The role of skin tests with polyethylene glycol and polysorbate 80 in the vaccination campaign for COVID-19: results from an Italian multicenter survey.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen–Sensitized Patients

Background: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen–hypersensitive patients.Objective: We investigated monosensitization to peamaclein among Italian cypress pollen–allergic patients.Patients: A total of 835 cypress pollen–hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7.Results: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein–allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP.Conclusion: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein (AU)

Antecedentes: La proteína del melocotón regulada por giberelina (peamacleina) ha sido descrita recientemente con alérgeno alimentarioen los pacientes con alergia al polen de ciprés.Objetivo: Determinar la presencia de monosensibilización a peamacleina en los pacientes italianos con alergia al polen de ciprés.Pacientes: Se estudiaron 835 pacientes italianos con alergia al polen de ciprés, provenientes de 28 centros hospitalarios. En todos ellosse realizó historia clínica dirigida a detectar alergia alimentaria así como prick test con extractos comerciales de melocotón que conteníanpeamacleína. En los pacientes sensibilizados a melocotón se determinó IgE específica a Pru p 3 y aquellos con resultado negativo seclasificaron como potencialmente monosensibilizados a peamacleina. Se realizó determinación de IgE específica a Pru p 7 medianteimmunoblot e ImmunoCAP con Pru p 7.Resultados: El prick test con melocotón fue positivo en 163 pacientes (19,5%), pero 127 de estos pacientes fueron excluidos por estarsensibilizados a Pru p 3. 24 pacientes (14,7%), que correspondían al 2,8% de la población global, fueron considerados como potencialmentemonosensibilizados a peamacleína. La distribución de estos pacientes no seguía ningún patrón geográfico. 17/24 (70,8%) tenían historiade alergia alimentaria, en la mayoría de los casos a melocotón (n=15). Los pacientes también referían síntomas con otros alimentoscomo otras frutas rosáceas, cítricos, higo, melón, frutos secos y kiwi. Solo 3/18 pacientes presentaban en el immunoblot una banda dealrededor de 7 kDa; otros 4 pacientes reconocían una banda de 50-60 kDa. 10/18 presentaron positividad en el ImmunoCAP a Pru p 7.Conclusión: En Italia, la alergia o sensibilización a peamacleina es baja. La mayor parte de los pacientes reaccionan con el melocotón,aunque otras frutas rosáceas y cítricos también desencadenan síntomas

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Effects of Encouraging the Use of Gestures on Speech.

Purpose Previous studies have investigated the effects of the inability to produce hand gestures on speakers' prosodic features of speech; however, the potential effects of encouraging speakers to gesture have received less attention, especially in naturalistic settings. This study aims at investigating the effects of encouraging the production of hand gestures on the following speech correlates: speech discourse length (number of words and discourse length in seconds), disfluencies (filled pauses, self-corrections, repetitions, insertions, interruptions, speech rate), and prosodic properties (measures of fundamental frequency [F0] and intensity). Method Twenty native Italian speakers took part in a narration task in which they had to describe the content of short comic strips to a confederate listener in 1 of the following 2 conditions: (a) nonencouraging condition (N), that is, no instructions about gesturing were given, and (b) encouraging condition (E), that is, the participants were instructed to gesture while telling the story. Results Instructing speakers to gesture led effectively to higher gesture rate and salience. Significant differences were found for (a) discourse length (e.g., the narratives had more words in E than in N) and (b) acoustic measures (F0 maximum, maximum intensity, and mean intensity metrics were higher in E than in N). Conclusion The study shows that asking speakers to use their hands while describing a story can have an effect on narration length and can also impact on F0 and intensity metrics. By showing that enhancing the gesture stream could affect speech prosody, this study provides further evidence that gestures and prosody interact in the process of speech production.

Anion transport in normal erythrocytes, sickle red cells, and ghosts in relation to hemoglobins and magnesium.

"Band 3," an integral membrane protein of red blood cells, plays a relevant role in anionic transport. The C- and N-terminal portions of band 3 are cytoplasmatics, and the last is the link site for different glycolitic enzymes, such as glyceraldehyde-3-phosphate dehydrogenase, aldolase, phosphofructokinase, and hemoglobin. All or some of these interactions on the CDB3 protein could allow a subtle modulation of anion flux. The interaction among HbA, Mg(2+), and membrane proteins has been sufficiently investigated, but not the effect of Mg(2+) on pathological hemoglobin in relation to the influx of the SO(4)(2-). The aim of this study was to evaluate the involvement of hemoglobin S in sulfate transport. This has been measured with native and increased concentrations of Mg(2+), using normal erythrocytes containing HbA, sickle red cells containing HbS, or ghosts obtained from both erythrocytes and normal erythrocytes ghosts with HbS added. The magnitude of the SO(4)(2-) rate constant measured in normal red blood cells increased markedly when measured in the presence of varied Mg(2+) concentrations. The results show that a low increase of intracellular Mg(2+) concentrations exercises a different HbA modulation on band 3 protein and consequently higher anion transport activity. The same experiments carried out in sickle red cells showed that the SO(4)(2-) rate constant measured in the presence of native concentrations of Mg(2+) was normal, compared to normal red cells, and was not affected by any increase of intracellular Mg(2+). Our suppositions with regard to the importance exercised by the hemoglobin and the Mg(2+) on the SO(4)(2-) influx were confirmed by comparison of the data obtained through measuring SO(4)(2-) influx with native and increased concentrations of Mg(2+) in both normal and sickle red cell ghosts. Both revealed the same sensitivity to Mg(2+) due to withdrawal of hemoglobins. The incorporation of HbS in normal as well as in sickle red cell ghosts reduced the Mg(2+) response to sulfate influx in both the reconstituted ghosts. Our research demonstrated that the different effects exercised on the rate constants of SO(4)(2-) influx in normal (HbA) and sickle red cells (HbS) by the increased intracellular Mg(2+) could be ascribed to the physical-chemical influence exercised either on the hemoglobins or on the intracellular contents of erythrocytes.

Susceptibility to mouse cytomegalovirus is associated with deletion of an activating natural killer cell receptor of the C-type lectin superfamily.

Cytomegalovirus is the leading cause of congenital viral disease and the most important opportunistic infection in immunocompromised patients. We have used a mouse experimental infection model (MCMV) to study the genetic parameters of host/virus interaction. Susceptibility to infection with MCMV is controlled by Cmv1, a chromosome 6 locus that regulates natural killer (NK) cell activity against virally infected targets. Here, we use a positional cloning strategy to isolate the gene mutated at the Cmv1 locus. Cmv1 maps within a 0.35-cM interval defined by markers D6Ott8 and D6Ott115, which corresponds to a physical distance of 1.6 Mb (refs. 6-8). A transcript map of the region identified 19 genes, including members of the killer cell lectin-like receptor family a (Klra, formerly Ly49; refs. 9-12), which encode inhibitory or activating NK cell receptors that interact with MHC class I molecules. Klra genes have different copy numbers and genomic organization, and are highly polymorphic among inbred strains, making it difficult to distinguish between normal allelic variants and distinct Klra genes, or possible mutations associated with Cmv1. The recombinant inbred strain BXD-8/Ty (BXD-8; ref. 18), derived from Cmv1r C57BL/6 (B6, resistant) and Cmv1s DBA/2 (susceptible), is of particular interest because it is highly susceptible to MCMV infection despite having a B6 haplotype at Cmv1. We determined that MCMV susceptibility in BXD-8 is associated with the deletion of Klra8 (formerly Ly49h).

Pharmacodynamic variability of flecainide assessed by QRS changes.

The effect of flecainide on the QRS interval was studied in 10 patients who were receiving long-term oral treatment (50 to 150 mg twice daily) for arrhythmias that were refractory to other drugs. Total and free drug plasma levels and QRS durations were measured at intervals after the morning administration. Free drug plasma levels were linearly correlated with QRS duration in each patient and the slope of the line was widely variable in the population studied. Even after the data from one patient with an unusually high slope (0.454) was excluded from the analysis, the slope range was 0.0284 to 0.144. Pharmacodynamic variability could not be explained by heart rate changes, active metabolites, electrolyte disturbances, or free drug concentration. None of the pharmacokinetic parameters measured (average steady-state concentration, fluctuation of maximum and minimum concentrations, time to peak concentration, final half-life, and protein binding) showed an intersubject variability greater than 4.4 times. Our findings suggest that the determination of flecainide free plasma concentration may not be sufficient to forecast electrophysiologic effects in individual patients.