The Putative Role of Human Peritoneal Adipocytes in the Fight against Bacteria: Synthesis of the Antimicrobial Active Peptide DEFA1-3

Background: Spontaneous peritonitis is a rather rare event, even in peritoneal dialysis (PD). As defensins are natural antimicrobial peptides, we hypothesized that adipocytes as the major constituents of the omentum could play an important role in protecting against infection by generating defensin (DEFA1-3). Methods: We isolated adipocytes from the omentum majus and conducted qualitative and quantitative RT-PCR and immunohistochemical analyses. Results: For the first time described, we were able to detect DEFA1-3 mRNA in highly purified isolated omental adipocytes. The expression of DEFA1-3 in adipocytes was confirmed on the protein level by immunohistochemistry. Conclusion: Our report of DEFA1-3 expression by human omental adipocytes adds to the role of adipocytes in the primary defense against bacterial infection. This may include PD, where the presence of the catheter as a foreign body and the nonphysiological dialysis solution may require constant defense measures to prevent peritonitis, a hypothesis that will require further testing. Copyright (C) 2010 S. Karger AG, Base

Humane peritoneale Adipozyten synthetisieren antimikrobiell wirksame Peptide (α-Defensine)

Wir haben in der vorliegenden Arbeit das Vorhandensein von Defensinen, einer Gruppe natürlich vorkommender antimikrobieller Peptide, in der Peritonealhöhle untersucht. Unser Augenmerk richteten wir dabei auf die Adipozyten des Omentum majus, da eine mögliche Expression von Defensinen in Fettzellen auf Grund deren ubiquitären Verteilung im menschlichen Körper wichtige Erkenntnisse und Implikationen für zukünftige klinische Anwendungen haben würde (siehe auch „Ziel der Studie“ im Abschnitt „Einleitung“). Wir benutzten Nachweismethoden auf RNA- (RT-PCR, quantitative TaqMan-PCR, Northern Blot) und Protein-Ebene (Western-Blot, Immunhistochemie). Tatsächlich ist es uns gelungen, das humane α-Defensin 1 in hochgereinigten Adipozyten des Omentum majus und des subkutanen Fettgewebes in der PCR und in der Immunhistochemie nachzuweisen. Die Durchfühhrung des Western Blots erwies sich als komplex (siehe „Diskussion“). Daher kann gesagt werden, dass humane peritoneale Adipozyten wahrscheinlich das humane α-Defensin 1 synthetisieren. Zur Expression von humanem α-Defensin 5 können wir aktuell keine abschliessende Aussage treffen. Einerseits gelang dessen Nachweis in der PCR; Western Blot und Immunhistochemie blieben jedoch negativ (siehe „Ergebnisse“ und „Diskussion“). Die α-Defensin-Expression durch humane Adipozyten des Omentums (und der Subkutis) stellt einen weiteren Hinweis bezüglich der Bedeutung von Adipozyten in der primären Abwehr gegen bakterielle Infektionen dar

Factor Analyses and Validity of the Transplant Evaluation Rating Scale (TERS) in a Large Sample of Lung Transplant Candidates

Objective: It is well known that the occurrence of mental disorders is more common in lung transplant candidates compared to the general population. After transplantation mental disorders may negatively affect quality of life, adherence to immunosuppressive medication, as well as overall survival. Therefore, the identification of patients at risk is of utmost importance and in Germany pre-transplant psychosocial evaluation of the patients is required. To ensure high quality and comparability of these assessments, the use of psychometrically sound instruments is recommended. We applied the Transplant Evaluation Rating Scale (TERS), a broadly used expert interview. Two research groups have detected a two-factor structure of the TERS in different transplant samples; however, with slightly different results. The present study investigated which of the models would fit best in our sample of lung transplant patients. Additionally, we assessed convergent and predictive validity of the best fitting model to evaluate its clinical usefulness. Methods: Between 2016 and 2019, 390 lung transplant candidates were evaluated and included in the study. The median age was 53 years and 54% were male. TERS interviews were conducted by trained medical doctors and psychologists. The participants completed questionnaires assessing quality of life and levels of depression and anxiety. Transplant- and disease-specific variables (lung disease, listing date, oxygen use) were taken from the patient charts. Confirmatory factor analysis was used to test the two proposed TERS-models in the present sample. Results: The two-factor structure of the TERS reported by Hoodin and Kalbfleisch fit our sample best, showing good psychometric properties. The factor “emotional sensitivity” was highly correlated with quality of life and measures of psychosocial health while the factor “defiance” correlated with obstructive lung disease and older age but not with quality of life. The two factors showed differential predictive validity with regard to time until listing and pulmonary-specific quality of life 1 year after transplantation. Conclusions: The two factors showed good psychometric properties, and differential convergent and predictive validity. However, further studies concentrating on the predictive value of the TERS and its factors regarding somatic outcomes (mortality, graft functioning) are required

Biological outcome measurements for behavioral interventions in multiple sclerosis

Behavioral interventions including exercise, stress management, patient education, psychotherapy and multidisciplinary neurorehabilitation in general are receiving increasing recognition in multiple sclerosis (MS) clinical practice and research. Most scientific evaluations of these approaches have focused on psychosocial outcome measures such as quality of life, fatigue or depression. However, it is becoming increasingly clear that neuropsychiatric symptoms of MS are at least partially mediated by biological processes such as inflammation, neuroendocrine dysfunction or regional brain damage. Thus, successful treatment of these symptoms with behavioral approaches could potentially also affect the underlying biology. Rigidly designed scientific studies are needed to explore the potential of such interventions to affect MS pathology and biological pathways linked to psychological and neuropsychiatric symptoms of MS. Such studies need to carefully select outcome measures on the behavioral level that are likely to be influenced by the specific intervention strategy and should include biomarkers with evidence for an association with the outcome parameter in question. In this overview, we illustrate how biological and psychological outcome parameters can be combined to evaluate behavioral interventions. We focus on two areas of interest as potential targets for behavioral interventions: depression and fatigue

Gender-related patterns of emotion regulation among patients with eating disorders

Difficulties in emotion regulation (ER) are common in females with eating disorders (ED). However, no study to date has analyzed ER in males with ED. In the study at hand, we assessed ER in males with ED and compared results to both females with ED and healthy controls (HC). We also examined associations between ER difficulties, personality, and psychopathology. A total of 62 males with ED were compared with 656 females with ED, as well as 78 male and 286 female HC. ER was assessed by means of the Difficulties in Emotion Regulation Scale (DERS). We found that males and females with ED showed greater ER difficulties compared to HC. Pronounced general psychopathology was a shared factor associated with higher ER difficulties in both males and females with ED. However, whereas higher novelty seeking, higher cooperativeness, lower reward dependence, and lower self-directedness were related to higher ER difficulties in females with ED, lower persistence was associated with ER difficulties in males with ED. In sum, males and females with ED show similar ER difficulties, yet they are distinct in how ER deficits relate to specific personality traits. Research on strategies promoting ER in the treatment of males with ED is warranted

Food addiction in eating disorders and obesity: Analysis of clusters and implications for treatment

Food addiction (FA) has been associated with greater psychopathology in individuals with eating disorders (ED) and obesity (OBE). The current study aims to provide a better phenotypic characterization of the FA construct by conducting a clustering analysis of FA in both conditions (ED and OBE). The total sample was comprised of 234 participants that scored positive on the Yale Food Addiction Scale 2.0. (YFAS-2) (119 bulimia nervosa (BN), 50 binge eating disorder (BED), 49 other specified feeding or eating disorder (OSFED) and 16 OBE). All participants completed a comprehensive battery of questionnaires. Three clusters of FA participants were identified. Cluster 1 (dysfunctional) was characterized by the highest prevalence of OSFED and BN, the highest ED severity and psychopathology, and more dysfunctional personality traits. Cluster 2 (moderate) showed a high prevalence of BN and BED and moderate levels of ED psychopathology. Finally, cluster 3 (adaptive) was characterized by a high prevalence of OBE and BED, low levels of ED psychopathology, and more functional personality traits. In conclusion, this study identified three distinct clusters of ED-OBE patients with FA and provides some insight into a better phenotypic characterization of the FA construct when considering psychopathology, personality and ED pathology. Future studies should address whether these three food addiction categories are indicative of therapy outcome

Comparison of choose-a-movie and approach-avoidance paradigms used to measure social motivation

Social motivation is a subjective state which is rather difficult to quantify. It has sometimes been conceptualised as “behavioural effort” to seek social contact. Two paradigms: approach–avoidance (AA) and choose a movie (CAM), based on the same conceptualisation, have been used to measure social motivation in people with and without autism. However, in absence of a direct comparison, it is hard to know which of these paradigms has higher sensitivity in estimating preference for social over non-social stimuli. Here we compare these two tasks for their utility in (1) evaluating social seeking in typical people and (2) identifying the influence of autistic traits on social motivation. Our results suggest that CAM reveals a clear preference for social stimuli over non-social in typical adults but AA fails to do so. Also, social seeking measured with CAM but not AA has a negative relationship between autistic traits

The Anti-Inflammatory and Antibacterial Basis of Human Omental Defense: Selective Expression of Cytokines and Antimicrobial Peptides

BACKGROUND: The wound healing properties of the human omentum are well known and have extensively been exploited clinically. However, the underlying mechanisms of these effects are not well understood. We hypothesize that the omentum tissue promotes wound healing via modulation of anti-inflammatory pathways, and because the omentum is rich in adipocytes, the adipocytes may modulate the anti-inflammatory response. Factors released by human omentum may affect healing, inflammation and immune defense. METHODOLOGY: Six human omentum tissues (non obese, free from malignancy, and any other systemic disorder) were obtained during diagnostic laparoscopies having a negative outcome. Healthy oral mucosa (obtained from routine oral biopsies) was used as control. Cultured adipocytes derived from human omentum were exposed to lipopolysaccharide (LPS) (1-50 ng/mL) for 12-72 hours to identify the non-cytotoxic doses. Levels of expression (mRNA and protein) were carried out for genes associated with pro- and anti-inflammatory cytokine responses and antibacterial/antimicrobial activity using qRT-PCR, western blotting, and cell-based ELISA assays. RESULTS: The study shows significant higher levels of expression (mRNA and protein) of several specific cytokines, and antibacterial peptides in the omentum tissues when compared to oral sub-mucosal tissues. In the validation studies, primary cultures of adipocytes, derived from human omentum were exposed to LPS (5 and 10 ng/mL) for 24 and 48 h. The altered expressions were more pronounced in cultured adipocytes cells when exposed to LPS as compared to the omentum tissue. CONCLUSIONS/SIGNIFICANCE: Perhaps, this is the first report that provides evidence of expressional changes in pro- and anti-inflammatory cytokines and antibacterial peptides in the normal human omentum tissue as well as adipocytes cultured from this tissue. The study provides new insights on the molecular and cellular mechanisms of healing and defense by the omentum, and suggests the potential applicability of cultured adipocytes derived from the omentum for future therapeutic applications

Is there Progress? An Overview of Select Biomarker Candidates for Major Depressive Disorder

Major Depressive Disorder (MDD) contributes to a significant worldwide disease burden, expected to be second only to heart disease by 2050. However, accurate diagnosis has been a historical weakness in clinical psychiatry. As a result, there is a demand for diagnostic modalities with greater objectivity that could improve on current psychiatric practice that relies mainly on self-reporting of symptoms and clinical interviews. Over the past two decades, literature on a growing number of putative biomarkers for MDD increasingly suggests that MDD patients have significantly different biological profiles compared to healthy controls. However, difficulty in elucidating their exact relationships within depression pathology renders individual markers inconsistent diagnostic tools. Consequently, further biomarker research could potentially improve our understanding of MDD pathophysiology as well as aid in interpreting response to treatment, narrow differential diagnoses, and help refine current MDD criteria. Representative of this, multiplex assays using multiple sources of biomarkers are reported to be more accurate options in comparison to individual markers that exhibit lower specificity and sensitivity, and are more prone to confounding factors. In the future, more sophisticated multiplex assays may hold promise for use in screening and diagnosing depression and determining clinical severity as an advance over relying solely on current subjective diagnostic criteria. A pervasive limitation in existing research is heterogeneity inherent in MDD studies, which impacts the validity of biomarker data. Additionally, small sample sizes of most studies limit statistical power. Yet, as the RDoC project evolves to decrease these limitations, and stronger studies with more generalizable data are developed, significant advances in the next decade are expected to yield important information in the development of MDD biomarkers for use in clinical settings