Smoking Habit Prevention in Schools: Report of a Pediatric Educational Intervention Held in Pisa

Introduction: Smoking is the leading preventable cause of death in the world and the detrimental effects of tobacco on health have been described across the full life span. There is no safe level of tobacco exposure and childhood is the more vulnerable period of life. Current estimates show that 10% of children aged 13-15 years are active smokers and most of them started smoking at ≥11 years of age, due to peer and/or family influence. Moreover, recently, e-cigarette use has spread, particularly among youth. Many school-based smoking prevention interventions have been carried out around the world, the efficacy of which has yet to be established. Materials and methods: In February 2018 we planned an educational program on smoking habit within the Italian Society of Pediatric Respiratory Diseases (SIMRI) (“Dai un calcio al fumo” program). In May 2018 we held 8 interventions at the Fibonacci School (Pisa, Italy), meeting 365 children aged 9 to 13 years and involving a pediatrician and a pediatric resident in a 2-hour lesson focusing on the importance of a healthy lifestyle and smoking habit effects. The children were invited to ask questions and talk about their experiences, with a subsequent 30-minutes collegial discussion. The most frequent questions were collected, as well as students’, physicians’ and teachers’ opinions on each meeting. Results: During our educational interventions the most frequently asked questions were about the discrepancy related to the fact that a dangerous product is legally sold and the potential harmful effects of e-cigarettes. All the children stated that they knew that combustible cigarette smoking was dangerous. Most of them admitted that they feel that smoking habits start from emulating friends and relatives. Almost 70% of the children reported to have at least one smoker relative. Teachers, physicians and students proposed to replicate the meetings the following year. Conclusions: The considerable interest shown by the students, together with the low cost and potential effectiveness of school-based educational measures, suggest that in our country a national educational program should be introduced in schools. Too many children are still exposed to tobacco smoke in the household environment

SINDROME DA INSENSIBILITA' COMPLETA AGLI ANDROGENI: ASPETTI CLINICI E GENETICI IN UN'AMPIA CASISTICA ITALIANA.

I disordini (o differenze) della differenziazione sessuale (DSD) con cariotipo 46, XY sono condizioni cliniche rare caratterizzate dalla presenza di gonadi disgenetiche o maschili (testicoli) in persone con un fenotipo femminile o con vari gradi di ambiguità dei genitali interni e/o esterni. Nell'ambito dei 46,XY DSD, la sindrome da insensibilità agli androgeni (Androgen Insensitivity Syndrome o AIS) rappresenta una delle condizioni più frequenti pur avendo una prevalenza stimata di circa 1: 20.000 - 1: 100.000 nati/anno con cariotipo 46,XY Scopo della tesi. Analizzare l’assetto genico in rapporto alle mutazioni del gene AR, il motivo di presentazione clinica, lo stato minerale osseo confrontando diverse metodiche densitometriche, lo status dell'asse riproduttivo compresa l'eventuale esecuzione di un intervento di rimozione delle gonadi, la gestione terapeutica in un ampio gruppo di persone con Sindrome da Insensibilità Completa agli Androgeni (CAIS) seguite presso l’UO Pediatria Universitaria, Dipartimento Materno-Infantile, Azienda Ospedaliero-Universitaria Pisana (AOUP) negli anni 2000-2020 e presso l’UO Ginecologia e Ostetricia, Policlinico S.Orsola-Malpighi, Università di Bologna. Risultati. La diagnosi di CAIS è stata formulata in 72 pazienti. L'età media al sospetto clinico e l'età media alla diagnosi genetica sono risultate rispettivamente pari a 13,1 ± 6,7 anni e 24,9 ± 13,6 anni (ritardo di diagnosi molecolare pari a 12,3 ± 11,4 anni). Sono state individuate 72 mutazioni del gene AR: tra esse il 65,1% sono risultate mutazioni puntiformi; il 12,15% inserzioni o delezioni; il 12,15% mutazioni da alterato splicing del RNA; il 7,6% delezioni complete o parziali del gene e il 3% rare delezioni complete del gene AR. L'amenorrea primaria è stata la principale causa di consultazione (25/53; 47,2%). L'ernia inguinale bilaterale è stata riscontrata in oltre 32% del campione (17/53), in 13,2% (7/53) la diagnosi è stata sospettata per un'anamnesi familiare positiva; una discordanza genotipo/fenotipo in diagnosi prenatale è avvenuta per tre delle pazienti (5,7%); in una paziente (1,9%) la diagnosi è stata sospettata per la presenza di massa inguinale all'ecografia addominale. Le caratteristiche auxologiche delle donne con CAIS oggetto di questo studio sono sovrapponibili alla popolazione femminile di riferimento ad eccezione di BMI e peso che sono risultati superiori nel sottogruppo con gonadi in sede e nelle donne CAIS gonadectomizzate dopo i 14 anni di età. La densità minerale ossea è risultata ridotta sia per i valori di riferimento di sesso femminile, sia per quello maschile con maggiore compromissione dei distretti lombare e femorale soprattutto nel gruppo delle donne CAIS gonadectomizzate precocemente. Disorders (or differences) of sexual differentiation (DSD) with 46, XY karyotype are rare clinical conditions characterized by the presence of dysgenetic or male gonads (testes) in persons with a female phenotype or with varying degrees of ambiguity of the internal genitals and / or external. Among the 46, XY DSDs, the Androgen Insensitivity Syndrome (AIS) represents one of the most frequent conditions despite having an estimated prevalence of about 1: 20,000 - 1: 100,000 births / year with 46, XY karyotype The aim: Analyze mutations of the AR gene, the reason for clinical presentation, the bone mineral status by comparing different densitometric methods, the status of the reproductive axis including the possible execution of a gonad removal, therapeutic management in a large group of females with Complete Androgen Insensitivity Syndrome (CAIS) followed at the University Pediatrics Unit, Maternal-Infantile Department, Pisa University Hospital (AOUP) in the years 2000-2020 and at the Gynecology and Obstetrics Unit , S. Orsola-Malpighi Polyclinic, University of Bologna. Results. The diagnosis of CAIS was made in 72 patients. The mean age at clinical suspicion and mean age at genetic diagnosis were respectively 13.1 ± 6.7 years and 24.9 ± 13.6 years (molecular delay of diagnosis equal to 12.3 ± 11, 4 years). 72 mutations of the AR gene were identified: among them 65.1% were point mutations; 12.15% insertions or deletions; 12.15% mutations due to impaired RNA splicing; 7.6% complete or partial deletions of the gene and 3% rare complete deletions of the AR gene. Primary amenorrhea was the main cause of consultation (25/53; 47.2%); bilateral inguinal hernia was found in over 32% of the sample (17/53), in 13.2% (7/53) the diagnosis was suspected due to a positive family history; a genotype / phenotype mismatch in prenatal diagnosis occurred for three of the patients (5.7%); in one patient (1.9%) the diagnosis was suspected due to the presence of inguinal mass on abdominal ultrasound. The auxological characteristics of the women with CAIS of this study are comparable to the reference female population with the exception of BMI and weight which were higher in the subgroup with intact gonads and in CAIS women gonadectomized after 14 years of age. Bone mineral density was reduced for both female and male reference values ​​with greater compromise of the lumbar and femoral districts especially in the group of early gonadectomized CAIS women

Central Precocious Puberty in Boys and Girls: Similarities and Differences

Central precocious puberty (CPP) is due to the premature activation of the hypothalamic–pituitary–gonadal axis, which is responsible for the appearance of secondary sexual characteristics. It occurs before the age of 8 and 9 in girls and boys, respectively. CPP shows higher incidence in females than in males. Causes of CPP are similar in both sexes, but the idiopathic form is more frequent in girls, while organic forms are more frequent in males. Recent studies demonstrated a role of some genetic variants in the pathogenesis of CPP. The diagnostic evaluation based on accurate physical examination, assessment of the pituitary–gonadal axis, pelvic sonography in girls, and determination of bone age. Magnetic resonance of the central nervous system should be done in all boys and selected girls. Since the 1980s, pharmacologic treatment involves the use of gonadotropin-releasing hormone (GnRH) analogs. These drugs are characterized by few side effects and long-term safety. Many data are available on the outcome of GnRH analog treated female patients, while poor data are reported in boys. Adult height is improved in both sexes

Complete Androgen Insensitivity Syndrome: From Bench to Bed

Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (AR). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the AR gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS

Complete Androgen Insensitivity Syndrome: From Bench to Bed

Complete androgen insensitivity syndrome (CAIS) is due to complete resistance to the action of androgens, determining a female phenotype in persons with a 46,XY karyotype and functioning testes. CAIS is caused by inactivating mutations in the androgen receptor gene (AR). It is organized in eight exons located on the X chromosome. Hundreds of genetic variants in the AR gene have been reported in CAIS. They are distributed throughout the gene with a preponderance located in the ligand-binding domain. CAIS mainly presents as primary amenorrhea in an adolescent female or as a bilateral inguinal/labial hernia containing testes in prepubertal children. Some issues regarding the management of females with CAIS remain poorly standardized (such as the follow-up of intact testes, the timing of gonadal removal and optimal hormone replacement therapy). Basic research will lead to the consideration of new issues to improve long-term well-being (such as bone health, immune and metabolic aspects and cardiovascular risk). An expert multidisciplinary approach is mandatory to increase the long-term quality of life of women with CAIS

Valutazione dell’efficacia del PICADAR nello screening della discinesia ciliare primaria

La Discinesia Ciliare Primaria (DCP) è una malattia congenita, clinicamente e geneticamente eterogenea, caratterizzata da un deficit del trasporto muco-ciliare legato a una disfunzione delle ciglia respiratorie (associata o meno ad un difetto della loro ultrastruttura), con conseguenti infezioni ricorrenti/recidivanti a carico delle vie aeree e del parenchima polmonare e progressivo decadimento della funzione respiratoria. Si tratta di una patologia rara, con una prevalenza stimata di circa 1:16.000, anche se si ritiene sia ancora ampiamente sotto-diagnosticata. La sua diagnosi è, infatti, di solito posta tardivamente a causa della scarsa conoscenza della malattia da parte degli operatori sanitari e di un iter diagnostico che si avvale di esami complessi e disponibili solo in pochi Centri. Inoltre, le manifestazioni cliniche non sono specifiche e variano con l’età dei pazienti. Pertanto, allo scopo di migliorare l’identificazione dei soggetti da avviare alle indagini diagnostiche, è stato recentemente proposto e va-lidato un questionario denominato PICADAR (PrImary CiliAry DyskinesiA Rule), che si può utilizzare fin dalle prime epoche della vita nei soggetti con tosse catarrale quotidiana insorta precocemente, condizione indispensabile per il sospetto diagnostico di DCP. Lo scopo del nostro studio è stato valutare l’efficacia di questo strumento nello screening della malattia attraverso un’analisi retrospettiva della storia clinica dei soggetti sottoposti agli accertamenti diagnostici per DCP presso il nostro Centro negli ultimi 10 anni