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We here describe a rare case of a 26-year-old male patient, presenting to our hospital after a motorcycle-car accident for the surgical management of long-bone fractures to the tibia and femur and shoulder dislocation and undergoing orthopedic surgery, who postoperatively developed seizure, coma, and respiratory failure due to a cerebral fat embolism. After some hours after the surgery, a loss of consciousness was described by caregivers, and the ICU team was alerted, and the patient was admitted to ICU. Intracranial hemorrhage and stroke were subsequently excluded and, finally, a whole-body computed tomography angiography scan and head magnetic resonance imaging showed lesions consistent with cerebral fat embolism. Patent foramen ovale was then suspected by contrasted echocardiography. An early diagnosis helped to choose the correct management, with early tracheostomy, and to correctly interpret and manage hemodynamic dysregulations. Overall, the care provided lead to positive long-term outcomes, as the patient was discharged alive and successfully completed neurological rehabilitation, regaining many functional abilities. The initial management, diagnostic pathway, and ICU management are here described., Competing Interests: MI is Associate Editor for the journal. All the other authors declare no conflicts of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Background: This case of psittacosis in children, is the first described in literature, in Italy. This respiratory infection can be transmitted to humans from the inhalation of respiratory secretions, feces and plumage aerosol of infected birds (and other animals). Usually it can have an asymptomatic or paucisymptomatic course, and the onset is often flu-like, but in this case the child risked his life for a severe respiratory failure. This report is unique because in children psittacosis is rare, and always misdiagnosed, or could cause a delayed diagnosis because of lack of awareness among the paediatricians and physicians. Furthermore, psittacosis enters a differential diagnosis with SARS-COV2 infection because both diseases may determine dyspnea and atypical pneumonia, up to acute respiratory failure., Case Presentation: This clinical case talks about a three-and-a-half-year-old male child affected by psittacosis (or ornithosis), with severe dyspnea and systemic symptoms who required oro-tracheal intubation for acute respiratory failure. The child had slept in a room at home, with some recently bought parrots affected by psittacosis. Initially the child was treated with empiric antibiotic therapy (i.v.ceftriaxone and teicoplanin), but after having isolated the DNA of the germ "Chlamydia psittaci" in both serological and through bronchoalveolar lavage (BAL), he was treated with targeted antibiotic therapy: tetracyclines (doxicillin)., Conclusions: Psittacosis is an extremely contagious disease, caused by an intracellular germ, called "Chlamydia psittaci", a Gram-negative bacterium, transmitted to humans in particular by infected birds, responsible for atypical pneumonia, with acute and chronic respiratory symptoms, sometimes with multi-organ failure and disseminated intravascular coagulation. Even if it is a rare respiratory disease among children, a good doctor must think about psittacosis as cause of respiratory symptoms (and not only flu or SARS-COV2), above all through a correct medical history, in order to provide a targeted antibiotic therapy. An interesting case of psittacosis in a child is being reported here, which has been treated successfully with doxycillin., (© 2023. Società Italiana di Pediatria.)

Objectives: We aim to describe the use of continuous infusion of neuromuscular blocking agents in mechanically ventilated critically ill children and to test its association with in-hospital mortality., Design: Multicenter, registry-based, observational, two-cohort-comparison retrospective study using prospectively collected data from a web-based national registry., Setting: Seventeen PICUs in Italy., Patients: We included children less than 18 years who received mechanical ventilation and a neuromuscular blocking agent infusion from January 2010 to October 2017. A propensity score-weighted Cox regression analysis was used to assess the relationship between the use of neuromuscular blocking agents and in-hospital mortality., Interventions: None., Measurements and Main Results: Of the 23,227 patients admitted to the PICUs during the study period, 3,823 patients were included. Patients who received a continuous infusion of neuromuscular blocking agent were more likely to be younger (p < 0.001), ex-premature (p < 0.001), and presenting with less chronic respiratory insufficiency requiring home mechanical ventilation (p < 0.001). Reasons for mechanical ventilation significantly differed between patients who received a continuous infusion of neuromuscular blocking agent and patients who did not receive a continuous infusion of neuromuscular blocking agent, with a higher frequency of respiratory and cardiac diagnosis among patients who received neuromuscular blocking agents compared with other diagnoses (all p < 0.001). The covariates were well balanced in the propensity-weighted cohort. The mortality rate significantly differed among the two cohorts (patients who received a continuous infusion of neuromuscular blocking agent 21% vs patients who did not receive a continuous infusion of neuromuscular blocking agent 11%; p < 0.001 by weighted logistic regression). Patients who received a continuous infusion of neuromuscular blocking agent experienced longer mechanical ventilation and PICU stay (both p < 0.001 by weighted logistic regression). A weighted Cox regression analysis found the use of neuromuscular blocking agents to be a significant predictor of in-hospital mortality both in the unadjusted analysis (hazard ratio, 1.7; 95% CI, 1.3-2.2) and in the adjusted one (hazard ratio, 1.6; 95% CI, 1.2-2.1)., Conclusions: Thirteen percent of mechanically ventilated children in PICUs received neuromuscular blocking agents. When adjusting for selection bias with a propensity score approach, the use of neuromuscular blocking agent was found to be a significant predictor of in-hospital mortality., Competing Interests: Dr. Biban received funding from Getinge and Chiesi Pharmaceutical. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

To survive in cold environments, psychrophilic organisms produce enzymes endowed with high specific activity at low temperature. The structure of these enzymes is usually flexible and mostly thermolabile. In this work, we investigate the structural basis of cold adaptation of a GH42 β-galactosidase from the psychrophilic Marinomonas ef1. This enzyme couples cold activity with astonishing robustness for a psychrophilic protein, for it retains 23% of its highest activity at 5 °C and it is stable for several days at 37 °C and even 50 °C. Phylogenetic analyses indicate a close relationship with thermophilic β-galactosidases, suggesting that the present-day enzyme evolved from a thermostable scaffold modeled by environmental selective pressure. The crystallographic structure reveals the overall similarity with GH42 enzymes, along with a hexameric arrangement (dimer of trimers) not found in psychrophilic, mesophilic, and thermophilic homologues. In the quaternary structure, protomers form a large central cavity, whose accessibility to the substrate is promoted by the dynamic behavior of surface loops, even at low temperature. A peculiar cooperative behavior of the enzyme is likely related to the increase of the internal cavity permeability triggered by heating. Overall, our results highlight a novel strategy of enzyme cold adaptation, based on the oligomerization state of the enzyme, which effectively challenges the paradigm of cold activity coupled with intrinsic thermolability. DATABASE: Structural data are available in the Protein Data Bank database under the accession number 6Y2K., (© 2020 Federation of European Biochemical Societies.)

NF-Y is a transcription factor (TF) comprising three subunits (NF-YA, NF-YB, NF-YC) that binds with high specificity to the CCAAT sequence, a widespread regulatory element in gene promoters of prosurvival, cell-cycle-promoting, and metabolic genes. Tumor cells undergo "metabolic rewiring" through overexpression of genes involved in such pathways, many of which are under NF-Y control. In addition, NF-YA appears to be overexpressed in many tumor types. Thus, limiting NF-Y activity may represent a desirable anti-cancer strategy, which is an ongoing field of research. With virtual-screening docking simulations on a library of pharmacologically active compounds, we identified suramin as a potential NF-Y inhibitor. We focused on suramin given its high water-solubility that is an important factor for in vitro testing, since NF-Y is sensitive to DMSO. By electrophoretic mobility shift assays (EMSA), isothermal titration calorimetry (ITC), STD NMR, X-ray crystallography, and molecular dynamics (MD) simulations, we showed that suramin binds to the histone fold domains (HFDs) of NF-Y, preventing DNA-binding. Our analyses, provide atomic-level detail on the interaction between suramin and NF-Y and reveal a region of the protein, nearby the suramin-binding site and poorly conserved in other HFD-containing TFs, that may represent a promising starting point for rational design of more specific and potent inhibitors with potential therapeutic applications.

Objectives: We sought to evaluate dexmedetomidine efficacy in assuring comfort and sparing conventional drugs when used for prolonged sedation (≥24 hr) in critically ill patients, by using validated clinical scores while systematically collecting drug dosages. We also evaluated the safety profile of dexmedetomidine and the risk factors associated with adverse events., Design: Observational prospective study., Setting: Nine tertiary-care PICUs., Patients: Patients less than 18 years who received dexmedetomidine for greater than or equal to 24 hours between January 2016 and December 2017., Interventions: None., Measurements and Main Results: One-hundred sixty-three patients (median age, 13 mo; interquartile range, 4-71 mo) were enrolled. The main indication for dexmedetomidine use was as an adjuvant for drug-sparing (42%). Twenty-three patients (14%) received dexmedetomidine as monotherapy. Seven percent of patients received a loading dose. The median infusion duration was 108 hours (interquartile range, 60-168 hr), with dosages between 0.4 (interquartile range, 0.3-0.5) and 0.8 µg/kg/hr (interquartile range, 0.6-1.2 µg/kg/hr). At 24 hours of dexmedetomidine infusion, values of COMFORT-B Scale (n = 114), Withdrawal Assessment Tool-1 (n = 43) and Cornell Assessment of Pediatric Delirum (n = 6) were significantly decreased compared with values registered immediately pre dexmedetomidine (p < 0.001, p < 0.001, p = 0.027). Dosages/kg/hr of benzodiazepines, opioids, propofol, and ketamine were also significantly decreased (p < 0.001, p < 0.001, p = 0.001, p = 0.027). The infusion was weaned off in 85% of patients, over a median time of 36 hours (interquartile range, 12-48 hr), and abruptly discontinued in 15% of them. Thirty-seven percent of patients showed hemodynamic changes, and 9% displayed hemodynamic adverse events that required intervention (dose reduction in 79% of cases). A multivariate logistic regression model showed that a loading dose (odds ratio, 4.8; CI, 1.2-18.7) and dosages greater than 1.2 µg/kg/hr (odds ratio, 5.4; CI, 1.9-15.2) increased the odds of hemodynamic changes., Conclusions: Dexmedetomidine used for prolonged sedation assures comfort, spares use of other sedation drugs, and helps to attenuate withdrawal syndrome and delirium symptoms. Adverse events are mainly hemodynamic and are reversible following dose reduction. A loading dose and higher infusion dosages are independent risk factors for hemodynamic adverse events.

Macrophages (MPs) are immune cells which are crucial for tissue repair. In skeletal muscle regeneration, pro-inflammatory cells first infiltrate to promote myogenic cell proliferation, then they switch into an anti-inflammatory phenotype to sustain myogenic cells differentiation and myofiber formation. This phenotypical switch is induced by dead cell phagocytosis. We previously demonstrated that the transcription factor Nfix, a member of the nuclear factor I (Nfi) family, plays a pivotal role during muscle development, regeneration and in the progression of muscular dystrophies. Here, we show that Nfix is mainly expressed by anti-inflammatory macrophages. Upon acute injury, mice deleted for Nfix in myeloid line displayed a significant defect in the process of muscle regeneration. Indeed, Nfix is involved in the macrophage phenotypical switch and macrophages lacking Nfix failed to adopt an anti-inflammatory phenotype and interact with myogenic cells. Moreover, we demonstrated that phagocytosis induced by the inhibition of the RhoA-ROCK1 pathway leads to Nfix expression and, consequently, to acquisition of the anti-inflammatory phenotype. Our study identified Nfix as a link between RhoA-ROCK1-dependent phagocytosis and the MP phenotypical switch, thus establishing a new role for Nfix in macrophage biology for the resolution of inflammation and tissue repair., Competing Interests: The authors declare no conflict of interest.

1. Random selections of the sera of trainees injected 2 months previously with the specific polysaccharides of Types I, II, V, and VII pneumococci contained quantities of antibody to Types I, II, and VII sufficient to account for the favorable results of the immunization procedure. 2. As in earlier studies, the levels of the antibody for the C polysaccharide remained relatively constant before and after the injections. 3. The serum from the preliminary bleedings often contained antibody to the Type VII polysaccharide. This remained relatively constant in a control group injected with saline.

A new experimental procedure for the production of arteriosclerosis in the bird is described. The subcutaneous implantation of diethylstilbestrol by means of which a sustained increase in the concentration of cholesterol, phospholipid, and neutral fat can be readily established, is shown to induce atherosclerosis of the aorta. The atherosclerosis has been compared with that artificially induced in the bird by the prolonged feeding of cholesterol and also with that occurring spontaneously. The stilbestrol-induced lesion more closely resembled the spontaneously occurring one in the bird than did that produced by cholesterol feeding. But all 3 lesions were fundamentally similar, differing only in the amounts and proportions of the various lipid constituents present. The concentrations of cholesterol in plasma of the stilbestrol-treated and cholesterol-fed birds were of the same order. Yet cholesterol constituted a greater proportion of the lipids deposited in the arterial wall of the cholesterol-fed than in that of the stilbestrol-treated birds. This finding suggests that the cholesterol content of the vascular lesion depends not only on the absolute concentration of cholesterol in plasma, but also on the proportion of cholesterol to other lipid constituents in plasma.