Methamphetamine abuse and “meth mouth” in Europe

With easy chemical synthesis from its precursor, methamphetamine (MA) is now widespread in many countries. The abuse of methamphetamine is associated with several negative effects on health, because MA is a neurotoxin and a dangerous central nervous system stimulant. It changes levels of neurotransmitters in the brain, releasing dopamine and inhibiting nor epinephrine uptake which increases sympathetic nervous system activity and can lead to cardiac arrhythmia, hypertension and tachypnea. The consequences of MA abuse are clearly manifested in oral diseases (like “meth mouth”) which is characterised by extensive caries, teeth grinding with ensuing dental wear and trismus. The present review was designed to fill the gap in knowledge about methamphetamine abuse in the European Union (EU) and to illustrate the main clinical effects of prolonged use. After describing the pharmacology and systemic effects of methamphetamine and concentrating on its effects on the mouth, the present review compares the epidemiology and incidence of abuse in the world, particularly the USA and the EU

THE 1562 DE DENTIBUS BY GIROLAMO CARDANO

“Nell’anno 1562, essendomi accorto che nessuno tra i medici antichi o moderni aveva trattato della cura dei denti, scrissi questo primo libro sui denti”: inizia così il proemio ai cinque libri degli “Opuscula Medica Senilia” di Gerolamo Cardano, nel quale l’autore rivendica il primato temporale nella compilazione del primo testo organico di Odontoiatria nella storia. Esso si troverebbe in competizione col celebre “Libellus De dentibus” di Bartolomeo Eustachio, apparso nel 1563 (ma scritto anch’esso nel 1562); in questa sede, però, non abbiamo voluto dimostrare precedenze temporali ma riportare all’interesse generale l’opera di Cardano che possiede un’impostazione diversa e complementare a quella di Eustachio: quest’ultimo si è occupato essenzialmente di anatomia e fisiologia dei denti, il primo della loro patologia e terapia. In questo contributo vengono presentate: una biografia essenziale del Cardano, una breve rivista della letteratura sul “De dentibus” e la sua prima traduzione integrale dal latino in italiano.“Godine 1562., uočivši da se nijedan antički, a ni suvremeni liječnik nije bavio njegom zubi, napisah ovu prvu knjigu o zubima.” Tako Girolamo Cardano započinje proslov svojih pet knjiga iz zbirke Opuscula medica senilia kao prvoga sustavnog teksta o zubarstvu općenito. Premda se po prvenstvu natječe sa slavnim naslovom Libellus de dentibus Bartolomea Eustachija iz 1563. (iako je napisan 1562.), nije nam namjera utvrđivati tko je bio prvi, već svratiti pozornost čitatelja na Cardanovo djelo kao nadopunu Eustachievoj anatomiji i fiziologiji zuba s gledišta nastanka bolesti i liječenja. Članak donosi sažet Cardanov životopis i pregled literature o djelu De dentibus te o prvom cjelovitom prijevodu djelu s latinskog na talijanski.“In the year 1562, having noticed that none of the ancient or modern physicians had treated the subject of dental care, I wrote this first book on the teeth”. So begins the preface to the five books of the Opuscula medica senilia by Girolamo Cardano, the first organic text on dentistry in history. It competed with the famous Libellus de dentibus by Bartolomeo Eustachio that appeared in 1563 (but was written in 1562). However, our intention is not to establish precedence but bring to reader’s attention Cardano’s work that complemented Eustachio’s anatomy and physiology of the teeth with their pathology and therapy. This article summarises Cardano’s biography and gives a brief review of literature on the De dentibus and of his first complete translation from Latin into Italian. De dentibus is the first of the five books of the Opuscula and is divided into three chapters, as described below. Chapter one, De dentibus, recalls briefly the anatomy and embryology of human teeth as bones and compares them with the teeth of some animals. Follows a description of systemic and local procedures, to preserve, protect, and cure the teeth. Preservation and protection are related to diet, sleep, physical activity, systemic and local medicaments, and amulets., whereas therapy involves remedies taken over from the Ancient Greek and Roman medicine (Hippocrates, Archigenes, Galen, Scribonius, Pliny the Younger, Ezio, Marcellus Empiricus ) and Arabic medicine (Avicenna in particular). The chapter continues with guidelines and procedures for shedding teeth that are damaged beyond repair using a special saltpetre and alum distillate of Cardano’s own invention, which he finds very effective. The chapter concludes with tooth extraction tools and methods, especially the one by Scribonius Largo with red-hot iron. Chapter two, –De morbis dentium in specie, describes diseases that affect the teeth and that can cause ache, mobility, weakness, numbness, or deformity (dolor, commotio, imbecillitas, stupor, deformitas). All these conditions may interact, creating a wide range of situations. Ache has seven possible causes that include altered humour, a cavity, a nerve injury, an abscess, breath (flatus), worms, and cold, and Cardano describes the remedies at physician’s disposal that even include spells. The causes of mobility are the same as for the ache plus periodontal problems such as dry root or alveolar laxity, and the author discusses local and systemic treatment options. Weakness is considered the worst of the dental pathologies, as it can easily require extraction. Stupor is caused by the corruption of the tooth or a nerve injury, and Cardano refers to it as a life-threatening condition (quoad vitam) in older people if untreated, but also easy to remedy if detected early. Cardano then identifies a whole series of deformities: tooth colour, roughness, fracture, position, number, absence, length, calculus, bad smell, and porosity, and for each of them he offers a wide variety of remedies, in part original and in part borrowed from the ancients. In the last part, Cardano stresses the need to extract as few teeth as possible: “I’ve never seen anyone die from the diseases of the teeth, except for a tooth extracted inappropriately” To emphasize the dichotomy between medicine and surgery, he explains that tooth care is medical, but extraction requires an experienced surgeon. Chapter three, De fluxione, frequentissima causa morborum dentium, identifies gumboil as a frequent cause of dental disease, and describes the pathogenesis and therapy of gumboil-related diseases, gout in particular

ARTURO BERETTA AND THE “TROPHOMICROBIC THEORY OF THE CARIES”

Il più originale contributo portato dalla Scuola italiana allo studio della eziopatogenesi della carie è senza dubbio rappresentato dalla “teoria trofomicrobica” elaborata da Arturo Beretta, primo docente ufficiale di Odontoiatria nell’Università di Bologna nel 1918. Nel presente lavoro, dopo aver presentato alcuni cenni biografici e bibliografici sull’Autore (ch fu, tra l’altro Preside della Facoltà Medica di Bologna e giunse ad essere nominato Senatore per chiara fama) vengono illustrati i principi di tale teoria precorritrice basata sulla aggiunta alla teoria chimico-parassitaria di Miller del ruolo della predisposizione dello smalto e della saliva dell’ospite. Viene anche ricordata l’opera dei principali autori italiani e non italiani che hanno utilizzato o modificato l’idea di Beretta.Najizvorniji doprinos talijanske škole istraživanju nastanka karijesa svakako je “trofomikrobijska teorija” Artura Berette, prvog profesora stomatologije na Sveučilištu u Bologni 1918. Ovaj članak sažima biografske i bibliografske zapise o Beretti (koji je, između ostalog, bio i dekan Medicinskog fakulteta u Bologni te član talijanskog Senata), kao i načela njegove teorije, koja se nastavljaju na Millerovu “kemijsko-parazitsku” teoriju o svojstvima cakline i sline domaćina koja pogoduju nastanku karijesa. U članku se spominju i najvažniji radovi talijanskih i drugih znanstvenika koji su prihvatili i dopunili Berettinu zamisao.The most original contribution made by the Italian School to the study of caries aetiology is undoubtedly the “trophomicrobic theory” proposed by Arturo Beretta, the first teacher of dentistry at the University of Bologna in 1918. This article brings biographical and bibliographical notes about Beretta (who was, among other things, Dean of the Faculty of Medicine of Bologna and Senator), and summarises the principles of his theory, which adds to Miller’s “chemical-parasitic” theory of caries-predisposing properties of the enamel and host saliva. It also recalls the work of major Italian and non-Italian researchers who have used or modified Beretta’s idea

The mRNA-1273 Vaccine Induces Cross-Variant Antibody Responses to SARS-CoV-2 With Distinct Profiles in Individuals With or Without Pre-Existing Immunity

mRNA-based vaccines effectively induce protective neutralizing antibodies against SARS-CoV-2, the etiological agent of COVID-19. Yet, the kinetics and compositional patterns of vaccine-induced antibody responses to the original strain and emerging variants of concern remain largely unknown. Here we characterized serum antibody classes and subclasses targeting the spike receptor-binding domain of SARS-CoV-2 wild type and α, β, γ and δ variants in a longitudinal cohort of SARS-CoV-2 naïve and COVID-19 recovered individuals receiving the mRNA-1273 vaccine. We found that mRNA-1273 vaccine recipients developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by natural infection. Importantly, these antibody responses targeted both wild type SARS-CoV-2 as well as its α, β, γ and δ variants. Following primary vaccination, individuals with pre-existing immunity showed higher induction of all antibodies but IgG3 compared to SARS-CoV-2-naïve subjects. Unlike naïve individuals, COVID-19 recovered subjects did not mount a recall antibody response upon the second vaccine dose. In these individuals, secondary immunization resulted in a slight reduction of IgG1 against the receptor-binding domain of β and γ variants. Despite the lack of recall humoral response, vaccinees with pre-existing immunity still showed higher titers of IgG1 and IgA to all variants analyzed compared to fully vaccinated naïve individuals. Our findings indicate that mRNA-1273 vaccine triggered cross-variant antibody responses with distinct profiles in vaccinees with or without pre-existing immunity and suggest that individuals with prior history of SARS-CoV-2 infection may not benefit from the second mRNA vaccine dose with the current standard regimen

SARS-CoV-2 Seroprevalence Study in Pediatric Patients and Health Care Workers Using Multiplex Antibody Immunoassays

SARS-CoV-2 infection has become a global health problem specially exacerbated with the continuous appearance of new variants. Healthcare workers (HCW) have been one of the most affected sectors. Children have also been affected, and although infection generally presents as a mild disease, some have developed the Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We recruited 190 adults (HCW and cohabitants, April to June 2020) and 57 children (April 2020 to September 2021), of whom 12 developed PIMS-TS, in a hospital-based study in Spain. Using an in-house Luminex assay previously validated, antibody levels were measured against different spike and nucleocapsid SARS-CoV-2 proteins, including the receptor-binding domain (RBD) of the Alpha, Beta, Gamma, and Delta variants of concern (VoC). Seropositivity rates obtained from children and adults, respectively, were: 49.1% and 11% for IgG, 45.6% and 5.8% for IgA, and 35.1% and 7.3% for IgM. Higher antibody levels were detected in children who developed PIMS-TS compared to those who did not. Using the COVID-19 IgM/IgA ELISA (Vircell, S.L.) kit, widely implemented in Spanish hospitals, a high number of false positives and lower seroprevalences compared with the Luminex estimates were found, indicating a significantly lower specificity and sensitivity. Comparison of antibody levels against RBD-Wuhan versus RBD-VoCs indicated that the strongest positive correlations for all three isotypes were with RBD-Alpha, while the lowest correlations were with RBD-Delta for IgG, RBD-Gamma for IgM, and RBD-Beta for IgA. This study highlights the differences in antibody levels between groups with different demographic and clinical characteristics, as well as reporting the IgG, IgM, and IgA response to RBD VoC circulating at the study period

Antibody conversion rates to SARS-CoV-2 in saliva from children attending summer schools in Barcelona, Spain.

Background: Surveillance tools to estimate viral transmission dynamics in young populations are essential to guide recommendations for school opening and management during viral epidemics. Ideally, sensitive techniques are required to detect low viral load exposures among asymptomatic children. We aimed to estimate SARS-CoV-2 infection rates in children and adult populations in a school-like environment during the initial COVID-19 pandemic waves using an antibody-based field-deployable and non-invasive approach. Methods: Saliva antibody conversion defined as ≥ 4-fold increase in IgM, IgA, and/or IgG levels to five SARS-CoV-2 antigens including spike and nucleocapsid constructs was evaluated in 1509 children and 396 adults by high-throughput Luminex assays in samples collected weekly in 22 summer schools and 2 pre-schools in 27 venues in Barcelona, Spain, from June 29th to July 31st, 2020. Results: Saliva antibody conversion between two visits over a 5-week period was 3.22% (49/1518) or 2.36% if accounting for potentially cross-reactive antibodies, six times higher than the cumulative infection rate (0.53%) assessed by weekly saliva RT-PCR screening. IgG conversion was higher in adults (2.94%, 11/374) than children (1.31%, 15/1144) (p=0.035), IgG and IgA levels moderately increased with age, and antibodies were higher in females. Most antibody converters increased both IgG and IgA antibodies but some augmented either IgG or IgA, with a faster decay over time for IgA than IgG. Nucleocapsid rather than spike was the main antigen target. Anti-spike antibodies were significantly higher in individuals not reporting symptoms than symptomatic individuals, suggesting a protective role against COVID-19. Conclusion: Saliva antibody profiling including three isotypes and multiplexing antigens is a useful and user-friendlier tool for screening pediatric populations to detect low viral load exposures among children, particularly while they are not vaccinated and vulnerable to highly contagious variants, and to recommend public health policies during pandemics

A Novel Monoclonal Antibody Targeting a Large Surface of the Receptor Binding Motif Shows Pan-neutralizing SARS-CoV-2 Activity Including BQ.1.1 Variant

In the present study we report the functional and structural characterization of 17T2, a new highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody (mAb) isolated from a convalescent COVID-19 individual infected during the first wave of the COVID-19 pandemic. 17T2 is a class 1 VH1-58/κ3-20 antibody, derived from a receptor binding domain (RBD)-specific IgA memory B cell and developed as a human recombinant IgG1. Functional characterization revealed that 17T2 mAb has a high and exceptionally broad neutralizing activity against all SARS-CoV-2 spike variants tested, including BQ.1.1. Moreover, 17T2 mAb has in vivo prophylactic activity against Omicron BA.1.1 infection in K18-hACE2 transgenic mice. 3D reconstruction from cryogenic-electron microscopy (cryo-EM) showed that 17T2 binds the Omicron BA.1 spike protein with the RBD domains in up position and recognizes an epitope overlapping with the receptor binding motif, as it is the case for other structurally similar neutralizing mAbs, including S2E12. Yet, unlike S2E12, 17T2 retains its high neutralizing activity against all Omicron sublineages tested, probably due to a larger contact area with the RBD, which could confer a higher resilience to spike mutations. These results highlight the impact of small structural antibody changes on neutralizing performance and identify 17T2 mAb as a potential candidate for future therapeutic and prophylactic interventions.We acknowledge access to the cryo-EM CNB-CSIC facility in the context of the CRIOMECORR project (ESFRI-2019-01-CSIC-16) and we thank the staff of the Protein Technology Unity (CRG) for the help in protein production. This study was supported by the COVID-19 call grant from Generalitat de Catalunya, Department of Health (to GM), grant Miguel Servet research program (to GM), and partially funded by the crowdfunding initiative #joemcorono and the Fundació Glòria Soler (to JB). A.P-G. was supported by a predoctoral grant from Generalitat de Catalunya and Fons Social Europeu (2022 FI_B 00698).N

Simulating Empathic Behavior in a Social Assistive Robot

When used as an interface in the context of Ambient Assisted Living (AAL), a social robot should not just provide a task-oriented support. It should also try to establish a social empathic relation with the user. To this aim, it is crucial to endow the robot with the capability of recognizing the user’s affective state and reason on it for triggering the most appropriate communicative behavior. In this paper we describe how such an affective reasoning has been implemented in the NAO robot for simulating empathic behaviors in the context of AAL. In particular, the robot is able to recognize the emotion of the user by analyzing communicative signals extracted from speech and facial expressions. The recognized emotion allows triggering the robot’s affective state and, consequently, the most appropriate empathic behavior. The robot’s empathic behaviors have been evaluated both by experts in communication and through a user study aimed at assessing the perception and interpretation of empathy by elderly users. Results are quite satisfactory and encourage us to further extend the social and affective capabilities of the robot