1,357 research outputs found

    A COMPARISON BETWEEN MOTIVATIONS AND PERSONALITY TRAITS IN RELIGIOUS TOURISTS AND CRUISE SHIP TOURISTS

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    The purpose of this paper is to analyze the motivations and the personality traits that characterize tourists who choose religious travels versus cruises. Participating in the research were 683 Italian tourists (345 males and 338 females, age range 18–63 years); 483 who went to a pilgrimage travel and 200 who chose a cruise ship in the Mediterranean Sea. Both groups of tourists completed the Travel Motivation Scale and the Big Five Questionnaire. Results show that different motivations and personality traits characterize the different types of tourists and, further, that motivations for traveling are predicted by specific —some similar, other divergent— personality trait

    A re-appraisal of pathogenic mechanisms bridging wet and dry age-related macular degeneration leads to reconsider a role for phytochemicals

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    Which pathogenic mechanisms underlie age-related macular degeneration (AMD)? Are they different for dry and wet variants, or do they stem from common metabolic alterations? Where shall we look for altered metabolism? Is it the inner choroid, or is it rather the choroid–retinal border? Again, since cell-clearing pathways are crucial to degrade altered proteins, which metabolic system is likely to be the most implicated, and in which cell type? Here we describe the unique clearing activity of the retinal pigment epithelium (RPE) and the relevant role of its autophagy machinery in removing altered debris, thus centering the RPE in the pathogenesis of AMD. The cell-clearing systems within the RPE may act as a kernel to regulate the redox homeostasis and the traffic of multiple proteins and organelles toward either the choroid border or the outer segments of photoreceptors. This is expected to cope with the polarity of various domains within RPE cells, with each one owning a specific metabolic activity. A defective clearance machinery may trigger unconventional solutions to avoid intracellular substrates’ accumulation through unconventional secretions. These components may be deposited between the RPE and Bruch’s membrane, thus generating the drusen, which remains the classic hallmark of AMD. These deposits may rather represent a witness of an abnormal RPE metabolism than a real pathogenic component. The empowerment of cell clearance, antioxidant, anti-inflammatory, and anti-angiogenic activity of the RPE by specific phytochemicals is here discussed

    Integrable and Chaotic Dynamics of Spins Coupled to an Optical Cavity

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    We show that a class of random all-to-all spin models, realizable in systems of atoms coupled to an optical cavity, gives rise to a rich dynamical phase diagram due to the pairwise separable nature of the couplings. By controlling the experimental parameters, one can tune between integrable and chaotic dynamics on the one hand and between classical and quantum regimes on the other hand. For two special values of a spin-anisotropy parameter, the model exhibits rational Gaudin-type integrability, and it is characterized by an extensive set of spin-bilinear integrals of motion, independent of the spin size. More generically, we find a novel integrable structure with conserved charges that are not purely bilinear. Instead, they develop "dressing tails" of higher-body terms, reminiscent of the dressed local integrals of motion found in many-body localized phases. Surprisingly, this new type of integrable dynamics found in finite-size spin-1/2 systems disappears in the large-S limit, giving way to classical chaos. We identify parameter regimes for characterizing these different dynamical behaviors in realistic experiments, in view of the limitations set by cavity dissipation

    Importance of molecular cell biology investigations in human medicine in the story of the Hutchinson-Gilford progeria syndrome

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    Ranged among laminopathies, Hutchinson–Gilford progeria syndrome is a syndrome that involves premature aging, leading usually to death at the age between 10 to 14 years predominatly due to a myocardial infarction or a stroke. In the lecture I shall overview the importance of molecular cell biology investigations that led to the discovery of the basic mechanism standing behind this rare syndrome. The genetic basis in most cases is a mutation at the nucleotide position 1824 of the lamin A gene. At this position, cytosine is substituted for thymine so that a cryptic splice site within the precursor mRNA for lamin A is generated. This results in a production of abnormal lamin A, termed progerin, its presence in cells having a deleterious dominant effect. Depending on the cell type and tissue, progerin induces a pleiotropy of defects that vary in different tissues. The present endeavour how to challenge this terrible disease will be also mentioned

    Time-dependent rate of multicomponent dark matter: reproducing the DAMA/LIBRA phase-2 results

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    The current paradigm for dark matter direct detection is to assume that the dark sector is solely composed of a single particle species. In this short paper, we make the observation that dark matter comprising both a light and a heavy component that modulate out of phase leads to interesting phenomenology in annual modulation experiments. For an illustrative example, we use the recently released DAMA/LIBRA phase-2 results with a lower energy threshold. Immediately after, it was argued that a one-component spin-independent dark matter explanation of the observed annual modulation is strongly disfavored or excluded unless isospin-violating couplings are invoked. We show that a simple two-component extension can reproduce the observed spectrum without the need to invoke fine-tuned couplings. Using the publicly available DAMA/LIBRA data, we perform a fit of the DAMA/LIBRA energy spectrum of the annual modulation amplitude to a scenario with two dark matter components. We also take into account how gravitational focusing affects the phases of the light and a heavy components differently, which leads to nontrivial effects in the total time-dependent rate. Our results show that there exists a unique solution in agreement with the data in the simplest case of isospin-conserving couplings with equal cross sections. The distinctive features found in this work are crucial for a dark matter interpretation of any observed annual modulation.Juan Herrero-Garcia, Andre Scaffidi, Martin White and Anthony G. William

    Video-based interventions to improve self-assessment accuracy among physicians: a systematic review

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    Purpose Self-assessment of a physician’s performance in both procedure and non-procedural activities can be used to identify their deficiencies to allow for appropriate corrective measures. Physicians are inaccurate in their self-assessments, which may compromise opportunities for self- development. To improve this accuracy, video-based interventions of physicians watching their own performance, an experts’ performance or both, have been proposed to inform their self-assessment. We conducted a systematic review of the effectiveness of video-based interventions targeting improved self-assessment accuracy among physicians. Materials and methods The authors performed a systematic search of MEDLINE, Embase, EBM reviews, and Scopus databases from inception to August 23, 2022, using combinations of terms for “self-assessment”, “video-recording”, and “physician”. Eligible studies were empirical investigations assessing the effect of video-based interventions on physicians’ self-assessment accuracy with a comparison of self-assessment accuracy pre- and post- video intervention. We defined self-assessment accuracy as a “direct comparison between an external evaluator and self-assessment that was quantified using formal statistical analysis”. Two reviewers independently screened records, extracted data, assessed risk of bias, and evaluated quality of evidence. A narrative synthesis was conducted, as variable outcomes precluded a meta-analysis. Results A total of 2,376 papers were initially retrieved. Of these, 22 papers were selected for full-text review; a final 9 studies met inclusion criteria for data extraction. Across studies, 240 participants from 5 specialties were represented. Video-based interventions included self-video review (8/9), benchmark video review (3/9), and/or a combination of both types (1/9). Five out of nine studies reported that participants had inaccurate self-assessment at baseline. After the intervention, 5 of 9 studies found a statistically significant improvement in self-assessment accuracy. Conclusions Overall, current data suggests video-based interventions can improve self-assessment accuracy. Benchmark video review may enable physicians to improve self-assessment accuracy, especially for those with limited experience performing a particular clinical skill. In contrast, self-video review may be able to provide improvement in self-assessment accuracy for more experience physicians. Future research should use standardized methods of comparison for self-assessment accuracy, such as the Bland-Altman analysis, to facilitate meta-analytic summation

    Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von hippel-lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities

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    E3 ubiquitin ligases are attractive targets in the ubiquitin-proteasome system, however, the development of small-molecule ligands has been rewarded with limited success. The von Hippel-Lindau protein (pVHL) is the substrate recognition subunit of the VHL E3 ligase that targets HIF-1α for degradation. We recently reported inhibitors of the pVHL:HIF-1α interaction, however they exhibited moderate potency. Herein, we report the design and optimization, guided by X-ray crystal structures, of a ligand series with nanomolar binding affinities

    Modulation of the CD95-Induced Apoptosis: The Role of CD95 N-Glycosylation

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    Protein modifications of death receptor pathways play a central role in the regulation of apoptosis. It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of CD95 (Fas/APO-1), another death receptor, influences DISC formation and procaspase-8 activation at the CD95 DISC and thereby the onset of apoptosis. We concentrated on N-glycostructure since O-glycosylation of CD95 was not found. We applied different approaches to analyze the role of CD95 N-glycosylation on the signal transduction: in silico modeling of CD95 DISC, generation of CD95 glycosylation mutants (at N136 and N118), modulation of N-glycosylation by deoxymannojirimycin (DMM) and sialidase from Vibrio cholerae (VCN). We demonstrate that N-deglycosylation of CD95 does not block DISC formation and results only in the reduction of the procaspase-8 activation at the DISC. These findings are important for the better understanding of CD95 apoptosis regulation and reveal differences between apoptotic signaling pathways of the TRAIL and CD95 systems

    The serological prevalence of SARS-CoV-2 infection in patients with chronic myeloid leukemia is similar to that in the general population

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    Background: Patients with hematological malignancies are at an increased risk of SARS-CoV-2 disease (COVID-19) and adverse outcome. However, a low mortality rate has been reported in patients with chronic myeloid leukemia (CML). Preclinical evidence suggests that tyrosine kinase inhibitors (TKIs) may have a protective role against severe COVID-19. Methods: We conducted a cross-sectional study of 564 consecutive patients with CML who were tested for anti-SARS-CoV-2 IgG/IgM antibodies at their first outpatient visit between May and early November 2020 in five hematologic centers representative of three Italian regions. Results: The estimated serological prevalence of SARS-CoV-2 infection in patients with CML after the first pandemic wave was similar to that in the general population (about 2%), both at national and regional levels. CML patients with positive anti-SARS-CoV-2\ua0serology were more frequently male (p\ua0=\ua00.027) and active workers (p\ua0=\ua00.012), while there was no significant association with TKI treatment type. Only 3 out of 11 IgG-positive patients had previously received a molecular diagnosis of COVID-19, while the remainders were asymptomatic or with mild symptoms. Conclusions: Our data confirm that the course of SARS-CoV-2 infection in patients with CML is generally mild and reassure about the safety of continuing TKIs during the COVID-19 pandemic. Furthermore, we suggest that patients with CML succeed to mount an antibody response after exposure to SARS-CoV-2, similar to the general population
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