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Abstract Background Amyloid precursor protein (APP) is a ubiquitously expressed cell surface protein reported to be involved in mediating cell-cell or cell-matrix interactions. Prior work has demonstrated that APP co-localizes with β1 integrin in different cell types. Methods In an effort to determine the function of APP on monocytic lineage cells, in particular, the human monocyte cell line, THP-1, was used to assess the role of APP during adhesion to the extracelluar matrix component type I collagen. Results Pull-down assays demonstrated that THP-1 adhesion to collagen stimulated a tyrosine kinase-associated signaling response which included subsequent phosphorylation of p38 MAP kinase and increased association of APP with α2β1 integrin, specifically. In addition, cell adhesion was dependent upon APP expression since APP siRNA knockdown attenuated THP-1 adhesion to collagen compared to mock transfected controls. One consequence of the tyrosine kinase-dependent signaling response was increased secretion of interleukin-1β (IL-1β) and Aβ1-40 but not the Aβ1-42 fragment of APP. Increased secretion of IL-1β was dependent upon p38 MAP kinase activity while Aβ1-40 secretion required Src family kinase activity since the specific p38 inhibitor, SB202190, and the Src family kinase inhibitor, PP2, attenuated IL-1β and Aβ1-40 secretion, respectively. Conclusions These data demonstrate that APP is involved in classic integrin-dependent tyrosine kinase-associated adhesion and activation of peripheral monocytic cells. Moreover, divergent APP-dependent signaling is required for increased secretion of both IL-1β and Aβ1-40 as a component of the adhesion-dependent change in phenotype. This suggests that APP may have a broad role in not only mediating cell-matrix adhesion but also in the function of peripheral immune cells.

Abstract Background Beta amyloid (Aβ) peptides are the major constituents of the senile plaques present in Alzheimer's diseased brain. Pathogenesis has been associated with the aggregated form of the peptide as these fibrils are the conformation readily found in the plaques. However, recent studies have shown that the nonaggregated, soluble assemblies of Aβ have the potential to stimulate neuronal dysfunction and may play a prominent role in the pathogenesis of Alzheimer's disease. Methods Soluble, synthetic Aβ1–42 oligomers were prepared producing mainly dimer-trimer conformations as assessed by SDS-PAGE. Similar analysis demonstrated fibril preparations to produce large insoluble aggregates unable to migrate out of the stacking portion of the gels. These peptide preparations were used to stimulate primary murine microglia and cortical neuron cultures. Microglia were analyzed for changes in signaling response and secretory phenotype via Western analysis and ELISA. Viability was examined by quantifying lactate dehydrogenase release from the cultures. Results Aβ oligomers and fibrils were used to stimulate microglia for comparison. Both the oligomers and fibrils stimulated proinflammatory activation of primary microglia but the specific conformation of the peptide determined the activation profile. Oligomers stimulated increased levels of active, phosphorylated Lyn and Syk kinase as well as p38 MAP kinase compared to fibrils. Moreover, oligomers stimulated a differential secretory profile for interleukin 6, monocyte chemoattractant protein-1 and keratinocyte chemoattractant when compared to fibrils. Finally, soluble oligomers stimulated death of cultured cortical neurons that was exacerbated by the presence of microglia. Conclusion These data suggest that fibrils and oligomers stimulate unique signaling responses in microglia leading to discrete secretory changes and effects on neuron survival. This suggests that inflammation changes during disease may be the consequence of unique peptide-stimulated events and each conformation may represent an individual anti-inflammatory therapeutic target.

Background: Anorexia nervosa is a serious and potentially lethal psychiatric disorder. Furthermore, there is significant evidence that some individuals develop a very long-standing form of the illness that requires a variety of different treatment interventions over time., Objective: The primary goal of this paper was to provide a review of treatment strategies for severe and enduring anorexia nervosa (SE-AN) with the particular focus on treatments involving hospital care. Additionally, we wish to highlight a contemporary approach to such care and provide qualitative reactions to this model from both staff and patients., Methods: A selective and strategic review of the treatment literature for SE-AN was conducted for the current paper. Emphasis was placed on clinical or scientific papers related to hospital-based care. Additionally, staff who work on a specific inpatient eating disorder unit with a substantial treatment program for SE-AN, along with a number of SE-AN patients were surveyed regarding their experiences working on, or receiving treatment on the unit. Importantly, the staff of this unit created a specific treatment protocol for individuals receiving hospital care. The results of the highlight both advantages and challenges of a hospital-based protocol oriented toward emphasizing quality of life, medical stability, and a health-promoting meal plan., Discussion: While there is general inconsistency with the type of treatment that is best suited to individuals with SE-AN, this is particularly true for higher levels of care that rely on inpatient hospital units or residential treatment settings. This is a highly significant clinical topic in need of further clinical and scientific examination., (© 2024. The Author(s).)

During the past 50 years, the mortality due to childhood cancers decreased dramatically thanks to improvements in supportive care and the use of multimodal approaches. In this context, the long-term follow up after childhood cancer has become a main concern for pediatric oncologists. The SALTO programme was developed in 2012 at the CHR Citadelle in Liège in order to organize a multidisciplinary long-term follow-up for the patients previously treated in our department for a childhood cancer. The aim of the present study was to review, for the most frequent childhood cancers, the long-term sequellae and the second cancers developed by the patients participating to the SALTO programme in order to define the follow-up needed. Our data confirm the importance of a multidisciplinary long-term follow-up, based on the treatments received and following international guidelines.

Sickle cell disease is a common genetic disorder that affects haemoglobin. It is manifested by haemolytic anaemia and vaso-occlusive crisis. It can affect all organs and its evolution is unpredictable. The multidisciplinary management of pediatric patients who suffer from it is essential to adapt their treatment and optimize their evolution. One of the major challenges is to succeed the transition to adult medicine. New therapeutic perspectives are in development and look promising.

Bariatric surgery is currently the most effective intervention for significant and sustained weight loss in obese individuals. While patients often realize numerous improvements in obesity-related comorbidities and health-related quality of life, a small minority of patients have less optimal outcomes following bariatric surgery. The literature on the emergence of alcohol use disorders (AUDs) following bariatric surgery has grown in the past several years and collectively provides convincing evidence that a significant minority of patients develop new-onset AUDs following bariatric surgery. Rouxen-Y gastric bypass (RYGB) has generally been associated with the risk of developing an AUD, while laparoscopic adjustable gastric banding generally has not, in several large studies. One theory that has been discussed at some length is the idea of 'addiction transfer' wherein patients substitute one 'addiction' (food) for a new 'addiction' (alcohol) following surgery. Animal work suggests a neurobiological basis for increased alcohol reward following RYGB. In addition, several pharmacokinetic studies have shown rapid and dramatically increased peak alcohol concentrations following RYGB. The prevalence of alcohol and other addictive disorders and potential etiological contributors to post-operative AUDs will be explored., (Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.)

Background: Recent literature suggests that some patients may develop addictive disorders after bariatric surgery, in particular after Roux-en-Y gastric bypass (RYGB). These may include traditional addictions and so called "behavioral addictions," although prevalence data on the latter have not been published. The objective of this study was to establish the prevalence of addictive behaviors in adults after RYGB., Methods: Participants from a large observational study of bariatric surgery who had undergone RYGB were recruited to complete additional measures. Of 241 consented participants, 201 provided data (i.e., Structured Clinical Interview for DSM-IV Axis I [SCID], additional Impulsive Control Disorder Modules, and various self-report measures, including the Alcohol Use Disorder Identification Test [AUDIT]) to assess status before surgery and in the first 3 postoperative years., Results: Based on the SCID, 16 (8.0%) developed alcohol use disorder [AUD] within 3 years post-RYGB, 7 (43.8%) of whom had no history of AUD. When both the SCID and AUDIT were used to identify AUD, the corresponding numbers/percentages were 32 (18.4%) and 13 (40.6%). Data on other behavioral addictive disorders indicated 19 (9.5%) had a postsurgery disorder, 6 (31.6%) of whom had no history., Conclusion: These data add to a growing literature suggesting there is a substantial risk for the development of AUD after bariatric surgery. Understanding the risk for nondrug-related addictive disorders requires more data from larger studies before clear conclusions can be drawn., (Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

While most conventional treatments for individuals with severe obesity have a modest and short lived impact bariatric surgery has been consistently shown to result in long-term marked weight loss and significant improvement in medical comorbidities. Empirical data suggest a high prevalence of mental disorders among bariatric surgery candidates. This article reviews specific areas of psychopathology, problems in using psychopharmacological medications post-surgery, body contouring, and recommendations for pre and post-surgery care. Available research indicates a decrease in psychiatric symptoms post-surgery. However, in some patients the improvement appears to erode over time. Therefore, bariatric surgery patients should be monitored not only before surgery but also following surgery and referred for mental health treatment if problems develop.

The authors offered to 296 consecutive cancer patients aged > or = 70 to undergo a joint comprehensive geriatric and oncological assessment. After pluridisciplinary discussion, several reflections have emerged: the need in 15 - 32% of cases to reinforce the role of the paramedical staff; the correlation between age, low clinical indices, alteration of renal function as well as geriatric characteristics; 67% of evaluated cases presented a significant geriatric profile; recommendations for patients' management in relation to their pattern of frailty and health aging (standard, adapted or palliative treatment).