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Background: Postsurgical gastroparesis, resulting from surgical interventions on the stomach or vagal nerve injury, poses significant clinical challenges with patients presenting symptoms such as nausea, vomiting, and abdominal pain. Although gastric electrical stimulation (GES) offers potential relief, its efficacy in refractory postsurgical gastroparesis requires further examination. This study evaluated the clinical response to GES in patients with refractory postsurgical gastroparesis., Methods: A retrospective study was conducted across 2 study sites, involving 185 patients with drug-refractory postsurgical gastroparesis who underwent both temporary and permanent GES placements. Patients were categorized based on their surgical history: bariatric surgery, Nissen fundoplication, and others. The impact of GES was evaluated using Food and Drug Administration-compliant patient-reported outcomes scores and other relevant clinical metrics at baseline, after temporary GES placement, and 6 months after permanent GES placement. All 3 groups were also analyzed by the symptom improved group vs the unimproved group at baseline and 6 months after GES placement., Results: After GES implantation, all patient groups significantly improved upper gastrointestinal symptoms. The bariatric surgery group and Nissen fundoplication group specifically identified anorexia as the most severe symptom after GES after temporary GES placement among 3 groups (2.5 [0.4-3.5] and 1.5 [0.0-2.5], respectively). Nissen fundoplication patients had the highest score of anorexia among the 3 groups 6 months after GES (3.0 [2.0-3.5], P = .018). Despite these improvements, GES did not enhance gastric emptying test results. Symptomatic improvements were notably significant in patients who initially reported higher symptom severity than those who did not., Conclusion: GES shows promise in alleviating symptoms of refractory postsurgical gastroparesis, particularly in those with severe initial symptoms. However, its impact on gastric emptying remains inconclusive. Further research is needed to establish GES as a standard treatment for postsurgical gastroparesis., Competing Interests: Declaration of competing interest eeeDr Abell received main funding from the National Institutes of Health GpCRC and Gastric Dysrhythmias; is an investigator of Vanda, Neurogastrx, Processa, and CinDome; is a consultant for Nuvaira, Enterra Medical, and Vanda; is a speaker for Enterra Medical; is a reviewer for UpToDate; is a GI electrical stimulation editor of Neuromodulation and Wikistim; and ADEPT-GI IP for autonomic/enteric and bioelectric diagnosis and therapies. The other authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Objective: This pilot study evaluated the relationships between appetite and oral function, and between appetite and the subjective symptoms of decreased oral function., Methods: Seventy-one adult dental clinic patients (22 males, 66.0 ± 14.0 years) participated in this study. A Council on Nutrition Appetite Questionnaire score of ≤28 indicated anorexia, and the Mini Nutritional Assessment Short-form, body mass index and skeletal muscle mass index were used to define subject characteristics. Seven oral function tests and seven subjective symptoms related to oral function were evaluated. The relationship between subject characteristics, oral function tests, subjective symptoms and anorexia was analysed using the chi-square test and univariate and multivariate logistic regression., Result: There were significant differences between the normal appetite group and the anorexia group for the 10-item Eating Assessment Tool (EAT-10) survey and the question 'Food remains in the oral cavity after eating' (p < .05). Univariate logistic regression found significant differences in the items of masticatory function, the EAT-10 survey and the question 'Food remains in the oral cavity after eating'. Multivariate logistic regression revealed significant differences in masticatory function (AOR 4.35; 95% CI: 1.03-18.35; p = .045) and EAT-10 (AOR 6.27; 95% CI: 1.40-24.02; p = .016)., Conclusion: This pilot study investigated the influence of factors related to oral function on appetite. Relationships were found among poor masticatory function, poor swallowing function and anorexia., (© 2024 John Wiley & Sons Ltd.)

Purpose of Review: This focused, narrative review mostly describes our team's investigations into the potential inflammatory mechanisms that contribute to the development of cancer-related gastrointestinal (GI) mucositis and its associated symptoms. This review summarizes details of our clinical and preclinical findings to test the role of inflammation in the development and occurrence of these cancer-related conditions., Recent Findings: GI mucositis (GIM) is a common, distressing condition reported by cancer patients. GIM is often clustered with other behaviors including fatigue, pain, anorexia, depression, and diarrhea. It is hypothesized that there is a common biologic mechanism underpinning this symptom cluster. Our multi-platform investigations revealed that GIM and its associated cluster of behaviors may be triggered by local inflammation spreading systemically causing pro-inflammatory-mediated toxicities, leading to alterations in immune, metabolic, and nervous system functions and activities. For example, behavioral toxicities related to local irradiation for non-metastatic cancer may be triggered by mGluR5 activation influencing prolonged T cell as well as NF-κB transcription factor activities. Thus, interventions targeting inflammation and associated pathways may be a reasonable strategy to alleviate GIM and its symptom cluster., Summary: GIM may be a sign of a broader systemic inflammatory response triggered by cancer or its treatment. Addressing GIM and its associated symptoms primarily involves supportive care strategies focused on relieving symptoms, promoting healing, and preventing complications., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Anorexia nervosa (AN) is characterized by hyperactivation of the hypothalamic-pituitary-adrenal axis and cognitive deficits. However, little is known about the rapid non-genomic stress response involvement. This study investigates the molecular, structural and behavioral signatures of the anorexic phenotype induction in female rats on stress-related mechanisms in the hippocampus., Method: Female adolescent rats, exposed to the combination of food restriction and wheel access, i.e., the activity-based anorexia (ABA) protocol, were sacrificed in the acute phase of the pathology (postnatal day [P]42) or following a 7-day recovery period (P49)., Results: ABA rats, in addition to body weight loss and increased wheel activity, alter their pattern of activity over days, showing increased food anticipatory activity, a readout of their motivation to engage in intense physical activity. Corticosterone plasma levels were enhanced at P42 while reduced at P49 in ABA rats. In the membrane fraction of the hippocampus, we found reduced glucocorticoid receptor levels together with reduced expression of caldesmon, n-cadherin and neuroligin-1, molecular markers of cytoskeletal stability and glutamatergic homeostasis. Accordingly, structural analyses revealed reduced dendritic spine density, a reduced number of mushroom-shaped spines, together with an increased number of thin-shaped spines. These events are paralleled by impairment in spatial memory measured in the spatial order object recognition test. These effects persisted even when body weight of ABA rats was restored., Discussion: Our findings indicate that ABA induction orchestrates hippocampal maladaptive structural and functional plasticity, contributing to cognitive deficits, providing a putative mechanism that could be targeted in AN patients., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mammalian hibernators survive prolonged periods of cold and resource scarcity by temporarily modulating normal physiological functions, but the mechanisms underlying these adaptations are poorly understood. The hibernation cycle of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) lasts for 5-7 months and comprises weeks of hypometabolic, hypothermic torpor interspersed with 24-48-h periods of an active-like interbout arousal (IBA) state. We show that ground squirrels, who endure the entire hibernation season without food, have negligible hunger during IBAs. These squirrels exhibit reversible inhibition of the hypothalamic feeding center, such that hypothalamic arcuate nucleus neurons exhibit reduced sensitivity to the orexigenic and anorexigenic effects of ghrelin and leptin, respectively. However, hypothalamic infusion of thyroid hormone during an IBA is sufficient to rescue hibernation anorexia. Our results reveal that thyroid hormone deficiency underlies hibernation anorexia and demonstrate the functional flexibility of the hypothalamic feeding center., (© 2024. The Author(s).)

Cancer-related anorexia-cachexia (CRAC) comprises one of the most common syndromes of advanced cancer patients. The prevalence of CRAC increases from 50% to 80% before death. CRAC is associated not only with impaired quality of life in patients and family members but also with shorter survival. The management of CRAC is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of CRAC. A multimodal strategy is the most effective way to treat anorexia-cachexia. Numerous medications have been suggested and used in clinical trials, while others are still being studied on experimental animals. These medications include branched-chain amino acids, eicosapentaenoic acid, thalidomide, cytokine inhibitors, steroids, antiserotoninergic medications, and appetite stimulants. The benefits of supportive care interventions and the advancement of exciting new pharmacological medicines for anorexia-cachexia are becoming more widely recognized. Health care professionals need to be aware of the psychosocial and biological effects of anorexia-cachexia, even though knowledge of the underlying molecular causes of the disorder has advanced significantly., Competing Interests: Declaration of Competing Interest We have no conflict of interest in this research, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The parasubthalamic nucleus (PSTN), a small nucleus located on the lateral edge of the posterior hypothalamus, has emerged in recent years as a highly interconnected node within the network of brain regions sensing and regulating autonomic function and homeostatic needs. Furthermore, the strong integration of the PSTN with extended amygdala circuits makes it ideally positioned to serve as an interface between interoception and emotions. While PSTN neurons are mostly glutamatergic, some of them also express neuropeptides that have been associated with stress-related affective and motivational dysfunction, including substance P, corticotropin-releasing factor, and pituitary adenylate-cyclase activating polypeptide. PSTN neurons respond to food ingestion and anorectic signals, as well as to arousing and distressing stimuli. Functional manipulation of defined pathways demonstrated that the PSTN serves as a central hub in multiple physiologically relevant networks and is notably implicated in appetite suppression, conditioned taste aversion, place avoidance, impulsive action, and fear-induced thermoregulation. We also discuss the putative role of the PSTN in interoceptive dysfunction and negative urgency. This review aims to synthesize the burgeoning preclinical literature dedicated to the PSTN and to stimulate interest in further investigating its influence on physiology and behavior., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Primary adrenal lymphoma (PAL) is a rare form of adrenal mass. We summarize our experience in its clinical presentation, biochemical indexes, radiological features, pathological information, therapy regimens, and outcomes., Methods: This was an institutional review board-approved retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of PAL at the Chinese People's Liberation Army General Hospital and the First Affiliate Hospital of Xiamen University between July 2007 and July 2017., Results: Twenty-six patients were identified. The mean age at presentation was 60.84 ± 13.14 years with a male-to-female ratio of 2.25:1 (18:8). The most common presenting symptoms were loss of appetite (65%, 17/26), weight loss (62%, 16/26), abdominal pain (58%, 15/26), and fatigue (58%, 15/26). The levels of lactate dehydrogenase (75%, 15/20), β 2 -microglobulin (100%, 10/10), C-reactive protein (82%, 14/17), and ferritin (88%, 7/8) and the erythrocyte sedimentation rate (83%, 10/12) were elevated. Bilateral involvement was seen in 21 of 26 patients (81%); 12 of 19 evaluated patients with bilateral lesions (63%) were confirmed to have adrenal insufficiency. On computed tomography (CT), the mean tumor diameter was 7.31 ± 3.35 cm and the median Hounsfield density was 37.0 HU (range: 31.0-45.0 HU); 67% (10/15) and 27% (4/15) of lesions presented with mild and moderate enhancement after injection of contrast medium. 18 F-fluorodeoxyglucose positron emission tomography (FDG PET)-CT revealed not only an adrenal tumor but also extra-adrenal lesions. Diffuse large B-cell lymphoma (DLBCL) was the most common phenotype (92%, 24/26). Ninety-two percent (24/26) of patients received chemotherapy while 8% (2/26) received unilateral adrenalectomy plus chemotherapy. The prognosis of PAL was poor, with a general survival time of 7.20 ± 5.18 months., Conclusion: PAL is a rare disease. The clinical characteristics of PAL include loss of appetite and weight loss. Endocrine evaluation should be performed to determine whether patients have adrenal insufficiency, especially patients with bilateral lesions. FDG-PET appears to be more accurate than other imaging modalities in revealing extra-adrenal sites. Better therapy is required to improve the poor prognosis of PAL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zeng, Yan, Chen, Zang, Chen, Lyu, Dou, Mu, Lin and Yang.)

Appetite loss/anorexia of aging is a highly prevalent and burdensome geriatric syndrome that strongly impairs the quality of life of older adults. Loss of appetite is associated with several clinical conditions, including comorbidities and other geriatric syndromes, such as frailty. Despite its importance, appetite loss has been under-evaluated and, consequently, under-diagnosed and under-treated in routine clinical care. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually on September 27th 2021 to debate issues related to appetite loss/anorexia of aging. In particular, topics related to the implementation and management of appetite loss in at-risk older adult populations, energy balance during aging, and the design of future clinical trials on this topic were discussed. Future actions in this field should focus on the systematic assessment of appetite in the care pathway of older people, such as the Integrated Care for Older People (ICOPE) program recommended by the World Health Organization. Moreover, clinical care should move from the assessment to the treatment of appetite loss/anorexia. Researchers continue to pursue their efforts to find out effective pharmacologic and non-pharmacologic interventions with a favorable risk/benefit ratio., Competing Interests: The Task Force was partially funded by registration fees from industrial participants. These corporations placed no restrictions on this work. Dr. Morley, Dr. Landi, Dr. Roberts, and Dr. Rolland declare no conflicts of interest related to this work; Dr de Souto Barreto reports consulting from Pfizer, outside the submitted work; Dr. Cederholm reports personal fees from Nutricia, personal fees from Abbott, personal fees from Fresenius Kabi, grants from Pfizer, outside the submitted work; Dr. Cesari reports personal fees from Nestlé Health Sciences, outside the submitted work; Dr. Vellas is an investigator in clinical trials sponsored by the Toulouse University Hospital (Inspire Geroscience Program); Dr Fielding reports grants from National Insitutes of Health, grants from USDA Agricultural Research Service, grants, personal fees and stock options from Axcella Health, stock options from Juvicell, stock options from Inside Tracker, grants and personal fees from Biophytis, personal fees from Amazentis, personal fees from Nestle, grants from Pfizer, outside the submitted work.

Calcitonin gene related peptide (CGRP) expressing neurons in the parabrachial nucleus have been shown to encode danger. Through projections to the amygdala and other forebrain structures, they regulate food intake and trigger adaptive behaviors in response to threats like inflammation, intoxication, tumors and pain. Despite the fact that this danger-encoding neuronal population has been defined based on its CGRP expression, it is not clear if CGRP is critical for its function. It is also not clear if CGRP in other neuronal structures is involved in danger-encoding. To examine the role of CGRP in danger-related motivational responses, we used male and female mice lacking αCGRP, which is the main form of CGRP in the brain. These mice had no, or only very weak, CGRP expression. Despite this, they did not behave differently compared to wildtype mice when they were tested for a battery of danger-related responses known to be mediated by CGRP neurons in the parabrachial nucleus. Mice lacking αCGRP and wildtype mice showed similar inflammation-induced anorexia, conditioned taste aversion, aversion to thermal pain and pain-induced escape behavior, although it should be pointed out that the study was not powered to detect any possible differences that were minor or sex-specific. Collectively, our findings suggest that αCGRP is not necessary for many threat-related responses, including some that are known to be mediated by CGRP neurons in the parabrachial nucleus., (© 2021. The Author(s).)

Anorexia nervosa (AN) is an eating disorder leading to malnutrition and, ultimately, to energy wasting and cachexia. Rodents develop activity-based anorexia (ABA) when simultaneously exposed to a restricted feeding schedule and allowed free access to running wheels. These conditions lead to a life-threatening reduction in body weight, resembling AN in human patients. Here, we investigate the effect of ABA on whole body energy homeostasis at different housing temperatures. Our data show that ABA rats develop hyperactivity and hypophagia, which account for a massive body weight loss and muscle cachexia, as well as reduced uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT), but increased browning of white adipose tissue (WAT). Increased housing temperature reverses not only the hyperactivity and weight loss of animals exposed to the ABA model, but also hypothermia and loss of body and muscle mass. Notably, despite the major metabolic impact of ABA, none of the changes observed are associated to changes in key hypothalamic pathways modulating energy metabolism, such as AMP-activated protein kinase (AMPK) or endoplasmic reticulum (ER) stress. Overall, this evidence indicates that although temperature control may account for an improvement of AN, key hypothalamic pathways regulating thermogenesis, such as AMPK and ER stress, are unlikely involved in later stages of the pathophysiology of this devastating disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fraga, Rial-Pensado, Nogueiras, Fernø, Diéguez, Gutierrez and López.)

Aim: The present study aims to extend the knowledge of the neural correlates of emotion processing in first episode subjects affected by anorexia nervosa (AN) or bulimia nervosa (BN). We applied an emotional distress paradigm targeting negative emotions thought to be relevant for interpersonal difficulties and therapeutic resistance mechanisms., Methods: The current study applied to 44 female participants with newly diagnosed AN or BN and 20 matched controls a neuroimaging paradigm eliciting affective responses. The measurements also included an extensive assessment comprising clinical scales, neuropsychological tests, measures of emotion processing and empathy., Results: AN and BN did not differ from controls in terms of emotional response, emotion matching, self-reported empathy and cognitive performance. However, eating disorder and psychopathological clinical scores, as well as alexithymia levels, were increased in AN and BN. On a neural level, no significant group differences emerged, even when focusing on a region of interest selected a priori: the amygdala. Some interesting findings put in relation the hippocampal activity with the level of Body Dissatisfaction of the participants, the relative importance of the key nodes for the common network in the decoding of different emotions (BN = right amygdala, AN = anterior cingulate area), and the qualitative profile of the deactivations., Conclusions: Our data do not support the hypothesis that participants with AN or BN display reduced emotional responsiveness. However, peculiar characteristics in emotion processing could be associated to the three different groups. Therefore, relational difficulties in eating disorders, as well as therapeutic resistance, could be not secondary to a simple difficulty in feeling and identifying basic negative emotions in AN and BN participants., Competing Interests: The authors have declared that no competing interests exist.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to more than 200 countries and regions globally. SARS-CoV-2 is thought to spread mainly through respiratory droplets and close contact. However, reports have shown that a notable proportion of patients with coronavirus disease 2019 (COVID-19) develop gastrointestinal symptoms and nearly half of patients confirmed to have COVID-19 have shown detectable SARS-CoV-2 RNA in their faecal samples. Moreover, SARS-CoV-2 infection reportedly alters intestinal microbiota, which correlated with the expression of inflammatory factors. Furthermore, multiple in vitro and in vivo animal studies have provided direct evidence of intestinal infection by SARS-CoV-2. These lines of evidence highlight the nature of SARS-CoV-2 gastrointestinal infection and its potential faecal-oral transmission. Here, we summarize the current findings on the gastrointestinal manifestations of COVID-19 and its possible mechanisms. We also discuss how SARS-CoV-2 gastrointestinal infection might occur and the current evidence and future studies needed to establish the occurrence of faecal-oral transmission.

Background: Nutrition plays an important role in maintaining the overall health of older people. Inadequate intake may lead to impaired body function, higher morbidity, and mortality. Oral nutritional supplements (ONS) showed positive effect on the nutritional status of the elderly; however, systematic evidence is currently lacking on the effect of ONS on the elderly with anorexia., Aims: The current systematic review and meta-analysis included randomized controlled trial (RCT) articles to investigate the effectiveness of ONS on the main aspects of anorexia of aging (AA)., Methods: By using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method, researchers independently searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and other gray literature resources for publications that met the inclusion criteria by October 2020. The Cochrane Risk of Bias Tools were used for quality assessment. The inverse-variance method was used for the fixed model (FM) while the DerSimonian-Laird method was used for the random model (RM). Respective 95% confidence intervals (95% CIs), mean difference (MD) or standardized mean difference (SMD) was used for indices in terms of effect size (ES)., Results: 2497 records were found through the systematic search, while 17 RCTs ( n = 1204) were included, with a mean age of 81.9 years (range: 74-87 years). Supplementation occurred in the morning, mid-day, and evening, while the times varied from one to three times a day. The results of meta-analysis showed that, generally, ONS had a positive effect on the overall appetite, MD = 0.18, 95% CI (0.03, 0.33), p = 0.02, and consumption, MD = 1.43, 95% CI (0.01, 2.86), p = 0.05; but not significant in terms of other aspects of appetite: hunger, p = 0.73; fullness, p = 0.60; desire to eat, p = 0.80; preoccupation, p = 0.15. Additionally, it showed an increase in the overall energy intake, SMD = 0.46, 95% CI (0.29, 0.63), p < 0.001, in protein intake, SMD = 0.59, 95% CI (0.16, 1.02), p = 0.007, and in fat intake, MD = 3.47, 95% CI (1.98, 4.97), p < 0.001, while no positive effect was found on carbohydrates intake, p = 0.06. Significance differences were also found in the body weight, SMD = 0.53, 95% CI (0.41, 0.65), p < 0.001, and body mass index (BMI), MD = 0.53, 95% CI (0.12, 0.95), p = 0.01. Moreover, subgroup analyses were conducted according to the nutrient density with no positive results showed except for the low-density ONS on overall energy intake., Conclusions: The results of the present study indicated that ONS had beneficial effects on overall appetite, energy intake, body weight and BMI.

Aim: This study aims to review the current evidence regarding appetite problem in cancer patients, mainly focusing on pathophysiology, diagnosis, and treatment., Introduction: Anorexia is the common symptom of malnutrition in cancer patients. Recently, the understanding of the pathophysiological mechanism of the appetite problem in cancer patients has been increasing that give impact to rigorous research to find the therapies for improving appetite in cancer patients., Discussion: The development of anorexia in cancer patients is a complex process that involves many cytokines, receptors, chemical mediators/substances, hormones, and peptides. Growth and differentiation factor-15 (GDF-15) and toll-like receptor (TLR-4) have recently been found to be implicated in the pathogenesis of anorexia. To help diagnose the appetite problem in cancer patients, several questionnaires can be used, starting from well-known questionnaires such as Functional Assessment of Anorexia Cachexia Therapy (FAACT), Visual Analog Scale (VAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ30). Several drugs with different mechanisms of action have been studied to help in improving appetite in cancer patients. New repurposed agents such as anamorelin, mirtazapine, thalidomide, and eicosapentaenoic acid (EPA) have shown a beneficial effect in improving appetite and quality of life in cancer patients, however more phase 3 clinical trial studies is still needed., Conclusion: The pathophysiology of appetite problems in cancer patients is a complex process that involves many factors. Several drugs that target those factors have been studied, however more phase 3 clinical trial studies are needed to confirm the findings from previous studies., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: In undergraduate medical education and in the subject of child and adolescent psychiatry, examining young patients face-to-face is a key element of teaching. With the abrupt shutdown of face-to-face teaching caused by the SARS-CoV-2 pandemic, a case-based online training program integrating audio and video of real patients was developed. Methods: The blended learning platform CaseTrain guides medical students in their final year through real child-psychiatric patient cases, such as anorexia, autism, or attention deficit disorder, through presentation of video and audio of real patients and parents. The teaching format complements lectures on child psychiatric topics, comprising asynchronous elements (self-study using the digital material) as well as synchronous elements (web-conferences with a specialist). Learning objectives for students were set to develop knowledge of the spectra of psychiatric disorders that affect children and to recognize approaches how to assess and manage common psychiatric problems of childhood and adolescence. Results: The feedback from medical students through oral and written evaluation was positive. They appreciated getting to know 'real-world patients' in times of such a pandemic, to learn explorative techniques from role models, and to be in close contact with the supervising specialist. In consequence of critical feedback on the length of some video sequences, these training units will undergo revision. Conclusions: Case-based online training may continue to be a useful option in a post-pandemic future as integral part of medical education, complementing face-to-face lectures and training in (child) psychiatry., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Taurines et al.)

Objective: To explore the clinical characteristics of Coronavirus Disease (COVID-19) patients with gastrointestinal symptoms., Methods: The clinical data of 164 COVID-19 patients with gastrointestinal symptoms were extracted and analysed retrospectively., Results: In total, 505 COVID-19 patients were divided into two groups: those with gastrointestinal symptoms (G group) and those without gastrointestinal symptoms (NG group). Common gastrointestinal symptoms included inappetence, diarrhoea, nausea, abdominal pain, and vomiting. Significantly higher proportions of patients with fever, dizziness, myalgia, and fatigue were noted in group G than in group NG. Compared with patients without fever, there was a significant difference between G group and NG group in moderate fever or above, while there was no significant difference between the two groups in low fever. The laboratory results showed that patients in the G group had significantly higher C-reactive protein, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase levels than those in the NG group. Moreover, the proportion of patients with severe pneumonia was significantly higher in the G group than in the NG group., Conclusion: In Wuhan, the proportion of COVID-19 patients who experience gastrointestinal symptoms is relatively high. Patients who experience gastrointestinal symptoms are more likely to suffer from severe pneumonia, which may help clinicians identify patients at high risk of COVID-19 and thus reduce the incidence of this condition., Competing Interests: None., (© 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Throughout history and to the present day, there have been reports of people claiming inedia, i.e., an anomalous long-term abstinence from food or from food and fluid. Some were isolated and monitored and their abstinences confirmed. This raises the question of whether there may be an anomaly with wide implications that science has overlooked. On the other hand, there have been cases of exposed fraud. The reports on the studies are scattered and it can be difficult to judge their rigor and the strength and implications of their evidence. A critical evaluation seems useful., Objectives: The objectives were to obtain an overview of investigated cases of claimed inedia, to assess the anomaly of the claims and study results, to assess the quality of the studies, and to identify deception methods to inform future safeguards., Method: I developed criteria for differentiating normal from anomalous nutrition and fasting and for assessing the quality of inedia studies. Studies found through a systematic search were then assessed and the features of cases of fraud extracted., Results: 47 eligible investigations of 38 claimants were found. Out of the 38 cases, results were assessed as (seemingly) anomalous in 11, with nine cases of monitored food and fluid deprivation ranging from 14 to 68 days (median 28 days), and two cases of food deprivation for 365 and 411 days. In 17 cases, anomaly was assessed as not confirmed due to issues with study design or reporting. Fraud was established in 10 cases. Deception methods were creative. Post-1900 studies were also assessed for quality. Quality was not considered adequate in any., Conclusions: I consider the evidential status of inedia unconfirmed as no assessed study had both anomalous findings and impeccable quality. However, quality was often downgraded due to reporting issues and it cannot be concluded in reverse that all claimants with anomalous results were able to deceive the investigators. The results of many studies are curious and demand further research. The conducted analysis provides guidance for improving rigor and transparency in future studies., (Copyright © 2020 The Author. Published by Elsevier Inc. All rights reserved.)

During the previous months, we have seen the rapid pandemic spread of SARS-CoV-2. Despite being considered a respiratory virus, it has become clear that other clinical presentations are possible and some of these are quite frequent. In this paper, a case of a man in his late 70s showing atypical symptoms in general practice is presented. Apart from fever, the patient complained of diarrhoea, borborygmus, loss of appetite and nausea. He developed no respiratory symptoms during his disease. Due to his symptoms, malignant disease was suspected, and he was referred for further testing which revealed typical COVID-19 findings on a chest CT scan. The occurrence of atypical symptoms is discussed, including the importance of recognising these in an ongoing pandemic., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Dehydration-Induced Anorexia (DIA) is a murine model that reproduces weight loss and avoidance of food, despite its availability. The prefrontal cortex (PFC) integrates sensory inputs and updates associative learning to promote (hunger) or inhibit (satiety) food-seeking behavior. In this study we tested if anorexia induces a pro-inflammatory environment associated with microglia in the medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC), specific subregions of the PFC involved in appetite. Our results showed that anorexia increased microglial density, promoted a de-ramified morphology and augmented the de-ramified/ramified ratio in the mPFC and OFC but not in the motor cortex. Anorexia also increased the expression of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β. This pro-inflammatory environment associated with microglia activation correlates with neuronal damage as revealed by Fluoro Jade C (FJC) and NeuN immunolabeling. We conclude that anorexia triggers a pro-inflammatory environment associated with microglia that correlates with neurodegeneration in the mPFC and OFC., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Food intake of carnivorous fish decreases after feeding on a carbohydrate-rich diet. However, the molecular mechanism underlying the anorexia caused by high-carbohydrate diets has remained elusive. We domesticated the mandarin fish to feed on carbohydrate-rich (8%) diets. After 61 days of feeding, several fish (Group A) fed well on artificial diets during the whole feeding period; the other fish (Group B) fed well on artificial diets at the beginning of the feeding period, with their food intake then decreasing to half (anorexia) and then to zero for 5 days; and, finally, a negative control (Group C) fed on live prey fish throughout the experimental process. The plasma glucose was significantly higher in the mandarin fish of Group B than in those of Group A, whereas levels of hepatic glycogen and plasma triglyceride were significantly lower. Using transcriptome sequencing, we investigated the differentially expressed genes between Groups A and B and excluded the genes that were not differentially expressed between Groups A and C. The activation of mTOR and Jak/STAT pathways were found in the mandarin fish with anorexia, which was consistent with the higher expression levels of pepck and pomc genes. We found a higher expression of histone methyltransferase setd1b gene and an increased histone H3 tri-methylated at lysine 4 (H3K4me3) in the fish of Group B. Furthermore, using ChIP assay and inhibitor treatment, we found that the up-regulated H3K4me3 could activate pepck expression, which might have contributed to the hyperglycemia and anorexia in the mandarin fish that fed on carbohydrate-rich diets. Our study initially indicated a link between histone methylation and pepck expression, which might be a novel regulatory mechanism of fish who are fed a carbohydrate-rich diet., (Copyright © 2020 You, Ren, He, Liang, Xiao and Zhang.)

Accumulating data have now shown strong evidence that COVID-19 infection leads to the occurrence of neurological signs with different injury severity. Anosmia and agueusia are now well documented and included in the criteria list for diagnosis, and specialists have stressed that doctors screen COVID-19 patients for these two signs. The eventual brainstem dysregulation, due to the invasion of SARS CoV-2, as a cause of respiratory problems linked to COVID-19, has also been extensively discussed. All these findings lead to an implication of the central nervous system in the pathophysiology of COVID-19. Here we provide additional elements that could explain other described signs like appetite loss, vomiting, and nausea. For this, we investigated the role of brainstem structures located in the medulla oblongata involved in food intake and vomiting control. We also discussed the possible pathways the virus uses to reach the brainstem, i.e., neurotropic and hematogenous (with its two variants) routes.

Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and other metabolic abnormalities leading to functional impairment. Cancer cachexia has long been recognized as a direct cause of complications in cancer patients, reducing quality of life and worsening disease outcomes. Some related conditions, like sarcopenia (age-related muscle wasting), anorexia (appetite loss) and asthenia (reduced muscular strength and fatigue), share some key features with cancer cachexia, such as weakness and systemic inflammation. Understanding the interplay and the differences between these conditions is critical to advance basic and translational research in this field, improving the accuracy of diagnosis and contributing to finally achieve effective therapies for affected patients., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Anorexia and cachexia, nausea and vomiting, and constipation are gastrointestinal symptoms that commonly accompany serious illness. Basic science and clinical research continue to improve the understanding of their pathophysiology. Thorough assessment necessitates history, physical examination, and laboratory and diagnostic testing. Pharmacologic management attempts to counteract or reverse the underlying pathophysiologic mechanisms that accompany each symptom, which may benefit from a multimodal approach to achieve adequate control. Future improvements in management require investments in clinical research to determine the efficacy of novel agents along with comparator studies to better understand which treatments should be used in what sequence or combination., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The aim of this study is the evaluation of clinical signs and outcomes of treatment in children under five years of age who underwent appendectomy because of acute appendicitis. Patients and Methods: From January 2009 until December 2018, 90 patients (54 boys and 36 girls) younger than five years of age, treated with appendectomy because of acute appendicitis, were included in this study. Patients were divided into two groups, depending on the intra-operative finding of non-perforated (Group I; n = 32) or perforated (Group II; n = 58) appendicitis. The groups were compared regarding demographic, clinical, and laboratory data and outcomes of treatment. Results: Of 1687 appendectomies in this period, 90 (5.3%) of them were performed in patients aged five years or younger. There were 58 (64.4%) patients with perforated appendix. Positive correlation between the rate of perforation and the age of patients was found. Perforation rates were significantly higher in younger patients (100%, <1 year; 100%, 1-2 y; 83.3%, 2-3 y; 71.4%, 3-4 y; 78.6%, 4-5 y, and 47.3%, 5 y) (p = 0.037). Vomiting and diarrhea were found more commonly in the group of perforated appendix (p < 0.002, p < 0.001), while constipation was found more often in the patients whose appendix was not perforated (p < 0.001). The median duration of symptoms (48 h vs. 16 h; p < 0.001) and median duration of hospitalization (7.5 d vs. 5 d; p < 0.001) were notably longer for the group of patients with perforated than the group of patients with non-perforated appendix. All complications occurred in the group of perforated appendix with total incidence of 4.4%. Conclusion: The clinical presentation of acute appendicitis for children aged five years or younger is often unusual, and establishing the proper diagnosis is often delayed. Patient age is tied closely to the stage of acute appendicitis, so the youngest patients present with more advanced stages of disease and are at greater risk of perforation. Acute appendicitis should be considered in all cases where a child is having abdominal pain, fever, and diarrhea, which has been shown to be present significantly more often in children with perforated appendix.

Exposure to negative events during the neonatal period is one of the leading factors contributing to the development of psychiatric disorders, including anorexia nervosa. In this study, we investigated the effects of maternal separation (MS) on the development of anorexia in rodents using the mild-stress form of the activity-based anorexia (ABA) model (2 hr of free access to a running wheel and a 1-hr feeding test) in both male and female rats. We assessed anxiety-like and locomotor behavior and hyperactivity with the open field and elevated plus maze tests. Our results showed that ABA rats of both sexes displayed hyperactive behavior associated with reduced anxiety-like behavior when compared to controls. However, a sexually dimorphic effect of MS emerged in anorexic rats: while the females exposed to MS + ABA were hyperactive with diminished anxiety-related behaviors compared to females of the ABA group, MS in males attenuated or did not alter the effects of the ABA protocol. In conclusion, our data reveal that the synergistic effects of MS and ABA on physical activity and anxiety-like behavior act in opposite directions in the two sexes., (© 2019 Wiley Periodicals, Inc.)

We report a case of a 47-year-old woman with hypercalcemia 6 months after discontinuation of denosumab. She underwent right mastectomy for breast cancer and had received aromatase inhibitor and denosumab therapy for 5 years. Thirst, appetite loss, and bilateral ankle pain began few months after cessation of denosumab. She was admitted to the hospital for hypercalcemia and hyperthyroidism 6 months after the last dose of denosumab. Laboratory investigations revealed hypercalcemia, normophosphatemia, normal renal function, and elevated levels of fibroblast growth factor 23 (FGF-23). Serum tartrate-resistant acid phosphatase 5b and urine N-terminal cross-linked telopeptide of type I collagen were both elevated, and bone scintigraphy revealed increase of whole bone uptake. Radiological examinations showed no recurrence of breast cancer or tumors that secrete intact PTH or FGF-23. Hypercalcemia, which lasted for 1 month, was refractory to discontinuation of the aromatase inhibitor, normalization of thyroid hormone levels, saline hydration, and calcitonin administration, but was effectively treated with zoledronic acid. Abnormal uptake on bone scintigraphy and ankle pain both resolved a few months after treatment, and hypercalcemia has not recurred in the ensuing 2 years. In conclusion, we found elevated levels of circulating FGF-23 with hypercalcemia following the discontinuation of denosumab. FGF-23 might be a surrogate marker for massive bone resorption triggered by discontinuation of long-term denosumab treatment.

Purpose : Dysgeusia can be found in 50% of cancer patients undergoing chemotherapy. Nonetheless, dysgeusia can be present in treatment-naïve patients, and may negatively impact nutrition and quality of life. Methods : Treatment-naïve non-small cell lung cancer (NSCLC) was assessed for dysgeusia using a self-reporting questionnaire and a rinse stimuli technique. Patients were evaluated in terms of health-related quality of life (HRQL) using the EORTC-QLQ-C30 questionnaire and in terms of nutrition using the subjective global assessment (SGA), energy consumption and body composition. Results : Among 65 treatment-naïve patients, dysgeusia was self-reported in 35%. Using the rinse stimuli technique, most of the patients perceived taste stimuli with a minimal concentration, but could not recognize the taste. Patients with dysgeusia presented significantly less lean-body mass ( P  = 0.027), and higher fat mass ( P  = 0.027). Additionally, these patients had significantly more gastrointestinal symptoms including nausea ( P  = 0.042), anorexia ( P  = 0.004), and early satiety ( P  < 0.0001). Dysgeusia was also associated with less food consumption ( P  = 0.010). Last, patients with dysgeusia had clinically-significant alterations in HRQL scales. Conclusion : Presence of dysgeusia in NSCLC patients before undergoing chemotherapy is associated with worse nutritional outcomes. The routine assessment of dysgeusia in treatment-naïve patients should be encouraged to timely assess and follow nutritional parameters.

Purpose of Review: Thoracic malignancies are amongst the most lethal of all cancers. Cancer cachexia lacks unanimously accepted diagnostic criteria, and therefore is referenced to as a conceptual framework whereby cancer cachexia is 'an ongoing loss of skeletal muscle mass (termed sarcopenia), with or without loss of fat mass that cannot be reversed by conventional nutritional support and leads to progressive functional impairment'. This review summarises the current evidence base in this field, including imaging techniques currently used to define sarcopenia, inflammatory and metabolic changes associated with the syndrome and ongoing research into potential treatment strategies., Recent Findings: Sarcopenia is a key component of the cancer cachexia syndrome. It is common in patients with both early-stage and advanced NSCLC. Patients with sarcopenia have more treatment-related side effects and poorer overall survival compared with nonsarcopenic patients., Summary: Early identification of cancer cachexia may facilitate stratification of patients most-at-risk and initiation of emerging anticachexia treatments. If these are proven to be effective, this strategy has the potential to improve tolerance to anti-cancer therapies, improving the quality of life, and perhaps the survival, of patients with thoracic malignancies.

Aim of Study: The aim of the study was to assess the impact of treatment with adjuvant vemurafenib monotherapy on health-related quality of life (HRQOL) in patients with resected stage IIC-IIIC melanoma., Methods: The phase 3 BRIM8 study (NCT01667419) randomised patients with BRAF V600 mutation-positive resected stage IIC-IIIC melanoma to 960 mg of vemurafenib twice daily or matching placebo for 52 weeks (13 × 28-day cycles). Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) version 3 at baseline, cycle 1 (days 1, 15 and 22), cycle 2 (days 1 and 15), day 1 of every subsequent 4-week cycle, the end-of-treatment visit and each visit during the follow-up period., Results: Completion rates for the EORTC QLQ-C30 questionnaire were high (>80%). There was a mean decline in the global health status (GHS)/quality of life (QOL) score of 17.4 (±22.9) and 17.3 (±24.1) points at days 15 and 22 of cycle 1, respectively, among vemurafenib-treated patients who recovered to approximately 10 points below baseline for the remainder of the treatment period. A similar trend was observed in all functional scales except for cognitive function (<10-point change from baseline at all visits) and in the symptom scores for appetite loss, fatigue and pain. As observed for the GHS/QOL score, all scores rapidly returned to baseline after completion of planned vemurafenib treatment or treatment discontinuation., Conclusions: The schedule of HRQOL assessments allowed for an accurate and complete evaluation of the impact of acute treatment-related symptoms. Vemurafenib-treated patients experience clinically meaningful moderate worsening in some treatment- or disease-related symptoms and GHS/QOL that resolve over time., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The burden of nonpain symptoms such as anorexia, constipation, nausea, and vomiting contribute to patient suffering throughout the course of advanced illness. It is important to address symptom control throughout the disease trajectory, and especially at the end of life. Primary care clinicians must recognize these symptoms early, provide ongoing assessment, and keep abreast of evidence-based management strategies, including valid clinical protocols., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The α2a-adrenergic agonist, lofexidine, reduced cannabis withdrawal-related sleep disruption in the laboratory, but side effects (e.g. fatigue, hypotension) limit its utility as a treatment for cannabis use disorder. This study tested the potential efficacy and tolerability of a daily bedtime administration of the FDA-approved α2a-adrenergic agonist, guanfacine, in a human laboratory model of cannabis use disorder. Daily, nontreatment-seeking cannabis smokers (13M, 2F) completed a within-subject study comprising two 9-day inpatient study phases. Each phase tested the effects of daily placebo or immediate-release guanfacine (2 mg) on cannabis intoxication (5.6 percent THC; 2 days), withdrawal (4 days of abstinence) and subsequent 'relapse' (3 days of cannabis self-administration). Ratings of mood, sleep, cardiovascular effects, food intake, psychomotor performance and cannabis self-administration were assessed. An outpatient phase preceded each inpatient phase for medication clearance or dose induction. Under placebo medication conditions, cannabis abstinence produced significant withdrawal, including irritability, sleep disruption and anorexia. Guanfacine reduced ratings of irritability and improved objective measures of sleep during cannabis withdrawal relative to placebo but did not reduce cannabis self-administration. Guanfacine was well tolerated with little evidence of fatigue and only small decreases in blood pressure: no dose was held due to hypotension. Thus, a single daily administration of guanfacine at bedtime improved sleep and mood during cannabis withdrawal relative to placebo. This positive signal supports further studies varying the guanfacine dose, formulation or frequency of administration, or combining it with other medications to increase the likelihood of having an impact on cannabis use., (© 2018 Society for the Study of Addiction.)

Loss of appetite or anorexia associated with inflammation impairs quality of life and increases morbidity in many diseases. However, the exact neural mechanism that mediates inflammation-associated anorexia is still poorly understood. Here we identified a population of neurons, marked by the expression of protein kinase C-delta, in the oval region of the bed nucleus of the stria terminalis (BNST), which are activated by various inflammatory signals. Silencing of these neurons attenuates the anorexia caused by these inflammatory signals. Our results demonstrate that these neurons mediate bidirectional control of general feeding behaviors. These neurons inhibit the lateral hypothalamus-projecting neurons in the ventrolateral part of BNST to regulate feeding, receive inputs from the canonical feeding regions of arcuate nucleus and parabrachial nucleus. Our data therefore define a BNST microcircuit that might coordinate canonical feeding centers to regulate food intake, which could offer therapeutic targets for feeding-related diseases such as anorexia and obesity.

Background: During activity-based anorexia (ABA) in mice, enhanced paracellular permeability and reduced protein synthesis have been shown in the colon while the gut-brain axis has received increasing attention in the regulation of intestinal and mood disorders that frequently occur during anorexia nervosa, a severe eating disorder for which there is no specific treatment. In the present study, we assessed the effects of oral glutamine (Gln) or branched-chain amino acids (BCAA) supplementation during ABA to target intestinal functions, body composition and feeding behavior., Methods: C57BL/6 male mice were randomized in Control (CTRL) and ABA groups. After ABA induction, mice received, or not, either 1% Gln or 2.5% BCAA (Leu, Ile, Val) for one week in drinking water., Results: Neither Gln nor BCAA supplementation affected body weight and body composition, while only Gln supplementation slightly increased food intake. ABA mice exhibited increased paracellular permeability and reduced protein synthesis in the colonic mucosa. Oral Gln restored colonic paracellular permeability and protein synthesis and increased the mucin-2 mRNA level, whereas BCAA did not affect colonic parameters., Conclusion: In conclusion, oral Gln specifically improves colonic response during ABA. These data should be further confirmed in AN patients.

The population of older adults is growing globally. This increase has led to an accumulation of chronic illnesses, so-called age-related diseases. Diet and nutrition are considered the main drivers of the global burden of diseases, and this situation applies especially to this population segment. It relates directly to the development of coronary heart disease, hypertension, some types of cancer, and type 2 diabetes, among other diseases, while age-associated changes in body composition (bone and muscle mass, fat, sarcopenia) constitute risk factors for functional limitations affecting health status and the quality of life. Older adults present eating and swallowing problems, dry mouth, taste loss, and anorexia among other problems causing "anorexia of aging" that affects their nutritional status. The strategies to overcome these situations are described in this study. The impact of oral food processing on nutrition is discussed, as well as approaches to improve food acceptance through the design of innovative foods. These foods should supply a growing demand as this group represents an increasing segment of the consumer market globally, whose needs must be fulfilled.

Chickens from lines selected for low (LWS) or high (HWS) body weight (BW) differ in appetite and adiposity. Mechanisms associated with the predisposition to becoming obese are unclear. The objective of the experiment was to evaluate developmental changes in depot-specific adipose tissue during the first 2 wk posthatch. Subcutaneous (SQ), clavicular (CL), and abdominal (AB) depots were collected at hatch (DOH) and days 4 (D4) and 14 (D14) posthatch for histological and mRNA measurements. LWS chicks had decreased SQ fat mass on a BW basis with reduced adipocyte size from DOH to D4 and increased BW and fat mass with unchanged adipocyte size from D4 to D14. HWS chicks increased in BW from DOH to D14 and increased in fat mass in all three depots with enlarged adipocytes in the AB depot from D4 to D14. Meanwhile, CCAAT/enhancer-binding protein-α, neuropeptide Y, peroxisome proliferator-activated receptor-γ, and acyl-CoA dehydrogenase mRNAs differed among depots between lines at different ages. Plasma nonesterified fatty acids were greater in LWS than HWS at D4 and D14. From DOH to D4, LWS chicks mobilized SQ fat and replenished the reservoir through hyperplasia, whereas HWS chicks were dependent on hyperplasia and hypertrophy to maintain adipocyte size and depot mass. From D4 to D14, adipose tissue catabolism and adipogenesis slowed. Whereas LWS fat depots and adipocyte sizes remained stable, HWS chicks rapidly accumulated fat in CL and AB depots. Chicks predisposed to be anorexic or obese have different fat development patterns during the first 2 wk posthatch.

Anorexia by osmotic dehydration is an adaptive response to hypernatremia and hyperosmolaemia induced by ingestion of a hypertonic solution. Dehydration-induced anorexia (DIA) reproduces weight loss and avoidance of food, despite its availability. By using this model, we previously showed increased reactive astrocyte density in the rat dorsal hippocampus, suggesting a pro-inflammatory environment where microglia may play an important role. However, whether such anorexic condition increases a pro-inflammatory response is unknown. The aim of this study was to test if DIA increases microglial density in the dorsal hippocampus, as well as the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and interleukin 1 beta (IL-1β) in the hippocampus of young female rats. Our results showed that DIA significantly increased microglial density in CA2-CA3 and dentate gyrus (DG) but not in CA1. However, forced food restriction (FFR) only increased microglial density in the DG. Accordingly, the activated/resting microglia ratio was significantly increased in CA2-CA3 and DG, in DIA and FFR groups. Finally, western blot analysis showed increased expression of IBA1, TNF-α, IL-6 and IL-1β in the hippocampus of both experimental groups. We conclude that anorexia triggers increased reactive microglial density and expression of TNF-α, IL-6 and IL-1β; this environment may result in hippocampal neuroinflammation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Anorexia Nervosa (AN) is a disorder with a dramatic impact on both the individual and society. Besides severe weight loss, excessive physical exercise and cognitive disturbances can be present in patients with AN as primary symptoms of the pathology or as secondary effects induced by physical and metabolic alterations. Mechanistic research in this field has taken advantage of a well characterized animal model, the activity-based anorexia model (ABA). ABA rodents and subjects with AN show clear behavioral and physiological similarities, but a throughout neurocognitive assessment of the model is still missing. Here, we review the available literature in the ABA field, highlighting similarities between ABA and AN at the behavioral, neurophysiological and cognitive level. Furthermore, based on availability, feasibility and adaptability of rodent behavioral protocols, we propose a set of neurocognitive assays that can be performed on the ABA. The proposed assessment represents an important step forward in the validation and extension of the ABA model, opening several routes of investigation related to AN and other eating disorders., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Anorexia of ageing (AA) may be considered as a risk factor for frailty and has an important impact on quality of life, morbidity and mortality., Methods: A systematic review and a meta-analysis were performed to summarise the results from several trials on the effectiveness of treatments in AA, as associated with depression, sensory impairment of taste and smell, decreased appetite or early satiety, and disability. Eligible studies were required to report baseline and follow-up values, the mean change (∆-change) from baseline, and/or the mean difference among intervention groups versus control group, concerning food intake (kcal/daily) and/or nutritional outcomes, such as body weight, body mass index, albumin and Mini Nutritional Assessment., Results: The systematic review included 20 papers based on different therapeutic approaches concerning food intake and/or nutritional outcomes. The results of the meta-analysis indicate that the interventions for AA have an important impact on body weight [+1.59 kg; 95% confidence interval (CI) = 1.48-+1.71 kg; P < 0.001) and on energy intake (+56.09 kcal; 95% CI = -54.05 to +166.25 kcal; P = 0.32). Regarding secondary outcomes, it was not possible to meta-analyse the limited amount of data availab le., Conclusions: The different variants of AA need to be defined because diverse therapeutic approaches are available. A more precise definition of the functional impairments associated with AA may allow a more correct decision about the most appropriate therapy to be prescribed. Moreover, this may allow for a more effective performance of the different therapeutic approaches once they are better targeted to the different scenarios of AA., (© 2018 The British Dietetic Association Ltd.)

The treatment of cancer cachexia remains an unmet medical need. One of the barriers to the development and approval of effective interventions has been the lack of agreement on the proper endpoints for study. The international consensus definition of cancer cachexia focuses on 3 major components of the syndrome. This includes altered body composition characterized specifically by loss of skeletal muscle mass. The muscle loss in turn is a result of negative protein and energy balance secondary to reduced food intake and abnormal metabolism. The result of muscle loss is progressive functional impairment. The assessment of interventions for cancer cachexia should include measures of all 3 components of cancer cachexia. For patients with cancer cachexia, body composition measurements of lean body mass (LBM) and fat mass may be best determined by CT imaging. Nutritional endpoints and measures of metabolism can be quite complex. However, change in appetite and body weight remain extremely useful measures of clinical benefit. The most controversial area relates to assessment of physical function. While stair climb power, 6-minute walk, hand grip strength and other measures have been used in clinical trials, none of them have shown consistent benefit that correlates with change in LBM. While we have much to learn about the inter-relationship between muscle mass and muscle function, improvement in physical function may be best measured by patient reported outcomes. Ongoing and future clinical trials in cancer cachexia should assess all 3 domains, which will improve our understanding of this syndrome and ultimately lead to better treatment options for our patients.

The anorexia of aging affects approximately a quarter of older people and is a major contributor to the development of under-nutrition and many other adverse health outcomes in older people. Despite the high prevalence, the anorexia of aging is frequently overlooked by clinicians and, of even more concern, it is commonly accepted as inevitable and a part of 'normal' aging. Early identification of risk coupled with efforts to mitigate these risks through appropriate interventions might stem the deleterious consequences of the anorexia of aging. This review aims to provide an update on the current knowledge base whilst making some practical suggestions that may be of use in clinical practice. Interventions such as exercise and good nutrition remain the preferred treatment while pharmacological options, whilst they continue to be trialed, are not currently recommended for routine clinical use., Competing Interests: R Visvanathan has received honorarium, speakers fee and travel support from Nutricia and Abbott. Nestle Australia has also provided grant support to the National Health and Medical Research Council Centre of Research Excellence in Frailty and Healthy Aging.

Introduction: Bone loss in anorexia nervosa (AN) is multifactorial; its mechanisms are not yet clearly understood and may vary depending on disease duration and severity. To determine to what extent adipokines may be involved in the bone alterations found in anorexic patients, we evaluated plasma levels for leptin, adiponectin and Pref-1 against other clinical and biological parameters in a population of anorexic patients split according to weight and bone status., Methods: Plasma concentrations of leptin, total adiponectin, high molecular weight (HMW) adiponectin, and Pref-1 were measured. The ratio of HMW adiponectin to total adiponectin - HMW (percentage) - was calculated. We divided our population into 5 groups with different phenotypes characterizing the severity of the disease and/or the severity of bone involvement: 1 - Normal BMD and body mass index (BMI): recovery from AN; 2 - Osteopenia (-217kg/m 2 ; 3 - Osteopenia and BMI≤17kg/m 2 ; 4 - Osteoporosis (Z-score≤-2) and BMI>17kg/m 2 ; 5 - Osteoporosis and BMI≤17kg/m 2 ., Results: The study involved 80 anorexia nervosa patients. Mean BMI was 16.8±2.4kg/m 2 . No significant difference was found in total and HMW adiponectin plasma concentrations between the 5 groups. HMW (percentage) was significantly higher in group 5 compared to group 1. Leptin was significantly lower in groups 3 and 5 compared to the other groups. For the whole group femoral neck and hip BMD correlated negatively with total adiponectin and HMW adiponectin. No correlation was found between BMD (whatever the site) and plasma leptin. Multivariate analysis revealed that 2 factors - leptin and BMI - explained 10% of the variance in spine BMD. For femoral neck BMD, the 2 explanatory factors were BMI and total adiponectin which explained 14% of the variance in BMD. For total hip BMD, 27% of the variance in BMD was explained by 3 factors: leptin, BMI, and total adiponectin., Conclusion: Bone status in anorexia nervosa is mainly determined by BMI, leptin and adiponectin., (Copyright © 2018. Published by Elsevier Masson SAS.)

Purpose of Review: To review recent finding on MIC-1/GDF15 and re-evaluate it as a potential target for the therapy of anorexia/cachexia syndromes., Recent Findings: MIC-1/GDF15 consistently induces anorexia/cachexia in animal models. Its actions on brainstem feeding centers leads to anorexia, inducing prolonged undernutrition and consequent loss of both lean and fat mass. Epidemiological studies by multiple groups have linked substantially elevated serum levels of this cytokine to anorexia/cachexia syndromes in diverse diseases such as cancer, chronic renal and cardiac failure, and chronic obstructive lung disease. These elevated serum levels are similar to those required to induce this syndrome in animals. Recent identifications of its previously elusive receptor as GFRAL, has enhanced understanding of its biology and suggests that modulating the MIC-1/GDF15-GFRAL pathway may be a therapeutic target for anorexia/cachexia syndrome., Summary: Inhibiting MIC-1/GDF15 or its receptor GFRAL are high-value potential targets for treatment of anorexia/cachexia syndrome in patients whose elevated serum levels may justify its use.

Patients suffering anorexia nervosa (AN) become anhedonic, in other words, unable or unwilling to derive normal pleasures and avoid rewarding outcomes, most profoundly in food intake. The neurobiological underpinnings of anhedonia are likely to involve mesolimbic reward circuitry. We propose here that this circuitry and its involvement in AN can be investigated using the activity-based anorexia (ABA) rodent model that recapitulates many of the characteristics of the human condition, most notably rapid weight loss. Preference for sweetened water was used to assay hedonic processing in female Sprague-Dawley rats exposed to the ABA protocol, which involves free access to running wheels paired with time-limited access to food. This protocol uncovered a transient anhedonia in only one quarter of cases; however, exposure to running wheels alone was associated with a rapid aversion to sweetened water (F 1.833, 20.17  = 78.29, p < .0001), and time-limited food access alone did not impact preference (F 2.205, 24.25  = 0.305, p = .761). High levels of running wheel activity prior to the onset of food restriction increased susceptibility to body weight loss in ABA (F 10,196.129  = 2.069, p = .029) and food anticipatory activity predicted subsequent food intake only for rats that were resistant to body weight loss (r = 0.44, p = .001). These data are inconsistent with the hypothesis that anhedonia underscores the precipitous weight loss in ABA, however, they highlight the predictive nature of hyperactivity in susceptibility to the ABA paradigm. These results will help inform the neurobiological framework of ABA and provide insight into the mechanisms of reward relevant to feeding and weight loss., (Copyright © 2018 Elsevier Inc. All rights reserved.)