It is feasible to flag 'near end-of-life' status in older patients from routine general practice data.

METHOD:A retrospective chart review was used to assess the feasibility of identifying these indicators in the data (160,897 patients from 464 practices across Australia). Conditional logistic regression was used to assess the independent contribution of nEOL indicators in patients aged 75-84 and ≥85 years using a case-control design matching by practice. RESULTS:The strongest indicators for nEOL status were advanced malignancy, residential aged care, nutritional vulnerability, anaemia, cognitive impairment and heart failure. Other indicators included hospital attendance, pneumonia, decubitus ulcer, chronic obstructive pulmonary disease, antipsychotic prescription, male sex and stroke. DISCUSSION:Consideration of routinely collected patient data may suggest nEOL status and trigger advance care planning discussions

JAB1 deletion in oligodendrocytes causes senescence-induced inflammation and neurodegeneration in mice

Oligodendrocytes are the primary target of demyelinating disorders, and progressive neurodegenerative changes may evolve in the CNS. DNA damage and oxidative stress are considered key pathogenic events, but the underlying molecular mechanisms remain unclear. Moreover, animal models do not fully recapitulate human diseases, complicating the path to effective treatments. Here we report that mice with cell-autonomous deletion of the nuclear COP9 signalosome component CSN5 (JAB1) in oligodendrocytes develop DNA damage and defective DNA repair in myelinating glial cells. Interestingly, oligodendrocytes lacking JAB1 expression underwent a senescence-like phenotype that fostered chronic inflammation and oxidative stress. These mutants developed progressive CNS demyelination, microglia inflammation, and neurodegeneration, with severe motor deficits and premature death. Notably, blocking microglia inflammation did not prevent neurodegeneration, whereas the deletion of p21CIP1 but not p16INK4a pathway ameliorated the disease. We suggest that senescence is key to sustaining neurodegeneration in demyelinating disorders and may be considered a potential therapeutic target

Multicentre translational Trial of Remote Ischaemic Conditioning in Acute Ischaemic Stroke (TRICS): Protocol of multicentre, parallel group, randomised, preclinical trial in female and male rat and mouse from the Italian Stroke Organization (ISO) Basic Science network

INTRODUCTION: Multicentre preclinical randomised controlled trials (pRCT) are emerging as a necessary step to confirm efficacy and improve translation into the clinic. The aim of this project is to perform two multicentre pRCTs (one in rats and one in mice) to investigate the efficacy of remote ischaemic conditioning (RIC) in an experimental model of severe ischaemic stroke. METHODS AND ANALYSIS: Seven research laboratories within the Italian Stroke Organization (ISO) Basic Science network will participate in the study. Transient endovascular occlusion of the proximal right middle cerebral artery will be performed in two species (rats and mice) and in both sexes. Animals will be randomised to receive RIC by transient surgical occlusion of the right femoral artery, or sham surgery, after reperfusion. Blinded outcome assessment will be performed for dichotomised functional neuroscore (primary endpoint) and infarct volume (secondary endpoint) at 48 hours. A sample size of 80 animals per species will yield 82% power to detect a significant difference of 30% in the primary outcome in both pRCTs. Analyses will be performed in a blind status and according to an intention-to-treat paradigm. The results of this study will provide robust, translationally oriented, high-quality evidence on the efficacy of RIC in multiple species of rodents with large ischaemic stroke. ETHICS AND DISSEMINATION: This is approved by the Animal Welfare Regulatory Body of the University of Milano Bicocca, under project license from the Italian Ministry of Health. Trial results will be subject to publication according to the definition of the outcome presented in this protocol. TRIAL REGISTRATION NUMBER: PCTE0000177

New PRSS1 and common CFTR mutations in a child with acute recurrent pancreatitis, could be considered an "Hereditary" form of pancreatitis ?

<p>Abstract</p> <p>Background</p> <p>acute recurrent pancreatitis is a complex multigenic disease, the diagnosis is even more difficult when this disease develops in a child.</p> <p>Case Presentation</p> <p>a 6-years old boy, hospitalized with epigastric pain radiating to the back showed high serum levels of serum amylase, lipase, CRP and erythrosedimentation rate. Several similar milder episodes of pain, followed by quick recovery and complete disappearance of symptoms were reported during the previous 13 months. The child was medically treated and after 7 days with normal clinic and laboratory tests was discharged with a hypolipidic diet. All the known aetiologic hypotheses were excluded by anamnestic investigation, clinical observation and biochemical evaluation, whereas, anatomic abnormality were excluded by a secretin stimulated magnetic resonance (MRI). At the last follow-up visit, (11 months later), the child showed a normal body weight and anthropometric profile, without further abdominal pain. Mutation screening for coding regions of <it>PRSS1, SPINK1, CFTR </it>and the new hereditary pancreatitis-associated chymotrypsin C (<it>CTRC</it>) genes showed a novel variation, c.541A > G (p.S181G), in the exon 4 of PRSS1 gene and the classical CF p.F508del mutation in the <it>CFTR. </it>Both mutations were present in his clinically normal mother and absent in the patient's father.</p> <p>Conclusions</p> <p>this report extend the spectrum of PRSS1 mutations, however, the absence of family history of pancreatitis leaves the present case without the hallmark of the hereditary origin of pancreatitis. At the present knowledge it can be only stated that the combined genotype CFTR (F508del)/PRSS1 (S181G) is associated to a mild phenotype of acute recurrent pancreatitis in this child without any further conclusion on its pathogenetic role or prediction on the course of the disease.</p

Changes of consultation-liaison psychiatry practice in Italian general hospitals: A comparative 20-year multicenter study

Introduction: Conducted under the auspices of the Italian Society of Consultation Liaison Psychiatry (SIPC) the aim of this study was to describe the characteristics of Consultation Liaison Psychiatry (CLP) activity in Italy (SIPC-2—2018) over the past 20 years by comparing with data from the first Italian nation-wide study (SIPC-1—1998). Methods: We collected data on CLP visits of 3,943 patients from 10 Italian hospitals over a period of 1 year. Data were compared with those from the SIPC-1 1998 study (4,183 participants). Patients were assessed with the same ad hoc 60-item Patient Registration Form recording information from five different areas: Sociodemographic, hospitalization-related, consultation-related, interventions and outcome. Results: Compared with participants from the previous study, SIPC-2-2018 participants were significantly older (d = 0.54) and hospitalized for a longer duration (d = 0.20). The current study detected an increase in the proportion of referrals from surgical wards and for individuals affected by onco-hematologic diseases. Depressive disorders still represented the most frequent psychiatric diagnosis, followed by adjustment and stress disorders and delirium/dementia. Also, CLP psychiatrists prescribed more often antidepressants (Φ = 0.13), antipsychotics (Φ = 0.09), mood stabilizers (Φ = 0.24), and less often benzodiazepines (Φ = 0.07). Conclusion: CLP workload has increased considerably in the past 20 years in Italy, with changes in patient demographic and clinical characteristics. A trend toward increase in medication-based patient management was observed. These findings suggest that the psychiatric needs of patients admitted to the general hospital are more frequently addressed by referring physicians, although Italian CLP services still deserve better organization and autonomy

Experience in Reducing Electron Cloud and Dynamic Pressure Rise in Warm and Cold Regions in Rhic.

The large scale application of non-evaporable getter coating in RHIC has been effective in reducing the electron cloud. Since beams with higher intensity and smaller bunch spacing became possible in operation, the emittance growth is of concern. Study results are reported together with experiences of machine improvements: saturated NEG coatings, anti-grazing ridges in warm sections, and the pre-pumping in cryogenic regions

Turner syndrome and sexual differentiation of the brain: implications for understanding male-biased neurodevelopmental disorders

Turner syndrome (TS) is one of the most common sex chromosome abnormalities. Affected individuals often show a unique pattern of cognitive strengths and weaknesses and are at increased risk for a number of other neurodevelopmental conditions, many of which are more common in typical males than typical females (e.g., autism and attention-deficit hyperactivity disorder). This phenotype may reflect gonadal steroid deficiency, haploinsufficiency of X chromosome genes, failure to express parentally imprinted genes, and the uncovering of X chromosome mutations. Understanding the contribution of these different mechanisms to outcome has the potential to improve clinical care for individuals with TS and to better our understanding of the differential vulnerability to and expression of neurodevelopmental disorders in males and females. In this paper, we review what is currently known about cognition and brain development in individuals with TS, discuss underlying mechanisms and their relevance to understanding male-biased neurodevelopmental conditions, and suggest directions for future research

Determination of gold alloy loss during the production of cast dental restorations

Values for the loss of high gold content dental alloy during the fabrication of three types of cast dental restorations were determined. The mass changes measured were for the melting, casting and cleaning processes and the docking and laboratory finishing procedures involved in producing the final restoration. The casting yield from the alloy cast was also determined. Five Brisbane dental laboratories participated and 407 cast restorations were assessed. The mean mass loss for the melting and casting process was 0.109 g (SD 0.326) per cast restoration, and 0.827 per cent (SD 1.805) of the total mass of alloy melted. The data were analysed in four categories: alloy crowns, metal-ceramic crowns, metal-ceramic bridges, and combined. The mean total mass loss per restoration from docking and finishing for each of the four groups of cast dental restorations examined was 0.329 g, 0.350 g, 0.927 g and 0.363 g; 13.11, 28.30, 22.07 and 22.18 as a per cent of the mass of the docked casting respectively. The yield of casting masses from the alloy cast were 19.97, 9.11, 29.10 and 13.71 per cent respectively, with all differences significant at the 0.001 level. These values indicate that the recommendation for 50 per cent addition of new alloy for each cast is impractical. The wide spread of the data precludes the establishment of a precise agreed value between dentists and technicians for expected loss. However, the use of the median or mean would provide a value which might be an equitable indicator in the long term. Alternatively, working values can be developed for individual dentist/ technician partnerships