.001) and income (p = 0.05) remained significant in the logistic models. 26 % of White, 43 % of AI, and 46 % of OR online respondents used a smartphone to respond (p = 0.01). Conclusions Response rates differed among races. An online version of the PRAMS is a viable method of response to offer participants. Response to the online version via smartphone may increase response from minority populations, emphasizing the importance of mobile friendly formats.     

Investigational α-synuclein aggregation inhibitors: hope for Parkinson’s disease

Introduction: The therapeutic management of Parkinson’s disease (PD) is challenging and has not been fully resolved. The main challenges include motor fluctuations and levodopa-induced dyskinesia. Moreover, no disease-modifying or neuroprotective therapy is currently available.

Areas covered: This review focuses on α-synuclein aggregation inhibitors and their therapeutic role in PD, with special attention to heat shock proteins, immunotherapy (active and passive), the potential of targeting the Ser129 phosphorylation site, and the antibiotic possibilities.

Expert opinion: The induction of chaperones may provide beneficial strategy to target synucleinopathies, but further investigations are needed to find the best options. The promising preclinical results with immunotherapy suggest that it may be a valuable disease-modifying therapy in PD in the future. Clinical trials are currently in the initial phases, and future studies need to confirm the beneficial therapeutic effect in humans and clarify open questions as regards the exact mode of action and potential safety concerns. In case of covalent modifications, phosphorylation of α-synuclein is of outstanding importance; however, conflicting results and open questions exist which necessitate clarification. In vitro results suggest that several antibiotics may also influence α-synuclein aggregation, but these results are to be confirmed in the future.     

The inheritance of corneal endothelial cell density

Background: Although it is known that some corneal diseases and degenerations have a significant heritable background, heritability on corneal endothelial cell density (ECD) has never been clearly determined. Our aim was to determine the heritability of corneal ECD.

Material and methods: Corneal ECD of 114 eyes (66 eyes of 33 monozygotic and 48 eyes of 24 dizygotic pairs; mean age 49.0 ± 15.5 years) was investigated by Konan Noncon Robo NSP-9900 specular microscopy. Structural equation modeling (ACE model) was applied.

Results: Endothelial corneal cell density was highly heritable (82.0%, 95%CI, 70.0–92.0%), whereas the unique environmental contribution was 18.0% (95%CI, 8.0–29.0%). Shared environmental factors had no influence on the endothelial corneal cell density.

Discussion: In this twin study, we established first that the density of the corneal endothelial cells is strongly heritable, which should stimulate future genetic studies to identify genes and pathways that are involved in determining ECD which might in turn lead to future treatments to prevent EC loss.     

Effectiveness of metacognitive interventions for mental disorders in adults—A systematic review and meta‐analysis (METACOG)

We evaluated the effectiveness and acceptability of metacognitive interventions for mental disorders. We searched electronic databases and included randomized and nonrandomized controlled trials comparing metacognitive interventions with other treatments in adults with mental disorders. Primary effectiveness and acceptability outcomes were symptom severity and dropout, respectively. We performed random‐effects meta‐analyses. We identified Metacognitive Training (MCTrain), Metacognitive Therapy (MCTherap), and Metacognition Reflection and Insight Therapy (MERIT). We included 49 trials with 2,609 patients. In patients with schizophrenia, MCTrain was more effective than a psychological treatment (cognitive remediation, SMD = ?0.39). It bordered significance when compared with standard or other psychological treatments. In a post hoc analysis, across all studies, the pooled effect was significant (SMD = ?0.31). MCTrain was more effective than standard treatment in patients with obsessive–compulsive disorder (SMD = ?0.40). MCTherap was more effective than a waitlist in patients with depression (SMD = ?2.80), posttraumatic stress disorder (SMD = ?2.36), and psychological treatments (cognitive–behavioural) in patients with anxiety (SMD = ?0.46). In patients with depression, MCTherap was not superior to psychological treatment (cognitive–behavioural). For MERIT, the database was too small to allow solid conclusions. Acceptability of metacognitive interventions among patients was high on average. Methodological quality was mostly unclear or moderate. Metacognitive interventions are likely to be effective in alleviating symptom severity in mental disorders. Although their add‐on value against existing psychological interventions awaits to be established, potential advantages are their low threshold and economy.     

Hypnotizability, sleepiness, and subjective experience

The relationships between hypnotizability, sleepiness, and the subjective experience of hypnotic suggestions were investigated in 90 participants. Scores from the Harvard Group Scale of Hypnotic Susceptibility Form A (HGSHS:A), the Karolinska Sleepiness Scale (KSS), the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and our self-developed Questionnaire on Subjective Hypnotic Experiences (QSHE) were analyzed. Findings show that hypnotizability correlates with both habitual daytime sleepiness and instantaneous sleepiness after the hypnotic procedure. Results also indicate that subjective self-evaluation of responses to hypnotic suggestions may be a useful tool in some cases when comparing with other subjectively rated scales, such as those concerning sleepiness.     

Leptin receptor (LEPR) SNP polymorphisms in HELLP syndrome patients determined by quantitative real-time PCR and melting curve analysis

Background  

Several studies have shown overexpression of leptin in microarray experiments in pre-eclampsia (PE) and in hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. We decided to study four leptin receptor (LEPR) SNP polymorphisms in HELLP syndrome patients by using quantitative real-time PCR and melting curve analysis.     

Family history of early-onset cardiovascular disorders is associated with a higher risk of severe preeclampsia

AIM: The aim was to evaluate familial early-onset cardiovascular disorders as potential risk factors for severe preeclampsia. STUDY DESIGN: A case-control study was carried out by interviewing 162 primiparous severely preeclamptic women and 521 primiparous healthy control patients after delivery to determine the frequency of cardiovascular disorders (chronic hypertension, myocardial infarction, stroke) developed before the age of 50 among their parents. The chi2-test was utilized to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The association was adjusted for pre-pregnancy body mass index, maternal age, and smoking habits before pregnancy using logistic regression analysis. RESULTS: Maternal and paternal early-onset chronic hypertension (adjusted OR: 3.84, 95% CI: 2.25-6.54; and adjusted OR: 3.26, 95% CI: 1.76-6.05) as well as paternal early-onset myocardial infarction (adjusted OR: 3.33; 95% CI: 1.51-7.32) were independent risk factors for severe preeclampsia. Early-onset stroke affected only the fathers of severely preeclamptic patients. Among the severely preeclamptic patients a positive family history of cardiovascular disorders developed before the age of 50 increased the risk of early-onset preeclampsia (developing before the 32nd gestational week) by 5.05-fold (95% CI: 3.08-8.31) compared with the control group. CONCLUSION: Our results suggest that the presence of familial early-onset cardiovascular disorders is a predisposing factor for severe preeclampsia.     

E-Learning – eine wichtige Unterstützung in der medizinischen Aus-, Fort- und Weiterbildung?

There is increasing activity in the development of e-learning modules for general medical training and continuing education. One of the central advantages of e-learning is flexibility regarding time and place of its use. The quality of the available e-learning opportunities varies quite considerably. For users it is often not easy to assess the quality of e-learning modules or to find offers of high quality. This could be a reason for the fact that despite the huge number of e-learning modules still only few students and physicians are using them. This is although e-learning has proven to be as effective as and even more efficient than learning in the classroom or with paper-based materials. This article summarizes the different models of e-learning, how and where to find offers of high quality, advantages of using e-learning, and the effectiveness and efficiency of such offers. In addition problems of e-learning and possibilities to overcome these problems are shown.