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Primary dentition is crucial in influencing the emergence of permanent teeth. Premature primary tooth loss can result in undesired tooth motions and space loss in the permanent dentition. Typically, fixed or removable dental appliances are adopted to maintain edentulous space until the eruption of permanent teeth. However, traditional space maintainers have limitations in terms of variability in tooth anatomy, potential allergic reactions in some individuals (i.e., nickel sensitivity), difficulties in maintaining oral hygiene, and patient acceptance. The present study introduces a fully digital framework for the design and manufacturing of customized pediatric unilateral space maintainers using generative algorithms. The proposed approach overcomes the current challenges by using a biocompatible resin material and optimizing the device’s size, design, and color. The methodology involves intraoral scanning, surface selection, and trim, generative 3D modeling, finite element analysis (FEA), and additive manufacturing (AM) through vat photopolymerization. FEA results demonstrate the device’s mechanical performance and reliability, while additive manufacturing ensures design freedom, high resolution, surface finishing, dimensional accuracy, and proper fit. The mechanical interlocking system facilitates easy and effective positioning of the device. This digital approach offers the potential for wider usage of space maintainers and can be further validated through experimental assessments and clinical studies.

Introduction: Shellfish allergy is an important cause of food allergies worldwide. Both in vivo and in vitro diagnostics failure nowadays is caused by the poor quality of the extracts associated with the scarce availability of allergenic molecules in the market. It is known that not all patients with shellfish allergies experience adverse reactions to mollusks. It is still unclear how to detect and diagnose these patients correctly. Aim: To investigate the features of shrimp-allergic patients either reactive or tolerant to mollusks, with the currently available diagnostic methods. Methods: Nineteen centers, scattered throughout Italy, participated in the real-life study, enrolling patients allergic to shrimp with or without associated reactions to mollusks. Patients underwent skin tests using commercial extracts or fresh raw and cooked shrimp and mollusks, and IgE reactivity to currently available allergenic extracts and molecules was measured in vitro. Results: Two hundred and forty-seven individuals with a self reported adverse reactions to shrimp participated in the study; of these 47.8% reported an adverse reaction to mollusks ingestion (cephalopod and/or bivalve). Neither of the tests used, in vivo nor in vitro, was able to detect all selected patients. Accordingly, a great heterogeneity of results was observed: in vivo and in vitro tests agreed in 52% and 62% of cases. Skin tests were able to identify the mollusk reactors (p

SonoVue (Bracco, Milan, Italy) is a drug used in ultrasonography for the purpose of increasing the echogenicity of blood or fluids by improving the signal-to-noise ratio. Background/Objectives/Methods: We described a case of anaphylaxis due to SonoVue and performed a literature review. Results and Conclusions: We reported a case of anaphylaxis secondary to the administration of SonoVue and described all the 13 literature cases. Given its widespread use and the potentially dangerous nature of the reactions it can cause, it is advisable to know how to promptly recognize fatal reactions. [ABSTRACT FROM AUTHOR]

Eleonora Nucera,1 Sara Urbani,1 Alessandro Buonomo,1 Tiziana De Pasquale,2 Angela Rizzi,1 Arianna Aruanno,1 Stefano Pucci2 1Allergy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 2Civitanova Marche Hospital, Civitanova Marche, ItalyCorrespondence: Eleonora NuceraAllergy Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo F. Vito, 1, Rome, 00168, ItalyTel +39 3394475931Fax +06 30156999Email eleonora.nucera@policlinicogemelli.itAbstract: Gadolinium-based contrast agents (GBCAs) are considered to be safe, although sometimes patients report a hypersensitivity reaction when undergoing magnetic resonance imaging (MRI). The mechanisms of these reactions and of the sensitization to GBCAs are still largely unknown. We describe four cases of patients who experienced immediate adverse reactions to GBCAs with a demonstrated cutaneous hypersensitivity suggesting an IgE-mediated mechanism.Keywords: gadolinium-based contrast agents, hypersensitivity, IgE-mediated reactions

Eleonora Nucera,* Arianna Aruanno,* Angela Rizzi,* Michele Centrone* Allergy Unit, Fondazione Policlinico Universitario A. Gemelli IRCSS, Università Cattolica del Sacro Cuore, Rome, Italy*These authors contributed equally to this workCorrespondence: Eleonora NuceraAllergy Unit, Fondazione Policlinico Universitario A. Gemelli IRCSS, Largo F. Vito, 1, Rome 00168, ItalyEmail eleonora.nucera@policlinicogemelli.itAbstract: Allergy to natural rubber latex (NRLA) from Hevea brasiliensis is a relevant public health issue, in particular in healthcare workers and groups at risk. Clinical manifestations of NRLA can range from mild skin disorders to life-threatening systemic reactions. Prevention measures remain the gold-standard treatment for patients suffering from NRLA, but the only etiological therapy able to influence the natural history of NRLA is specific desensitization. This review aims to underline the epidemiological, clinical and diagnostic aspects of NRLA, and carries out a complete and wide-ranging review of the current literature on NRLA management and immunotherapy.Keywords: latex, immunotherapy, desensitization

Abstract Background Ficus carica is an edible fruit, belonging to the Moraceae family, rarely described as cause of food allergy. We describe the first case of fig allergy that occurred as a cross-reactivity between fig and Derp 1. Case presentation We present a case of a 10-years-old-girl, with a history of no-seasonal mild intermittent rhinitis, who experienced an immediate reaction after ingestion of a fresh fig. Skin prick tests (SPT) with commercial extracts of food, airborne allergens, latex and panallergens (profilin, PR-10 and lipid transfer protein) were performed. SPT revealed a sensitization only for dermatophagoides farina and dermatophagoides pteronyssinus which was then confirmed with by specific IgE assay (UniCAP, Phadia, Uppsala, Sweden). We also carried out a positive SPT with a commercial fig allergen (Lofarma, Milan, Italy) and prick-by-prick (PBP) both with skin and pulp of green raw and cooked fig. Fig specific serum IgE levels were 1.08 U/ml and specific IgE for rDer p1 was 16.20 U/ml (total serum IgE = 377 U/ml). In contrast specific IgE levels for latex, LTP, profilin, PR-10 and pollen allergens were negative. Conclusion The ficin, the major fig allergen, belongs to cysteine protease family like Der p 1. The symptoms presented by our patient could be related to a cross reactivity between these two proteins which present a structural homology.

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods: Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results: 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions: The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

Abstract Background The α-l-arabinofuranosidases (α-l-ABFs) are exoenzymes involved in the hydrolysis of α-l-arabinosyl linkages in plant cell wall polysaccharides. They play a crucial role in the degradation of arabinoxylan and arabinan and they are used in many biotechnological applications. Analysis of the genome of R. cellulolyticum showed that putative cellulosomal α-l-ABFs are exclusively encoded by the xyl-doc gene cluster, a large 32-kb gene cluster. Indeed, among the 14 Xyl-Doc enzymes encoded by this gene cluster, 6 are predicted to be α-l-ABFs belonging to the CAZyme families GH43 and GH62. Results The biochemical characterization of these six Xyl-Doc enzymes revealed that four of them are α-l-ABFs. GH4316-1229 (RcAbf43A) which belongs to the subfamily 16 of the GH43, encoded by the gene at locus Ccel_1229, has a low specific activity on natural substrates and can cleave off arabinose decorations located at arabinoxylan chain extremities. GH4310-1233 (RcAbf43Ad2,3), the product of the gene at locus Ccel_1233, belonging to subfamily 10 of the GH43, can convert the double arabinose decorations present on arabinoxylan into single O2- or O3-linked decorations with high velocity (k cat = 16.6 ± 0.6 s−1). This enzyme acts in synergy with GH62-1234 (RcAbf62Am2,3), the product of the gene at locus Ccel_1234, a GH62 α-l-ABF which hydrolyzes α-(1 → 3) or α-(1 → 2)-arabinosyl linkages present on polysaccharides and arabinoxylooligosaccharides monodecorated. Finally, a bifunctional enzyme, GH62-CE6-1240 (RcAbf62Bm2,3Axe6), encoded by the gene at locus Ccel_1240, which contains a GH62-α-l-ABF module and a carbohydrate esterase (CE6) module, catalyzes deacylation of plant cell wall polymers and cleavage of arabinosyl mono-substitutions. These enzymes are also active on arabinan, a component of the type I rhamnogalacturonan, showing their involvement in pectin degradation. Conclusion Arabinofuranosyl decorations on arabinoxylan and pectin strongly inhibit the action of xylan-degrading enzymes and pectinases. α-l-ABFs encoded by the xyl-doc gene cluster of R. cellulolyticum can remove all the decorations present in the backbone of arabinoxylan and arabinan, act synergistically, and, thus, play a crucial role in the degradation of plant cell wall polysaccharides.

Background and aims: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods: Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. Results: 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24). Conclusions: Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.

Hypersensitivity reactions (HRs) to contrast media (CM) are a major problem. We compared differences of HRs to iodinated contrast media (ICM) versus gadolinium-based contrast media (GBCM), collecting data on prevalence, type, latency and severity. Secondly, the predisposition to perform new contrast tests, use of premedication and possible appearance of new reactions were explored in a long-term follow-up of 5 years. Clinical data, comorbidities, skin test (ST) results, re-exposure to CM procedures with any new reactions, premedication and CM used were collected. In a retrospective single-center study, 350 patients with mild to moderate HRs were enrolled. Asthma, food allergy, non-allergic drug hypersensitivity and neurologic disease were significantly more frequent in patients with HRs to GBCM compared to the high evidence of cardiovascular disease and history of cancer in patients with HRs to ICM. A marked delay in performing STs was reported by patients with negative results (66 months, p < 0.01). Iomeprol, iopamidol and gadobenic acid were the culprit CM most involved in HRs in patients with positive STs. During follow-up, 7.1% of responders reported new HRs to CM despite negative STs, premedication and infusion of alternative CM in most cases.