Natural and hybrid immunity after SARS-CoV-2 infection in children and adolescents.

PURPOSE: In contrast to adults, immune protection against SARS-CoV-2 in children and adolescents with natural or hybrid immunity is still poorly understood. The aim of this study was to analyze different immune compartments in different age groups and whether humoral immune reactions correlate with a cellular immune response. METHODS: 72 children and adolescents with a preceding SARS-CoV-2 infection were recruited. 37 were vaccinated with an RNA vaccine (BNT162b2). Humoral immunity was analyzed 3-26 months (median 10 months) after infection by measuring Spike protein (S), nucleocapsid (NCP), and neutralizing antibodies (nAB). Cellular immunity was analyzed using a SARS-CoV-2-specific interferon-γ release assay (IGRA). RESULTS: All children and adolescents had S antibodies; titers were higher in those with hybrid immunity (14,900 BAU/ml vs. 2118 BAU/ml). NCP antibodies were detectable in > 90%. Neutralizing antibodies (nAB) were more frequently detected (90%) with higher titers (1914 RLU) in adolescents with hybrid immunity than in children with natural immunity (62.5%, 476 RLU). Children with natural immunity were less likely to have reactive IGRAs (43.8%) than adolescents with hybrid immunity (85%). The amount of interferon-γ released by T cells was comparable in natural and hybrid immunity. CONCLUSION: Spike antibodies are the most reliable markers to monitor an immune reaction against SARS-CoV-2. High antibody titers of spike antibodies and nAB correlated with cellular immunity, a phenomenon found only in adolescents with hybrid immunity. Hybrid immunity is associated with markedly higher antibody titers and a higher probability of a cellular immune response than a natural immunity.

PML nuclear body disruption impairs DNA double-strand break sensing and repair in APL.

Proteins involved in DNA double-strand break (DSB) repair localize within the promyelocytic leukemia nuclear bodies (PML-NBs), whose disruption is at the root of the acute promyelocytic leukemia (APL) pathogenesis. All-trans-retinoic acid (RA) treatment induces PML-RARα degradation, restores PML-NB functions, and causes terminal cell differentiation of APL blasts. However, the precise role of the APL-associated PML-RARα oncoprotein and PML-NB integrity in the DSB response in APL leukemogenesis and tumor suppression is still lacking. Primary leukemia blasts isolated from APL patients showed high phosphorylation levels of H2AX (γ-H2AX), an initial DSBs sensor. By addressing the consequences of ionizing radiation (IR)-induced DSB response in primary APL blasts and RA-responsive and -resistant myeloid cell lines carrying endogenous or ectopically expressed PML-RARα, before and after treatment with RA, we found that the disruption of PML-NBs is associated with delayed DSB response, as revealed by the impaired kinetic of disappearance of γ-H2AX and 53BP1 foci and activation of ATM and of its substrates H2AX, NBN, and CHK2. The disruption of PML-NB integrity by PML-RARα also affects the IR-induced DSB response in a preleukemic mouse model of APL in vivo. We propose the oncoprotein-dependent PML-NB disruption and DDR impairment as relevant early events in APL tumorigenesis.

Impact of alcohol consumption on winter sports-related injuries.

INTRODUCTION: This study was carried out to evaluate data about trauma-related winter sports, including risk factors such as high speed, gender, age, alcohol consumption, details about the accident and snow conditions. METHODS: A retrospective review was conducted to determine the injury patterns and crash circumstances in holiday skiers and snowboarders. The data recorded were obtained from the database of the Pre-Hospital Emergency Registry of six skiing areas in the Dolomite mountains during the winter seasons November 2004-May 2009, injury data for major traumas from Ski Patrol Injury reports (helicopter, ambulance or ski slopes' patrol reports), and intrahospital Emergency Department data. Alcohol concentration in blood was detected in 200 individuals suffering from major trauma. RESULTS: A total of 4550 injured patients, predominantly male (69%), mean age 22 years (range 16-72), were included in the observational analysis. Knee, wrist and shoulder injuries were frequently associated with major thoracic, abdominal or head traumas (64% of cases). Suboptimal technical level, high speed, low concentration, snow or weather conditions, faulty equipment and protective devices were among the various causes of accidents. The analysis revealed that high alcohol blood concentration was present in 43% of 200 patients. CONCLUSIONS: Even though the major causes of accidents were excessive speed, excessive fatigue, technical errors and bad weather conditions, alcohol abuse was often discovered. Random sampling and a non-systematic detection of alcohol blood levels likely led to an underestimation of alcohol consumption-related injuries. It is recommended that investigations into alcoholic intoxication in injured skiers should be carried out on a large scale.

[Extracorporeal shock wave lithotripsy in the treatment of sialolithiasis. Long-term results]. / La litotrissia extracorporea ad onde d'urto nella terapia della scialolitiasi. Risultati a distanza.

The Authors report the results of a short term follow-up in 28 patients treated for sialolithiasis. Extracorporeal lithotripsy is safe, effective and minimally invasive therapeutical option. Open surgery is reserved to cases of failure of noninvasive procedure.

[A health education program for the prevention of heart diseases carried out in a population in Calabria]. / Un programma di educazione sanitaria per la prevenzione delle cardiopatie realizzato in un ambito di popolazione della Calabria.

BACKGROUND: To evaluate the behaviour and knowledge of students on cardiovascular risk factors and to programme a campaign for the prevention of cardiovascular diseases. METHODS: All students attending the last year of the secondary school of this province answered a questionnaire. An educational campaign followed the analysis of the questionnaire. RESULTS: The analysis of 3675 questionnaires shows that almost all students were between 18 and 20; 16% of males (m) and 7.4% of females (f) were overweight; 1.5% and 0.4% respectively were obese; 88.8% of m and 44% of were doing physical activity; 32.4% of m and 26.8% of f were cigarette smokers. Knowledge about cardiovascular risk factors were poor. Development of the prevention campaign. In the school districts four seminars were organized to discuss about cardiovascular prevention with science teachers of the province, using audiovisual materials. The same teachers devote 4-6 hours to the same matters during school lessons. In the next months conferences destined to the population of the province will be organized. CONCLUSIONS: This program allows to promote health education in the whole population, through the students, with a low cost.

New introducer technique for implanting pacemakers and defibrillator leads: percutaneous incannulation of the cephalic vein.

OBJECTIVES: This study was designed to assess the feasibility of percutaneous incannulation of cephalic vein for the implantation of pacemaker and defibrillator leads. BACKGROUND: The development of the subclavian vein puncture technique for pacemaker lead implantation has many advantages compared to surgical isolation of cephalic vein. However, initial enthusiasm has been dampened by reports of serious complications because of the anatomical relationships of the subclavian vein. METHODS AND RESULTS: Percutaneous incannulation of the right cephalic vein was attempted in 75 patients who were candidates for permanent pacemaker or ICD implantation. The technique was effective in 46 patients. It was shown to be ineffective in 18, despite the presence of a normal vein. In seven patients, the cephalic vein was found to be unusable for passing the electrocatheter and in four patients, the vein was absent. In the patients in whom the vein was present, the success rate was 46/71 (64%). The average implantation time was 7.2 minutes (range 5-10), while the average time for conventional surgical technique was 15.2 minutes (range 14-20) (p < 0.001). All patients remained free from complications during a mean follow-up period of 8.2 months (range 1 to 18). CONCLUSIONS: In our opinion, percutaneous incannulation of cephalic vein could be adopted as the first step in pacemaker or defibrillator implantation procedures, as it shows satisfactory success rates, simplicity of execution and absence of complications. Most importantly, in the event of failure, it does not compromise the use of a conventional technique.

[Massive pseudocysto-jejunal hemorrhage caused by rupture of pseudoaneurysm of the splenic artery]. / Hemorragia pseudoquisto-yeyunal masiva por rotura de pseudoaneurisma de la arteria esplénica.

The authors report a case of massive intestinal hemorrhage caused by rupture of a splenic artery pseudoaneurysm into a pseudocystojejunostomy. The pathologic and clinical features of this unusual complication of pancreatitis are discussed. One hundred and seventy one cases of major bleeding associated with pseudocysts and/or pseudoaneurysms have been reported in the literature during the period 1989-May 1991. Acute and chronic pancreatitis may be the underlying etiologies and the overall mortality rate of this complication is 35.1%. According to the authors experience, angiographic localization of the bleeding sources and steel coil embolization play a key role in the diagnostic and therapeutic approach to what is generally regarded as the most rapidly lethal sequelae of pancreatitis.

A Mutant of Arabidopsis thaliana with a Reduced Response to Fusicoccin. I.

Because fusicoccin (FC) has the the capacity to promote solute uptake, a selective procedure for isolating mutants of Arabidopsis thaliana with a reduced response to the toxin has been developed. The procedure is based on the incubation of A. thaliana seedlings in a solution containing the cation Paraquat (Pq) at a concentration that per se does not produce bleaching of the leaves upon illumination but does in the presence of FC because of the increased uptake of the toxic cation. Using this procedure, we identified, among the progenies of 2010 M1 ethyl methanesulfonate-mutagenized plants, two mutants that stay green after exposure to FC and Pq. Some properties and inheritance of one of the two mutants (5-2) are described. Morphology of mutant plants is almost indistinguishable from that of the wild type. However, 5-2 seeds germinate and produce viable seedlings in the presence of FC plus the aminoglycoside antibiotic hygromycin B: plants of the mutant do not wilt when exposed to FC and stomata do not open or open only partially. In the presence of FC, the mutant appears less responsive than the wild type as far as the increment in fresh weight, the enlargement of leaf disc area, or the stimulation of H+ extrusion is concerned. Inheritance of the trait is monogenic dominant or semidominant, depending on the test used.

[Clinical evaluation of the efficacy of Ro 15-1788, Anexate after balanced intravenous anesthesia with flunitrazepam and fentanyl]. / Valutazione clinica dell'efficacia del Ro 15-1788, Anexate dopo anestesia endovenosa bilanciata condotta con flunitrazepam e fentanil.

Benzodiazepines are widely used as neuroleptics in anaesthesia, but they give rise to drowsiness at the end of surgery. Anexate is an imidazobenzodiazepine with specific antagonistic activity for benzodiazepines. We have administered 0.2 mg i.v. of the drug to 20 adult patients after anaesthesia with tiopentale (250 mg), pancuronium bromide (0.07 mg.kg-1), flunitrazepam (2 mg) and fentanyl (0.10 mg); after the first dose fentanyl was administered (0.10 mg) about every 30 minute. Analgesia was supplemented with nitrous oxide 66%. Blood pressure and heart rate did not changes significantly after Anexate; respiratory volume increased significantly in all cases (ANOVA P less than 0.001). Consciousness was rapidly resumed in all cases and patients demonstrated to be oriented in time and space soon after Anexate. In 14 out of 20 patients drowsiness reappeared after about 30 minute and further doses of 0.1 mg of the drug (to a maximum of 0.4 mg in some cases) were necessary. Side effects were rare and slight, their occurrence depending on the speed of administration. In our opinion a total dose of 0.3 to 0.4 mg Anexate is need to fully antagonize the sedative effect of 2 mg flunitrazepam.