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In patients with multiple myeloma (MM) not-eligible for autologous haematopoietic cell transplantation (autoHCT), a simplified frailty index (SFI) identifies frail patients at risk for poor outcomes, but data are limited for transplant-eligible patients. In this registry-based retrospective study, we used an adapted version of the SFI to determine the prevalence of frailty in patients ≥65 years of age with MM undergoing autoHCT. Out of 5563 patients, 37.9% of patients were classified as frail and although they had increased non-relapse mortality (NRM) and inferior overall survival, the NRM at 100 days remained low (<2%) compared with non-frail patients., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Autologous peripheral blood stem cell (PBSC) transplantation is a standard treatment of multiple myeloma (MM), Hodgkin lymphoma and various subtypes of non-Hodgkin lymphoma. Cryopreservation of hematopoietic stem cells is standard practice that allows time for delivery of conditioning regimen prior to cell infusion. The aim of this Worldwide Network for Blood & Marrow Transplantation (WBMT) work was to assess existing evidence on non-cryopreserved autologous transplants through a systematic review/meta-analysis, to study feasibility and safety of this approach. We searched PubMed, Web of Science and SCOPUS for studies that utilized non-cryopreserved autologous PBSC transplantation. Identified literature was reviewed for information on mobilization, apheresis, preservation and viability, conditioning regimen, engraftment, response, and survival. Results highlight collective experience from 19 transplant centers (1686 patients), that performed autologous transplants using non-cryopreserved PBSCs. The mean of infused CD34+ was 5.6 × 10 6 /kg. Stem cell viability at transplantation was >90% in MM and >75% in lymphomas, after a storage time of 24-144 h at +4 °C. Mean time-to-neutrophil engraftment was 12 days and 15.3 days for platelets. Pooled proportion estimates of day 100 transplant-related mortality and graft failure were 1% and 0%, respectively. Non-cryopreservation of apheresed autologous PBSCs appears feasible and safe., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In this study, we compare outcomes of older patients with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) undergoing autologous hematopoietic cell transplantation (autoHCT) with either thiotepa/carmustine (BCNU/Thio) or thiotepa/busulfan/cyclophosphamide (TBC) conditioning. We used a postpublication dataset made available by the Center for International Blood and Marrow Transplantation Research including patients who were ≥65 years in age with PCNSL and underwent autoHCT as consolidation with TBC or BCNU/Thio conditioning. Out of 147 patients; n = 84 received BCNU/Thio and n = 63 received TBC. The 1-year NRM in the BCNU/Thio group was 10% versus 22% in the TBC group (P = .05) and the 2-year relapse rate was 5% versus 5%, respectively (P = 1.00). The 2-year progression-free survival (PFS) in the BCNU/Thio group was 85% versus 71% in the TBC group (P = .05) and 2-year overall survival (OS) was 86% versus 74% (P = .08). In a multivariable regression model, BCNU/Thio was associated with a lower risk for NRM (hazard ratio [HR], 0.33, P = .009), improved PFS (HR, 0.41, P = .008) and OS (HR, 0.37, P = .007), but there was no association with relapse risk. We found that in older adults with PCNSL undergoing consolidation with autoHCT, BCNU/Thio conditioning is associated with lower NRM and improved OS compared to TBC., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Lombardy represents the largest region of Italy by population, with almost 10 million residents, a dimension similar to a medium size country like Sweden or Belgium. The CML subcommittee of the Lombardy Hematology Network (REL-CML) conducted a study at the beginning of 2023. Prevalence was calculated by direct input from the 21 centers participating in REL-CML. Tyrosine Kinase Inhibitors (TKI) prescription records collected from the ARIA regional registry were used to estimate the number of CML patients followed in smaller centers not participating in REL-CML. A total of 2285 patients were registered, representing a prevalence of 0.23 ‰. These data were compared to a similar census conducted in 2005, at the beginning of the TKI era, where a prevalence of 0.029‰ was calculated. This indicates that an almost 10 times increase took place during this period of time. Imatinib represents the most frequently prescribed first-line TKI; its use in 2022 still represented 75% of total first line prescriptions. An increased concentration of the care of CML patients in specialized REL centers with a decreased dispersion of patients in small centers was also evident over this 18 year period of time. Nineteen % of patients discontinued treatment, highlighting persisting logistical and biological challenges; one some recommendations on CML management are included to this aim., (© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

In recent years, the online sale of kratom ( Mitragyna speciosa ), a Southeast Asian plant with both medicinal and psychoactive properties, has raised health concerns mainly due to the uncontrolled diffusion of adulterated kratom-related products. This exploratory study provides, for the first time, a snapshot of the availability of kratom products on the darknet which has been further validated by data searches on the surface web. A total of 231 listings of kratom across 23 darknet marketplaces were identified between March 2020 and October 2021. Among these, 40 were found actively sold across five markets by thirteen vendors. Listed items were mainly advertised as "safe" substitutes for medicinal products for the self-management of pain and other health conditions and offered in various forms (e.g., dry leaf powder, pills, capsules). Purchases were made using cryptocurrencies, with some vendors offering Pretty Good Privacy, and were shipped from Europe, Australia, the United States, and the United Kingdom. Goods sold by the same sellers also included illicit drugs and fraud-related products. Our study discovered a previously unknown diffusion of kratom products on the darknet mainly for self-treating a variety of medical conditions, suggesting the need for further research and immediate interventions to safeguard the well-being and health of kratom consumers.

Abstract: Recent studies demonstrating the feasibility of outpatient chimeric antigen receptor (CAR)-modified T-cell therapy administration are either restricted to CARs with 41BB costimulatory domains or use intensive at-home monitoring. We report outcomes of outpatient administration of all commercially available CD19- and B-cell maturation antigen (BCMA)-directed CAR T-cell therapy using a strategy of no remote at-home monitoring and an early cytokine release syndrome (CRS) intervention strategy. Patients with hematologic malignancies who received CAR T-cell therapy in the outpatient setting during 2022 to 2023 were included. Patients were seen daily in the cancer center day hospital for the first 7 to 10 days and then twice weekly through day 30. The primary end point was to determine 3-, 7-, and 30-day post-CAR T-cell infusion hospitalizations. Early CRS intervention involved administering tocilizumab as an outpatient for grade ≥1 CRS. Fifty-eight patients received outpatient CAR T-cell infusion (33 myeloma, 24 lymphoma, and 1 acute lymphoblastic leukemia). Of these, 17 (41%), 16 (38%), and 9 patients (21%) were admitted between days 0 to 3, 4 to 7, and 8 to 30 after CAR T-cell infusion, respectively. The most common reason for admission was CAR T-cell-related toxicities (33/42). Hospitalization was prevented in 15 of 35 patients who received tocilizumab for CRS as an outpatient. The nonrelapse mortality rates were 1.7% at 1 month and 3.4% at 6 months. In conclusion, we demonstrate that the administration of commercial CAR T-cell therapies in an outpatient setting is safe and feasible without intensive remote monitoring using an early CRS intervention strategy., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Supraventricular tachyarrhythmias (ST) are the most common cardiac arrhythmias. Little is known about the potential impact of demoralization, which is considered as partially distinct from depression, on the course of ST. A correct assessment of both depressive symptoms and demoralization appears relevant for the treatment of these cardiac diseases, potentially influencing their course., Methods: The sample consisted of 110 subjects affected by different ST, such as atrial fibrillation (AF), atrial flutter (AFL) and paroxysmal supraventricular tachycardia (PSVT). They all underwent a psychiatric evaluation; the Italian version of 9-item Patient Health Questionnaire (PHQ-9) and the Italian version of Demoralization Scale (DS) were administered. Descriptive statistics, pairwise comparisons, and correlational analysis have been implemented., Results: 26 individuals (23.6%) presented high levels of demoralization. Of these, 20 (76.9%) had a diagnosis of AF and six patients (23.1%) received a diagnosis of other ST. No differences in demoralization levels resulted in regard of sex, cardiac diagnoses and anticoagulant therapies. Amongst people with high levels of demoralization, 13 (50%) received no formal psychiatric diagnosis, and 12 (46.2%) showed moderate/severe depressive symptoms. Demoralization levels and PHQ-9 scores showed a significant positive correlation in the whole sample (r=0.550, p<0.001)., Discussion: The present study found that in a sample of patients suffering from ST, high levels of demoralization were more frequent than clinically relevant depressive symptoms. We propose that demoralization and depression show partially distinguished psychopathological features, potentially associated with different therapeutic trajectories., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Accinni, Maraone, Bonucci, D’Amato, Lavalle, Bersani, Severino and Pasquini.)

Background: Traumatic Brain Injury (TBI) represents one of the main causes of brain damage in young people and the elderly population with a very high rate of psycho-physical disability and death. TBI is characterized by extensive cell death, tissue damage and neuro-inflammation with a symptomatology that varies depending on the severity of the trauma from memory loss to a state of irreversible coma and death. Recently, preclinical studies on mouse models have demonstrated that the post-traumatic adult Neural Stem/Progenitor cells response could represent an excellent model to shed light on the neuro-reparative role of adult neurogenesis following damage. The cyclin-dependent kinase inhibitor p21 Waf1/Cip1 plays a pivotal role in modulating the quiescence/activation balance of adult Neural Stem Cells (aNSCs) and in restraining the proliferation progression of progenitor cells. Based on these considerations, the aim of this work is to evaluate how the conditional ablation of p21 Waf1/Cip1 in the aNSCS can alter the adult hippocampal neurogenesis in physiological and post-traumatic conditions., Methods: We designed a novel conditional p21 Waf1/Cip1 knock-out mouse model, in which the deletion of p21 Waf1/Cip1 (referred as p21) is temporally controlled and occurs in Nestin-positive aNSCs, following administration of Tamoxifen. This mouse model (referred as p21 cKO mice) was subjected to Controlled Cortical Impact to analyze how the deletion of p21 could influence the post-traumatic neurogenic response within the hippocampal niche., Results: The data demonstrates that the conditional deletion of p21 in the aNSCs induces a strong increase in activation of aNSCs as well as proliferation and differentiation of neural progenitors in the adult dentate gyrus of the hippocampus, resulting in an enhancement of neurogenesis and the hippocampal-dependent working memory. However, following traumatic brain injury, the increased neurogenic response of aNSCs in p21 cKO mice leads to a fast depletion of the aNSCs pool, followed by declined neurogenesis and impaired hippocampal functionality., Conclusions: These data demonstrate for the first time a fundamental role of p21 in modulating the post-traumatic hippocampal neurogenic response, by the regulation of the proliferative and differentiative steps of aNSCs/progenitor populations after brain damage., (© 2024. The Author(s).)

Odad3 gene loss-of-function mutation leads to Primary Ciliary Dyskinesia (PCD), a disease caused by motile cilia dysfunction. Previously, we demonstrated that knockout of the Odad3 gene in mice replicates several features of PCD, such as hydrocephalus, defects in left-right body symmetry, and male infertility, with a complete absence of sperm in the reproductive tract. The majority of Odad3 knockout animals die before sexual maturation due to severe hydrocephalus and failure to thrive, which precludes fertility studies. Here, we performed the expression analysis of the Odad3 gene during gonad development and in adult testes. We showed that Odad3 starts its expression during the first wave of spermatogenesis, specifically at the meiotic stage, and that its expression is restricted to the germ cells in the adult testes, suggesting that Odad3 plays a role in spermatozoa formation. Subsequently, we conditionally deleted the Odad3 gene in adult males and demonstrated that even partial ablation of the Odad3 gene leads to asthenoteratozoospermia with multiple morphological abnormalities of sperm flagella (MMAF) in mice. The analysis of the seminiferous tubules in Odad3 -deficient mice revealed defects in spermatogenesis with accumulation of seminiferous tubules at the spermiogenesis and spermiation phases. Furthermore, analysis of fertility in heterozygous Odad3 +/- knockout mice revealed a reduction in sperm count and motility as well as abnormal sperm morphology. Additionally, Odad3 +/- males exhibited a shorter fertile lifespan. Overall, these results suggest the important role of Odad3 and Odad3 gene dosage in male fertility. These findings may have an impact on the genetic and fertility counseling practice of PCD patients carrying Odad3 loss-of-function mutations.

Objective: Obsessive and compulsive symptoms (OCS) are cross-cutting psychopathological manifestations frequently detected in a variety of clinical and non-clinical samples. It has been suggested that impaired mentalization abilities and traumatic experiences during childhood may be relevant etiopathogenetic factors in the development of OCS. The purpose of the current study was to cross-sectionally assess these variables in a non-clinical sample, testing the mediational role of mentalization abilities in the association between childhood trauma (CT) and OCS., Method: 667 participants (488 females; mean age= 29.76 ± 11.87 years; age range: 18-80) answered a survey including the Childhood Trauma Questionnaire, the Mentalization Questionnaire and the Obsession-Compulsion subscale of the Brief Symptom Inventory., Results: The mediation model was significant for the total effect (p< .001), showing that CT was positively associated with OCS (95% CI: .006; .019) and that this association was mediated by reduced levels of mentalization capacity (95% CI: .003; .009). Such results were significant controlling for potential sociodemographic and clinical confounding variables., Conclusions: The findings contribute to elucidate the complex relationships between CT, mentalization capacity, and OCS, supporting the possibility that mentalization impairments, arising from CT, may affect top-down control mechanisms thus contributing to the development of OCS., Competing Interests: Competing interests: None., (© 2024 Giovanni Fioriti Editore s.r.l.)

Italy has a long history in beef production, with local breeds such as Marchigiana, Chianina, Romagnola, Maremmana, and Podolica which produce high-quality meat. Selection has improved meat production, precocity, growth ability and muscle development, but the genetic determinism of such traits is mostly unknown. Using 33K SNPs-data from young bulls (N = 4064) belonging to these five Italian breeds, we demonstrated that the Maremmana and Podolica rustic breeds are closely related, while the specialised Marchigiana, Chianina, and Romagnola breeds are more differentiated. A genome-wide association study for growth and muscle development traits (average daily gain during the performance test, weight at 1 year old, muscularity) was conducted in the five Italian breeds. Results indicated a region on chromosome 2, containing the myostatin gene (MSTN), which displayed significant genome-wide associations with muscularity in Marchigiana cattle, a breed in which the muscle hypertrophy phenotype is segregating. Moreover, a significant SNP on chromosome 14 was associated, in the Chianina breed, to muscularity. The identification of diverse genomic regions associated with conformation traits might increase our knowledge about the genomic basis of such traits in Italian beef cattle and, eventually, such information could be used to implement marker-assisted selection of young bulls tested in the performance test., (© 2024. The Author(s).)

Computational tools are revolutionizing our understanding and prediction of chemical reactivity by combining traditional data analysis techniques with new predictive models. These tools extract additional value from the reaction data corpus , but to effectively convert this value into actionable knowledge, domain specialists need to interact easily with the computer-generated output. In this application note, we demonstrate the capabilities of the open-source Python toolkit LinChemIn, which simplifies the manipulation of reaction networks and provides advanced functionality for working with synthetic routes. LinChemIn ensures chemical consistency when merging, editing, mining, and analyzing reaction networks. Its flexible input interface can process routes from various sources, including predictive models and expert input. The toolkit also efficiently extracts individual routes from the combined synthetic tree, identifying alternative paths and reaction combinations. By reducing the operational barrier to accessing and analyzing synthetic routes from multiple sources, LinChemIn facilitates a constructive interplay between artificial intelligence and human expertise.

Chimeric antigen receptor T-cell (CAR-T) therapy and bispecific T-cell engagers (BsAb) have emerged as promising immunotherapeutic modalities in patients with relapsed and/or refractory multiple myeloma (RRMM). However, there is limited data on the safety and efficacy of CAR-T and BsAb therapies in MM patients with a prior history of allogeneic transplantation (allo-HCT). Thirty-three MM patients with prior allo-HCT received CAR-T (n = 24) or BsAb (n = 9) therapy. CAR-T therapy demonstrated an ORR of 92% (67% ≥ CR), and 73% were MRD negative. BsAb therapy resulted in an ORR of 44% (44% ≥ CR) and 44% MRD negative. Safety analysis showed grade ≥3 AEs in 92% of CAR-T and 56% of BsAb patients. Cytokine release syndrome (CRS) occurred in 83% of CAR-T and 78% of BsAb recipients, while immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in three CAR-T patients. Infections of grade ≥3 were reported in 50% of CAR-T and 44% of BsAb recipients. No exacerbation of graft-versus-host disease occurred except in one BsAb recipient. CAR-T and BsAb therapies appear to be feasible, safe and provide deep and durable responses in MM patients with prior allo-HCT., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

The presence of carbapenem-resistant bacteria and carbapenem resistance genes (CRGs) in livestock is increasing. To evaluate the presence of carbapenemase-producing Enterobacteriaceae (CPE) and the main CRGs along swine food chains of the Marche Region (Central Italy), samples of faeces, feed, and animal-food derived products were collected from seven small/medium, medium, and large-scale pig farms. A total of 191 samples were analysed using a culture-dependent method, with the aim of isolating CPE. Isolates were analysed for their resistance to carbapenems using a modified Hodge test and the microdilution method for the minimum inhibitory concentration (MIC) determination. Moreover, the extraction of microbial DNA from each sample was performed to directly detect selected CRGs via qPCR. Among the 164 presumptive resistant isolates, only one strain from a liver sample, identified as Aeromonas veronii, had an ertapenem MIC of 256 μg/mL and carried a carbapenemase- (cphA) and a β-lactamase- (blaOXA-12) encoding genes. A low incidence of CRGs was found; only nine and four faecal samples tested positive for blaNDM-1 and blaOXA-48, respectively. Overall, the importance of monitoring CPE and CRGs in livestock and their food chains should be stressed to control all potential non-human CPE and CRGs reservoirs and to determine safety levels for human health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Garofalo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Primary retroperitoneal mucinous cystadenocarcinomas (PRMCs) are extremely rare tumors with limited understanding of their pathogenesis and biological behavior. We describe a case of a 50-year-old female patient who underwent surgical treatment. The patient had a history of previous surgeries for mesenteric mucinous cystadenoma, without evidence of recurrence. During routine abdominal ultrasound a new tumor was found. An abdomen magnetic resonance imaging was done and confirmed the presence of a cystic lesion in the right iliac fossa. After discussion in multidisciplinary committee, surgical complete resection of the tumor, along with bilateral adnexectomy, was performed successfully. Histopathological examination revealed a mucinous adenocarcinoma adjacent to a mucinous cystadenoma. Immunohistochemical analysis supported the diagnosis of a primary retroperitoneal lesion. The patient had an uneventful recovery and has remained disease-free during the two-year postoperative follow-up. PRMCs are challenging to diagnose preoperatively due to nonspecific symptoms. Surgical excision is the mainstay of treatment. The long-term prognosis and optimal therapeutic strategies require further investigation.

Introduction: Although therapeutic advances have improved results of cutaneous melanoma (CM), sentinel node-positive patients still have substantial risk to develop recurrent disease. We aim to investigate prognostic indicators associated with disease recurrence in positive-sentinel lymph node biopsy (SLNB) patients in a Latin-American population., Methods: Retrospective analysis of CM patients and positive-SLNB (2010-2020). Patients were divided into two groups: Group A (completion lymph node dissection, CLND), Group B (active surveillance, AS). Association of demographics, tumor data and SLN features with recurrence-free (RFS), distant metastases-free (DMFS) and melanoma specific (MSS) survival was analyzed., Results: Of 205 patients, 45 had a positive SLNB; 27(60%) belonged to Group A and 18(40%) to Group B. With a median follow-up of 36 months, 16 patients (12 in Group A and 4 in Group B) developed recurrent disease and estimated 5-yr RFS at any site was 60% (CI95%, 0.39 - 0.77) (44.5% in CLND group vs. 22% in AS group; P = 0.20). Estimated 5-yr DMFS and MSS: 65% (CI 95%, 0.44 - 0.81) and 73% (CI 95%, 0.59 - 0.89) with no differences between groups (p = 0.41 and 0.37, respectively). Independent predictors of poorer MSS were extranodal extension (ENE) and MaxSize > 2 mm of melanoma deposit in SLN. Factors independently associated with DMFS: Breslow depth > 2 mm, ENE, number (≥ 2) of positive SN and CLND status., Conclusion: Primary tumor and SN features in melanoma provide important prognostic information that help optimize prognosis and clinical management. AS is now the preferred approach for most positive-SLNB CM patients.

Background: Autistic symptoms represent a frequent feature in schizophrenia spectrum disorders (SSD). However, the prevalence and the cognitive and functional correlates of autistic symptoms in unaffected first-degree relatives of people with SSD remain to be assessed., Methods: A total of 342 unaffected first-degree relatives related to 247 outpatients with schizophrenia were recruited as part of the multicenter study of the Italian Network for Research on Psychoses (NIRP). Autistic features were measured with the PANSS Autism Severity Scale. Three groups of participants, defined on the presence and severity of autistic symptoms, were compared on a wide array of cognitive and functional measures., Results: Of the total sample, 44.9% presented autistic symptoms; 22.8% showed moderate levels of autistic symptoms, which can be observed in the majority of people with SSD. Participants with higher levels of autistic symptoms showed worse performance on Working Memory ( p  = 0.014) and Social Cognition ( p  = 0.025) domains and in the Global Cognition composite score ( p  = 0.008), as well as worse on functional capacity ( p  = 0.001), global psychosocial functioning ( p  < 0.001), real-world interpersonal relationships ( p  < 0.001), participation in community activities ( p  = 0.017), and work skills ( p  = 0.006)., Conclusions: A high prevalence of autistic symptoms was observed in first-degree relatives of people with SSD. Autistic symptoms severity showed a negative correlation with cognitive performance and functional outcomes also in this population and may represent a diagnostic and treatment target of considerable scientific and clinical interest in both patients and their first-degree relatives.

Patients with the 22q11.2 deletion syndrome (DS) show an increased risk of developing a psychotic illness lifetime. 22q11.2DS may represent a reliable model for studying the neurobiological underpinnings of schizophrenia. The study of social inference abilities in a genetic condition at high risk for psychosis, like 22q11.2DS, may shed light on the relationships between neurocognitive processes and patients' daily general functioning. The study sample consisted of 1736 participants, divided into four groups: 22q11.2DS patients with diagnosis of psychotic disorder (DEL SCZ, N = 20); 22q11.2DS subjects with no diagnosis of psychosis (DEL, N = 43); patients diagnosed with schizophrenia without 22q11.2DS (SCZ, N = 893); and healthy controls (HC, N = 780). Social cognition was assessed through The Awareness of Social Inference Test (TASIT) and general functioning through the Specific Levels of Functioning (SLoF) scale. We analysed data through regression analysis. The SCZ and DEL groups had similar levels of global functioning; they both had significantly lower SLoF Total scores than HC (p < .001); the DEL SCZ group showed significantly lower scores compared to the other groups (SCZ, p = .004; DEL, p = .003; HC, p < .001). A significant deficit in social cognition was observed in the three clinical groups. In the DEL SCZ and SCZ groups, TASIT scores significantly predicted global functioning (p < .05). Our findings of social cognition deficit in psychosis-prone patients point to the possible future adoption of rehabilitation programmes, like Social Skills Training and Cognitive Remediation, during premorbid stages of psychosis., (© 2023 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Mistrust is increasingly a daily reality of healthcare delivery worldwide. Yet it remains understudied as a form of relationship and a force in its own right. I address this gap through the ethnography of an Italian Emergency Department (ED), where conflicts have increased since the 2008 financial crisis. I show how mistrust does not result in a breakdown of healthcare interactions. Rather, mistrust is used in ambivalent care relationships to negotiate the roles, the risks, and the power that patients and staff are willing to entrust to others. Mistrust manifests in risk management strategies within relationships of "mistrustful dependency."

Ehlers-Danlos syndromes are a heterogeneous group of Heritable Connective Tissue Disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Among the different types, the hypermobile Ehlers-Danlos syndrome is the most frequent and includes generalized joint hypermobility as the major diagnostic criterion. Joint hypermobility in hypermobile Ehlers-Danlos syndrome is often associated with pain that does not always allow the use of effective pain-reducing treatments. Patients with hEDS constantly describe their pain in detail. Eighty-nine patients with hEDS diagnoses were recruited and evaluated. They were asked to describe their pain in writing. The texts were examined through Linguistic Inquiry and Word Count. Correlational analyses were conducted between pain perception and language. A comparison of high/low pain perception and the quality of metaphors was carried out. The results showed that language quality varies depending on how much pain is perceived. The greater the pain is perceived, the lesser the positive effects and the greater the negative effects and dehumanizing metaphors are being used. Moreover, a greater pain seems to be related to a verbal experience of greater isolation and less self-care. In conclusion, the use of metaphors is a useful tool for examining illness experience and may help clinicians in the rehabilitation program.

Planning and execution of voluntary movement depend on the contribution of distinct classes of neurons in primary motor and premotor areas. However, timing and pattern of activation of GABAergic cells during specific motor behaviors remain only partly understood. Here, we directly compared the response properties of putative pyramidal neurons (PNs) and GABAergic fast-spiking neurons (FSNs) during spontaneous licking and forelimb movements in male mice. Recordings centered on the face/mouth motor field of the anterolateral motor cortex (ALM) revealed that FSNs fire longer than PNs and earlier for licking, but not for forelimb movements. Computational analysis revealed that FSNs carry vastly more information than PNs about the onset of movement. While PNs differently modulate their discharge during distinct motor acts, most FSNs respond with a stereotyped increase in firing rate. Accordingly, the informational redundancy was greater among FSNs than PNs. Finally, optogenetic silencing of a subset of FSNs reduced spontaneous licking movement. These data suggest that a global rise of inhibition contributes to the initiation and execution of spontaneous motor actions. SIGNIFICANCE STATEMENT Our study contributes to clarifying the causal role of fast-spiking neurons (FSNs) in driving initiation and execution of specific, spontaneous movements. Within the face/mouth motor field of mice premotor cortex, FSNs fire before pyramidal neurons (PNs) with a specific activation pattern: they reach their peak of activity earlier than PNs during the initiation of licking, but not of forelimb, movements; duration of FSNs activity is also greater and exhibits less selectivity for the movement type, as compared with that of PNs. Accordingly, FSNs appear to carry more redundant information than PNs. Optogenetic silencing of FSNs reduced spontaneous licking movement, suggesting that FSNs contribute to the initiation and execution of specific spontaneous movements, possibly by sculpting response selectivity of nearby PNs., (Copyright © 2023 Giordano, Alia et al.)

Background: Obsessive-compulsive disorder (OCD) is a psychiatric syndrome characterized by unwanted and repetitive thoughts and repeated ritualistic compulsions for decreasing distress. Symptoms can cause severe distress and functional impairment. OCD affects 2% to 3% of the population and is ranked within the 10 leading neuropsychiatric causes of disability. Cortico-striatal-thalamo-cortical circuitry dysfunction has been implicated in OCD, including altered brain activation and connectivity. Complex glutamatergic signaling dysregulation within cortico-striatal circuitry has been proposed in OCD. Data obtained by several studies indicate reduced glutamatergic concentrations in the anterior cingulate cortex, combined with overactive glutamatergic signaling in the striatum and orbitofrontal cortex. A growing number of randomized controlled trials have assessed the utility of different glutamate-modulating drugs as augmentation medications or monotherapies for OCD, including refractory OCD. However, there are relevant variations among studies in terms of patients' treatment resistance, comorbidity, age, and gender. At present, 4 randomized controlled trials are available on the efficacy of memantine as an augmentation medication for refractory OCD., Objective: Our study's main purpose is to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of moderate to severe OCD. The study's second aim is to evaluate the effect of memantine on cognitive functions in patients with OCD. The third aim is to investigate if responses to memantine are modulated by variables such as gender, symptom subtypes, and the duration of untreated illness., Methods: Investigators intend to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of patients affected by severe refractory OCD. Participants will be rated via the Yale-Brown Obsessive Compulsive Scale at baseline and at 2, 4, 6, 8, 10, and 12 months. During the screening period and T4 and T6 follow-up visits, all participants will undergo an extensive neuropsychological evaluation. The 52-week study duration will consist of 4 distinct periods, including memantine titration and follow-up periods., Results: Recruitment has not yet started. The study will be conducted from June 2023 to December 2024. Results are expected to be available in January 2025. Throughout the slow-titration period, we will observe the minimum effective dose of memantine, and the follow-up procedure will detail its residual efficacy after drug withdrawal., Conclusions: The innovation of this research proposal is not limited to the evaluation of the efficacy and safety of memantine as an augmentation medication for OCD. We will also test if memantine acts as a pure antiobsessive medication or if memantine's ability to improve concentration and attention mimics an antiobsessive effect., Trial Registration: ClinicalTrials.gov NCT05015595; https://clinicaltrials.gov/ct2/show/NCT05015595., International Registered Report Identifier (irrid): PRR1-10.2196/39223., (©Annalisa Maraone, Alessandro Trebbastoni, Antonella Di Vita, Fabrizia D'Antonio, Carlo De Lena, Massimo Pasquini. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.05.2023.)

Objectives: Acute ischemic stroke (AIS) is an emergency requiring both fast and informative MR sequences. We aimed to assess the performance of an artificial intelligence-enhanced ultrafast (UF) protocol, compared to the reference protocol, in the AIS management., Methods: We included patients admitted in the emergency department for suspected AIS. Each patient underwent a 3-T MR protocol, including reference acquisitions of T2-FLAIR, DWI, and SWI (duration: 7 min 54 s) and their accelerated multishot EPI counterparts for T2-FLAIR and T2*, complemented by a single-shot EPI DWI (duration: 1 min 54 s). Two blinded neuroradiologists reviewed each dataset, assessing DWI (detection, location, number of acute lesions), FLAIR (vascular hyperintensities, visibility of acute lesions), and SWI/T2* (hemorrhagic transformation, thrombus). We compared the agreement between the diagnoses obtained with both protocols using kappa coefficients., Results: A total of 173 patients were included consecutively, of whom 80 with an AIS in DWI. We found an almost perfect agreement between the UF and reference protocols regarding the detection, distribution, number of AIS in DWI (κ = 0.98, 0.98, and 0.87 respectively), the presence of vascular hyperintensities, and the presence of a parenchymal hyperintensity in the AIS region in FLAIR (κ = 0.93 and 0.89 respectively). Agreement was substantial in T2*/SWI for thrombus detection, and fair for hemorrhagic transformation detection (κ = 0.64 and 0.38 respectively). Differential diagnoses were similarly detected by both protocols (κ = 1)., Conclusions: Our AI-enhanced ultrafast MRI protocol allowed an effective detection and characterization of both AIS and differential diagnoses in less than 2 min., Key Points: • The AI-enhanced ultrafast MRI protocol allowed an effective detection of acute stroke. • Characterization of stroke features with the UF protocol was equivalent to the reference sequences. • Differential diagnoses were detected similarly by the UF and reference protocols., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Interactions between childhood trauma (CT) and dissociation can contribute to psychiatric disturbances. We explored this phenomenon in relation to behavioral addictions (BAs) in a sample ( n  = 633) of young adults (age: 18-34 years). Self-report measures investigating CT, dissociation, and symptoms related to gambling disorder, internet gaming disorder, problematic social media use, exercise dependence and compulsive buying were used. Scales related to BAs were summarized into a single measure ("Total Behavioral Addiction Index" - TBAI) for inferential analyses. A model analyzing the direct and indirect effects of CT on TBAI through the mediation of pathological dissociation was performed, controlling for confounding factors. Measures on CT, dissociation, and TBAI were significantly associated with each other (all p  < .001). The total effect of CT on TBAI was significant (B = 0.063; CI: 0.045; 0.081); pathological dissociation significantly mediated such association (B = 0.023; CI: 0.013; 0.036). Our findings support the possibility that the interaction between CT and dissociation contributes to increase disturbances related to BAs.

Background: In asylum seekers and refugees, the frequency of mental disorders, such as depression, anxiety and post-traumatic stress disorder, is higher than the general population, but there is a lack of data on risk factors for the development of mental disorders in this population., Aim: This study investigated the risk factors for mental disorder development in a large group of asylum seekers and refugees resettled in high- and middle-income settings., Methods: Participant-level data from two randomized prevention studies involving asylum seekers and refugees resettled in Western European countries and in Turkey were pooled. The two studies randomized participants with psychological distress, but without a diagnosis of mental disorder, to the Self-Help Plus psychological intervention or enhanced care as usual. At baseline, exposure to potentially traumatic events was measured using the Harvard Trauma Questionnaire-part I, while psychological distress and depressive symptoms were assessed with the General Health Questionnaire and the Patient Health Questionnaire. After 3 and 6 months of follow-up, the proportion of participants who developed a mental disorder was calculated using the Mini International Neuropsychiatric Interview., Results: A total of 1,101 participants were included in the analysis. At 3- and 6-month follow-up the observed frequency of mental disorders was 13.51% (115/851) and 24.30% (207/852), respectively, while the frequency estimates after missing data imputation were 13.95% and 23.78%, respectively. After controlling for confounders, logistic regression analysis showed that participants with a lower education level ( p  = .034), a shorter duration of journey ( p  = .057) and arriving from countries with war-related contexts ( p  = .017), were more at risk of developing mental disorders. Psychological distress ( p  = .004), depression ( p  = .001) and exposure to potentially traumatic events ( p  = .020) were predictors of mental disorder development., Conclusions: This study identified several risk factors for the development of mental disorders in asylum seekers and refugees, some of which may be the target of risk reduction policies. The identification of asylum seekers and refugees at increased risk of mental disorders should guide the implementation of focused preventative psychological interventions.

Understanding a drug candidate's mechanism of action is crucial for its further development. However, kinetic schemes are often complex and multi-parametric, especially for proteins in oligomerization equilibria. Here, we demonstrate the use of particle swarm optimization (PSO) as a method to select between different sets of parameters that are too far apart in the parameter space to be found by conventional approaches. PSO is based upon the swarming of birds: each bird in the flock assesses multiple landing spots while at the same time sharing that information with its neighbors. We applied this approach to the kinetics of HSD17β13 enzyme inhibitors, which displayed unusually large thermal shifts. Thermal shift data for HSD17β13 indicated that the inhibitor shifted the oligomerization equilibrium toward the dimeric state. Validation of the PSO approach was provided by experimental mass photometry data. These results encourage further exploration of multi-parameter optimization algorithms as tools in drug discovery., Competing Interests: A.F., F.B., S.B., M.P., P.A., S.V., L.B., D.D., and M.R. are employees and shareholders of Exscientia plc but declare no further conflict of interest., (© 2023 The Authors.)

Background: To enhance and extend the knowledge about the global historical and phylogenetic relationships between Merino and Merino-derived breeds, 19 populations were genotyped with the OvineSNP50 BeadChip specifically for this study, while an additional 23 populations from the publicly available genotypes were retrieved. Three complementary statistical tests, Rsb (extended haplotype homozygosity between-populations), XP-EHH (cross-population extended haplotype homozygosity), and runs of homozygosity (ROH) islands were applied to identify genomic variants with potential impact on the adaptability of Merino genetic type in two contrasting climate zones., Results: The results indicate that a large part of the Merino's genetic relatedness and admixture patterns are explained by their genetic background and/or geographic origin, followed by local admixture. Multi-dimensional scaling, Neighbor-Net, Admixture, and TREEMIX analyses consistently provided evidence of the role of Australian, Rambouillet and German strains in the extensive gene introgression into the other Merino and Merino-derived breeds. The close relationship between Iberian Merinos and other South-western European breeds is consistent with the Iberian origin of the Merino genetic type, with traces from previous contributions of other Mediterranean stocks. Using Rsb and XP-EHH approaches, signatures of selection were detected spanning four genomic regions located on Ovis aries chromosomes (OAR) 1, 6 and 16, whereas two genomic regions on OAR6, that partially overlapped with the previous ones, were highlighted by ROH islands. Overall, the three approaches identified 106 candidate genes putatively under selection. Among them, genes related to immune response were identified via the gene interaction network. In addition, several candidate genes were found, such as LEKR1, LCORL, GHR, RBPJ, BMPR1B, PPARGC1A, and PRKAA1, related to morphological, growth and reproductive traits, adaptive thermogenesis, and hypoxia responses., Conclusions: To the best of our knowledge, this is the first comprehensive dataset that includes most of the Merino and Merino-derived sheep breeds raised in different regions of the world. The results provide an in-depth picture of the genetic makeup of the current Merino and Merino-derived breeds, highlighting the possible selection pressures associated with the combined effect of anthropic and environmental factors. The study underlines the importance of Merino genetic types as invaluable resources of possible adaptive diversity in the context of the occurring climate changes., (© 2023. The Author(s).)

As the number and type of regulatory authority-approved cellular therapies grow, clinical treatment centers face a heavy burden of duplicative documentation around initial qualification, ongoing auditing, and reporting, with overlapping requirements from each manufacturer to ensure safe use of their specific product, which in the United States are stipulated under individual Food and Drug Administration (FDA) Biologic License Applications. The American Society for Transplantation and Cellular Therapy (ASTCT) convened the 80/20 Task Force to consider challenges and potential solutions to these issues. The Task Force proposed that 80% of manufacturers' requirements for onboarding and ongoing operations of commercially available products could be standardized and streamlined. Task Force members interviewed dozens of stakeholders, including clinicians at large academic medical centers already using commercial and investigational immune effector cell (IEC) products, regulators, members of accrediting bodies and professional cellular therapy societies, and manufacturers of IEC therapies for oncologic indications. In November 2021, the Task Force organized and led virtual discussions in a public forum and at a private ASTCT 80/20 Workshop at the online AcCELLerate Forum, a cellular-therapy stakeholders' meeting organized by the ASTCT, National Marrow Donor Program (NMDP), and Center for International Blood and Marrow Transplant Research (CIBMTR). At the workshop, approximately 60 stakeholders worked to identify and prioritize common challenges in onboarding and maintenance of operations at clinical sites for commercial FDA-approved and future IEC therapies and ways to streamline the process. It was agreed that standardization would improve efficiency of onboarding, allowing more cost-effective, sustainable growth of approved IEC therapies at treatment centers, and facilitate wider access while maintaining safety and clinical success. This early but extensive survey of stakeholders resulted in 5 overarching suggestions for both established and emerging treatment centers: (1) eliminate duplication in accreditation and auditing of clinical sites; (2) define expectations for the education about and management of CAR-T therapy toxicities to potentially replace product-specific REMS programs; (3) streamline current REMS education, testing, and data reporting; (4) standardize information technology (IT) platforms supporting enrollment, clinical site-manufacturer communication, and logistics of maintaining chain of identity/chain of custody across multiple transportation steps; and (5) encourage the use of universal nomenclature by cell therapy manufacturers. Future discussions need to engage a broader range of stakeholders, including administrators, pharmacists, nurses, data coordinators, surgeons, pathologists, and those developing promising cellular therapies for solid tumors, as well as teams from smaller academic or community cancer center settings. Continued collaboration with stakeholders outside of clinical sites will include accrediting bodies/auditors, established and emerging cell therapy companies, software developers, professional societies, and the patients who receive these therapies. Active dialog with government regulators remains essential. Such joint efforts are critical as the number of IEC therapies for myriad oncologic and nononcologic indications grows., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: The increasing amount of chemical reaction data makes traditional ways to navigate its corpus less effective, while the demand for novel approaches and instruments is rising. Recent data science and machine learning techniques support the development of new ways to extract value from the available reaction data. On the one side, Computer-Aided Synthesis Planning tools can predict synthetic routes in a model-driven approach; on the other side, experimental routes can be extracted from the Network of Organic Chemistry, in which reaction data are linked in a network. In this context, the need to combine, compare and analyze synthetic routes generated by different sources arises naturally., Results: Here we present LinChemIn, a python toolkit that allows chemoinformatics operations on synthetic routes and reaction networks. Wrapping some third-party packages for handling graph arithmetic and chemoinformatics and implementing new data models and functionalities, LinChemIn allows the interconversion between data formats and data models and enables route-level analysis and operations, including route comparison and descriptors calculation. Object-Oriented Design principles inspire the software architecture, and the modules are structured to maximize code reusability and support code testing and refactoring. The code structure should facilitate external contributions, thus encouraging open and collaborative software development., Conclusions: The current version of LinChemIn allows users to combine synthetic routes generated from various tools and analyze them, and constitutes an open and extensible framework capable of incorporating contributions from the community and fostering scientific discussion. Our roadmap envisages the development of sophisticated metrics for routes evaluation, a multi-parameter scoring system, and the implementation of an entire "ecosystem" of functionalities operating on synthetic routes. LinChemIn is freely available at https://github.com/syngenta/linchemin., (© 2023. The Author(s).)

Purpose: Studies have shown significant associations of dissociative symptoms with both eating and addictive disorders; however, the different forms of dissociation have been relatively understudied in relation to food addiction (FA). The main aim of this study was to investigate the association of certain forms of dissociative experiences (i.e., absorption, detachment and compartmentalization) with FA symptoms in a nonclinical sample., Methods: Participants (N = 755; 543 women; age range: 18-65; mean age: 28.22 ± 9.99 years) were evaluated using self-report measures of FA, dissociation, eating disturbances, and general psychopathology., Results: Compartmentalization experiences (defined as pathological over-segregation of higher mental functions) were independently associated with FA symptoms (β = 0.174; p = 0.013; CI = [0.008; 0.064]) even when confounding factors were controlled for., Conclusion: This finding suggests that compartmentalization symptoms can have a role in the conceptualization of FA, with such two phenomena possibly sharing common pathogenic processes., Level of Evidence: Level V, cross-sectional descriptive study., (© 2023. The Author(s).)

Background: Despite advances in laparoscopic ventral hernia repair (LVHR) with the Intra-peritoneal onlay mesh technique (IPOM), recurrence continues to be a frequent postoperative complication. The aim of this study is to analyze the long-term recurrence rate in two series, by incorporating in IPOM technique the laparoscopic closure of the defect (IPOM plus). We also want to determine the ring size cut-off point from which the recurrence risk increases in IPOM technique and determine if the cut-off point is modified with IPOM plus technique., Methods: A comparative retrospective study was conducted analyzing patients who underwent LVHR. They were divided into 2 groups according to the surgical technique used: IPOM or IPOM plus. We determined in each group the cut-off point where the ring size presents a greater recurrence risk by calculating the better point of sensitivity/specificity relationship of the ROC curve., Results: Between 2007 and 2018, 286 patients underwent LVHR. The ROC curve for IPOM technique has shown a cut-off point of higher recurrence risk for rings larger than 63 cm 2 . While the ROC curve in IPOM plus group showed an increase in the cut-off point, with a higher recurrence risk in rings > 168 cm 2 . Overall median ring size was 30 cm 2 (range 4-225; IQR 16-61). However, when comparing the ring size between techniques we found a relatively larger size in IPOM plus (p: 0.013). The recurrence rate in the IPOM group was 19.51% while in the IPOM plus group was 3.57% (p: 0.005)., Conclusions: For standard LVHR with IPOM technique, the greatest recurrence risk occurs in rings larger than 63 cm 2 . The addition of ring closure (IPOM plus) was associated with a recurrence risk reduction, which occurs in rings larger than 168 cm 2 . These findings would allow expanding the indication for LVHR, using the IPOM plus technique., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Insomnia is commonly reported by cancer patients. Its multifaceted pathophysiology makes this symptom a complex challenge for the clinician, who should bear in mind the manifold world of causes and consequences of sleep disturbances in these patients and the importance of accurate treatment that should consider the frequent co-prescription of multiple medications. With our work, we aim to provide a tool to better master the treatment of this symptom in cancer patients, considering the gap between clinical and pharmacodynamic knowledge about the efficacy of different molecules and evidence-based prescribing., Methods: A narrative review of the studies investigating the pharmacological treatment of insomnia in cancer patients was conducted. Three hundred and seventy-six randomised controlled trials (RCTs), systematic reviews and meta-analyses were identified through PubMed. Only publications that investigated the efficacy of the pharmacological treatment of insomnia symptoms in cancer patient were considered., Results: Among the 376 publications that were individuated, fifteen studies were eligible for inclusion in the review and were described. Pharmacological treatments were outlined, with a broad look at specific clinical situations., Conclusions: The management of insomnia in cancer patients should be personalised, as is already the case for the treatment of pain, taking into account both the pathophysiology and the other medical treatments prescribed to these patients.

Allogeneic hematopoietic cell transplantation is a curative procedure for hematologic malignancies but is associated with a significant risk of non-relapse mortality (NRM). The Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) is a prognostic tool that discriminates this risk in all age groups. A recent survey of transplant physicians demonstrated that 79% of pediatric providers used the HCT-CI infrequently, and most reported concerns about its applicability in the younger population. We conducted a retrospective study using the Center for International Blood and Marrow Transplant Research database to examine the impact of expanded HCT-CI definitions on NRM in pediatric and young adult patients with hematologic malignancies. We included 5790 patients <40 years old receiving allogeneic transplants between 2008 and 2017 to examine broader definitions of comorbidities in the HCT-CI, including history of mechanical ventilation and fungal infection, estimated glomerular filtration rate, and body mass index (BMI) percentiles. Multivariable Fine-Gray models were created to determine the effect of each HCT-CI defining comorbidity and its modification on NRM and were used to develop 2 novel risk scores. We next developed the expanded HCT-CI for children and young adults (youth with malignancies; expanded ymHCT-CI), where 23% patients had an increased comorbidity score, compared to the HCT-CI. Comorbidities with hazard ratio < 1.2 were then removed to create the simplified HCT-CI for children and young adults (youth with malignancies; simplified ymHCT-CI), which demonstrated higher scores corresponded to a greater risk of NRM (P < .001). These novel comorbidity indexes with broader definitions are more relevant to pediatric and young adult patients, and prospective studies are needed to validate these in the younger patient population. It remains to be seen whether the development of these pediatric-specific and practical risk indexes increases their use by the pediatric transplant community., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Allogeneic hematopoietic cell transplantation (HCT) can cure many nonmalignant conditions, but concern for morbidity and mortality remains. To help physicians estimate patient-specific transplant mortality risk, the HCT comorbidity index (HCT-CI) is used. However, pediatric physicians use the HCT-CI less frequently than adult counterparts. We used the Center for International Blood and Marrow Transplant Research database to expand the HCT-CI comorbidity definitions to be more inclusive of children and adolescent and young adult (AYA) patients, adding history of mechanical ventilation, history of invasive fungal infection, assessment of chronic kidney disease (CKD) by estimated glomerular filtration rate, expanding the definition of obesity, and adding an underweight category. A total of 2815 children and AYAs (<40 years old) who received first allogeneic HCT for nonmalignant diseases from 2008 to 2017 were included to create an expanded youth nonmalignant HCT-CI (expanded ynHCT-CI) and a simplified non-malignant (simplified ynHCT-CI) HCT-CI. The expanded comorbidities occurred frequently-history of mechanical ventilation (9.6%), history of invasive fungal infection (5.9%), mild CKD (12.2%), moderate/severe CKD (2.1%), obesity (10.9%), and underweight (14.5%). Thirty-nine percent of patients had an increase in their comorbidity score using the expanded ynHCT-CI, leading to a redistribution of scores: ynHCT-CI score 0 (35%), 1-2 (36.4%), and ≥3 (28.6%). Patients with an increase in their comorbidity score had an increased hazard of mortality compared to those whose score remained the same (hazard ratio = 1.41; 95% confidence interval, 1.01-1.98). Modifications to the HCT-CI can benefit children and AYA patients with nonmalignant diseases, creating a risk assessment tool that is clinically relevant and better captures comorbidity in this younger population., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: The 22q11.2 Deletion Syndrome (22q11.2DS) is considered the most reliable biological model to study genetic vulnerability to schizophrenia. It appears useful to investigate neuroanatomical characteristics of people with 22q11.2DS compared to chronic schizophrenia and healthy controls., Methods: The sample consisted of 16 individuals with a diagnosis of schizophrenia for over 10 years (SCZ>10), 14 with a diagnosis for less than 10 years (SCZ≤10), 11 patients with 22q11.2DS with no diagnosis of psychotic disorder (DEL, n=11) and 19 healthy controls (HCs, n=19). Global intelligence (IQ) was evaluated for all subjects. Voxel-Based Morphometry (VBM) was employed to investigate potential differences between groups in grey matter volumes., Results: VBM located the most significant difference between SCZ and HCs in the left medial frontal gyrus, where SCZ>10 group showed a significant reduction of grey matter volume; the same cluster resulted significantly decreased in DEL group compared to HCs as well. Despite the extensive grey matter abnormalities observed in 22q11.2DS, the DEL group showed the only significant differences compared to the SCZ>10 group in the right lingual gyrus volumes., Conclusions: Despite the small sample, our study identified a common area of grey matter loss both in idiopathic schizophrenia and 22q11.2DS.

While violence against health care workers is being progressively recognised as a serious problem in the healthcare industry, it remains an under-studied area of enquiry in global public health. Anthropologists have long observed that violence toward patients is tied to institutional care practises in multiple ways, including repression, misrecognition and silencing. But research on health care staff's experience of violence is still lacking. This article aims to address this literature gap by providing research on the daily experience of vulnerability to violence that health care providers face during their work. To do so, the paper ethnographically explores the effects and perception of violence against health care workers in an emergency department (ED) in northern Italy, a place with a dramatic escalation of violent incidents. The article illustrates how the ED staff attended to the experience of suffering of potentially violent patients. In so doing, ED professionals shifted the responsibility of violence against them from violent individuals to violent structures shaping health inequities. The paper thus argues that ED professionals display a structural competence perspective when dealing with violence.

Purpose of Review: This work aims to provide an up-to-date review of the preclinical and clinical scientific literature on the therapeutic value of kratom to better understand the underlying mechanisms related to its use and inform future therapeutic applications., Recent Findings: A growing number of studies, mainly of cross-sectional nature, describe the widespread use of kratom by individuals to self-treat pain, psychiatric symptoms, and substance use disorders (SUD) outside a controlled clinical setting. Preclinical evidence suggests kratom is effective as an analgesic agent and might decrease the self-administration of other drugs. A randomized controlled trial has further supported kratom's therapeutic value as an analgesic. Investigations in nonclinical samples of long-term kratom users also indicate its therapeutic benefit in managing SUD symptoms (e.g., craving) and long-term or acute symptoms (e.g., withdrawal) for alcohol, opioids, and other illicit drugs. However, episodes of kratom-related intoxications have also been reported, often due to the adulteration and the contamination of kratom products mainly sold online or mixed toxicities when consumed outside clinical and traditional settings., Summary: Evidence on the clinical implications of kratom use is still limited and uncertain, with kratom research constantly evolving. Therefore, further randomized trials are needed., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2023.)

Background: Social cognition (SC) deficits and of its facial emotion expression (FEE) component have been described in 22q11.2 Deletion Syndrome (22q11.2DS), a high-risk for schizophrenia (SCZ) systemic genetic syndrome. Correlations between deficits in FEE skills and visual-spatial abilities in people with 22q11.2DS warrant investigation., Methods: The sample consisted of 37 patients with 22q11.2DS (DEL), 19 with 22q11.2DS and psychosis (DEL-SCZ), 23 with idiopathic SCZ, and 48 healthy controls. We assessed FEE through The Ekman 60 Faces test (EK-F60), visual-spatial skills with Raven's Standard Progressive Matrices, and symptom severity with the positive And negative syndrome scale. Statistics were conducted through multivariate analysis of variance and correlation analysis., Results: Patients with 22q11.2DS performed worse that the other groups in recognizing Surprise, Disgust, Rage, Fear, and Neutral expressions on the EK-F60. Recognition of Surprise and Disgust correlated positively with visual-spatial abilities in patients with 22q11.2DS; negative and cognitive symptoms correlated negatively with recognition of Sadness, Surprise, and Disgust., Conclusions: Patients with 22q11.2DS show impairments of both peripheral and central steps of the emotional recognition process, leading to SC deficits. The latter are present regardless of the presence of a full-blown psychosis., (© 2022 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Purpose: This research aims to analyze the relationship between emotional regulation and the symbolic process in autobiographical narratives of a group of individuals diagnosed with restrictive anorexia nervosa (AN), compared to a non-clinical group. The study is framed within multiple code theory (MCT) (Bucci, 1997; 2021), which considers mind-body integration. The purposes of this study are to investigate whether participants of the AN group will show greater alexithymia and emotional dysregulation than the non-clinical group; and whether the specific linguistic and symbolic features, such as somato-sensory words, affect words, and difficulty in the symbolizing process will predict the AN group., Methods: Twenty-nine female participants hospitalized with AN during an acute phase (mean age 19.8 ± 4.1) and 36 non-clinical female participants (mean age 21 ± 2.4) were selected through snow-ball sampling. The participants completed the Toronto Alexithymia Scale (TAS-20), the Profile of Mood of State (POMS), the Emotion Regulation Questionnaire (ERQ), and the Relationship Anecdotes Paradigm Interview (RAP). The RAP interview was audio-recorded and transcribed to apply the Referential Process (RP) Linguistic Measures. A T test for paired samples and a logistic binary regression was performed., Results: AN presented a significantly higher emotional dysregulation through the ERQ, TAS20 and POMS measures. Specifically, AN showed higher ER expression/suppression strategies, fewer functional cognitive strategies, higher alexithymia, and higher mood dysregulation. Specific linguistic features such as sensory-somatic, word affect, and difficulty in RP symbolizing predict the AN group (R2 = 0.349; χ2 = 27,929; df = 3; p = .001)., Conclusions: Emotional dysregulation is connected to AN symptoms and autobiographical narratives. The results can help a clinical assessment phase showing specific linguistic features in AN patients., Level of Evidence: Level II, controlled trial without randomization., (© 2022. The Author(s).)

Background: Insufficient effectiveness and a difficult tolerability profile of antidepressant drugs for the treatment of major depressive disorder (MDD) have been reported, and polyunsaturated fatty acids (PUFAs) have been posited as reliable therapeutic alternatives. The present study investigated the efficacy of omega-3 PUFAs as monotherapy for MDD., Methods: Two well-trained reviewers independently looked at the most significant randomized clinical trials (RCTs) from the PubMed database regarding PUFAs' employment in MDD compared to placebo; "major depressive disorder" and "omega-3 fatty acids," or "omega-6 fatty acids," or "polyunsaturated fatty acids (PUFA)," or " n  - 3 polyunsaturated fatty acids," or "eicosapentaenoic acid (EPA)," or "docosahexaenoic acid (DHA)" were used as the medical subject keywords., Results: Of the initial 96 potential RCTs based on titles and abstracts, 82 studies did not meet the inclusion criteria and were excluded. Six studies were excluded from the remaining 14 after full text revision. Eight RCTs met all the inclusion/exclusion criteria without reporting clear evidence of PUFAs' effectiveness in the treatment of MDD., Conclusion: At present, there is no opportunity to recommend the use of omega-3 PUFAs monotherapy for the treatment of MDD, although their supplementation may be useful in some specific populations., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Tommaso Accinni et al.)

According to the gender paradox in suicidology, an important sex difference has been reported with a preponderance of females in nonfatal suicidal behavior and a preponderance of males in completed suicide. Furthermore, females and males present different risk factors for suicide. The present study explored possible clinical differences between male and female psychiatric inpatients who had recently attempted suicide. The study included 177 adult inpatients hospitalized following a suicide attempt at the University Psychiatric Clinic, Sant'Andrea Hospital, Sapienza University of Rome. Clinical features assessed included psychiatric diagnosis, method and lethality of suicide attempts using the Risk/Rescue Rating Scale, the history of suicide attempts, age at onset of psychiatric illness, the presence of substance or alcohol use, and the length of stay. The results found that males and females differed in the method used for the suicide attempt, the scores for risk and rescue, and the length of hospitalization post-suicide attempt. In conclusion, identifying gender characteristics of patients at higher risk of suicide is important for implementing specific suicide prevention strategies and reducing the risk of future suicidal behavior in psychiatric inpatients.

Backgrounds: Individuals with chronic medical conditions are considered highly exposed to COVID-19 pandemic stress, but emerging evidence is demonstrating that resilience is common even among them. We aimed at identifying sustained resilient outcomes and their predictors in chronically ill people during the first year of the pandemic., Methods: This international 4-wave 1-year longitudinal online survey included items on socio-demographic characteristics, economic and living situation, lifestyle and habits, pandemic-related issues, and history of mental disorders. Adherence to and approval of imposed restrictions, trust in governments and in scientific community during the pandemic were also investigated. The following tools were administered: the Patient Health Questionnaire, the Generalized Anxiety Disorder scale, the PTSD Checklist DSM-5, the Oslo Social Support Scale, the Padua Inventory, and the Portrait Values Questionnaire., Results: One thousand fifty-two individuals reporting a chronic condition out of 8011 total participants from 13 countries were included in the study, and 965 had data available for the final model. The estimated probability of being "sustained-resilient" was 34%. Older male individuals, participants employed before and during the pandemic or with perceived social support were more likely to belong to the sustained-resilience group. Loneliness, a previous mental disorder, high hedonism, fear of COVID-19 contamination, concern for the health of loved ones, and non-approving pandemic restrictions were predictors of not-resilient outcomes in our sample., Conclusions: We found similarities and differences from established predictors of resilience and identified some new ones specific to pandemics. Further investigation is warranted and could inform the design of resilience-building interventions in people with chronic diseases., (© 2022. The Author(s).)

Background: Symptoms of depression are transdiagnostic heterogenous features frequently assessed in psychiatric disorders, that impact the response to first-line treatment and are associated with higher suicide risk. This study assessed whether severe mental pain could characterize a specific phenotype of severely depressed high-risk psychiatric patients. We also aimed to analyze differences in treatments administered., Methods: 2,297 adult patients (1,404 females and 893 males; mean age = 43.25 years, SD = 15.15) treated in several Italian psychiatric departments. Patients were assessed for psychiatric diagnoses, mental pain, symptoms of depression, hopelessness, and suicide risk., Results: More than 23% of the patients reported high depression symptomatology and high mental pain (HI DEP/HI PAIN). Compared to patients with lower symptoms of depression, HI DEP/HI PAIN is more frequent among females admitted to an inpatient department and is associated with higher hopelessness and suicide risk. In addition, HI DEP/HI PAIN (compared to both patients with lower symptoms of depression and patients with higher symptoms of depression but lower mental pain) were more frequently diagnosed in patients with personality disorders and had different treatments., Conclusions: Patients reporting severe symptoms of depression and high mental pain presented a mixture of particular dangerousness (high trait hopelessness and the presence of suicide ideation with more frequency and less controllability and previous suicide behaviors). The presence of severe mental pain may act synergically in expressing a clinical phenotype that is likewise treated with a more complex therapeutic regime than that administered to those experiencing symptoms of depression without mental pain.

Hematopoietic cell transplantation (HCT) has been successfully used to treat many malignant and nonmalignant conditions. As supportive care, donor selection, and treatment modalities evolve, documenting HCT trends and outcomes is critical. This report from the Center for International Blood and Marrow Transplant Research (CIBMTR) provides an update on current transplantation activity and survival rates in the United States. Additional data on the use and outcomes of HCT in the adolescent and young adult (AYA) population are included. AYA patients more frequently receive peripheral blood stem cell grafts than pediatric patients, which may reflect differences in practice in pediatric versus adult treatment centers. The proportions of donor types also differ those in adult and pediatric populations. Outcomes for patients in the AYA age range are similar to those of pediatric patients for acute myelogenous leukemia but worse for acute lymphoblastic leukemia. Outcomes for both leukemias are better in AYA patients compared with older adults. Comparing the time periods 2000 to 2009 and 2010 to 2019 revealed significant improvement in overall survival across the age spectrum, but the greatest improvement in the AYA age group., (Copyright © 2022. Published by Elsevier Inc.)

As cancer immunotherapies continue to expand across all areas of oncology, it is imperative to establish a standardized approach for defining and capturing clinically important toxicities, such as cytokine release syndrome (CRS). In this paper, we provide considerations for categorizing the variety of adverse events that may accompany CRS and for recognizing that presentations of CRS may differ among various immunotherapies (e.g., monoclonal antibodies, CAR T cell therapies and T cell engagers, which can include bispecific antibodies and other constructs). The goals of this paper are to ensure accurate and consistent identification of CRS in patients receiving immunotherapies in clinical studies to aid in reporting; enable more precise evaluation of the therapeutic risk-benefit profile and cross-study analyses; support evidence-based monitoring and management of important toxicities related to cancer immunotherapies; and improve patient care and outcomes. These efforts will become more important as the number and variety of molecular targets for immunotherapies broaden and as therapies with novel mechanisms continue to be developed., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Mental pain and exposure to maltreatment are significant risk factors for suicidal behavior. This study aimed to investigate whether mental pain could be associated with a recent suicide attempt and whether it could mediate the relationship between childhood traumatic experiences and suicide risk in psychiatric patients., Methods: A multicenter observational study was organized as a joint project with representatives of numerous mixed Italian academic and clinical settings. Between December 2017 and March 2020, batteries of tests were administered to patients, assessing suicidal ideation and behavior, mental pain (usual and worst mental pain in the past 15 days), depression, and childhood maltreatment., Results: A total of 2,137 psychiatric patients (1,313 women and 824 men) were included in the final sample, and 315 reported having attempted suicide in the last 3 months. Suicide attempters (compared to nonattempters) had higher odds of reporting worse mental pain (odds ratios [ORs] between 1.02 and 1.17; P  < .001) and suicidal intent with/without a specific plan (ORs between 11.57 and 11.77; P  < .001). They also had higher odds of having a personality disorder (borderline personality disorder: ORs between 2.65 and 3.01; P  < .001; other personality disorders: ORs between 1.96 and 2.28; P  < .01) and major depression (ORs between 1.62 and 1.70; P  < .05). Childhood trauma was associated with suicide risk directly (standardized effects between 0.06 and 0.07; P  < .01) and indirectly through mental pain (usual mental pain: standardized indirect effect = 0.11, P  < .001; worst mental pain in the past 15 days: standardized indirect effect = 0.12, P  < .001)., Conclusions: Mental pain constitutes a crucial framework for assessing the individual need for psychiatric help. Assessing mental pain allows identification of the main ingredient of suicide risk and puts the clinician in a strategic position to unlock some motives behind the wish to die. Further research is needed to learn if childhood adversities may interact with adult mental pain and thus foster suicide risk., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Suicide is a major public health problem, and it is urgent to investigate its underlying clinical and psychological concomitants. It has been suggested that low mentalization skills and problematic use of the internet (PUI) are factors that can play a role in suicidal behaviors. It is possible that poor mentalization skills contribute to leading to forms of PUI, which, in turn, can represent triggers for suicidal ideation (SI). We tested this hypothesis through a quantitative and cross-sectional study on a sample (n = 623) of young adults (age range: 18−34). Self-report measures investigating symptoms related to Social Media Addiction (SMA), Internet Gaming Disorder (IGD), mentalization capacity, and SI were used. A single mediation analysis with two mediators was carried out to evaluate the direct and indirect effects of mentalization on SI through the mediating role of SMA- and IGD-related symptoms, controlling for potential confounding factors (e.g., socio-demographic and addiction-related variables). The four explored variables were significantly associated with each other (all p < 0.001) across all subjects; the mediational model showed that the total effect of mentalization on SI was significant (B = −0.821, SE = 0.092 (95% CI: −1.001; −0.641)) and that both SMA- (B = −0.073, SE = 0.034 (95% CI: −0.145; −0.008)) and IGD-related symptoms (B = 0.046, SE = 0.027 (95% CI: −0.107; −0.001)) were significant mediators of such association. Our findings support the possibility that PUI severity plays a relevant role in mediating the association between low mentalization skills and levels of SI.