INFN What Next: Ultra-relativistic Heavy-Ion Collisions

This document was prepared by the community that is active in Italy, within INFN (Istituto Nazionale di Fisica Nucleare), in the field of ultra-relativistic heavy-ion collisions. The experimental study of the phase diagram of strongly-interacting matter and of the Quark-Gluon Plasma (QGP) deconfined state will proceed, in the next 10-15 years, along two directions: the high-energy regime at RHIC and at the LHC, and the low-energy regime at FAIR, NICA, SPS and RHIC. The Italian community is strongly involved in the present and future programme of the ALICE experiment, the upgrade of which will open, in the 2020s, a new phase of high-precision characterisation of the QGP properties at the LHC. As a complement of this main activity, there is a growing interest in a possible future experiment at the SPS, which would target the search for the onset of deconfinement using dimuon measurements. On a longer timescale, the community looks with interest at the ongoing studies and discussions on a possible fixed-target programme using the LHC ion beams and on the Future Circular Collider.Comment: 99 pages, 56 figure

The Reasons for Unfinished Nursing Care during the COVID-19 Pandemic: An Integrative Review.

Background: The concept of unfinished nursing care (UNC) describes nursing interventions required by patients and families that nurses postpone or omit. UNC reasons have been documented; however, no studies have summarised the underlying factors triggering the UNC during the pandemic. Therefore, the aim was to synthesise the available studies exploring factors affecting UNC during a pandemic. Methods: We conducted an integrative review following Whittemore and Knafl's framework according to the Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. PubMed, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Scopus databases were searched for primary studies that collected data from 1 January 2020 to 1 May 2023. Both qualitative and quantitative studies assessing the reasons for UNC were eligible and evaluated in their quality using the Critical Appraisal Skills Programme and the Mixed Methods Appraisal Tool. Results: Four studies were included-three qualitative and one cross-sectional. The reasons for UNC have been documented at the following levels: (a) system (e.g., new healthcare system priorities); (b) unit (e.g., ineffective work processes); (c) nurse management (e.g., inadequate nurse manager's leadership); (d) nurse (e.g., nurses' attitudes, competences, performances); and (e) patient (increased demand for care). Conclusion: The reasons for UNC during the COVID-19 pandemic are different to those documented in the pre-pandemic times and reflect a pre-existing frailty of the National Health Service towards nursing care

Thymus transplantation for complete DiGeorge syndrome: European experience

Background: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). Methods: Twelve patients with cDGS were transplanted with allogeneic cultured thymus. Objective: To confirm and extend the results previously obtained in a single centre. Results: Two patients died of pre-existing viral infections without developing thymopoeisis and one late death occurred from autoimmune thrombocytopaenia. One infant suffered septic shock shortly after transplant resulting in graft loss and the need for a second transplant. Evidence of thymopoeisis developed from 5-6 months after transplantation in ten patients. The median (range) of circulating naïve CD4 counts (x10663 /L) were 44(11-440) and 200(5-310) at twelve and twenty-four months post-transplant and T-cell receptor excision circles were 2238 (320-8807) and 4184 (1582 -24596) per106 65 T-cells. Counts did not usually reach normal levels for age but patients were able to clear pre-existing and later acquired infections. At a median of 49 months (22-80), eight have ceased prophylactic antimicrobials and five immunoglobulin replacement. Histological confirmation of thymopoeisis was seen in seven of eleven patients undergoing biopsy of transplanted tissue including five showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator (AIRE) expression was also demonstrated. Autoimmune complications were seen in 7/12 patients. In two, early transient autoimmune haemolysis settled after treatment and did not recur. The other five suffered ongoing autoimmune problems including: thyroiditis (3); haemolysis (1), thrombocytopaenia (4) and neutropenia (1). Conclusions: This study confirms the previous reports that thymus transplantation can reconstitute T cells in cDGS but with frequent autoimmune complications in survivors

Lipocalin 2 Influences Bone and Muscle Phenotype in the MDX Mouse Model of Duchenne Muscular Dystrophy

Lipocalin 2 (Lcn2) is an adipokine involved in bone and energy metabolism. Its serum levels correlate with bone mechanical unloading and inflammation, two conditions representing hallmarks of Duchenne Muscular Dystrophy (DMD). Therefore, we investigated the role of Lcn2 in bone loss induced by muscle failure in the MDX mouse model of DMD. We found increased Lcn2 serum levels in MDX mice at 1, 3, 6, and 12 months of age. Consistently, Lcn2 mRNA was higher in MDX versus WT muscles. Immunohistochemistry showed Lcn2 expression in mononuclear cells between muscle fibres and in muscle fibres, thus confirming the gene expression results. We then ablated Lcn2 in MDX mice, breeding them with Lcn2−/− mice (MDXxLcn2−/− ), resulting in a higher percentage of trabecular volume/total tissue volume compared to MDX mice, likely due to reduced bone resorption. Moreover, MDXxLcn2−/− mice presented with higher grip strength, increased intact muscle fibres, and reduced serum creatine kinase levels compared to MDX. Consistently, blocking Lcn2 by treating 2-month-old MDX mice with an anti-Lcn2 monoclonal antibody (Lcn2Ab) increased trabecular volume, while reducing osteoclast surface/bone surface compared to MDX mice treated with irrelevant IgG. Grip force was also increased, and diaphragm fibrosis was reduced by the Lcn2Ab. These results suggest that Lcn2 could be a possible therapeutic target to treat DMD-induced bone loss

Individualized Whole-Body Vibration: Neuromuscular, Biochemical, Muscle Damage and Inflammatory Acute Responses

Objective. We aimed to investigate the acute residual hormonal, biochemical, and neuromuscular responses to a single session of individualized whole-body vibration (WBV) while maintaining a half-squat position. Methods. Twenty male sport science students voluntarily participated in the present study and were randomly assigned to an individualized WBV group (with the acceleration load determined for each participant) or an isometric group (ISOM). A double-blind, controlled parallel study design with repeated measures was employed. Results. Testosterone and growth hormone increased significantly over time in the WBV group (P <.05 and P <.01, respectively; effect size [ES] ranged from 1.00 to 1.23), whereas cortisol increased over time in both groups (P <.01; ES ranged from 1.04 and 1.36). Interleukin-6 and creatine kinase increased significantly over time only in the WBV group (P <.05; ES = 1.07). The maximal voluntary contraction decreased significantly over time in the ISOM group (P =.019; ES = 0.42), whereas in the WBV group, the decrease did not reach a significant level (P =.05). The ratio of electromyographic activity and power decreased significantly over time in the WBV group (P <.01; ES ranged from 0.57 to 0.72). Conclusion. Individualized WBV increased serum hormonal concentrations, muscle damage, and inflammation to levels similar to those induced by resistance training and hypertrophy exercises

CMHC Adherence to National Mental Health Plan Standards in Italy: A Survey 30 Years After National Reform Law

none6OBJECTIVE: The PROG-CSM (Progetto Centri di Salute Mentale) survey was conducted in all Italian community mental health centers (CMHCs) with the aim of evaluating the extent to which these services adhered to the standards defined by the Italian National Mental Health Plan 1998-2000. METHODS: The policy recommendations of the Italian National Mental Health Plan were translated by a multidisciplinary group of experts into key indicators, including continuity of care, coordination with other community-based services, accessibility, implementation of specific programs, and provision of care. RESULTS: There was high adherence to the standards of the National Mental Health Plan in continuity of care and coordination with other services, but there were lower levels of accessibility and implementation of specific projects. CONCLUSIONS: CMHCs were sufficiently developed throughout Italy, and continuity of care and service coordination levels were satisfactory; however, adherence to the standards was unrelated to the duration of activity of the CMHCs.noneMunizza C.; Gonella R.; Pinciaroli L.; Rucci P.; Picci RL.; Tibaldi G.Munizza C.; Gonella R.; Pinciaroli L.; Rucci P.; Picci RL.; Tibaldi G

Outcomes of Pressure Sore Surgery in Patients with Spinal Cord Injury and Spasticity

Background:Spasticity is a serious complication of spinal cord injury/disease (SCI/D) that affects 60%-80% of patients with this condition. The presence of spasticity can have a significant impact on the outcomes of reconstructive surgical interventions, such as those on pressure sores (PSs). Moreover, in the conservative treatment of PSs, spasticity may prevent maintaining adequate postures to avoid skin friction or traction. The aim of this study is to describe the PS reconstruction outcomes in a cohort of patients with SCI/D affected by spasticity.Methods:In this retrospective study of patients with SCI/D consecutively admitted to Montecatone Rehabilitation Institute between October 2013 and March 2022, 54 PSs were treated in 46 people with spasticity.Results:Postsurgery complications occurred in 26 of 54 treated PS, of which seven were major. Eleven patients experienced more than one complication. The overall incidence of postsurgical complications was 48.1%, and the incidence of major complications was 13%. Median length of hospital stay was 3.8 versus 1.8 months. Compared with other reports in the literature of PS reconstruction in patients with SCI/D, we found higher rates of overall, minor, and major complications.Conclusions:Spasticity proved to be an important condition to consider, and its treatment requires specialized physicians. The collaboration between plastic surgeons and spasticity specialists is crucial to define the best treatment to reduce postoperative complications

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

Prioritization Patterns of Nurses in the Management of a Patient With Delirium: Results of a Q-Methodology Study

Nurses are required to decide on priorities; however, how they prioritize the interventions toward patients with delirium is still unclear. Therefore, expanding the knowledge on (a) how nurses prioritize interventions to manage episodes of delirium and (b) the underlying prioritization patterns were the aims of this study. The Q-methodology was applied in 2021. A systematic review to identify the recommended interventions for patients with delirium was performed, and a nominal group technique was used to select those interventions that are applicable in daily practice (35 out of 96 identified). Then, using a specific scenario, 56 clinical nurses working in hospital medical (n = 31), geriatric (n = 15), and postacute (n = 10) units were asked to order the 35 interventions (from -4 the lowest to +4 the highest priority) using a Q-sort table. Averages (confidence interval at 95%) were calculated at the group level, and a by-person factor analysis was applied to discover underlying patterns of prioritization at the overall and at the individual levels. At the group level, "Ensuring a safe environment (e.g., reducing bed height)" was ranked as the highest priority (2.29 out of four); at the individual level, three prioritization patterns accounting for a total variance of 50.21% have emerged: "Individual needs-oriented" (33.82% variance explained; 41 nurses); "Prevention-oriented" (8.47%; five nurses); and "Cognitive-oriented" (7.92%; six nurses). At the group level, nurses prioritize safety while caring for patients with delirium; however, at the individual level, they follow three different patterns of prioritization oriented toward diverse aspects, suggesting uncertainty in the actions to be taken-with potential implications for patients

TRIM5α associates with proteasomal subunits in cells while in complex with HIV-1 virions

<p>Abstract</p> <p>Background</p> <p>The TRIM5 proteins are cellular restriction factors that prevent retroviral infection in a species-specific manner. Multiple experiments indicate that restriction activity requires accessory host factors, including E2-enzymes. To better understand the mechanism of restriction, we conducted yeast-two hybrid screens to identify proteins that bind to two TRIM5 orthologues.</p> <p>Results</p> <p>The only cDNAs that scored on repeat testing with both TRIM5 orthologues were the proteasome subunit PSMC2 and ubiquitin. Using co-immunoprecipitation assays, we demonstrated an interaction between TRIM5α and PSMC2, as well as numerous other proteasome subunits. Fluorescence microscopy revealed co-localization of proteasomes and TRIM5α cytoplasmic bodies. Forster resonance energy transfer (FRET) analysis indicated that the interaction between TRIM5 and PSMC2 was direct. Previous imaging experiments demonstrated that, when cells are challenged with fluorescently-labeled HIV-1 virions, restrictive TRIM5α orthologues assemble cytoplasmic bodies around incoming virion particles. Following virus challenge, we observed localization of proteasome subunits to rhTRIM5α cytoplasmic bodies that contained fluorescently labeled HIV-1 virions.</p> <p>Conclusions</p> <p>Taken together, the results presented here suggest that localization of the proteasome to TRIM5α cytoplasmic bodies makes an important contribution to TRIM5α-mediated restriction.</p