Diagnosis, assessment and management of constipation in advanced cancer: ESMO Clinical Practice Guidelines.

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The prevention of analgesic opioids abuse: expert opinion

Opioids are drugs of reference for the treatment of moderate to severe pain. Their proper use and a periodic assessment of the patient are crucial to prevent misuse. A multidisciplinary group suggests strategies for all stakeholders involved in the management of pain and suggests the importance of the doctor-patient relationship

Dark Stars and Boosted Dark Matter Annihilation Rates

Dark Stars (DS) may constitute the first phase of stellar evolution, powered by dark matter (DM) annihilation. We will investigate here the properties of DS assuming the DM particle has the required properties to explain the excess positron and elec- tron signals in the cosmic rays detected by the PAMELA and FERMI satellites. Any possible DM interpretation of these signals requires exotic DM candidates, with an- nihilation cross sections a few orders of magnitude higher than the canonical value required for correct thermal relic abundance for Weakly Interacting Dark Matter can- didates; additionally in most models the annihilation must be preferentially to lep- tons. Secondly, we study the dependence of DS properties on the concentration pa- rameter of the initial DM density profile of the halos where the first stars are formed. We restrict our study to the DM in the star due to simple (vs. extended) adiabatic contraction and minimal (vs. extended) capture; this simple study is sufficient to illustrate dependence on the cross section and concentration parameter. Our basic results are that the final stellar properties, once the star enters the main sequence, are always roughly the same, regardless of the value of boosted annihilation or concentration parameter in the range between c=2 and c=5: stellar mass ~ 1000M\odot, luminosity ~ 10^7 L\odot, lifetime ~ 10^6 yrs (for the minimal DM models considered here; additional DM would lead to more massive dark stars). However, the lifetime, final mass, and final luminosity of the DS show some dependence on boost factor and concentration parameter as discussed in the paper.Comment: 37 pages, 11 figure

Linguistic and content validation of the translated and culturally adapted patient-generated subjective global assessment (PG-SGA)

The Patient-Generated Subjective Global Assessment (PG-SGA) is an instrument to screen, assess and monitor malnutrition and risk factors, and to triage for interventions. After having translated and culturally adapted the original PG-SGA for the Italian setting, according to International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles, we tested linguistic validity, i.e., perceived comprehensibility and difficulty, and content validity (relevance) of the Italian version of the PG-SGA in patients with cancer and a multidisciplinary sample of healthcare professionals (HCPs). Methods: After the translation and cultural adaptation of the original PG-SGA for the Italian setting, the patient component (i.e., PG-SGA Short Form (SF) was tested for linguistic validity (i.e., comprehensibility ad difficulty) in 120 Italian patients with cancer and 81 Italian HCPs. The full PG-SGA, i.e., patient and professional component of the PG-SGA, was tested for content validity, i.e., relevance, in 81 Italian HCPs. The data were collected by a questionnaire and evaluations were operationalized by a 4-point scale. Through item and scale indices we evaluated the comprehensibility (I–CI, S–CI), difficulty (I-DI, S-DI) and content validity (I-CVI, S-CVI). Scale indices 0.80–0.89 were considered acceptable, and scale indices ≥0.90 were considered excellent. Results: Patients perceived comprehensibility and difficulty of the PG-SGA SF (Boxes) as excellent (S–CI = 0.98, S-DI = 0.96). Professionals perceived comprehensibility of the professional component (Worksheets) as excellent (S–CI = 0.92), difficulty as acceptable (S-DI = 0.85), and content validity of the full PG-SGA as excellent (S-CVI = 0.92). Dietitians gave higher scores (indicating better scores) on comprehensibility, difficulty, and content validity of Worksheet 4 (physical exam) than the other professions. In Worksheet 4, four items were considered most difficult to complete and were considered below acceptable range. Relevance was perceived as excellent by professionals for both the patient component (S-CVI = 0.93) and the professional component (S-CVI = 0.90), resulting in S-CVI = 0.92 for the full PG-SGA. Slight textual modifications were implemented resulting in the final version of the Italian PG-SGA. Conclusions: Translation and cultural adaptation of the original PG-SGA resulted in the Italian version of the PG-SGA that maintained its original purpose and meaning and can be completed adequately and easily by patients and professionals. The Italian PG-SGA is considered relevant for screening, assessing and monitoring malnutrition and risk factors, as well as triaging for interventions by Italian HCPs.</p

Highly variable clinical pictures in dogs naturally infected with angiostrongylus vasorum

Canine angiostrongylosis by Angiostrongylus vasorum is increasingly reported in both enzootic and previously free areas. The complex pathogenesis of the disease makes the clinical workup challenging. Infected dogs show highly variable clinical pictures, characterized by subclinical to life-threatening general, cardio-respiratory, neurological and/or gastrointestinal signs. The present study reports the high variability of clinical pictures from 36 dogs across central and southern Italy that were naturally infected by A. vasorum. Of them, 23 (63.9%) presented at least one clinical sign, while 13 (36.1%) were subclinically infected and apparently healthy. Overall, 19 dogs (52.8%) showed cardiorespiratory signs, 14 (38.9%) had non-specific abnormalities, 2 (5.6%) presented coagulation disorders and 1 (2.8%) had a severe neurological condition. Importantly, four dogs presenting with clinical signs had neither cough nor dyspnea. These results underline that angiostrongylosis should be included in the differential diagnosis, even when dogs display only non-specific clinical signs. The proportion of apparently healthy dogs highlights the relevance of routine copromicroscopic and/or antigenic tests in enzootic areas to avoid the sudden onset of potentially life-threatening signs

Stem Cell Modeling of Neuroferritinopathy Reveals Iron as a Determinant of Senescence and Ferroptosis during Neuronal Aging

Neuroferritinopathy (NF) is a movement disorder caused by alterations in the L-ferritin gene that generate cytosolic free iron. NF is a unique pathophysiological model for determining the direct consequences of cell iron dysregulation. We established lines of induced pluripotent stem cells from fibroblasts from two NF patients and one isogenic control obtained by CRISPR/Cas9 technology. NF fibroblasts, neural progenitors, and neurons exhibited the presence of increased cytosolic iron, which was also detectable as: ferritin aggregates, alterations in the iron parameters, oxidative damage, and the onset of a senescence phenotype, particularly severe in the neurons. In this spontaneous senescence model, NF cells had impaired survival and died by ferroptosis. Thus, non-ferritin-bound iron is sufficient per se to cause both cell senescence and ferroptotic cell death in human fibroblasts and neurons. These results provide strong evidence supporting the primary role of iron in neuronal aging and degeneration

Observational Manifestations of the First Protogalaxies in the 21 cm Line

The absorption properties of the first low-mass protogalaxies (mini-halos) forming at high redshifts in the 21-cm line of atomic hydrogen are considered. The absorption properties of these protogalaxies are shown to depend strongly on both their mass and evolutionary status. The optical depths in the line reach $\sim$0.1-0.2 for small impact parameters of the line of sight. When a protogalaxy being compressed, the influence of gas accretion can be seen manifested in a non-monotonic frequency dependence of the optical depth. The absorption characteristics in the 21-cm line are determined by the thermal and dynamical evolution of the gas in protogalaxies. Since the theoretical line width in the observer's reference frame is 1-6 kHz and the expected separation between lines 8.4 kHz, the lines from low mass protogalaxies can be resolved using ongoing and future low frequency interferometers.Comment: 12 pages, 5 figure

Prognostic evaluation in patients with advanced cancer in the last months of life:ESMO Clinical Practice Guideline

: • This ESMO Clinical Practice Guideline provides key recommendations for using prognostic estimates in advanced cancer. • The guideline covers recommendations for patients with cancer and an expected survival of months or less. • An algorithm for use of clinical predictions, prognostic factors and multivariable risk prediction models is presented. • The author group encompasses a multidisciplinary group of experts from different institutions in Europe, USA and Asia. • Recommendations are based on available scientific data and the authors’ collective expert opinion

Dark Matter Capture in the First Stars: a Power Source and Limit on Stellar Mass

The annihilation of weakly interacting massive particles can provide an important heat source for the first (Pop. III) stars, potentially leading to a new phase of stellar evolution known as a "Dark Star". When dark matter (DM) capture via scattering off of baryons is included, the luminosity from DM annihilation may dominate over the luminosity due to fusion, depending on the DM density and scattering cross-section. The influx of DM due to capture may thus prolong the lifetime of the Dark Stars. Comparison of DM luminosity with the Eddington luminosity for the star may constrain the stellar mass of zero metallicity stars; in this case DM will uniquely determine the mass of the first stars. Alternatively, if sufficiently massive Pop. III stars are found, they might be used to bound dark matter properties.Comment: 19 pages, 4 figures, 3 Tables updated captions and graphs, corrected grammer, and added citations revised for submission to JCA