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With nearly 700 structures solved and a growing number of customized structure prediction algorithms being developed at a fast pace, G protein-coupled receptors (GPCRs) are an optimal test case for validating new approaches for the prediction of receptor active state and ligand bioactive conformation complexes. In this study, we leveraged the availability of hundreds of peptide GPCRs in the active state and both classical homology and artificial intelligence (AI) based protein modeling combined with docking and AI-based peptide structure prediction approaches to predict the nociceptin/orphanin FQ-NOP receptor active state complex (N/OFQ-NOPa). The In Silicogenerated hypotheses were validated via the design, synthesis, and pharmacological characterization of novel linear N/OFQ(1–13)-NH2analogues, leading to the discovery of a novel antagonist (3B; pKB= 6.63) bearing a single ring-constrained residue in place of the Gly2–Gly3motif of the N/OFQ message sequence (FGGF). While the experimental validation was ongoing, the availability of the Cryo-EM structure of the predicted complex enabled us to unambiguously validate the generated hypotheses. To the best of our knowledge, this is the first example of a peptide–GPCR complex predicted with atomistic accuracy (full complex Cα RMSD < 1.0 Å) and of the N/OFQ message moiety being successfully modified with a rigid scaffold.

Introduction:Dissecting cellulitis of the scalp (DCS) is a neutrophilic scarring alopecia typically presenting with pustules and fluctuant nodules, followed by suppuration and sinus tract formation. DCS is often associated with other diseases, such as hidradenitis suppurativa (HS) and conglobate acne (CA) which share similar pathogenetic mechanisms. Case Presentation:The authors report the case of a patient affected by a severe form of DCS, HS, and CA of the face. Previous treatments with isotretinoin, antibiotics, and adalimumab did not have a considerable efficacy. Off-label treatment with secukinumab showed a gradual improvement in the clinical presentation bringing to a reduction in the number of HS lesions and to an almost complete resolution of the inflammatory manifestations of DCS. Conclusion:Management of DCS is challenging and is typically based on retinoids which are considered the first line of treatment. The efficacy of biologic drugs, especially TNFα inhibitors, in severe and relapsing forms of DCS has been reported in recent literature. To our knowledge, only one case of isolated DCS treated with secukinumab is reported. No cases of concomitant DCS and HS, treated with this type of IL-17 inhibitor, have been described.

AbstractBackgroundThe clinical value of the identification of mood disorders in patients with acute coronary syndrome (ACS) is well established. However, assessment based on DSM criteria presents some limitations. This study aimed to provide an innovative strategy for evaluating the spectrum of mood disturbances in ACS.MethodsA total of 288 patients with a first episode of ACS underwent interviews based on DSM-IV-TR criteria (major depressive disorder, minor depression, and dysthymia), Diagnostic Criteria for Psychosomatic Research-DCPR (demoralization and type A behavior), and the Clinical Interview for Depression-CID. Additional self-report inventories (psychological well-being and distress) were administered. A total of 100 consecutive patients who satisfied criteria for DSM-IV-TR depression or DCPR demoralization were enrolled in a randomized controlled trial on a sequential combination of cognitive-behavioral and well-being therapy (CBT/WBT) vs clinical management (CM) and reassessed up to 30-month post-intervention.ResultsA total of 29.9% of patients showed a DSM-IV-TR depressive syndrome. Inclusion of demoralization and type A identified psychological distress in 58% of the sample. According to CID, reactivity to social environment, fatigue, depressed mood, and somatic anxiety were the most common symptoms. Somatic symptoms were significantly associated with DSM-IV-TR depression (fatigue and changes of appetite), whereas environmental reactivity with demoralization. Both depression and demoralization were associated with higher distress and lower well-being. Unlike CM, CBT/WBT was significantly associated with decrease of guilt, pessimism, fatigue, and early insomnia (CID).ConclusionsThe findings indicate that standard psychiatric approach identifies only a narrow part of mood disturbances affecting ACS patients. A more articulated assessment unravels specific clinical configurations that may entail prognostic and therapeutic implications.

Purpose: This study was set up to investigate the reliability, factorial, concurrent, and criterion validity of the Italian version of the 34-item Body Shape Questionnaire (BSQ) and its shorter versions. Methods: The study included 231 patients diagnosed with an eating disorder and 58 putatively healthy people (comparison sample). The Italian BSQ-34 was administered to participants together with the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale. Information on body mass index, caloric intake at baseline, and the number of episodes of self-vomiting per week was also acquired. Results: Cronbach’s alpha of BSQ-34 was 0.971 (95% confidence interval [CI] 0.965–0.976) in patients and 0.960 (0.944–0.974) in controls. Test–retest stability in patients (n= 69), measured with intraclass correlation coefficient, was 0.987 (0.983–0.991). Confirmatory factor analysis of the single-factor model yielded acceptable fit for all versions of the BSQ. On all BSQ versions, patients scored higher than controls with a large effect size when calculated as Cliff’s delta. BMI and mean caloric intake at baseline had a stronger association with BSQ-34 than levels of anxiety and depression. The analysis with the receiver operating characteristics (ROC) curve showed that the BSQ-34 distinguished patients with an eating disorder from controls with good accuracy (Area Under the Curve = 86.5; 95% CI 82.2–90.7). Conclusion: The Italian version of the BSQ possesses good psychometric properties, in both the long and the shortened versions, and it can be applied to measure body dissatisfaction for both clinical and research purposes. Level of evidence: Level III, Evidence obtained from well-designed cohort or case–control analytic studies.

Purpose: Anorexia nervosa (AN) is a life-threatening condition in which temperament, anxiety, depression, and core AN body-related psychopathology (drive for thinness, DT, and body dissatisfaction, BD) are intertwined. This relationship has not been to date disentangled; therefore, we performed a multiple mediation analysis aiming to quantify the effect of each component. Methods: An innovative multiple mediation statistical method has been applied to data from 184 inpatients with AN completing: Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire, Eating Disorders Inventory-2, State-Trait Anxiety Inventory, and Beck Depression Inventory. Results: All affective temperaments but the hyperthymic one were involved in the relationship with DT and BD. Only the anxious temperament had a significant unmediated direct effect on DT after the strictest correction for multiple comparisons, while the depressive temperament had a significant direct effect on DT at a less strict significance level. State anxiety was the strongest mediator of the link between affective temperament and core AN body-related psychopathology. Depression showed intermediate results while trait anxiety was not a significant mediator at all. Conclusion: Affective temperaments had a relevant impact on body-related core components of AN; however, a clear direct effect could be identified only for the anxious and depressive temperaments. Also, state anxiety was the strongest mediator thus entailing interesting implications in clinical practice. Level of evidence: V, cross-sectional study.

Purpose: Eating disorders (EDs) are mental illnesses with severe consequences and high mortality rates. Notwithstanding, EDs are considered a niche specialty making it often difficult for researchers to publish in high-impact journals. Subsequently, research on EDs receives less funding than other fields of psychiatry potentially slowing treatment progress. This study aimed to compare research vitality between EDs and schizophrenia focusing on: number and type of publications; top-cited articles; geographical distribution of top-ten publishing countries; journal distribution of scientific production as measured by bibliometric analysis; funded research and collaborations. Methods: We used the Scopus database, then we adopted the Bibliometrix R-package software with the web interface app Biblioshiny. We included in the analyses 1,916 papers on EDs and 6491 on schizophrenia. Results: The ED field published three times less than schizophrenia in top-ranking journals – with letters and notes particularly lacking—notwithstanding a comparable number of papers published per author. Only 50% of top-cited articles focused on EDs and a smaller pool of journals available for ED research (i.e., Zones 1 and 2 according to Bradford's law) emerged; journals publishing on EDs showed an overall lower rank compared to the schizophrenia field. Schizophrenia research was more geographically distributed and more funded; in contrast, a comparable collaboration index was found between the fields. Conclusion: These data show that research on EDs is currently marginalized and top-rank journals are seldom achievable by researchers in EDs. Such difficulties in research dissemination entail potentially serious repercussions on clinical advancements. Level of evidence: Level V: opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Background: The Reading the Mind in the Eyes Test (RMET) is listed in the National Institute of Mental Health’s Research Domain Criteria as a tool apt to measure the understanding of others’ mental states. People diagnosed with anorexia nervosa (AN) showed poorer performances on the RMET than healthy controls. Less data are available concerning other eating disorders. Methods: Systematic review of four major databases from inception to July 15, 2021 following the PRISMA guidelines. Meta-analysis of cross-sectional observational studies comparing the scores of the RMET between patients with eating disorders and age- and-gender matched control groups. Results: Out of 21 studies, we retrieved 29 independent samples of patients diagnosed with an eating disorder. Patients with active AN (n= 580) showed worse performances on the RMET than controls (n= 1019). Year of publication accounted for 61% of the (substantial: I2= 81%) heterogeneity in the meta-analysis. Earlier studies were more likely to find worse performances on the RMET of patients with active AN than later studies. Patients with bulimia nervosa (n= 185) performed poorly as compared to controls (n= 249), but the results were not statistically significant on the random-effect model. Obese patients with binge-eating disorder (n= 54) did not differ on the RMET from obese controls (n= 52). Patients with eating disorder not otherwise specified (n= 57) showed minimal differences compared to controls (n= 96). Study quality was good in six studies only. Conclusions: Patients with eating disorders do not suffer from an impaired understanding of others’ mental states, except for a still-to-be-identified subgroup of patients with active AN. Level of evidence: I, systematic review and meta-analysis.

Purpose: Orthorexia nervosa (ON) is an obsession for healthy and proper nutrition. Diagnostic criteria for ON are lacking and the psychopathology of ON is still a matter of debate in the clinical and scientific community. Our aim was to better understand the Italian clinical and scientific community’s opinion about ON. Methods: Anonymous online survey for Italian healthcare professionals, implemented with the REDCap platform and spread through a multicenter collaboration. Information was gathered about socio-demographic, educational and occupational features, as well as about experience in the diagnosis and treatment of EDs. The main part of the survey focused on ON and its features, classification and sociocultural correlates. Results: The survey was completed by 343 participants. Most responders (68.2%) considered ON as a variant of Eating Disorders (EDs), and 58.6% a possible prodromal phase or evolution of Anorexia Nervosa (AN). Most participants (68.5%) thought the next DSM should include a specific diagnostic category for ON, preferably in the EDs macro-category (82.1%). Moreover, 77.3% of responders thought that ON deserves more attention on behalf of researchers and clinicians, and that its treatment should be similar to that for EDs (60.9%). Participants thinking that ON should have its own diagnostic category in the next DSM edition had greater odds of being younger (p= 0.004) and of considering ON a prodromic phase of another ED, such as AN (p= 0.039). Discussion: Our survey suggests that the scientific community still seems split between those who consider ON as a separate disorder and those who do not. More research is still needed to better understand the construct of ON and its relationship with EDs; disadvantages and advantages of giving ON its own diagnosis should be balanced. Level of evidence: V (descriptive cohort study).

Purpose: Obesity unit attrition is frequent and contributes to treatment failure. Many studies evaluating attrition predictors were part of randomized trials, and different terminology and criteria were used in the engagement field. We aimed to investigate the factors potentially implicated in early (&lt; 12 weeks) and late (> 12 weeks) attrition from an obesity unit in a community setting Methods: This was a retrospective cohort study of 250 patients with obesity who were followed-up at our obesity unit. Our program included at least 6 meetings in 12 months. Sociodemographic and anthropometric data, and psychometric questionnaires were collected from all participants. Results: One-hundred thirty-four (53.6%) participants dropped out. Those individuals showed lower BMI, lower overall health status, and increased depression scores. In a multiple regression model, BMI (inversely; OR = 0.90; 95%CI 0.84–0.96) and depression score (directly, OR = 1.05; 1.00–1.10) were associated with attrition risk. Early dropouts (n = 47) had lower weights, smaller waist circumferences and worse mental health scores than late dropouts (n= 87) and more frequently lived alone. When compared to completers, early dropouts had lower weights, BMIs, waist circumferences, overall health and mental status scores, increased depression scores and percentage of individuals living alone. In a multiple regression, lower BMI (OR = 0.83; 0.75–0.92), lower mental status score (OR = 3.17; 1.17–8.59) and living alone (OR = 2.25; 1.02–4.97) were associated with early attrition risk. Conclusion: Lower BMI and increased depression score were associated with attrition. Early attrition was associated with lower weight, decreased mental well-being, and living alone. Individuals with these characteristics might need tailored approaches to enhance their engagement. Level of evidence: Level V, retrospective descriptive study.

El antibiograma evalúa la susceptibilidad de un patógeno a un fármaco. Los resultados se expresan en las categorías sensible, intermedio o resistente, y se analizan teniendo en cuenta los puntos de cohorte establecidos por los distintos comités. Sin embargo, la lectura del antibiograma va más allá de la determinación del perfil de sensibilidad bacteriano. Actualmente se propone la lectura interpretada del antibiograma, la cual provee una aproximación al mecanismo de resistencia de la bacteria, la detección de patrones inusuales y finalmente un cambio en la conducta terapéutica. Este abordaje implica 5 pilares: el paciente, conocimiento de la especie del microorganismo, los fenotipos de resistencia de este, la epidemiología local y los fármacos marcadores.

Purpose: In patients with obesity, micronutrient deficiencies have been reported both before and after bariatric surgery (BS). Obesity is a chronic pro-inflammatory status, and inflammation increases the risk of micronutrient malnutrition. Our objective was to assess in pre-BS patients the prevalence of micronutrient deficiencies and their correlation with blood values of C-reactive protein (CRP). Methods: Anthropometric data, instrumental examinations, and blood variables were centrally measured in the first 200 patients undergoing a pre-BS evaluation at the “Città della Salute e della Scienza” Hospital of Torino, starting from January 2018. Results: At least one micronutrient deficiency was present in 85.5% of pre-BS patients. Vitamin D deficiency was the most prevalent (74.5%), followed by folate (33.5%), iron (32%), calcium (13%), vitamin B12 (10%), and albumin (5.5%) deficiency. CRP values were high (> 5 mg/L) in 65% of the patients. These individuals showed increased rate of iron, folate, vitamin B12 deficiency, and a higher number of micronutrient deficiencies. In a multiple logistic regression model, increased CRP levels were significantly associated with deficiencies of vitamin B12 (OR = 5.84; 95% CI 1.25–27.2; p= 0.024), folate (OR = 4.02; 1.87–8.66; p&lt; 0.001), and with the presence of ≥ 2 micronutrient deficiencies (OR = 2.31; 1.21–4.42; p= 0.01). Conclusions: Micronutrient deficiencies are common in patients with severe obesity undergoing BS, especially when inflammation is present. In the presence of increased CRP values before surgery, it might be advisable to search for possible multiple micronutrient deficiencies.

The nociceptin/orphanin FQ (N/OFQ)/N/OFQ receptor (NOP) system controls different biological functions including pain and cough reflex. Mixed NOP/opioid receptor agonists elicit similar effects to strong opioids but with reduced side effects. In this work, 31 peptides with the general sequence [Tyr/Dmt1,Xaa5]N/OFQ(1-13)-NH2were synthesized and pharmacologically characterized for their action at human recombinant NOP/opioid receptors. The best results in terms of NOP versus mu opioid receptor potency were obtained by substituting both Tyr1and Thr5at the N-terminal portion of N/OFQ(1-13)-NH2with the noncanonical amino acid Dmt. [Dmt1,5]N/OFQ(1-13)-NH2has been identified as the most potent dual NOP/mu receptor peptide agonist so far described. Experimental data have been complemented by in silicostudies to shed light on the molecular mechanisms by which the peptide binds the active form of the mu receptor. Finally, the compound exerted antitussive effects in an in vivomodel of cough.

Neuropeptide S modulates important neurobiological functions including locomotion, anxiety, and drug abuse through interaction with its G protein-coupled receptor known as neuropeptide S receptor (NPSR). NPSR antagonists are potentially useful for the treatment of substance abuse disorders against which there is an urgent need for new effective therapeutic approaches. Potent NPSR antagonists in vitrohave been discovered which, however, require further optimization of their in vivopharmacological profile. This work describes a new series of NPSR antagonists of the oxazolo[3,4-a]pyrazine class. The guanidine derivative 16exhibited nanomolar activity in vitroand 5-fold improved potency in vivocompared to SHA-68, a reference pharmacological tool in this field. Compound 16can be considered a new tool for research studies on the translational potential of the NPSergic system. An in-depth molecular modeling investigation was also performed to gain new insights into the observed structure–activity relationships and provide an updated model of ligand/NPSR interactions.

Purpose: The COVID-19 pandemic restrictions had negative impact on the psychopathology of people with Eating Disorders (EDs). Factors involved in the vulnerability to stressful events have been under-investigated in this population. We aimed to assess which factors contributed to COVID-19-induced worsening in both general and specific psychopathology. Methods: Three-hundred and twelve people with a clinically defined diagnosis of an ED and undergoing a specialist ED treatment in different Italian ED services before the spreading of COVID-19 pandemic filled in an online survey. ED specific and general psychopathology changes after COVID-19 quarantine were retrospectively evaluated. Factors related to COVID-19 concerns (financial condition, fear of contagion, perceived social isolation/support, satisfaction in peer, family or sentimental relationships), illness duration and treatment-related variables (type of treatment provided, type of access to care, satisfaction with therapeutic relationships) were included as predicting factors in a structural equational model, which included latent variables consisting of general and ED psychopathology items as outcomes. Results: A perceived low quality of therapeutic relationships, fear of contagion and increased isolation were positively associated with psychopathology worsening. Reduced satisfaction with family and with friends’ relationships and reduced perceived social support were associated with ED and general symptoms deterioration, respectively. No significant effect emerged for intimate relationships, illness duration, economic condition and type of treatment. Conclusions: This study provides a comprehensive evaluation of clinical variables associated with psychopathological changes during the COVID-19 lockdown period highlighting potential risk and resilience factors and, possibly, informing treatment as well as prevention strategies for EDs. Level of evidence IV: Evidence obtained from multiple time series analysis such as case studies

Coronavirus disease (COVID-19) outbreak has profoundly changed the organization of hospital activities. We present our experience of reorganization of a nuclear medicine service settled in Northern Italy during the pandemic period of March and April 2020 characterized a government-mandated lockdown. Our service remained open during the whole period, performing approximately 80% of the routine practice, while maintaining it COVID-free despite the geographical context characterized by a high risk of infection. Reorganization involved all aspects of a nuclear medicine department, following local, national, and international guidelines for prioritizing patients, telephone and physical triages, deployment of appropriate personal protective equipment, social distancing, and logistic changes for scheduling examinations and disinfection procedures. All staff remained COVID-19–negative despite the unintentional admission of 4 patients who later turned out to be positive for the severe acute respiratory syndrome coronavirus 2. These adopted measures would serve as the basis for safe nuclear medicine services in the post–lockdown phase.

Several examples of nanosized therapeutic and imaging agents have been proposed to date, yet for most of them there is a low chance of clinical translation due to long-term in vivoretention and toxicity risks. The realization of nanoagents that can be removed from the body after use remains thus a great challenge. Here, we demonstrate that nonequilibrium gold–iron alloys behave as shape-morphing nanocrystals with the properties of self-degradable multifunctional nanomedicines. DFT calculations combined with mixing enthalpy-weighted alloying simulations predict that Au–Fe solid solutions can exhibit self-degradation in an aqueous environment if the Fe content exceeds a threshold that depends upon element topology in the nanocrystals. Exploiting a laser-assisted synthesis route, we experimentally confirm that nonequilibrium Au–Fe nanoalloys have a 4D behavior, that is, the ability to change shape, size, and structure over time, becoming ultrasmall Au-rich nanocrystals. In vivotests show the potential of these transformable Au–Fe nanoalloys as efficient multimodal contrast agents for magnetic resonance imaging and computed X-ray absorption tomography and further demonstrate their self-degradation over time, with a significant reduction of long-term accumulation in the body, when compared to benchmark gold or iron oxide contrast agents. Hence, Au–Fe alloy nanoparticles exhibiting 4D behavior can respond to the need for safe and degradable inorganic multifunctional nanomedicines required in clinical translation.

Nociceptin/orphanin FQ (N/OFQ) controls different biological functions viaselective stimulation of the N/OFQ peptide (NOP) receptor. The pleiotropic actions of N/OFQ may limit the development of NOP ligands as innovative drugs in different therapeutic areas. The pharmacological concept of functional selectivity (aka biased agonism) might be useful for amplifying beneficial actions and/or counteracting side effects. Thus, molecules with large bias factors toward G protein or β arrestin are required for investigating the translational value of NOP biased modulation. Herein, the biased behavior of a heterogeneous library of NOP-targeting peptide derivatives was evaluated in vitrowith the aim to provide possible insights into the structural determinants that govern the selective activation of G protein versusβ-arrestin. Our results demonstrate that lipidation of N/OFQ(1–13)-NH2is a useful strategy for obtaining G protein biased agonists for the NOP receptor.

The article present an excerpt from the archives of the periodical related to the arrival of German Cinema a bold new style during the 1920s and 1930s to American motion picture industry.

In this paper we report on a successful management of multiple bone metastases from differentiated thyroid cancer.

Nicotinamide riboside (NR), a NAD+precursor, has received attention due to several health benefits it has induced in experimental models. Studies in cultured cells, animals, and humans consistently show increased NAD+availability after NR supplementation, which is considered the only mode of NR action that leads to health benefits. In the present study, we show that a persistently low NR concentration (1 μM) in the growth medium of BEAS-2B human cells, grown in a monolayer, induces energy stress, which precedes a cellular NAD+increase after 192 h. NR concentrations greater than 1 μM under the specified conditions were cytotoxic in the 2D cell culture model, while all concentrations tested in the 3D cell culture model (BEAS-2B cell spheroids exposed to 1, 5, 10, and 50 μM NR) induced apoptosis. Shotgun proteomics revealed that NR modulated the abundance of proteins, agreeing with the observed effects on cellular energy metabolism and cell growth or survival. Energy stress may activate pathways that lead to health benefits such as cancer prevention. Accordingly, the premalignant 1198 cell line was more sensitive to NR cytotoxicity than the phenotypically normal parent BEAS-2B cell line. The role of a mild energy stress induced by low concentrations of NR in its beneficial effects deserves further investigation. On the other hand, strategies to increase the bioavailability of NR require attention to toxic effects that may arise.

The development of efficient and biocompatible contrast agents is particularly urgent for modern clinical surgery. Nanostructured materials raised great interest as contrast agents for different imaging techniques, for which essential features are high contrasts, and in the case of precise clinical surgery, minimization of the signal spatial dispersion when embedded in biological tissues. This study deals with the development of a multimodal contrast agent based on an injectable hydrogel nanocomposite containing a lanthanide-activated layered double hydroxide coupled to a biocompatible dye (indocyanine green), emitting in the first biological window. This novel nanostructured thermogelling hydrogel behaves as an efficient tissue marker for optical and magnetic resonance imaging because the particular formulation strongly limits its spatial diffusion in biological tissue by exploiting a simple injection. The synergistic combination of these properties permits to employ the hydrogel ink simultaneously for both optical and magnetic resonance imaging, easy monitoring of the biological target, and, at the same time, increasing the spatial resolution during a clinical surgery. The biocompatibility and excellent performance as contrast agents are very promising for possible use in image-guided surgery, which is currently one of the most challenging topics in clinical research.

Purpose: Some features of eating disorders (EDs) are often present in childhood before the onset of the ED. We developed a novel questionnaire to retrospectively capture such childhood traits. Methods: Focus groups were conducted at the University of California–San Diego, USA, and at the University of Turin, Italy. Three focus groups were conducted at each site, interviewing patients and parents to identify those traits that most commonly characterize childhood of patients with EDs. A preliminary version of the Premorbid Childhood Traits Questionnaire (PCT-Q) derived from these focus groups was then administered to 94 consecutive inpatients with an ED and to 286 healthy controls (HCs) at the Turin site. Also, 208 participants’ parents were enrolled as well; in fact, the PCT-Q was developed with both a proband and an informant version. Results: A 37-item final version of the PCT-Q was generated. Reliability analyses suggested acceptability for harm avoidance (HA), social phobia, alexithymia, interoceptive awareness (IA), and food obsessions. Inter-rater reliability ranged from fair to moderate. ED sufferers scored significantly higher than HCs on HA, social phobia, alexithymia, IA, and food obsessions. Conclusions: These findings support the possibility that premorbid traits contribute to a risk to develop an ED in some individuals. Level of evidence: III: case–control analytic study.

The general aim of the work was the validation of a new synthetic methodology designed for obtaining bifunctional heterotetrabranched peptide ligands. Applying an easily accessible synthetic route, we provided a small series of heteromultimeric peptide conjugates targeting the nociceptin/orphanin FQ (N/OFQ) peptide receptors (NOP) and mu opioid receptors. Among these, H-PWT1-N/OFQ-[Dmt1]dermorphin demonstrated a similar and high agonist potency at the NOP and mu receptors. The achieved results confirmed the robustness of the approach that is extremely versatile and virtually applicable to different peptide sequences whose pharmacological activity can be combined for generating dual acting multimeric compounds. These innovative pharmacological tools will be extremely helpful for investigating the consequences of the simultaneous activation and/or blockage of different peptidergic receptors.

To explore personological and psychopathological characteristics in individuals with obesity presenting for bariatric surgery compared with individuals with obesity not seeking bariatric surgery and healthy individuals to help clinician decision for surgical treatment. 379 participants [160 candidates for bariatric surgery (B) vs 219 not seeking bariatric surgery (NB)] and 304 healthy subjects (HS) were assessed with a battery of well-validated psychometric tests. The B group showed an intermediate personality profile between HS and NB. They also exhibited lower depressive and anxiety scores. Eating and attachment impairment were found lower in the B group with respect to the NB. Candidates for bariatric surgery display advantageous personality features and lower rates in psychopathology compared to other participants with obesity. These features may represent both traits facilitating the search for a bariatric treatment, and the preferred ones selected by the surgeon. Implications for clinicians addressing obese participants towards bariatric surgery and limitations concerning “impression management” are discussed. Level III, case-control analytic study.