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BackgroundIn recent decades, the relationship between emotional disorders (i.e., depression and anxiety) and alterations in physiological functions (i.e., inflammation or metabolism) have been well supported. However, studies on a symptom-based approach have provided mixed results. Our study aims to gain insight into how subclinical statuses, featured by elevated depressive and/or anxious symptoms, may influence immunometabolic alterations in the concurrent relationship; and the development of metabolic diseases at 10-year follow-up: diabetes, hypertension and hypercholesterolemia.MethodsData from 758 Greek adults [394 men (aged 41 ± 10 years) and 364 women (aged 37 ± 12 years)] were used. Four groups were created according to the levels of depressive and anxiety symptoms: (1) control group (CG), (2) depressive group (DG), (3) anxiety group (AG) and (4) depressive and anxiety group (DAG). Multi-indicator multi-causes (MIMIC) modeling was used to estimate metabolic function and inflammatory response scores, on a wide selection of blood biomarkers. Finally, a binary logistic regression was carried out to study the influence of symptoms on the development of the aforementioned metabolic diseases on a 10-year follow-up.ResultsGroup membership was not associated with metabolic function score. Conversely, DAG membership was related with higher inflammatory response score (B = 0.20, CI95 = 0.01, 0.40), with respect to the CG (p < 0.05). Both age and sex were significant variables in the calculation of both scores. Regarding disease at 10-year follow-up effect, risk of developing diabetes, hypertension and hypercholesterolemia was associated with age and socioeconomic status. Moreover, DG membership was significant for diabetes risk (OR = 2.08, CI95 = 1.00, 4.22) and DAG for hypercholesterolemia (OR = 1.68, CI95 = 1.16, 2.43).LimitationsData on anti-inflammatory drugs and psychopharmacological medication were not collected in this study.ConclusionsElevated symptoms of depression and anxiety accounts for inflammatory alterations at concurrent relationship and a higher risk of 10-year follow-up metabolic diseases.

Many organisms avoid habitats posing risks of parasitism. Parasites are not generally conspicuous, however, which raises the question of what cues individuals use to detect parasitism risk. Here, we provide evidence in alpine newts (Ichthyosaura alpestris) that non-visual cues from parasite-exposed conspecifics inform habitat avoidance. Alpine newts breed in aquatic habitats and occasionally move among adjacent terrestrial habitat during breeding seasons. We completed experiments with newts whereby individuals had access to both habitats, and the aquatic habitats varied in prior occupancy by conspecifics with different histories of exposure to the parasitic skin fungus, Batrachochytrium dendrobatidis (Bd). Continuous filming of newt activity for 2 days provided little evidence that prior use of aquatic habitats by conspecifics, regardless of their Bd exposure history, immediately influenced newt habitat use. However, newts that encountered aquatic habitats used specifically by Bd-exposed conspecifics on day 1 spent less time aquatic on day 2, whereas other newts did not alter habitat use. Responses could have been elicited by cues generated by Bd stages on the conspecifics or, perhaps more likely, cues emitted by the conspecifics themselves. In either case, these observations suggest that newts use non-visual cues sourced from exposed conspecifics to detect Bd risk and that those cues cause newts to avoid aquatic habitats. Bd may therefore influence host behavior in early phases of interactions, and possibly before any contact with infectious stages is made, creating potential for non-consumptive effects.

IntroductionHigh-fat diet (HFD) consumption is known to trigger an inflammatory response in the brain that prompts the dysregulation of energy balance, leads to insulin and leptin resistance, and ultimately obesity. Obesity, at the same, has been related to cerebral magnetic resonance imaging (MRI) alterations, but the onset of HFD-induced neuroinflammation, however, has been principally reported on male rodents and by ex vivo methods, with the effects on females and the origin of MRI changes remaining unassessed.MethodsWe characterized the onset and evolution of obesity on male and female mice during standard or HFD administration by physiological markers and multiparametric MRI on four cerebral regions involved in appetite regulation and energy homeostasis. We investigated the effects of diet, time under diet, brain region and sex by identifying their significant contributions to sequential linear mixed-effects models, and obtained their regional neurochemical profiles by high-resolution magic angle spinning spectroscopy.ResultsMale mice developed an obese phenotype paralleled by fast increases in magnetization transfer ratio values, while females delayed the obesity progress and showed no MRI-signs of cerebral inflammation, but larger metabolic rearrangements on the neurochemical profile.DiscussionOur study reveals early MRI-detectable changes compatible with the development of HFD-induced cerebral cytotoxic inflammation on males but suggest the existence of compensatory metabolic adaptations on females that preclude the corresponding detection of MRI alterations.

Myelin basic protein (MBP) is thought to be one of the key autoantigens in multiple sclerosis (MS) development. A recent study described the association of the single nucleotide polymorphism (SNP) rs12959006, within the MBP gene, with a higher risk of relapse and worse prognosis. We aim at studying potential associations of this SNP to MS in an independent population. Clinical data of the first 5 years of the disease were collected retrospectively from 291 MS confirmed patients. MBP polymorphism rs12959006 was genotyped in all patients. Associations with EDSS, number of relapses and serology for Herpesvirus 6 (HHV-6) and Epstein Barr (EBV) viruses were studied. Lymphocyte activation measured by CD69 expression was also analyzed according to sex and rs12959006 genotype. The rs12959006 polymorphism contributed significantly to a higher number of relapses at 5 years after onset only in male patients (rs12959006∗TT β = 0.74 [0.36–1.09]; p = 7 × 10–5). Titers of anti-HHV6 IgG antibodies showed also a mild association with relapses, both in male and female patients (β = 0.01 [0.01–0.02]; p = 3.7 × 10–8). Both the genetic variation in MBP and HHV-6 infection aid in predicting a higher number of relapses during the first years of MS. The association described in MBP rs12959006∗T is exclusive to male patients.

The hypothalamus is the principal regulator of global energy balance, enclosing additionally essential neuronal centers for glucose-sensing and osmoregulation. Disturbances in these tightly regulated neuronal networks are thought to underlie the development of severe pandemic syndromes, including obesity and diabetes. In this work, we investigate in vivo the response of individual hypothalamic nuclei to the i.p. administration of glucose or vehicle solutions, using two groups of adult male C57BL6/J fasted mice and a combination of non-invasive T2∗-weighted and diffusion-weighted functional magnetic resonance imaging (fMRI) approaches. MRI parameters were assessed in both groups of animals before, during and in a post-stimulus phase, following the administration of glucose or vehicle solutions. Hypothalamic nuclei depicted different patterns of activation characterized by: (i) generalized glucose-induced increases of neuronal activation and perfusion-markers in the lateral hypothalamus, arcuate and dorsomedial nuclei, (ii) cellular shrinking events and decreases in microvascular blood flow in the dorsomedial, ventromedial and lateral hypothalamus, following the administration of vehicle solutions and (iii) increased neuronal activity markers and decreased microperfusion parameters in the ARC nuclei of vehicle-administered animals. Immunohistochemical studies performed after the post-stimulus phase confirmed the presence of c-Fos immunoreactive neurons in the arcuate nucleus (ARC) from both animal groups, with significantly higher numbers in the glucose-treated animals. Together, our results reveal that fMRI methods are able to detect in vivo diverse patterns of glucose or vehicle-induced effects in the different hypothalamic nuclei.

Objective: We assess the efficacy of the metabolomic profile from glioma biopsies in providing estimates of postsurgical Overall Survival in glioma patients.Methods: Tumor biopsies from 46 patients bearing gliomas, obtained neurosurgically in the period 1992–1998, were analyzed by high resolution 1H magnetic resonance spectroscopy (HR- 1H MRS), following retrospectively individual postsurgical Overall Survival up to 720 weeks.Results: The Overall Survival profile could be resolved in three groups; Short (shorter than 52 weeks, n = 19), Intermediate (between 53 and 364 weeks, n = 19) or Long (longer than 365 weeks, n = 8), respectively. Classical histopathological analysis assigned WHO grades II–IV to every biopsy but notably, some patients with low grade glioma depicted unexpectedly Short Overall Survival, while some patients with high grade glioma, presented unpredictably Long Overall Survival. To explore the reasons underlying these different responses, we analyzed HR-1H MRS spectra from acid extracts of the same biopsies, to characterize the metabolite patterns associated to OS predictions. Poor prognosis was found in biopsies with higher contents of alanine, acetate, glutamate, total choline, phosphorylcholine, and glycine, while more favorable prognosis was achieved in biopsies with larger contents of total creatine, glycerol-phosphorylcholine, and myo-inositol. We then implemented a multivariate analysis to identify hierarchically the influence of metabolomic biomarkers on OS predictions, using a Classification Regression Tree (CRT) approach. The CRT based in metabolomic biomarkers grew up to three branches and split into eight nodes, predicting correctly the outcome of 94.7% of the patients in the Short Overall Survival group, 78.9% of the patients in the Intermediate Overall Survival group, and 75% of the patients in the Long Overall Survival group, respectively.Conclusion: Present results indicate that metabolic profiling by HR-1H MRS improves the Overall Survival predictions derived exclusively from classical histopathological gradings, thus favoring more precise therapeutic decisions.

Background: Eosinophilic esophagitis (EoE) was first described in the 1990s, showing an increasing incidence and prevalence since then, being the leading cause of food impaction and the major cause of dysphagia. Probably, in a few years, EoE may no longer be considered a rare disease.Methods: This article discusses new aspects of the pathogenesis, symptoms, diagnosis, and treatment of EoE according to the last published guidelines.Results: The epidemiological studies indicate a multifactorial origin for EoE, where environmental and genetic factors take part. EoE affects both children and adults and it is frequently associated with atopic disease and IgE-mediated food allergies. In patients undergoing oral immunotherapy for desensitization from IgE-mediated food allergy the risk of developing EoE is 2.72%. Barrier dysfunction and T-helper 2 inflammation is considered to be pathogenetically important factors. There are different patterns of clinical presentation varying with age and can be masked by adaptation habits. Besides, symptoms do not usually correlate with histologic disease activity. The diagnostic criteria for EoE has evolved but mainly requires symptoms of esophageal dysfunction with histologic evidence of a peak value of at least 15 eosinophils per high-power field. Endoscopies have to be repeated in order to diagnose, monitor, and treat EoE. Treatment of EoE can be started either by drugs (PPIs and topical corticosteroids) or elimination diets. The multistage step-up elimination diet management approach of EoE is promising. Endoscopic dilation is used for patients with severe dysphagia/food impaction with inadequate response to anti-inflammatory treatment.Conclusions: Research in recent years has contributed to a better understanding of EoE's pathogenesis, genetic background, natural history, allergy workup, standardization in assessment of disease activity, evaluation of minimally invasive diagnostic tools, and new therapeutic approaches. However, several unmet needs are to be solved urgently, as finding a non-invasive disease-monitoring methods and biomarkers for routine practice, the development or new therapies, novel food allergy testing to detect triggering foods, drug, and doses required for initial therapy and safety issues with long-term maintenance therapy, amongst others. Besides, multidisciplinary management units of EoE, involving gastroenterologists, pediatricians, allergists, pathologists, dietitians, and ENT specialists are needed.