Rizični čimbenici za nastanak cerebrovaskularnih bolesti s osvrtom na prevenciju

Stroke risk factors can be divided into those with evidence-based relationship and those with supposed relationship to ischemic stroke, and into potentially treatable risk factors and risk factors with no therapeutic options. Age, gender and race are risk factors with no therapeutic options, while among treatable stroke risk factors most important are high blood pressure, atrial fibrillation, patent foramen ovale, cardiac disorders, diabetes mellitus, hiperhomocysteinemia, hiperlipidemia, and living conditions such as smoking and heavy alcohol drinking. Data about the use of antioxidant vitamins (A,C,E,) are still controversial as well as the role of infection in the development of atherosclerosis.Rizični čimbenici za nastanak moždanog udara mogu se podijeliti na one kod kojih je povezanost s moždanim udarom dokazana i na one kod kojih se ta povezanost pretpostavlja, na one na koje se može terapijski djelovati i one na koje se ne može djelovati. Rizični čimbenici na koje se ne može djelovati su dob, spol, rasa, dok su među onima na koje se može djelovati najvažniji povišen tlak, atrijska fibrilacija, otvoreni foramen ovale, srčani poremećaji, šećerna bolest, hiperhomocisteinemija, hiperlipidemija, te čimbenici povezani s načinom života, kao što su pušenje i prekomjerno pijenje alkohola. Podaci o primjeni antiokdisativnih vitamina (A, C i E) još uvijek nisu nedvosmisleni, što također vrijedi i za ulogu upale u nastanku ateroskleroze

Horizontal rotation signals detected by "G-Pisa" ring laser for the Mw=9.0, March 2011, Japan earthquake

We report the observation of the ground rotation induced by the Mw=9.0, 11th of March 2011, Japan earthquake. The rotation measurements have been conducted with a ring laser gyroscope operating in a vertical plane, thus detecting rotations around the horizontal axis. Comparison of ground rotations with vertical accelerations from a co-located force-balance accelerometer shows excellent ring laser coupling at periods longer than 100s. Under the plane wave assumption, we derive a theoretical relationship between horizontal rotation and vertical acceleration for Rayleigh waves. Due to the oblique mounting of the gyroscope with respect to the wave direction-of-arrival, apparent velocities derived from the acceleration / rotation rate ratio are expected to be always larger than, or equal to the true wave propagation velocity. This hypothesis is confirmed through comparison with fundamental-mode, Rayleigh wave phase velocities predicted for a standard Earth model.Comment: Accepted for publication in Journal of Seismolog

Lytic Water Dynamics Reveal Evolutionarily Conserved Mechanisms of ATP Hydrolysis by TIP49 AAA+ ATPases

SummaryEukaryotic TIP49a (Pontin) and TIP49b (Reptin) AAA+ ATPases play essential roles in key cellular processes. How their weak ATPase activity contributes to their important functions remains largely unknown and difficult to analyze because of the divergent properties of TIP49a and TIP49b proteins and of their homo- and hetero-oligomeric assemblies. To circumvent these complexities, we have analyzed the single ancient TIP49 ortholog found in the archaeon Methanopyrus kandleri (mkTIP49). All-atom homology modeling and molecular dynamics simulations validated by biochemical assays reveal highly conserved organizational principles and identify key residues for ATP hydrolysis. An unanticipated crosstalk between Walker B and Sensor I motifs impacts the dynamics of water molecules and highlights a critical role of trans-acting aspartates in the lytic water activation step that is essential for the associative mechanism of ATP hydrolysis

Inducible IL-7 Hyperexpression Influences Lymphocyte Homeostasis and Function and Increases Allograft Rejection

The IL-7/IL-7R pathway is essential for lymphocyte development and disturbances in the pathway can lead to immune deficiency or T cell mediated destruction. Here, the effect of transient hyperexpression of IL-7 was investigated on immune regulation and allograft rejection under immunosuppression. An experimental in vivo immunosuppressive mouse model of IL-7 hyperexpression was developed using transgenic mice (C57BL/6 background) carrying a tetracycline inducible IL-7 expression cassette, which allowed the temporally controlled induction of IL-7 hyperexpression by Dexamethasone and Doxycycline treatment. Upon induction of IL-7, the B220+ c-kit+ Pro/Pre-B I compartment in the bone marrow increased as compared to control mice in a serum IL-7 concentration-correlated manner. IL-7 hyperexpression also preferentially increased the population size of memory CD8+ T cells in secondary lymphoid organs, and reduced the proportion of CD4+Foxp3+ T regulatory cells. Of relevance to disease, conventional CD4+ T cells from an IL-7-rich milieu escaped T regulatory cell-mediated suppression in vitro and in a model of autoimmune diabetes in vivo. These findings were validated using an IL-7/anti-IL7 complex treatment mouse model to create an IL-7 rich environment. To study the effect of IL-7 on islet graft survival in a mismatched allograft model, BALB/c mice were rendered diabetic by streptozotocin und transplanted with IL-7-inducible or control islets from C57BL/6 mice. As expected, Dexamethasone and Doxycycline treatment prolonged graft median survival as compared to the untreated control group in this transplantation mouse model. However, upon induction of local IL-7 hyperexpression in the transplanted islets, graft survival time was decreased and this was accompanied by an increased CD4+ and CD8+ T cell infiltration in the islets. Altogether, the findings show that transient elevations of IL-7 can impair immune regulation and lead to graft loss also under immune suppression

Integrated safety analysis of filgotinib for ulcerative colitis: Results from SELECTION and SELECTIONLTE

BACKGROUND: Filgotinib 200 mg (FIL200) is an approved treatment for adults with moderately to severely active ulcerative colitis (UC). AIM: To report integrated safety data from the phase 2b/3 SELECTION study (NCT02914522) and its ongoing long-term extension study SELECTIONLTE (NCT02914535). METHODS: Safety outcomes were analysed in adults with moderately to severely active UC who received FIL200, filgotinib 100 mg (FIL100) or placebo once daily throughout the 11-week SELECTION induction study, the 47-week SELECTION maintenance study (if applicable) and SELECTIONLTE (if applicable). Exposure-adjusted incidence rates (EAIRs) per 100 censored patient-years of exposure with 95% confidence intervals were reported for treatment-emergent adverse events (AEs). Certain AE data were presented in subgroups, including age and prior biologic exposure status. RESULTS: This interim analysis included 1348 patients representing 3326.2 patient-years of exposure. Baseline characteristics of patients entering SELECTION were similar across treatment groups. EAIRs for serious infection, thromboembolic events and major adverse cardiovascular events (MACE) were consistently low across treatment groups. Most patients with MACE had cardiovascular risk factors. The EAIR for herpes zoster was numerically higher for FIL200 than for placebo. Infection incidences were numerically higher in biologic-experienced than biologic-naive patients. Higher incidences of certain AEs in patients 65 years of age or older were as expected. Four deaths occurred, including three cardiovascular deaths, none of which was considered related to filgotinib. CONCLUSION: FIL200 and FIL100 were well tolerated with no unexpected safety signals in patients with moderately to severely active UC, regardless of previous biologic exposure or age

The COVID-19 Worsening Score (COWS)-a predictive bedside tool for critical illness

18Objectives: To evaluate the accuracy of a new COVID-19 prognostic score based on lung ultrasound (LUS) and previously validated variables in predicting critical illness. Methods: We conducted a single-center retrospective cohort development and internal validation study of the COVID-19 Worsening Score (COWS), based on a combination of the previously validated COVID-GRAM score (GRAM) variables and LUS. Adult COVID-19 patients admitted to the emergency department (ED) were enrolled. Ten variables previously identified by GRAM, days from symptom onset, LUS findings, and peripheral oxygen saturation/fraction of inspired oxygen (P/F) ratio were analyzed. LUS score as a single predictor was assessed. We evaluated GRAM model's performance, the impact of adding LUS, and then developed a new model based on the most predictive variables. Results: Among 274 COVID-19 patients enrolled, 174 developed critical illness. The GRAM score identified 51 patients at high risk of developing critical illness and 132 at low risk. LUS score over 15 (range 0 to 36) was associated with a higher risk ratio of critical illness (RR, 2.05; 95% confidence interval [CI], 1.52-2.77; area under the curve [AUC], 0.63; 95% CI 0.676-0.634). The newly developed COVID-19 Worsening Score relies on five variables to classify high- and low-risk patients with an overall accuracy of 80% and negative predictive value of 93% (95% CI, 87%-98%). Patients scoring more than 0.183 on COWS showed a RR of developing critical illness of 8.07 (95% CI, 4.97-11.1). Conclusions: COWS accurately identify patients who are unlikely to need intensive care unit (ICU) admission, preserving resources for the remaining high-risk patients.openopenBoero, Enrico; Rovida, Serena; Schreiber, Annia; Berchialla, Paola; Charrier, Lorena; Cravino, Marta Maria; Converso, Marcella; Gollini, Paola; Puppo, Mattia; Gravina, Angela; Fornelli, Giorgia; Labarile, Giulia; Sciacca, Santi; Bove, Tiziana; Karakitsos, Dimitrios; Aprà, Franco; Blaivas, Michael; Vetrugno, LuigiBoero, Enrico; Rovida, Serena; Schreiber, Annia; Berchialla, Paola; Charrier, Lorena; Cravino, Marta Maria; Converso, Marcella; Gollini, Paola; Puppo, Mattia; Gravina, Angela; Fornelli, Giorgia; Labarile, Giulia; Sciacca, Santi; Bove, Tiziana; Karakitsos, Dimitrios; Aprà, Franco; Blaivas, Michael; Vetrugno, Luig

ERIS: revitalising an adaptive optics instrument for the VLT

ERIS is an instrument that will both extend and enhance the fundamental diffraction limited imaging and spectroscopy capability for the VLT. It will replace two instruments that are now being maintained beyond their operational lifetimes, combine their functionality on a single focus, provide a new wavefront sensing module that makes use of the facility Adaptive Optics System, and considerably improve their performance. The instrument will be competitive with respect to JWST in several regimes, and has outstanding potential for studies of the Galactic Center, exoplanets, and high redshift galaxies. ERIS had its final design review in 2017, and is expected to be on sky in 2020. This contribution describes the instrument concept, outlines its expected performance, and highlights where it will most excel.Comment: 12 pages, Proc SPIE 10702 "Ground-Based and Airborne Instrumentation for Astronomy VII

Establishing a core outcome set for peritoneal dialysis : report of the SONG-PD (standardized outcomes in nephrology-peritoneal dialysis) consensus workshop

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD

The Human Transcriptome During Nontyphoid Salmonella and HIV Coinfection Reveals Attenuated NFκB-Mediated Inflammation and Persistent Cell Cycle Disruption

Background. Invasive nontyphoid Salmonella (iNTS) disease is common and severe in adults with human immunodeficiency virus (HIV) infection in Africa. We previously observed that ex vivo macrophages from HIV-infected subjects challenged with Salmonella Typhimurium exhibit dysregulated proinflammatory cytokine responses