Mechanism of action and therapeutic use of bempedoic acid in atherosclerosis and metabolic syndrome

Bempedoic acid is a new cholesterol-lowering drug, which has recently received US FDA and EMA approval. This drug targets lipid and glucose metabolism as well as inflammation via downregulation of ATP-citrate lyase and upregulation of AMP-activated protein kinase (AMPK). The primary effect is the reduction of cholesterol synthesis in the liver and its administration is generally not associated to unwanted muscle effects. Suppression of hepatic fatty acid synthesis leads to decreased triglycerides and, possibly, improved non-alcoholic fatty liver disease. Bempedoic acid may decrease gluconeogenesis leading to improved insulin sensitivity, glucose metabolism, and metabolic syndrome. The anti-inflammatory action of bempedoic acid is mainly achieved via activation of AMPK pathway in the immune cells, leading to decreased plasma levels of C-reactive protein. Effects of bempedoic acid on atherosclerotic cardiovascular disease, type 2 diabetes and chronic liver disease have been assessed in randomized clinical trials but require further confirmation. Safety clinical trials in phase III indicate that bempedoic acid administration is generally well-tolerated in combination with statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to achieve low-density lipoprotein cholesterol targets. The aim of this narrative review on bempedoic acid is to explore the underlying mechanisms of action and potential clinical targets, present existing evidence from clinical trials, and describe practical management of patients

Early lean mass sparing effect of high-protein diet with excess leucine during long-term bed rest in women

Muscle inactivity leads to muscle atrophy. Leucine is known to inhibit protein degradation and to promote protein synthesis in skeletal muscle. We tested the ability of a high-protein diet enriched with branched-chain amino acids (BCAAs) to prevent muscle atrophy during long-term bed rest (BR). We determined body composition (using dual energy x-ray absorptiometry) at baseline and every 2-weeks during 60 days of BR in 16 healthy young women. Nitrogen (N) balance was assessed daily as the difference between N intake and N urinary excretion. The subjects were randomized into two groups: one received a conventional diet (1.1 ± 0.03 g protein/kg, 4.9 ± 0.3 g leucine per day) and the other a high protein, BCAA-enriched regimen (1.6 ± 0.03 g protein-amino acid/kg, 11.4 ± 0.6 g leucine per day). There were significant BR and BR × diet interaction effects on changes in lean body mass (LBM) and N balance throughout the experimental period (repeated measures ANCOVA). During the first 15 days of BR, lean mass decreased by 4.1 ± 0.9 and 2.4 ± 2.1% (p < 0.05) in the conventional and high protein-BCAA diet groups, respectively, while at the end of the 60-day BR, LBM decreased similarly in the two groups by 7.4 ± 0.7 and 6.8 ± 2.4%. During the first 15 days of BR, mean N balance was 2.5 times greater (p < 0.05) in subjects on the high protein-BCAA diet than in those on the conventional diet, while we did not find significant differences during the following time intervals. In conclusion, during 60 days of BR in females, a high protein-BCAA diet was associated with an early protein-LBM sparing effect, which ceased in the medium and long term

5PSQ-100 Comparative analysis of the safety and tolerability profile of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis

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Ruling out coronavirus disease 2019 in patients with pneumonia: The role of blood cell count and lung ultrasound

Coronavirus disease 2019 (COVID-19) is characterized by a distinctive blood leucocyte pattern and B-lines on lung ultrasound (LUS) as marker of alveolar-interstitial syndrome. We aimed to evaluate the accuracy of blood leucocyte count alone or in combination with LUS for COVID-19 diagnosis. We retrospectively enrolled consecutive patients diagnosed with community acquired pneumonia (CAP) at hospital admission to derive and validate cutoff values for blood cell count that could be predictive of COVID-19 before confirmation by the nucleic acid amplification test (NAAT). Cutoff values, generated and confirmed in inception (41/115, positive/negative patients) and validation (100/180, positive/negative patients) cohorts, were ≤17 and ≤10 cells/mm3 for basophils and eosinophils, respectively. Basophils and/or eosinophils below cutoff were associated with sensitivity of 98% (95%CI, 94–100) and negative likelihood ratio of 0.04 (95%CI, 0.01–0.11). In a subgroup of 265 subjects, the sensitivity of B-line on LUS was 15% lower (p &lt; 0.001) than that of basophils and/or eosinophils below cutoff. The combination of B-lines with basophils and eosinophils below cutoff was associated with a moderate increase of the positive likelihood ratio: 5.0 (95%CI, 3.2–7.7). In conclusion, basophil and eosinophil counts above the generated cutoff virtually rule out COVID-19 in patients with CAP. Our findings can help optimize patient triage pending the NAAT results

Integration of multiple platforms for the analysis of multifluorescent marking technology applied to pediatric GBM and dipg

The intratumor heterogeneity represents one of the most difficult challenges for the development of effective therapies to treat pediatric glioblastoma (pGBM) and diffuse intrinsic pontine glioma (DIPG). These brain tumors are composed of heterogeneous cell subpopulations that coexist and cooperate to build a functional network responsible for their aggressive phenotype. Understanding the cellular and molecular mechanisms sustaining such network will be crucial for the identification of new therapeutic strategies. To study more in-depth these mechanisms, we sought to apply the Multifluorescent Marking Technology. We generated multifluorescent pGBM and DIPG bulk cell lines randomly expressing six different fluorescent proteins and from which we derived stable optical barcoded single cell-derived clones. In this study, we focused on the application of the Multifluorescent Marking Technology in 2D and 3D in vitro/ex vivo culture systems. We discuss how we integrated different multimodal fluorescence analysis platforms, identifying their strengths and limitations, to establish the tools that will enable further studies on the intratumor heterogeneity and interclonal interactions in pGBM and DIPG

Cannabis sativa L. inflorescences from monoecious cultivars grown in central Italy: an untargeted chemical characterization from early flowering to ripening

The chemical composition of the inflorescences from four Cannabis sativa L. monoecious cultivars (Ferimon, Uso-31, Felina 32 and Fedora 17), recently introduced in the Lazio Region, was monitored over the season from June to September giving indications on their sensorial, pharmaceutical/nutraceutical proprieties. Both untargeted (NMR) and targeted (GC/MS, UHPLC, HPLC-PDA/FD and spectrophotometry) analyses were carried out to identify and quantify compounds of different classes (sugars, organic acids, amino acids, cannabinoids, terpenoids, phenols, tannins, flavonoids and biogenic amines). All cultivars in each harvesting period showed a THC content below the Italian legal limit, although in general THC content increased over the season. Citric acid, malic acid and glucose showed the highest content in the late flowering period, whereas the content of proline drastically decreased after June in all cultivars. Neophytadiene, nerolidol and chlorogenic acid were quantified only in Felina 32 cultivar, characterized also by a very high content of flavonoids, whereas alloaromadendrene and trans-cinnamic acid were detected only in Uso-31 cultivar. Naringenin and naringin were present only in Fedora 17 and Ferimon cultivars, respectively. Moreover, Ferimon had the highest concentration of biogenic amines, especially in July and August. Cadaverine was present in all cultivars but only in September. These results suggest that the chemical composition of Cannabis sativa L. inflorescences depends on the cultivar and on the harvesting period. Producers can use this information as a guide to obtain inflorescences with peculiar chemical characteristics according to the specific use

Need for psychological support and disability management programs during and after the COVID-19 pandemic in Italy: Preliminary findings from a hospital-based occupational health surveillance program

Introduction: Since the beginning of COVID-19 pandemic, healthcare workers (HCWs) have undoubtedly experienced overwhelming levels of strain associated with social and occupational stressors. This study aimed to investigate the potential psychological effects experienced by hospital workers and HCWs and their associated demographical and occupational characteristics during the COVID-19 pandemic. Methods: A cross-sectional study was carried out in a public hospital in Rome, Italy, from June 2020 to July 2021. 635 hospital workers (HCWs, administrative and technicians) were enrolled in the study. The “Psychological Injury Risk Indicator” questionnaire was used. Statistical analyses have been made using Student’s T test for categorical binomial variables and analysis of variance for multi-categorical variables. Logistic regression analysis was then performed. Results: 30.6% of the sample was at risk for general psychological impairment; reduced energy recovery was found in 48.0% and sleep problems in 44.7% of them. Female workers reported a two-fold risk for potential psychological impairment compared to male colleagues. Nurses presented a three-fold risk while physicians a two-fold risk for the overall score. Additionally, physicians had a four-fold risk to develop a lack of energy recovery and a three-fold risk for chronic fatigue. Technicians showed a significant double risk for sleep problems and chronic fatigue as well as a three-fold risk for reduced energy recovery. Administrative personnel reported a tendency on sleep problems. Interestingly, agile working was a two-fold protecting factor. No-night shifters have a half risk for reporting problems in energy recovery. Discussion and Conclusion: The measure of agile working is effective to mitigate the impacts of COVID-19 on mental health by protecting and promoting the psychological wellbeing of HCWs during and after the outbreak

Effectiveness of psychological support to healthcare workers by the occupational health service: a pilot experience

Work-related stress is a significant risk for healthcare workers (HCWs). This study aims aevaluating the effectiveness of an individual psychological support programme for hospital workersIn all, 35 workers participated (n). A control group of 245 workers (7n) was set. Occupationadistress was measured by the General Health Questionnaire, (GHQ-12), the quality of life by the Short Form-36 health survey, (SF-36), and sickness absence was recorded. Costs and benefits of the service were evaluated and the return on investment (ROI) was calculated. The level of distress was significantly reduced in the treated group at the end of the follow-up (p &lt; 0.001). Quality of life had significantly improved (p &lt; 0.003). A 60% reduction of sickness absence days (SADs) following the intervention was recorded. After the treatment, absenteeism in cases was significantly lower than in controls (p &lt; 0.02). The individual improvement of mental health and quality of life was significantly correlated with the number of meetings with the psychologist (p &lt; 0.01 and p &lt; 0.03, respectively)The recovery of direct costs due to reduced sick leave absence was significantly higher than the costs of the programme; ROI was 2.73. The results must be examined with caution, given the very limited number of workers treated; this first study, however, encouraged us to continue the experience

Vulcani: esplosioni ed effusioni

Si tratta dei pannelli realizzati per la mostraVulcani: Esplosioni ed effusioni Festival della Scienza di Genova 2007 Palazzo Ducale – Sottoporticato, Genova Una nuova mostra interattiva delll’Istituto Nazionale di Geofisica e Vucanologia, alla scoperta dei segreti del nostro pianeta e del mondo spettacolare dei vulcani. Organizzato come un “racconto”, è un lungo viaggio dalla nascita Terra ad oggi che aiuta a comprendere il ruolo fondamentale dei vulcani nella storia del nostro pianeta. Inizia con una proiezione 3d seguita da un filmato spettacolare e coinvolgente di eruzioni vulcaniche. Nella mostra si incontrano poi un grande modello di vulcano che può essere “acceso” in modalità interattiva, producendo un’eruzione esplosiva con gran fragore, sezioni di vulcano per scoprire “cosa c’è sotto”, plastici associati ad una speciale proiezione che permette di visualizzare sia l’eruzione sia l’interno del vulcano. E ancora rocce vulcaniche e un laboratorio per esperienze guidate, per capire il meccanismo che provoca l’eruzione, studiando il legame tra gas, pressione ed esplosione, anche utilizzando ulteriori modellini di vulcano. Il fatto che spesso le eruzioni vulcaniche siano accompagnate da attività sismica ci introduce alla parte finale della mostra, dedicata ai terremoti. L’obiettivo complessivo della mostra è quello di comunicare e far comprendere l’importanza del lavoro di ricerca e di controllo che svolge l’INGV e il riflesso che questo ha nella vita di ciascuno di noi. Si tratta, in sostanza, di “raccontare” le attività scientifiche svolte dall’Istituto inquadrandole dal punto di vista del visitatore.Con i contributi dell’Associazione per il Festival della Scienza e del Dipartimento della Protezione CivilePublished5.8. TTC - Formazione e informazionereserve