a-rapid-method-for-blood-processing-to-increase-yield-plasma-peptide

A RAPID Method for Blood Processing to Increase the Yield of Plasma Peptide Levels in Human Blood

Research in the field of food intake regulation is gaining importance. This often includes the measurement of peptides regulating food intake. For the ...

sucrose-preference-novelty-induced-hypophagia-tests-rats-using-an

Sucrose Preference and Novelty-Induced Hypophagia Tests in Rats using an Automated Food Intake Monitoring System

The prevalence and incidence of depressive disorders are rising worldwide, affecting about 322 million individuals, underlining the need for behavioral ...

Charité Universitätsmedizin Berlin, Campus Benjamin Franklin

Humboldt-Universität zu Berlin and Berlin Institute of Health

University of Massachusetts Medical School

Computerized adaptive testing (CAT) based on Item Response Theory, (IRT) offers an efficient way for accurate measurement of patient reported outcomes. The efficiency lies within a minimal response burden and a high measurement precision over a broad measurement range. The objective of the study was to evaluate and compare the responsiveness of CATs measuring anxiety, depression, and stress reaction to standard static self-assessment tools.

Evaluation of Computerized Adaptive Tests (CATs) for longitudinal monitoring of depression, anxiety, and stress reactions.

To compare treatment effect estimates obtained from a regression discontinuity (RD) design with results from an actual randomized controlled trial (RCT).

The regression discontinuity design showed to be a valid alternative to a randomized controlled trial for estimating treatment effects.

Activity-based anorexia (ABA) is an established animal model for the eating disorder anorexia nervosa (AN). The pathophysiology of AN and the involvement of food intake-regulatory peptides is still poorly understood. Nesfatin-1, an anorexigenic peptide also involved in the mediation of stress, anxiety and depression might be a likely candidate involved in the pathogenesis of AN. Therefore, activation of nesfatin-1 immunoreactive (ir) brain nuclei was investigated under conditions of ABA. Female Sprague-Dawley rats were used and divided into four groups (n=6/group): activity-based anorexia (ABA), restricted feeding (RF), activity (AC) and ad libitum fed (AL). After the 21-day experimental period and development of ABA, brains were processed for c-Fos/nesfatin-1 double labeling immunohistochemistry. ABA increased the number of nesfatin-1 immunopositive neurons in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, locus coeruleus and in the rostral part of the nucleus of the solitary tract compared to AL and AC groups (p<0.05) but not to RF rats (p>0.05). Moreover, we observed significantly more c-Fos and nesfatin-1 ir double-labeled cells in ABA rats compared to RF, AL and AC in the supraoptic nucleus (p<0.05) and compared to AL and AC in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, dorsal raphe nucleus and the rostral raphe pallidus (p<0.05). Since nesfatin-1 plays a role in the inhibition of food intake and the response to stress, we hypothesize that the observed changes of brain nesfatin-1 might play a role in the pathophysiology and symptomatology under conditions of ABA and potentially also in patients with AN.

Activity-based anorexia activates nesfatin-1 immunoreactive neurons in distinct brain nuclei of female rats.

To study pathogenic stress-effects in health and disease, it is paramount to define easy access parameters for non-invasive analysis of biological change in response to stress. Hair samples successfully provide this access for the study of hypothalamus-pituitary-adrenal axis (HPA) changes. In this study, we assess the hair expression and corresponding epigenetic changes of a neurotrophin essential for autonomic nervous system function and mental health: brain derived neurotrophic factor (BDNF). In three independent studies in healthy academic volunteers (study I: German students, N=36; study II, German academic population sample, N=28; study III: Mexican students, N=115), BDNF protein expression or BDNF gene (BDNF) histone acetylation was determined. Simultaneously, mental distress and distress-associated somatic complaints were assessed by self-report. In study I, we found a negative correlation between hair-BDNF protein level and hair-cortisol as well as between hair-BDNF and somatic complaints, while hair-cortisol correlated positively with mental distress. In study II, we found a negative correlation between H4 histone acetylation at the BDNF gene P4-promoter and somatic complaints. Regression analysis confirmed confounder stability of associations in both studies. In study III, we confirmed study I and found lower hair-BDNF protein level in volunteers with high somatic complaints, who also reported higher mental distress during the end of term exams. The results indicate that BDNF protein levels can be detected in clipped hair and are associated with somatic complaints and stress in life. In addition, we concluded that plucked hair can provide material for the study of epigenetic changes in stress-affected tissues. These tools can prove valuable for future studies on distress, both under experimental and field conditions.

Assessment of Brain Derived Neurotrophic Factor in hair to study stress responses: A pilot investigation.

High physical activity (PA) in patients with anorexia nervosa (AN) is hypothesized to be, at least in part, a consequence of hypoleptinemia. However, most studies on the association of leptin and PA in AN were performed in adolescents or young adults, and PA was generally measured with subjective tools. We aimed to explore the association of leptin and PA in adults with AN using an objective technique to quantify PA. Using a cross-sectional, observational design, we analyzed body fat (bioelectrical impedance), PA (accelerometry, SenseWear™ armband) and plasma leptin (ELISA) in 61 women with AN (median age: 25 years, range: 18-52 years; median BMI: 14.8 ± 2.0 kg/m²) at the start of hospitalization. Results indicated a mean step count per day of 12,841 ± 6408 (range: 3956-37,750). Leptin was closely associated with BMI and body fat (ρ = 0.508 and ρ = 0.669,  < 0.001), but not with steps (ρ = 0.015,  = 0.908). Moreover, no significant association was observed between BMI and steps (ρ = 0.189,  = 0.146). In conclusion, there was no simple, linear association of leptin and PA, highlighting the need for more complex and non-linear models to analyze the association of leptin and PA in adults with AN in future studies.

Leptin and Physical Activity in Adult Patients with Anorexia Nervosa: Failure to Demonstrate a Simple Linear Association.

Activity-based anorexia (ABA) is a well-established animal model mimicking the eating disorder anorexia nervosa (AN). Since the pathophysiology of AN is yet poorly understood and specific drug treatments are lacking so far, animal models might be useful to further understand this disease. ABA consists of time-restricted access to food for 1.5 h/day and the possibility to exercise in a running wheel for 24 h/day. This combination leads to robust body weight loss as observed in AN. Here, we investigated the activation of brain corticotropin-releasing factor (CRF) neurons, a transmitter involved in the response to stress, emotional processes and also food intake. After development of ABA, rat brains were processed for c-Fos and CRF double immunohistochemistry. ABA increased the number of c-Fos/CRF double labeled neurons in the paraventricular nucleus (PVN) and the dorsomedial hypothalamic nucleus (DMH) compared to the ad libitum (AL, ad libitum fed, no running wheel) and activity (AC, ad libitum fed, running wheel, p < 0.05) but not to the restricted feeding (RF, food for 1.5 h/day, no running wheel, p > 0.05) group. Also the number of CRF neurons was increased in the DMH of ABA rats compared to AL and AC (p < 0.05). In the Edinger-Westphal nucleus (EW) the number of c-Fos positive neurons was increased in ABA and RF compared to AC (p < 0.05), while the number of double labeled neurons was not different (p > 0.05). Taken together, brain CRF activated under conditions of ABA might play a role in the development and maintenance of this animal model and possibly also in human AN.

Activity-based anorexia activates CRF immunoreactive neurons in female rats.

The number of patients seeking help in emergency departments is steadily increasing. In part, this is due to patients who have acute symptoms, but do not require emergency care, as well as multimorbid patients needing complex medical care. Emergency departments serve as an interface between primary care and in-patient as well as out-patient care. The ongoing public discussion about the need to readjust emergency care structures in Germany does not adequately address this aspect. The knowledge of characteristics and needs of patients seeking help in emergency departments is insufficient. In order to develop interventions matching these needs it is necessary to gain deeper insight into these characteristics and needs. EMANet is a health services research project funded by the Federal Ministry of Education and Research. Its aim is to collect representative data on the course of medical care of emergency patients with ambulatory care sensitive conditions in all eight emergency departments in Mitte, the inner city district of Berlin. The EMANet project focuses on three patient groups: a) patients with cardiac symptoms and possible psychiatric comorbidities, b) ambulatory patients with acute or chronic diseases of the respiratory tract, and c) geriatric patients with hip fractures. The collected data shall be used to gain a better understanding of health care utilization patterns, patient-perceived satisfaction and risk factors for potentially avoidable medical conditions or worsening of chronic disease. The mixed methods design of EMANet includes quantitative data of 1,650 patients at two time points and corresponding secondary (i. e. routine) data from hospital information systems. In addition, qualitative interviews with patients and health care professionals shall reveal unmet needs for medical care. The results will give us more in-depth insight into the perceived current capacity overload and help implement structural changes in the health care system.

[EMANet: A regional network for health services research in emergency and acute medicine].

Increased physical activity (PA) affects outcomes in patients with anorexia nervosa (AN). To objectively assess PA patterns of hospitalized AN patients in comparison with healthy, outpatient controls (HC), and to analyze the effect of PA on Body Mass Index (BMI) change in patients with AN, we measured PA in 50 female patients with AN (median age = 25 years, range = 18⁻52 years; mean BMI = 14.4 ± 2.0 kg/m²) at the initiation of inpatient treatment and in 30 female healthy controls (median age = 26 years, range = 19⁻53 years; mean BMI = 21.3 ± 1.7 kg/m²) using the SenseWear™ armband. Duration of inpatient stay and weight at discharge were abstracted from medical records. Compared with controls, AN patients spent more time in very light-intensity physical activity (VLPA) (median VLPA = 647 vs. 566 min/day,  = 0.004) and light-intensity physical activity (LPA) (median LPA = 126 vs. 84 min/day,  < 0.001) and less time in moderate-intensity physical activity (MPA) (median MPA = 82 vs. 114 min/day,  = 0.022) and vigorous physical activity (VPA) (median VPA = 0 vs. 16 min/day,  < 0.001). PA and BMI increase were not associated in a linear model, and BMI increase was mostly explained by lower admission BMI and longer inpatient stay. In a non-linear model, an influence of PA on BMI increase seemed probable (jack knife validation, ² = 0.203;  < 0.001). No direct association was observed between physical inactivity and BMI increase in AN. An altered PA pattern exists in AN patients compared to controls, yet the origin and consequences thereof deserve further investigation.

The Role of Objectively Measured, Altered Physical Activity Patterns for Body Mass Index Change during Inpatient Treatment in Female Patients with Anorexia Nervosa.

Nesfatin-1 is a well-established anorexigenic peptide. Recent studies indicated an association between nesfatin-1 and anxiety/depression-like behavior. However, it is unclear whether this effect is retained in obesity. The aim was to investigate the effect of nesfatin-1-the active core of nesfatin-1-on anxiety and depression-like behavior in normal weight (NW) and diet-induced (DIO) obese rats. Male rats were intracerebroventricularly (ICV) cannulated and received nesfatin-1 (0.1, 0.3, or 0.9 nmol/rat) or vehicle 30 min before testing. Nesfatin-1 at a dose of 0.3 nmol reduced sucrose consumption in the sucrose preference test in NW rats compared to vehicle (⁻33%,  < 0.05), indicating depression-like/anhedonic behavior. This dose was used for all following experiments. Nesfatin-1 also reduced cookie intake during the novelty-induced hypophagia test (-62%,  < 0.05). Moreover, nesfatin-1 reduced the number of entries into the center zone in the open field test (-45%,  < 0.01) and the visits of open arms in the elevated zero maze test (-39%,  < 0.01) in NW rats indicating anxiety. Interestingly, DIO rats showed no behavioral alterations after the injection of nesfatin-1 ( > 0.05). These results indicate an implication of nesfatin-1 in the mediation of anxiety and depression-like behavior/anhedonia under normal weight conditions, while in DIO rats, a desensitization might occur.

ArticleTotal : 2	Year
Publication title Cited by 2	2016
Publication title Cited by 9	2020

Article	Year
Evaluation of Computerized Adaptive Tests (CATs) for longitudinal monitoring of depression, anxiety, and stress reactions. Journal of affective disorders\| PubMed ID: 25481813	2016
The regression discontinuity design showed to be a valid alternative to a randomized controlled trial for estimating treatment effects. Journal of clinical epidemiology\| PubMed ID: 27865902	2017
Activity-based anorexia activates nesfatin-1 immunoreactive neurons in distinct brain nuclei of female rats. Brain research\| PubMed ID: 28951234	2017
Assessment of Brain Derived Neurotrophic Factor in hair to study stress responses: A pilot investigation. Psychoneuroendocrinology\| PubMed ID: 28957772	2017
Leptin and Physical Activity in Adult Patients with Anorexia Nervosa: Failure to Demonstrate a Simple Linear Association. Nutrients\| PubMed ID: 29099750	2017
Activity-based anorexia activates CRF immunoreactive neurons in female rats. Neuroscience letters\| PubMed ID: 29574216	2018
[EMANet: A regional network for health services research in emergency and acute medicine]. Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen\| PubMed ID: 30122458	2018
The Role of Objectively Measured, Altered Physical Activity Patterns for Body Mass Index Change during Inpatient Treatment in Female Patients with Anorexia Nervosa. Journal of clinical medicine\| PubMed ID: 30231527	2018
Nesfatin-1 Injected Intracerebroventricularly Increases Anxiety, Depression-Like Behavior, and Anhedonia in Normal Weight Rats. Nutrients\| PubMed ID: 30513901	2018

Matthias Rose

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