Uporaba ultrazvuka u procjeni rizika od profesionalnog oboljenja donjeg dijela kralježnice

The aim of the study was to evaluate ultrasound tehnique in preemployment medical assessment of the risk for low-back pain. Volunteers for the study were recruited among agricultural workers employed in the »Agraria Department« of the University of Bologna, Italy. The group consisted of 90 subjects, 52 male and 38 female, aged 25 to 58 years. The subjects filled in a questionnaire on medical history of low-back pain and were examined using an ultrasonograph equipped with a high linear frequency probe (3.5 MHz). The oblique parasagittal diameter of the lumbar spinal canal was measured by transabdominal ultrasonic imaging in the lumbar (L4–L5) and lumbosacral (L5–S1) region. Individuals with significantly narrower canals (<14 mm) had an increased risk of low-back pain. The paper concludes that ultrasound imaging could become a valuable screening tool in industry, permitting selective job placement for workers at high risk for disorders of the back.Cilj je ovoga istraživanja bio ocijeniti vrijednost ultrazvuka kao sredstva za ocjenjivanje rizika od oboljenja donjeg dijela kralježnice prilikom pregleda za zaposlenje. Ispitano je 90 dobrovoljaca s Agrarnog odjela Sveučilišta u Bologni, od kojih 52 žene i 38 muškaraca u dobi između 25 i 58 godina. Ispitanici su popunili upitnik o anamnezi oboljenja donjeg dijela kralježnice te su pregledani s pomoću ultrazvuka s visokofrekventnom linearnom sondom (3,5 MHz). Promjer kanala leđne moždine mjeren je s pomoću transabdominalne primjene ultrazvuka u lumbalnom (L4–L5) i lumbosakralnom (L5–S1) području. Osobe sa značajnim suženjem kanala leđne moždine (<14 mm) pokazivale su povećani rizik od oboljenja donjeg dijela kralježnice. Autori zaključuju da ultrazvučna dijagnostika može biti vrlo korisna za provjeru radne sposobnosti u proizvodnji, omogućujući selektivan pristup raspoređivanju radne snage s visokim rizikom od smetnji u leđima

GEN-O-MA project: an Italian network studying clinical course and pathogenic pathways of moyamoya disease—study protocol and preliminary results

Background: GENetics of mOyaMoyA (GEN-O-MA) project is a multicenter observational study implemented in Italy aimed at creating a network of centers involved in moyamoya angiopathy (MA) care and research and at collecting a large series and bio-repository of MA patients, finally aimed at describing the disease phenotype and clinical course as well as at identifying biological or cellular markers for disease progression. The present paper resumes the most important study methodological issues and preliminary results. Methods: Nineteen centers are participating to the study. Patients with both bilateral and unilateral radiologically defined MA are included in the study. For each patient, detailed demographic and clinical as well as neuroimaging data are being collected. When available, biological samples (blood, DNA, CSF, middle cerebral artery samples) are being also collected for biological and cellular studies. Results: Ninety-eight patients (age of onset mean ± SD 35.5 ± 19.6 years; 68.4% females) have been collected so far. 65.3% of patients presented ischemic (50%) and haemorrhagic (15.3%) stroke. A higher female predominance concomitantly with a similar age of onset and clinical features to what was reported in previous studies on Western patients has been confirmed. Conclusion: An accurate and detailed clinical and neuroimaging classification represents the best strategy to provide the characterization of the disease phenotype and clinical course. The collection of a large number of biological samples will permit the identification of biological markers and genetic factors associated with the disease susceptibility in Italy

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

ROLE OF AKAP-LBC SIGNALING IN PROTECTION AGAINST DOXORUBICIN-INDUCED CARDIOTOXICITY

La doxorubicine (DOX) est un antibiotique qui appartient à la famille des anthracyclines. La DOX est largement utilisée dans la thérapie anti-cancer pour traiter les tumeurs hématologiques et solides. Malgré son efficacité, la DOX présente une toxicité cardiaque significative associée à la mort des cardiomyocytes, la fibrose cardiaque, la cardiomyopathie dilatée et l'insuffisance cardiaque. La toxicité cardiaque de la DOX est principalement liée à l'induction d'un stress oxydatif générant des dérivés réactifs de l'oxygène (DRO) et à la modification de la fonction mitochondriale. Le manque actuel de traitements pour prévenir efficacement la cardiotoxicité de la DOX souligne la nécessité de nouvelles approches thérapeutiques. Les récentes données montrent que l'activation des récepteurs al-adrénergiques (al-ARs) peut protéger le cœur contre l'infarctus du myocarde, ainsi que la mort des cardiomyocytes induite par l'ischémie-reperfusion. Dans la présente étude, nous montrons que la stimulation des cardiomyocytes avec des petites doses de la phényléphrine (PE), un agoniste de al-ARs, inhibe de manière significative l'apoptose induite par un traitement avec la DOX. Nos résultats montrent surtout qu'AKAP-Lbc, une protéine d'ancrage de la protéine kinase A exprimé dans les cardiomyocytes, est essentiel pour la transduction des signaux de protection en aval des al- ARs. En particulier, en infectant des cultures primaires de myocytes ventriculaires avec lentivirus codant pour des petits ARN en épingle à cheveux (shRNAs) spécifiques pour AKAP- Lbc, nous avons pu montrer que la suppression de l'expression AKAP-Lbc compromet fortement la capacité de la PE à réduire l'apoptose induite par DOX. La protection des cardiomyocytes médiée par AKAP-Lbc semble nécessiter de l'activation d'une voie de prosurvival protéine kinase D (PKD) dépendante. En conclusion, AKAP-Lbc semble jouer le rôle de coordinateur de signaux qui protègent les cardiomyocytes contre les effets toxiques de la DOX. -- Doxorubicin (DOX) is an anthracycline antibiotic that is widely used in anti-cancer therapy to treat hematological and solid tumors. Despite its efficacy, DOX displays significant cardiac toxicity associated with cardiomyocytes death, cardiac fibrosis, dilated cardiomyopathy and heart failure. Cardiac toxicity is mainly associated with the ability of DOX to promote oxidative stress through the génération of reactive oxygen species (ROS) and to alter mitochondrial function. The current lack of treatments to efficiently prevent DOX cardiotoxicity underscores the need of new therapeutic approaches. Recent evidence indicates that activation of al-adrenergic receptors (al-ARs) can protect the heart against myocardial infarction as well as cardiomyocytes death induced by ischemia- reperfusion. In the current study, we show that stimulation of cardiomyocytes with low doses of al-ARs agonist phenylephrine (PE) significantly inhibits the apoptosis induced by DOX treatment. Importantly, our results indicate that AKAP-Lbc, a cardiac A-kinase anchoring protein, is critical for transducing protective signais downstream of al-ARs. In particular, we could show that suppression of AKAP-Lbc expression by infecting primary cultures of ventricular myocytes with lentiviruses encoding AKAP-Lbc speciflc short hairpin (sh) RNAs strongly impairs the ability of PE to reduce DOX-induced apoptosis. AKAP-Lbc-mediated cardiomyocytes protection appears to require the activation of a protein kinase D (PKD) - dépendent prosurvival pathway. In conclusion, AKAP-Lbc emerges as a coordinator of signais that protect cardiomyocytes against the toxic effects of DOX

Emerging roles of A-kinase anchoring proteins in cardiovascular pathophysiology

Heart and blood vessels ensure adequate perfusion of peripheral organs with blood and nutrients. Alteration of the homeostatic functions of the cardiovascular system can cause hypertension, atherosclerosis, and coronary artery disease leading to heart injury and failure. A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins that are crucially involved in modulating the function of the cardiovascular system both under physiological and pathological conditions. AKAPs assemble multifunctional signaling complexes that ensure correct targeting of the cAMP-dependent protein kinase (PKA) as well as other signaling enzymes to precise subcellular compartments. This allows local regulation of specific effector proteins that control the function of vascular and cardiac cells. This review will focus on recent advances illustrating the role of AKAPs in cardiovascular pathophysiology. The accent will be mainly placed on the molecular events linked to the control of vascular integrity and blood pressure as well as on the cardiac remodeling process associated with heart failure. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel

Prolyl endopeptidase from Aspergillus niger immobilized on a food-grade carrier for the production of gluten-reduced beer

The recently growing demand of gluten-reduced beer is leading to the development of diverse approaches to be applied in brewing. The current work focuses on the development of an innovative and sustainable biocatalytic tool for the continuous production of gluten-reduced beer, based on the application of immobilized prolyl endopeptidase from Aspergillus niger (AN-PEP). This food-grade protease has been immobilized on A. niger chitosan beads and applied, for the first time, for the reduction of gluten in a commercial beer from barley malt. The immobilization procedure was optimized for maximizing the specific activity of the biocatalyst (0.016 I.U./mgBSAeq) and the best performance was reached using an immobilization solution at an initial protein concentration of 0.3 mgBSAeq/mL. The immobilization increased the thermal stability of the protease, which showed similar catalytic properties in synthetic beer (toward the synthetic substrate Z-Gly-Pro-pNA) when it was applied at 20 °C or at 50 °C. The continuous treatment in fluidized bed reactor (FBR), containing 10 g of immobilized AN-PEP (corresponding to 0.0036 gBSAeq), was optimized varying the flow rate (Qv). The suitable conditions to achieve reduction of the intact gluten of authentic beer was Qv of 728 mL/min. The continuous treatment in FBR allowed us to reduce the initial gluten content (65 mg/kg) in the commercial beer from barley malt, reaching the concentration of 19 mg/kg after 9 h and 15 mg/kg after 10 h of treatment

Smenamide a analogues. Synthesis and biological activity on multiple myeloma cells

Smenamides are an intriguing class of peptide/polyketide molecules of marine origin showing antiproliferative activity against lung cancer Calu-1 cells at nanomolar concentrations through a clear pro-apoptotic mechanism. To probe the role of the activity-determining structural features, the 16-epi-analogue of smenamide A and eight simplified analogues in the 16-epi series were prepared using a flexible synthetic route. The synthetic analogues were tested on multiple myeloma (MM) cell lines showing that the configuration at C-16 slightly affects the activity, since the 16-epi-derivative is still active at nanomolar concentrations. Interestingly, it was found that the truncated compound 8, mainly composed of the pyrrolinone terminus, was not active, while compound 13, essentially lacking the pyrrolinone moiety, was 1000-fold less active than the intact substance and was the most active among all the synthesized compounds