Microbiota Sensing by Mincle-Syk Axis in Dendritic Cells Regulates Interleukin-17 and -22 Production and Promotes Intestinal Barrier Integrity.

Production of interleukin-17 (IL-17) and IL-22 by T helper 17 (Th17) cells and group 3 innate lymphoid cells (ILC3s) in response to the gut microbiota ensures maintenance of intestinal barrier function. Here, we examined the mechanisms whereby the immune system detects microbiota in the steady state. A Syk-kinase-coupled signaling pathway in dendritic cells (DCs) was critical for commensal-dependent production of IL-17 and IL-22 by CD4+ T cells. The Syk-coupled C-type lectin receptor Mincle detected mucosal-resident commensals in the Peyer's patches (PPs), triggered IL-6 and IL-23p19 expression, and thereby regulated function of intestinal Th17- and IL-17-secreting ILCs. Mice deficient in Mincle or with selective depletion of Syk in CD11c+ cells had impaired production of intestinal RegIIIγ and IgA and increased systemic translocation of gut microbiota. Consequently, Mincle deficiency led to liver inflammation and deregulated lipid metabolism. Thus, sensing of commensals by Mincle and Syk signaling in CD11c+ cells reinforces intestinal immune barrier and promotes host-microbiota mutualism, preventing systemic inflammation.

DNA methylation profiling of myelodysplastic syndromes and clinical response to azacitidine: A multicentre retrospective study.

Real-world data have revealed that a substantial portion of patients with myelodysplastic syndromes (MDS) does not respond to epigenetic therapy with hypomethylating agents (HMAs). The cellular and molecular reasons for this resistance to the demethylating agent and biomarkers that would be able to predict the treatment refractoriness are largely unknown. In this study, we shed light on this enigma by characterizing the epigenomic profiles of patients with MDS treated with azacitidine. Our approach provides a comprehensive view of the evolving DNA methylation architecture of the disease and holds great potential for advancing our understanding of MDS treatment responses to HMAs.

Identification of ß2 microglobulin, the product of B2M gene, as a Host Factor for Vaccinia Virus Infection by Genome-Wide CRISPR genetic screens.

Genome-wide genetic screens are powerful tools to identify genes that act as host factors of viruses. We have applied this technique to analyze the infection of HeLa cells by Vaccinia virus, in an attempt to find genes necessary for infection. Infection of cell populations harboring single gene inactivations resulted in no surviving cells, suggesting that no single gene knock-out was able to provide complete resistance to Vaccinia virus and thus allow cells to survive infection. In the absence of an absolute infection blockage, we explored if some gene inactivations could provide partial protection leading to a reduced probability of infection. Multiple experiments using modified screening procedures involving replication restricted viruses led to the identification of multiple genes whose inactivation potentially increase resistance to infection and therefore cell survival. As expected, significant gene hits were related to proteins known to act in virus entry, such as ITGB1 and AXL as well as genes belonging to their downstream related pathways. Additionally, we consistently found ß2-microglobulin, encoded by the B2M gene, among the screening top hits, a novel finding that was further explored. Inactivation of B2M resulted in 54% and 91% reduced VV infection efficiency in HeLa and HAP1 cell lines respectively. In the absence of B2M, while virus binding to the cells was unaffected, virus internalization and early gene expression were significantly diminished. These results point to ß2-microglobulin as a relevant factor in the Vaccinia virus entry process.

Sarcopenic obesity and the impact on bone health.

PURPOSE OF REVIEW: Sarcopenic obesity is a newly identified pathological entity defined by an increase in body fat mass with an associated sarcopenia, characterized by loss of muscle mass, strength, and function. Recently, the concomitant presence of skeletal alteration with sarcopenic obesity has been described leading to a new clinical entity defined osteosarcopenic obesity (OSO). Many studies have tried to unravel the metabolic complex mechanism leading to this clinical entity in order to understand the pathophysiology of this complex condition with the aim of posing an early diagnosis to improve the therapeutic approaches. The purpose of this narrative review is to highlight and revise recent studies on this issue. RECENT FINDINGS: Recent research in the field of OSO has highlighted the role of nutrition and physical activity in the development and management of these conditions. While molecular and cellular pathways remain partially understood, there is a growing focus on lifestyle interventions as key factors in reducing the impact of OSO. These studies emphasize the need for early diagnosis and appropriate therapeutic strategies to improve quality of life and decrease morbidity and mortality associated with OSO. SUMMARY: Although the pathophysiological pathways underlying OSO are not fully understood, the clinical implications underscore the need for expanded research in this field. This research is crucial for enabling early diagnosis and implementing effective therapeutic interventions, with the goal of reducing morbidity and mortality and enhancing quality of life.

Dieting, obsessive-compulsive thoughts, and orthorexia nervosa: Assessing the mediating role of worries about food through a structural equation model approach.

BACKGROUND: Orthorexia Nervosa (ON) is a condition characterized by an obsessive focus on healthy eating, inflexible dietary rules, and persistent preoccupations with food. Despite it has been recently the subject of increasingly relevant studies, little is known about the mechanisms that might foster ON symptoms. OBJECTIVE: This study used a structural equation modeling approach to test the mediating effect of thoughts, worries, and preoccupations about food on the relationship that eating disorders (EDs) attitudes (e.g., dieting) and obsessive-compulsive thoughts and symptoms have with ON in a large community sample. It was hypothesized that the effect of dieting and obsessive-compulsive thoughts and symptoms on ON would be partially mediated by the presence of thoughts, worries, and preoccupations about food. METHODS: Data from a cross-sectional sample of 1328 participants (females = 976) recruited from the general population were asked to fill in an online survey comprising the Eating Attitude Test-26 (EAT-26), the Obsessive-compulsive subscale of the Symptom Checklist-90 Revised (SCL-90R-OC) and the Orthorexia Scale-15 (ORTO-15). RESULTS: Structural equation models indicated that both obsessive-compulsive thoughts and symptoms and dieting had a direct effect on ON and that food preoccupation partially mediated these relationships. CONCLUSION: These findings provide novel insight into the nature of ON that could aid its conceptualization and treatment.

Neophobia, sensory experience and child's schemata contribute to food choices.

PURPOSE: The aim of the present review is to analyze dynamic interactions between nutrigenomics, environmental cues, and parental influence, which can all lead to children's neophobic reactions and its persistence in time. METHODS: We reviewed studies available on electronic databases, conducted on children aged from birth to 18 years. We also considered official websites of Italian Institutions, providing advice on healthy eating during infancy. RESULTS: Modern day societies are faced with an eating paradox, which has severe and ever-growing implications for health. In face of a wider availability of healthy foods, individuals instead often choose processed foods high in fat, salt and sugar content. Economic reasons surely influence consumers' access to foods. However, there is mounting evidence that food choices depend on the interplay between social learning and genetic predispositions (e.g., individual eating traits and food schemata). Neophobia, the behavioral avoidance of new foods, represents an interesting trait, which can significantly influence children's food refusal. Early sensory experiences and negative cognitive schemata, in the context of primary caregiver-child interactions, importantly contribute to the priming of children's food rejection. CONCLUSIONS: As neophobia strongly affects consumption of healthy foods, it will be relevant to rule definitively out its role in the genesis of maladaptive food choices and weight status in longitudinal studies tracking to adulthood and, in meanwhile, implement early in life effective social learning strategies, to reduce long-term effects of neophobia on dietary patterns and weight status. LEVEL OF EVIDENCE: Level II, controlled trials without randomization.

Post-voided residual urine ratio as a predictor of bladder outlet obstruction in men with lower urinary tract symptoms: development of a clinical nomogram.

PURPOSE: To confirm the correlation between post-void residual urine ratio (PVR-R) and BOO diagnosed by pressure-flow studies (PFS) in males with lower urinary tract symptoms (LUTS) and to develop a clinical nomogram. METHODS: A consecutive series of patients aged 45 years or older with non-neurogenic LUTS were prospectively enrolled. Patients underwent standard diagnostic assessment for BOO including International Prostatic Symptoms Score, uroflowmetry, urodynamic studies, suprapubic ultrasound of the prostate, and ultrasound measurements of the bladder wall thickness (BTW). PVR-R was defined as follows: PVR-R = (PVR/total Bladder Volume [BV]) × 100). Logistic regression analysis was used to investigate predictors of pathological bladder emptying (BOO) defined as Schafer > II. A nomogram to predict BOO based on the multivariable logistic regression model was then developed. RESULTS: Overall 335 patients were enrolled. Overall, 131/335 (40%) presented BOO on PFS. In a multivariable logistic age-adjusted regression model BWT (odds ratio [OR]: 2.21 per mm; 95% confidence interval [CI], 1.57-3.09; p = 0.001), PVR-R (OR: 1.02 per %; 95% CI, 1.01-1.03; p = 0.034) and prostate volume (OR: 0.97 per mL; 95% CI, 0.95-0.98; p = 0.001) were significant predictors for BOO. The model presented an accuracy of 0.82 and a clinical net benefit in the range of 10-90%. CONCLUSIONS: The present study confirms the important role of PVR-ratio in the prediction of BOO. For the first time, we present a clinical nomogram including PVR-ratio for the prediction of BOO.

Effects of the addition of insulin-transferrin-selenium (ITS) and/or metformin to the in vitro maturation of porcine oocytes on cytoplasmic maturation and embryo development.

CONTEXT: One of the main problems of porcine in vitro maturation (IVM) is incomplete cytoplasmatic maturation. Nuclear and cytoplasmic maturation will determine the future success of fertilisation and embryo development. Insulin-transferrin-selenium (ITS) has insulin-like and antioxidant effects, and metformin (M) is an insulin-sensitiser and antioxidant drug. AIMS: To assess the effects of adding ITS and/or M in porcine IVM media on cytoplasmic maturation and early embryo development. METHODS: Cumulus -oocyte complexes (COC) were IVM with M (10-4 M), ITS (0.1% v/v), M+ITS or no adding (Control). KEY RESULTS: ITS increased glucose consumption compared to Control and M (P <0.01), and M+ITS did not differ from ITS or Control. Redox balance: M, ITS and M+ITS increased glutathione (P <0.01) and decreased lipid peroxidation (P <0.005). The viability of cumulus cells by flow cytometry increased with M (P <0.005) and decreased with ITS (P <0.001); M+ITS did not differ from Control. After IVF, M increased penetration and decreased male pronucleus (P <0.05). Embryo development: cleavage increased with M (P <0.05), and blastocysts increased with ITS and M+ITS (P <0.05). The number of blastocyst cells increased with ITS (P <0.05). CONCLUSIONS: Adding ITS and M+ITS to porcine IVM media benefits embryo development to blastocysts, but ITS alone has better effects than M+ITS. IMPLICATIONS: ITS is an excellent tool to improve IVM and embryo development after IVF in pigs.

Impact of SARS-CoV2 infection on mortality and hospitalization in nursing home residents during the "Omicron era".

BACKGROUND: Widespread vaccination and emergence of less aggressive SARS-CoV2 variants may have blunted the unfavourable outcomes of COVID-19 in nursing home (NH) residents. We analysed the course of COVID-19 epidemic in NHs of Florence, Italy, during the "Omicron era" and investigated the independent effect of SARS-CoV2 infection on death and hospitalization risk. METHODS: Weekly SARS-CoV2 infection rates between November 2021 and March 2022 were calculated. Detailed clinical data were collected in a sample of NHs. RESULTS: Among 2044 residents, 667 SARS-CoV2 cases were confirmed. SARS-CoV2 incidence sharply increased during the Omicron era. Mortality rates did not differ between SARS-CoV2-positive (6.9%) and SARS-CoV2-negative residents (7.3%, p = 0.71). Chronic obstructive pulmonary disease and poor functional status, but not SARS-CoV2 infection independently predicted death and hospitalization. CONCLUSIONS: Despite that SARS-CoV2 incidence increased during the Omicron era, SARS-CoV2 infection was not a significant predictor of hospitalization and death in the NH setting.

Pediatric liver cirrhosis interventional procedures: from biopsy to transjugular intrahepatic portosystemic shunt.

Cirrhosis is a complex diffuse process whereby the architecture of the liver is replaced by abnormal nodules because of the presence of fibrosis. Several pediatric diseases such as extrahepatic portal vein obstruction, biliary atresia, alpha-1-antitrypsin deficit and autoimmune hepatitis can lead to cirrhosis and portal hypertension in children. In this article the authors describe interventional radiology procedures that can facilitate the diagnosis and treatment of diseases associated with liver cirrhosis and portal hypertension in the pediatric population. These procedures include image-guided liver biopsy, mesenteric-intrahepatic left portal vein shunts, balloon-occluded retrograde transvenous obliteration, transjugular intrahepatic portosystemic shunts and splenic embolization.

Isolated Orbital Apex Mucocele: A Case Study and Literature Review.

Isolated orbital mucocele without connection between the mass and paranasal sinuses is extremely rare and poorly understood. Literature review of these cases are very few and present more anteriorly in the orbit. Here, the authors present a 33-year-old female with an isolated left orbital apex mucocele without direct communication with the adjacent paranasal sinuses and other vital orbital structures. Endoscopic sinus surgery with marsupialization was performed, and an orbital mucocele was confirmed on histopathology. Although uncommon, previously reported cases, including our patient have remained disease free of recurrence for at least 1 year post-operatively.

Thermal and Morphological Analysis of Linear Low-Density Polyethylene Composites Containing d-limonene/ß-cyclodextrin for Active Food Packaging.

Composites made of linear low-density polyethylene (LLDPE) and ß-cyclodextrin/d-limonene inclusion complex (CD-lim) were prepared by melt extrusion to develop a novel food packaging material. Scanning electron microscopy evidenced a fairly good dispersion of the filler within the polymeric matrix. Infrared spectroscopy coupled with thermogravimetric analysis confirmed the presence of CD-lim in the composites, proving that the applied technology of including the essential oil within ß-CD cages allows for preventing a sizable loss of d-limonene despite a high temperature and shear applied upon extrusion processing. Moreover, the influence of the filler on the thermal properties of PE was assessed. It was found that the cyclodextrin-based inclusion complex significantly fastens the crystallization path of the polyethylene matrix with an improved crystallization rate of the PE/CD-lim composites compared to the neat polymer.

Effects of mealtime assistance in the nutritional rehabilitation of eating disorders.

PURPOSE: The aim of the study was to examine the effects of meal supervision, provided by health professionals, volunteers or family members, on anthropometric, nutritional, psychological, and behavioural outcomes in patients with eating disorders (EDs). METHODS: The present systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The last search was conducted in three databases (PubMed, Scopus, and the Cochrane library). Inclusion criteria considered paediatric and adult patients suffering from EDs, regardless of ethnicity, and treated in different therapeutic settings. The quality of the studies was evaluated using the Newcastle Ottawa Scale (NOS) adapted for cross-sectional studies and Version 2 of the Cochrane risk-of-bias assessment tool for randomised trials. RESULTS: 3282 articles were retrieved, out of which only 6 met the eligibility criteria. A marked heterogeneity in definitions and approaches to supervised mealtime was observed. This variability emerged in the methodologies used in the supervised meal, and in the reference values for the outcome measures that were used, such as the analysis of different parameters. Based on these observations, mealtime assistance provided to patients with EDs shows an overall positive effect on eating behaviour and dysfunctional attitudes. Future research should be prompted to provide a thorough definition of a structured procedure for meal assistance to be potentially and systematically included in the nutritional rehabilitation protocols for patients with EDs. LEVEL OF EVIDENCE: Level IV systematic reviews of uncontrolled trials.

A polymorphic variant in telomere maintenance is associated with worrisome features and high-risk stigmata development in IPMNs.

Intraductal papillary mucinous neoplasms (IPMNs) are nonobligatory precursor lesions of pancreatic ductal adenocarcinoma (PDAC). The identification of molecular biomarkers able to predict the risk of progression of IPMNs toward malignancy is largely lacking and sorely needed. Telomere length (TL) is associated with the susceptibility of developing cancers, including PDAC. Moreover, several PDAC risk factors have been shown to be associated with IPMN transition to malignancy. TL is genetically determined, and the aim of this study was to use 11 SNPs, alone or combined in a score (teloscore), to estimate the causal relation between genetically determined TL and IPMNs progression. For this purpose, 173 IPMN patients under surveillance were investigated. The teloscore did not show any correlation, however, we observed an association between PXK-rs6772228-A and an increased risk of IPMN transition to malignancy (HR = 3.17; 95%CI 1.47-6.84; P = 3.24 × 10-3). This effect was also observed in a validation cohort of 142 IPMNs even though the association was not statistically significant. The combined analysis was consistent showing an association between PXK-rs6772228-A and increased risk of progression. The A allele of this SNP is strongly associated with shorter LTL that in turn have been reported to be associated with increased risk of developing PDAC. These results clearly highlight the importance of looking for genetic variants as potential biomarkers in this setting in order to further our understanding the etiopathogenesis of PDAC and suggest that genetically determined TL might be an additional marker of IPMN prognosis.

Effect of PCSK9 inhibitors on remnant cholesterol and lipid residual risk: The LIPID-REAL registry.

BACKGROUND: Monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 55%, regardless of baseline treatments. Nonetheless, the effect of other lipid parameters, such as cholesterol remnants or, the so-called lipid residual risk, is unknown. METHODS: Multicenter and retrospective registry of patients treated with PCSK9 inhibitors from 14 different hospitals in Spain. Before and on-treatment lipid parameters were recorded. Residual lipid risk was estimated by (1) cholesterol remnants, (2) triglycerides/HDLc ratio (TG/HDL), (3) total cholesterol/HDLc (TC/HDL) and (4) the triglycerides-to-glucose index (TGGi). RESULTS: Six hundred fifty-two patients were analysed, mean age of 60.2 (9.63) years, 24.69% women and mean LDLc before treatment 149.24 (49.86) mg/dl. Median time to second blood determination was 187.5 days. On-treatment LDLc was 67.46 (45.78) mg/dl, which represented a 55% reduction. Significant reductions were observed for TG/HDL ratio, cholesterol remnants, TC/HDL ratio and TGGi. As consequence, 34.61% patients had LDLc <55 mg/dl and cholesterol remnants <30 mg/dl; additionally, 31.95% had cholesterol remnants <30 mg/dl but LDLc >55 mg/dl. Patients who had levels of cholesterol remnants >30 mg/dl before initiating the treatment with PCSK9 had higher reductions in cholesterol remnants, TG/HDL ratio, TC/HDL and TGGi. By contrast, no reduction differences were observed according to baseline LDLc (< or > the mean), age, gender or obesity. CONCLUSIONS: This multicenter and retrospective registry of real-world patients treated with PCSK9 inhibitors demonstrates a positive effect on cholesterol remnants and lipid residual risk beyond LDLc reductions.

p53 regulation by MDM2 contributes to self-renewal and differentiation of basal stem cells in mouse and human airway epithelium.

Proper physiological function of mammalian airways requires the differentiation of basal stem cells into secretory or multiciliated cells, among others. In addition, the self-renewal ability of these basal stem cells is crucial for developing a quick response to toxic agents in order to re-establish the epithelial barrier function of the airways. Although these epithelial missions are vital, little is known about those mechanism controlling airway epithelial regeneration in health and disease. p53 has been recently proposed as the guardian of homeostasis, promoting differentiation programs, and antagonizing a de-differentiation program. Here, we exploit mouse and human tracheal epithelial cell culture models to study the role of MDM2-p53 signaling in self-renewal and differentiation in the airway epithelium. We show that p53 protein regulation by MDM2 is crucial for basal stem cell differentiation and to keep proper cell proliferation. Therefore, we suggest that MDM2/p53 interaction modulation is a potential target to control regeneration of the mammalian airway epithelia without massively affecting the epithelium integrity and differentiation potential.

Sex Differences in Low-Density Lipoprotein Cholesterol Reduction With PCSK9 Inhibitors in Real-world Patients: The LIPID-REAL Registry.

BACKGROUND: Previous evidence supports that monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 50%-65%, regardless of baseline treatments. We tested possible sex differences in a multicentre registry of real-world patients treated with PCSK9 inhibitors. METHODS: This is a multicentre and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 18 different hospitals. Before-treatment and on-treatment LDLc and medical treatments, clinical indication, and clinical features were recorded. RESULTS: Women represented 24.69% of the cohort. The use of statins was similar in both sexes, but women were receiving most frequently ezetimibe. Before-treatment median LDLc was 135 (interquartile range 115-166) mg, and it was higher in women. The median on-treatment LDLc was 57 (interquartile range 38-84) mg/dL, which represented a mean 54.5% reduction. On-treatment LDLc was higher in women, and the mean LDLc reduction was lower in women (47.4% vs. 56.9%; P = 0.0002) receiving evolocumab or alirocumab. The percentage of patients who achieved ≥50% LDLc reduction was higher in men (71.36% vs. 57.62%; P = 0.002). According to LDLc before-treatment quartiles, LDLc reduction was statistically lower in women in the 2 highest and a significant interaction of women and baseline LDLc >135 mg/dL was observed. Women were negatively associated with lower rates of LDLc treatment target achievement (odds ratio: 0.31). Differences were also observed in women with body mas index >25 kg/m2. Only 14 patients (2.14%) presented side effects. CONCLUSIONS: This multicentre and retrospective registry of real-world patients treated with PCSK9 inhibitors highlights significant gender differences in LDLc reduction.

Ensemble deep learning for the prediction of proficiency at a virtual simulator for robot-assisted surgery.

BACKGROUND: Artificial intelligence (AI) has the potential to enhance patient safety in surgery, and all its aspects, including education and training, will derive considerable benefit from AI. In the present study, deep-learning models were used to predict the rates of proficiency acquisition in robot-assisted surgery (RAS), thereby providing surgical programs directors information on the levels of the innate ability of trainees to facilitate the implementation of flexible personalized training. METHODS: 176 medical students, without prior experience with surgical simulators, were trained to reach proficiency in five tasks on a virtual simulator for RAS. Ensemble deep neural networks (DNN) models were developed and compared with other ensemble AI algorithms, i.e., random forests and gradient boosted regression trees (GBRT). RESULTS: DNN models achieved a higher accuracy than random forests and GBRT in predicting time to proficiency, 0.84 vs. 0.70 and 0.77, respectively (Peg board 2), 0.83 vs. 0.79 and 0.78 (Ring walk 2), 0.81 vs 0.81 and 0.80 (Match board 1), 0.79 vs. 0.75 and 0.71 (Ring and rail 2), and 0.87 vs. 0.86 and 0.84 (Thread the rings 2). Ensemble DNN models outperformed random forests and GBRT in predicting number of attempts to proficiency, with an accuracy of 0.87 vs. 0.86 and 0.83, respectively (Peg board 2), 0.89 vs. 0.88 and 0.89 (Ring walk 2), 0.91 vs. 0.89 and 0.89 (Match board 1), 0.89 vs. 0.87 and 0.83 (Ring and rail 2), and 0.96 vs. 0.94 and 0.94 (Thread the rings 2). CONCLUSIONS: Ensemble DNN models can identify at an early stage the acquisition rates of surgical technical proficiency of trainees and identify those struggling to reach the required expected proficiency level.

Disruption of IRE1α through its kinase domain attenuates multiple myeloma.

Multiple myeloma (MM) arises from malignant immunoglobulin (Ig)-secreting plasma cells and remains an incurable, often lethal disease despite therapeutic advances. The unfolded-protein response sensor IRE1α supports protein secretion by deploying a kinase-endoribonuclease module to activate the transcription factor XBP1s. MM cells may co-opt the IRE1α-XBP1s pathway; however, the validity of IRE1α as a potential MM therapeutic target is controversial. Genetic disruption of IRE1α or XBP1s, or pharmacologic IRE1α kinase inhibition, attenuated subcutaneous or orthometastatic growth of MM tumors in mice and augmented efficacy of two established frontline antimyeloma agents, bortezomib and lenalidomide. Mechanistically, IRE1α perturbation inhibited expression of key components of the endoplasmic reticulum-associated degradation machinery, as well as secretion of Ig light chains and of cytokines and chemokines known to promote MM growth. Selective IRE1α kinase inhibition reduced viability of CD138+ plasma cells while sparing CD138- cells derived from bone marrows of newly diagnosed or posttreatment-relapsed MM patients, in both US- and European Union-based cohorts. Effective IRE1α inhibition preserved glucose-induced insulin secretion by pancreatic microislets and viability of primary hepatocytes in vitro, as well as normal tissue homeostasis in mice. These results establish a strong rationale for developing kinase-directed inhibitors of IRE1α for MM therapy.

Italian adaptation of the Düsseldorf Orthorexia Scale (I-DOS): psychometric properties and prevalence of orthorexia nervosa among an Italian sample.

PURPOSE: Orthorexia Nervosa (ON) is described as an extreme level of preoccupation around healthy eating, accompanied by restrictive eating behaviors. During the years, different assessment instruments have been developed. The aim of the study is to adapt into Italian the Düsseldorf Orthorexia Scale (I-DOS) and to test its psychometric properties. METHOD: A total sample of 422 volunteer university students (mean age = 20.70 ± 3.44, women 71.8%) completed a group of self-report questionnaires in large group sessions during their lecture time. The scales assessed ON (the I-DOS and the Orhto-15), disordered eating (Disordered Eating Questionnaire, DEQ), depressive symptoms (Beck Depression Inventory-II, BDI-II), obsessive and compulsive symptoms (Obsessive Compulsive Inventory-Revised, OCI-R), and self-reported height and weight. RESULTS: The fit of the unidimensional structure and reliability of the I-DOS was tested trough Confirmatory Factor Analysis (CFA) as well as its criterion validity computing correlation coefficients among Ortho-15, DEQ, BDI-II, OCI-R, BMI. Analyses confirmed the unidimensional structure of the I-DOS with acceptable or great fit indices (CFI = 0.984; TLI = 0.978; SRMR = 0.043; RMSEA = 0.076) and the strong internal consistency (α = 0.888). The correlations path supported the criterion validity of the scale. The estimated total prevalence of both ON and ON risk was 8.1%. CONCLUSIONS: This 10-item scale appears to be a valid and reliable measure to assess orthorexic behaviors and attitudes. LEVEL OF EVIDENCE: Level V, descriptive cross-sectional study.