The loneliness factor in eating disorders: Implications for psychopathology and biological signatures.

OBJECTIVES: Eating disorders (ED) are severe psychiatric conditions. While the biological consequences of EDs are well established, including an increase in inflammatory biomarkers, the influence of psychological factors, such as loneliness, has only recently gained attention in research. Loneliness has been associated with more severe psychopathology in ED patients, while its association with inflammatory biomarkers has only been explored in the general population. For these reasons, we aimed to investigate any possible associations between psychological features, trauma, and inflammatory biomarkers with loneliness in people with ED. METHODS: This study examined the interaction between loneliness, eating psychopathology, and biological markers in people with EDs. A group of 97 female patients with various diagnoses of ED was assessed for loneliness, general and eating psychopathology, traumatic history during childhood, and clinical biomarkers such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and urinary-free cortisol (UFC). RESULTS: The results indicated that individuals with ED who reported moderate to severe loneliness also displayed greater general psychopathology (p = 0.001), weight concerns (p = 0.007), and physical neglect during childhood (p = 0.006). Furthermore, people with higher levels of loneliness also had higher inflammatory indexes (ESR p = 0.001, CRP p = 0.027) and were positively correlated with markers of stress reaction such as UFC (p < 0.05). CONCLUSION: The findings underscore the importance of considering loneliness in the assessment of individuals with an ED. We observed notable associations between loneliness and increased psychopathology (both general and specific to eating), as well as higher levels of inflammation and childhood physical neglect. Addressing loneliness may contribute to improving overall well-being and potentially support recovery. This consideration encompasses both psychological and physical factors that interplay in the clinical presentation of individuals.

Main role of fractal-like nature of conformational space in subdiffusion in proteins.

Protein dynamics involves a myriad of mechanical movements happening at different time and space scales, which make it highly complex. One of the less understood features of protein dynamics is subdiffusivity, defined as sublinear dependence between displacement and time. Here, we use all-atoms molecular dynamics (MD) simulations to directly interrogate an already well-established theory and demonstrate that subdiffusivity arises from the fractal nature of the network of metastable conformations over which the dynamics, thought of as a diffusion process, takes place.

CT colonography evaluation of the relationship between colon anatomy and diverticula.

OBJECTIVES: In this study, we aimed at investigating the relationship between diverticula and in vivo colonic features such as total colon length (TCL), using CTC. We also evaluated polyps, neoplastic lesions and the correlation among them. METHODS: This retrospective study considered a series of patients who underwent CTC in our Hospital from 2010 to 2018. We evaluated TCL, the length of each colon segments and sigmoid colon diameter using dedicated software. We verified the presence of diverticula, polyps and neoplasm and measured the number of diverticula using a five-point class scale, evaluating the colonic segments involved by the disease and the number of diverticula for each segment. A logistic regression model was used to analyse the relationship between diverticula and the patients' age, sigmoid colonic diameter and the length of each colonic segments. RESULTS: The population finally included 467 patients, 177 males and 290 females (average age of 67 ± 12; range 45-96). The mean TCL was 169 ± 25 cm (range 115-241 cm). Out of the 467, 323 patients (69%) had at least one analyse. The patients with diverticula had a mean TCL significantly shorter than patients without diverticula (164 ± 22 vs 181 ± 27 cm; p = 0.001). Among the different variables, sigmoid colon length, sigmoid colon diameter and patient's age were correlated with diverticula (p < 0.01). Otherwise there is no association among diverticula, polyps and neoplasm. CONCLUSIONS: The presence of colonic diverticula was significantly inversely correlated with TCL.The TCL was not significantly correlated with polyps and cancers. ADVANCES IN KNOWLEDGE: The presence of colonic diverticula was significantly inversely correlated with total colon length, and in particular they significantly decreased with increasing colon length; our observation could contribute to the comprehension of diverticula pathogenesis.

Percutaneous US-guided MWA of small liver HCC: predictors of outcome and risk factors for complications from a single center experience.

The aim of the present study was to identify predictors of outcome and complications in patients with small hepatocellular carcinoma (HCC) treated by percutaneous microwave ablation (MWA). Patients with non-previously treated small (≤ 3 cm) HCCs who underwent ultrasound (US)-guided percutaneous MWA between July 2016 and January 2019 were included. For each patient, the following variables were registered: age, sex, albumin, platelet count, INR/PT, PTT ratio, total bilirubin, liver status, etiology of liver disease, Child-Pugh classification, tumor dimension, margin, and hepatic segment, tumor subcapsular, perihilar or perivascular location, HCC focality, ascites. During follow-up, complications and outcomes were registered. Variables were then analyzed in relation to both outcomes and complications. 74 patients were included. Mean CT follow-up was 6.2 months (range 1-24 months). At least one complication occurred in 48% of patients, the majority being asymptomatic imaging findings not requiring intervention. One major complication was registered (duodenal perforation: 1.3%). The occurrence of complications was associated with HCC multifocality and abnormal INR/PT, duodenal wall edema with tumor dimension, portal vein thrombosis with Child Pugh score, perihepatic free fluid with abnormal platelet count and comorbidities. Incomplete response rate at 1 month was 18.9%. Local tumor progression and new HCC nodules rates were 13.5% and 27%, respectively. Incomplete response at 1 month was associated with both alcoholic etiology of liver disease and II segment tumor location, new HCC nodules with PBC. Despite the small series analyzed, significant factors related with complications and outcomes may be kept in mind when planning the best treatment for each patient.

Unifying view of mechanical and functional hotspots across class A GPCRs.

G protein-coupled receptors (GPCRs) are the largest superfamily of signaling proteins. Their activation process is accompanied by conformational changes that have not yet been fully uncovered. Here, we carry out a novel comparative analysis of internal structural fluctuations across a variety of receptors from class A GPCRs, which currently has the richest structural coverage. We infer the local mechanical couplings underpinning the receptors' functional dynamics and finally identify those amino acids whose virtual deletion causes a significant softening of the mechanical network. The relevance of these amino acids is demonstrated by their overlap with those known to be crucial for GPCR function, based on static structural criteria. The differences with the latter set allow us to identify those sites whose functional role is more clearly detected by considering dynamical and mechanical properties. Of these sites with a genuine mechanical/dynamical character, the top ranking is amino acid 7x52, a previously unexplored, and experimentally verifiable key site for GPCR conformational response to ligand binding.

The role of psychomotor activation in discriminating unipolar from bipolar disorders: a classification-tree analysis.

OBJECTIVE: Multiple studies indicate that bipolar disorders are often underrecognized, misdiagnosed, and incorrectly treated. The aim of the present report is to determine which combination of clinical, demographic, and psychopathological factors and corresponding cutoff scores best discriminate patients with unipolar disorder from those with bipolar disorders. METHOD: The study sample includes outpatients and inpatients (N = 1,158) participating in 5 studies carried out in the United States and Italy between October 2001 and March 2008, one of which was a randomized clinical trial. Diagnostic assessment was carried out with the SCID, which allows diagnoses to be made according to DSM-IV-TR criteria. Using an exploratory statistical approach based on a classification tree, we employed 5 mania spectrum factors and 6 depression spectrum factors derived from the Mood Spectrum Self-Report Instrument (MOODS-SR) in combination with demographic and clinical characteristics to discriminate participants with unipolar versus bipolar disorders. RESULTS: The psychomotor activation factor, assessing the presence of thought acceleration, distractibility, hyperactivity, and restlessness for 1 or more periods of at least 3 to 5 days in the lifetime, identified subgroups with an increasing likelihood of bipolar disorder diagnosis. Mixed instability and suicidality contributed to further subtyping the sample into mutually exclusive groups, characterized by a different likelihood of receiving a diagnosis of bipolar disorder. Of the demographic and clinical characteristics included in the analysis, only sex proved to be useful to improve the discrimination. CONCLUSIONS: The psychomotor activation factor proved to be the most potent discriminator of those with unipolar versus bipolar diagnoses. The items that constitute this factor, together with those that constitute the mixed instability, suicidality, and euphoria factors, might be useful in making the differential diagnosis.

Incidence and predictors of relapse during continuation treatment of major depression with SSRI, interpersonal psychotherapy, or their combination.

BACKGROUND: Despite the availability of many effective treatments, patients with major depression remain at risk for relapse following remission of a depressive episode. The aims of this report are to estimate the relapse rates associated with the acute treatment strategies employed in this study and to investigate demographic and clinical predictors of relapse. METHODS: The study sample includes 225 patients who entered the 6-month continuation treatment phase after remitting from an acute depressive episode. Treatment during the acute phase was interpersonal psychotherapy, SSRI (escitalopram), or the combination of the two when monotherapy did not lead to response. Relapse was defined by a Hamilton Depression Rating Scale score ≥15, confirmed by the diagnosis of major depression. The probability of relapsing was modeled using logistic regression. Three separate models were fit with subgroups of covariates. RESULTS: Of the 225 patients, 29 (12.9%) relapsed and 28 (12.4%) discontinued the protocol prematurely. The proportion of patients who relapsed among the group requiring combination treatment to achieve remission was three times as high as among patients who had remitted with monotherapy. In the final logistic regression model, older age, higher baseline HDRS scores, last month (residual) depressive mood spectrum factor score, and requiring combination treatment to achieve remission were each associated with an increased likelihood of relapse. CONCLUSIONS: Our results suggest that greater initial depression severity, greater difficulty in stabilizing symptoms, and presence of residual mood spectrum symptoms once remission is achieved are predictive of relapse. Risk of relapse is more likely as age increases, partly because aging confers lower resilience.

A robust and self-paced BCI system based on a four class SSVEP paradigm: algorithms and protocols for a high-transfer-rate direct brain communication.

In this paper, we present, with particular focus on the adopted processing and identification chain and protocol-related solutions, a whole self-paced brain-computer interface system based on a 4-class steady-state visual evoked potentials (SSVEPs) paradigm. The proposed system incorporates an automated spatial filtering technique centred on the common spatial patterns (CSPs) method, an autoscaled and effective signal features extraction which is used for providing an unsupervised biofeedback, and a robust self-paced classifier based on the discriminant analysis theory. The adopted operating protocol is structured in a screening, training, and testing phase aimed at collecting user-specific information regarding best stimulation frequencies, optimal sources identification, and overall system processing chain calibration in only a few minutes. The system, validated on 11 healthy/pathologic subjects, has proven to be reliable in terms of achievable communication speed (up to 70 bit/min) and very robust to false positive identifications.

Addressing the challenges of a cross-national investigation: lessons from the Pittsburgh-Pisa study of treatment-relevant phenotypes of unipolar depression.

BACKGROUND: To date, no cross-national RCT has addressed the mechanisms underlying the relative success of pharmacological and psychotherapeutic interventions for depression. A multi-site clinical trial that includes psychotherapy as one of the treatments presents numerous challenges related to cross-site consistency and communication. PURPOSE: This report describes how those challenges were met in the study "Depression: The Search for Treatment Relevant Phenotypes'', being carried out at the University of Pittsburgh and the University of Pisa, Italy. METHODS: Implementing the study required the investigators to address methodological and practical challenges related to the different requirements of the two Institutional Review Boards (IRBs), psychotherapy training, independent evaluator training, patient recruitment, development of common tools for data entry, quality control and generation of weekly reports of patient progress as well as establishing a similar clinical and research framework in two countries with substantially different health care systems. RESULTS: By having bilingual investigators and staff members who spent time at one another's sites, making use of frequent conference-call staff meetings and being flexible within the bounds of the sometimes contradictory requirements of the IRBs, the investigators were able to meet the human subjects protection requirements of both institutions, surmount language barriers to consistent therapist and evaluator training and develop common tools for study management. As a result, recruitment goals were met at both sites and retention rates were high. One instance of inconsistent implementation of the protocol was corrected within the first year. LIMITATIONS: This study was conducted in two Western cultures by researchers with long-standing collaboration. Our findings may not be generalizable to other countries or research settings. CONCLUSIONS: The implementation of a cross-national protocol and the adoption and maintenance of common procedures is possible when investigators are aware of the challenges this may present and are proactive in trying to address them.

Subthreshold mania as predictor of depression during interferon treatment in HCV+ patients without current or lifetime psychiatric disorders.

BACKGROUND: Depression is considered the most frequent interferon (IFN)-alpha-induced psychiatric disorder. However, other neuropsychiatric side effects of IFN treatment, such as irritability, anxiety, and manic episodes, are reported as well. We analyzed the impact of lifetime manic-hypomanic symptoms and anxiety on the development of depression in hepatitis-C-virus-infected subjects treated with two different types of IFN-alpha. METHODS: At baseline, subjects received thorough diagnostic assessment to exclude lifetime or current psychiatric symptoms. During treatment, subjects were administered interviewer-based and self-report instruments. RESULTS: Six (12%) of 49 individuals with a negative history of psychiatric disorders developed major depression during treatment with IFN. The onset of depression was significantly associated with the presence of lifetime subthreshold manic-hypomanic symptoms. Subjects exceeding manic threshold were more likely to develop depression than those below threshold (33.3% vs. 7.5%, P=.033). CONCLUSIONS: Our data suggest that individuals treated with IFN with no past history of psychiatric disorders are more likely to develop depression if they experienced subthreshold manic-hypomanic symptoms in their lifetime. These findings derive from an exploratory study and may have important implications for the prevention of IFN-induced depression if replicated in larger studies.

A Wearable Home BCI system: preliminary results with SSVEP protocol.

This paper presents and discusses the realization and the performances of a wearable system for EEG-based BCI applications. The system (called Kimera) consists of a two-layer hardware architecture (the wireless acquisition and transmission board based on a Bluetooth ® ARM chip, and a low power miniaturized biosignal acquisition analog front end) together with a software suite (called Bellerophonte) for the Graphic User Interface management, protocol execution, data recording, transmission and processing. The implemented BCI system was based on the SSVEP protocol, applied to a two state selection by using standards display/monitor with a couple of high efficiency LEDs. The frequency features of the signal were computed and used in the intention detection. The BCI algorithm is based on a supervised classifier implemented through a multi-class Canonical Discriminant Analysis (CDA) with a continuous realtime feedback based on the mahalanobis distance parameter. Five healthy subjects participated in the first phase for a preliminary device validation. The obtained results are very interesting and promising, being lined out to the most recent performance reported in literature with a significant improvement both in system and in classification capabilities. The user-friendliness and low cost of the Kimera& Bellerophonte platform make it suitable for the development of home BCI applications.

Treatment of patients with tardive dystonia with olanzapine.

Tardive dystonia represents a complication of long-term use of neuroleptics and its treatment is often unsatisfactory. Atypical neuroleptics appear to improve tardive dystonia, and cases of tardive dystonia successfully managed with clozapine have been reported. The aim of this open-label video-blinded study was to evaluate the antidystonic efficacy of olanzapine, a new atypical neuroleptic with a low risk of agranulocytosis, in a group of four patients (one man and three women) with tardive cervical dystonia. They developed severe dystonia after several years of neuroleptic treatment. Extensive laboratory evaluations, as well as neurophysiologic and neuroradiologic investigations, were negative. Olanzapine was started at a dose of 5 mg/d and increased up to 7.5 mg/d. All patients were evaluated at baseline and after 2, 4, 8, and 12 weeks of treatment, using the Toronto Western Spasmodic Torticollis Rating Scale, and videotaped. At the end of the trial, the videotapes were reviewed and scored by a blind observer. A self-rating visual analog scale completed the disability evaluation.A moderate to marked improvement in dystonia was observed in all patients, and significant differences were observed in Toronto Western Spasmodic Torticollis Rating Scale scores and videotape ratings after 8 and 12 weeks of treatment compared with the basal values (p < 0.05). The average percentage of improvement in Toronto Western Spasmodic Torticollis Rating Scale score and visual analog scale was 26.4% and 42.6%, respectively. No serious side effects were reported at the maximum dosage reached (7.5 mg/d). This study warrants a larger controlled study to conclusively demonstrate the efficacy of olanzapine in tardive dystonia.