Antidepressant mechanism of ketamine: perspective from preclinical studies

A debilitating mental disorder, major depressive disorder is a leading cause of global disease burden. Existing antidepressant drugs are not adequate for the majority of depressed patients, and large clinical studies have demonstrated their limited efficacy and slow response onset. Growing evidence of low-dose ketamine’s rapid and potent antidepressant effects offers strong potential for future antidepressant agents. However, ketamine has considerable drawbacks such as its abuse potential, psychomimetic effects, and increased oxidative stress in the brain, thus limiting its widespread clinical use. To develop superior antidepressant drugs, it is crucial to better understand ketamine’s antidepressant mechanism of action. Recent preclinical studies indicate that ketamine’s antidepressant mechanism involves mammalian target of rapamycin pathway activation and subsequent synaptogenesis in the prefrontal cortex, as well as glycogen synthase kinase-3 beta (GSK-3B) inactivation. Adjunct GSK-3B inhibitors, such as lithium, can enhance ketamine’s efficacy by augmenting and prolonging its antidepressant effects. Given the potential for depressive relapses, lithium in addition to ketamine is a promising solution for this clinical issue

A Multicenter Screening Study

Background In cystic fibrosis, highly variable glucose tolerance is suspected. However, no study provided within-patient coefficients of variation. The main objective of this short report was to evaluate within-patient variability of oral glucose tolerance. Methods In total, 4,643 standardized oral glucose tolerance tests of 1,128 cystic fibrosis patients (median age at first test: 15.5 [11.5; 21.5] years, 48.8% females) were studied. Patients included were clinically stable, non-pregnant, and had at least two oral glucose tolerance tests, with no prior lung transplantation or systemic steroid therapy. Transition frequency from any one test to the subsequent test was analyzed and within-patient coefficients of variation were calculated for fasting and two hour blood glucose values. All statistical analysis was implemented with SAS 9.4. Results A diabetic glucose tolerance was confirmed in 41.2% by the subsequent test. A regression to normal glucose tolerance at the subsequent test was observed in 21.7% and to impaired fasting glucose, impaired glucose tolerance or both in 15.2%, 12.0% or 9.9%. The average within-patient coefficient of variation for fasting blood glucose was 11.1% and for two hour blood glucose 25.3%. Conclusion In the cystic fibrosis patients studied, a highly variable glucose tolerance was observed. Compared to the general population, variability of two hour blood glucose was 1.5 to 1.8-fold higher

A robust sequential hypothesis testing method for brake squeal localisation

This contribution deals with the in situ detection and localisation of brake squeal in an automobile. As brake squeal is emitted from regions known a priori, i.e., near the wheels, the localisation is treated as a hypothesis testing problem. Distributed microphone arrays, situated under the automobile, are used to capture the directional properties of the sound field generated by a squealing brake. The spatial characteristics of the sampled sound field is then used to formulate the hypothesis tests. However, in contrast to standard hypothesis testing approaches of this kind, the propagation environment is complex and time-varying. Coupled with inaccuracies in the knowledge of the sensor and source positions as well as sensor gain mismatches, modelling the sound field is difficult and standard approaches fail in this case. A previously proposed approach implicitly tried to account for such incomplete system knowledge and was based on ad hoc likelihood formulations. The current paper builds upon this approach and proposes a second approach, based on more solid theoretical foundations, that can systematically account for the model uncertainties. Results from tests in a real setting show that the proposed approach is more consistent than the prior state-of-the-art. In both approaches, the tasks of detection and localisation are decoupled for complexity reasons. The localisation (hypothesis testing) is subject to a prior detection of brake squeal and identification of the squeal frequencies. The approaches used for the detection and identification of squeal frequencies are also presented. The paper, further, briefly addresses some practical issues related to array design and placement. (C) 2019 Author(s)

„West-Papua ist nicht sicher“

Indonesien: Nachdem die indonesische Regierung im September weitere Truppenkontingente nach West-Papua verlegte und Internetverbindungen kappte, ist es für Aktivist*innen noch schwieriger geworden, sich Gehör zu verschaffen. Ein Interview mit zwei Vertreter*innen der lokalen, gewaltfreien Bewegung Pasifika, dem jüngsten Mitglied der globalen pazifistischen Bewegung War Resisters International

Female sex, young and old age, northern German residency, high HbA1c and insulin use predict depressed mood in 35,691 T2D patients

Background and aims: A bidirectional relationship between type 2 diabetes (T2D) and depressive symptoms has been reported. The primary aim was to analyze predictors of depressed mood in T2D. Secondly, the odds ratio of developing a clinically recognized depression in patients with conspicuous screening result was evaluated. Materials and methods: 35,691 T2D patients aged ≥18 years (median [IQR]: 68.9 [59.2-76.5] years) from the German/Austrian multicenter prospective diabetes follow-up registry (DPV) were analyzed. All patients had completed the WHO-5 questionnaire, a reliable and validated 5-item screening tool for depression (score ≤7: likely depression). Logistic regression modeling (SAS 9.4) was applied to study potential predictors (e.g. demographics, regional aspect, diabetes therapy, glycemic S414 Diabetologia (2015) 58 (Suppl 1):S1–S607 control) for depressed mood as well as the risk of developing clinically recognized depression. Results: Depressed mood was present in 11.2% (n=4,000) of patients screened and thereby significantly more prevalent compared to the adult German population (DEGS study: 8.1%, p<0.001). Patients with likely depression had a later diabetes onset (60.5 [49.6-70.2] vs. 58.3 [49.1- 67.7] years, p<0.001) and were more often female (54.0 vs. 48.0%, p< 0.001) compared to patients with inconspicuous results. Duration of diabetes did not differ significantly between groups (7.6 [2.4-12.9] vs. 7.0 [2.1-13.5] years, p=0.76). Young and very old age as well as female sex were associated with depressed mood (table 1, model 1). Moreover, living in northern federal states of Germany, poor glycemic control (HbA1c ≥58 mmol/mol) and insulin treatment were significantly related to depressed mood in T2D (table 1). Overall, the odds of developing a clinical diagnosis of depression was 1.95 (95%CI: 1.66-2.29) times higher in patients scored ≤7 in the WHO-5 questionnaire. Conclusion: Depressed mood is a frequent psychological comorbidity in adult T2D patients. In clinical care, routinely screening for psychological problems as recommended by guidelines is absolutely advisable, especially in high-risk patients

Clinical Characteristics and Outcome of 467 Patients With a Clinically Recognized Eating Disorder Identified Among 52,215 Patients With Type 1 Diabetes: A Multicenter German/Austrian Study

OBJECTIVE To compare clinical characteristics and outcome of type 1 diabetes mellitus (T1DM) between patients with and without a clinically recognized eating disorder (ED). RESEARCH DESIGN AND METHODS A total of 52,215 T1DM patients aged 8 to &amp;lt;30 years from the prospective diabetes data acquisition system DPV were analyzed. A total of 467 patients had an additional diagnosis of ED according to DSM-IV criteria (anorexia nervosa [AN], n = 141 [female: 94.3%]; bulimia nervosa [BN], n = 62 [90.3%]; and EDs not otherwise specified, including binge-eating disorder [EDNOS], n = 264 [74.2%]). Groups were compared using multivariable regression. Cox proportional hazard ratios were calculated for the association between ED and retinopathy. RESULTS After adjustment for age, sex, and duration of diabetes, patients with ED revealed higher HbA1c (no ED vs. AN, BN, or EDNOS, respectively: 8.29 ± 0.01% [67.1 ± 0.1 mmol/mol] vs. 8.61 ± 0.15% [70.6 ± 1.6 mmol/mol], 9.11 ± 0.23% [76.1 ± 2.5 mmol/mol], or 9.00 ± 0.11% [74.9 ± 1.2 mmol/mol]) and a higher rate of pathological insulin injection sites (48.4 vs. 64.3, 64.1, or 62.1%). Furthermore, ketoacidosis (5.7 ± 0.1 vs. 12.1 ± 2.1, 18.0 ± 4.1, or 12.9 ± 1.6 events per 100 person-years) and hospitalization (54.9 ± 0.3 vs. 89.3 ± 6.0, 132.0 ± 12.7, or 91.0 ± 4.4 per 100 person-years) were more common, and duration of hospital stay was longer (4.81 ± 0.01 vs. 11.31 ± 0.21, 18.05 ± 0.48, or 8.44 ± 0.13 days per year). All P values were &amp;lt;0.05. Patients with BN and EDNOS had a 2.5-fold (95% CI 1.3–4.8) and a 1.4-fold (0.8–2.3) higher risk for retinopathy, whereas AN patients had no increased risk (0.9 [95% CI 0.4–2.3]). CONCLUSIONS Diabetes health care professionals should be aware of comorbid EDs in pediatric/young-adult T1DM patients. An ED diagnosis is associated with worse metabolic control and higher rates of diabetes complications. </jats:sec

Beryllium Nitrate Inhibits Fibroblast Migration to Disrupt Epimorphic Regeneration

Epimorphic regeneration proceeds with or without formation of a blastema, as observed for the limb and skin, respectively. Inhibition of epimorphic regeneration provides a means to interrogate the cellular and molecular mechanisms that regulate it. In this study, we show that exposing amputated limbs to beryllium nitrate disrupts blastema formation and causes severe patterning defects in limb regeneration. In contrast, exposing full-thickness skin wounds to beryllium only causes a delay in skin regeneration. By transplanting full-thickness skin from ubiquitous GFP-expressing axolotls to wild-type hosts, we demonstrate that beryllium inhibits fibroblast migration during limb and skin regeneration in vivo. Moreover, we show that beryllium also inhibits cell migration in vitro using axolotl and human fibroblasts. Interestingly, beryllium did not act as an immunostimulatory agent as it does in Anurans and mammals, nor did it affect keratinocyte migration, proliferation or re-epithelialization, suggesting that the effect of beryllium is cell type-specific. While we did not detect an increase in cell death during regeneration in response to beryllium, it did disrupt cell proliferation in mesenchymal cells. Taken together, our data show that normal blastema organogenesis cannot occur without timely infiltration of local fibroblasts and highlights the importance of positional information to instruct pattern formation during regeneration. In contrast, non-blastemal-based skin regeneration can occur despite early inhibition of fibroblast migration and cell proliferation

Social and health epidemiology of immigrants in Germany: past, present and future

Razum O, Wenner J. Social and health epidemiology of immigrants in Germany: past, present and future. Public Health Reviews. 2016;37(1): 4.Germany has experienced different forms of immigration for many decades. At the end of and after the Second World War, refugees, displaced persons and German resettlers constituted the largest immigrant group. In the 1950s, labor migration started, followed by family reunification. There has been a constant migration of refugees and asylum seekers reaching peaks in the early 1990s as well as today. Epidemiological research has increasingly considered the health, and the access to health care, of immigrants and people with migration background. In this narrative review we discuss the current knowledge on health of immigrants in Germany. The paper is based on a selective literature research with a focus on studies using representative data from the health reporting system. Our review shows that immigrants in Germany do not suffer from different diseases than non-immigrants, but they differ in their risk for certain diseases, in the resources to cope with theses risk and regarding access to treatment. We also identified the need for differentiation within the immigrant population, considering among others social and legal status, country of origin and duration of stay. Though most of the studies acknowledge the need for differentiation, the lack of data currently rules out analyses accounting for the existing diversity and thus a full understanding of health inequalities related to migration to Germany