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The TRansition Age Management in Turner syndrome in Italy (TRAMITI) project aims to improve care for individuals with Turner Syndrome (TS) during their transition from pediatric to adult care. A team of 15 physicians and 1 psychologist collaborated to create a comprehensive set of 41 consensus statements, covering four key areas: transition and referral, sexual and bone health and oncological risks, social and psychological aspects and systemic and metabolic disorders. The consensus statements highlight the importance of patient-centered care, early intervention and long-term monitoring. They emphasize a multidisciplinary approach to address the complex medical and psychosocial aspects of TS. During the critical transition period, tailored approaches and early disclosure of the diagnosis are recommended to promote self-reliance and healthcare autonomy. To mitigate long-term complications, the consensus addresses fertility preservation and bone health strategies. It also recommends psychological or psychiatric evaluations to tackle the increased prevalence of anxiety and depression in patients with TS. In addition, strategies for addressing the heightened risk of metabolic, cardiovascular and autoimmune disorders in patients with TS are proposed. Regular screenings and interventions are advised to effectively manage these conditions. Furthermore, cardiac abnormalities, including aortic dissections, require close monitoring and early surgical intervention if specific criteria are met. Overall, the TRAMITI consensus statement provides valuable insights and evidence-based recommendations. It offers guidance for healthcare practitioners in delivering comprehensive and patient-centered care for individuals with TS. By addressing both medical and psychosocial aspects, the consensus aims to enhance TS management and improve the well-being and long-term outcomes of those affected by this genetic disorder.

Background: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison’s disease (AD). Methods: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIREmutations were determined. Results: The prevalence of APS-1 was 2.6 cases/million (range 0.5–17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIREmutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases. Conclusions: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIREgene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.

The problem of failure envelopes of pile groups subjected to vertical and eccentric load is investigated both theoretically and experimentally. A critical review of literature works on failure envelopes for pile groups under combined axial-moment loading is first provided. Emphasis is placed on a recent, exact solution derived from theorems of limit analysis by idealizing piles as uniaxial rigid-perfectly plastic elements. The application of the relevant equations over a practical range of problems needs only the axial capacities in compression and uplift of the isolated piles. An intense program of centrifuge experiments carried out along with different load paths on annular shaped pile groups aimed at validating the equations pertinent to the above solution is presented and discussed. The endpoints of the load paths followed in the centrifuge lie approximately above the analytical failure envelope, giving confidence that the reference equations can be reliably adopted to assess the capacity of a pile group under combined axial-moment loading. Finally, the kinematics of the collapse mechanism observed experimentally is compared to that determined from the application of the reference theory.

L’obésité est avec l’hypertrophie des végétations et des amygdales un des facteurs de risque principaux du syndrome d’apnées obstructives du sommeil (SAOS) de l’enfant. Elle est associée à une fréquence et une sévérité accrue du SAOS, et constitue également un facteur prédictif de la persistance et de l’aggravation du SAOS dans le temps. Le SAOS de l’enfant est associé à une morbidité d’organe qui touche avant tout le développement neurocognitif et comportemental. Les conséquences cardiovasculaires et métaboliques sont moins importantes chez l’enfant que chez l’adulte. Des interactions réciproques entre le sommeil en général, le SAOS, l’obésité et des dysrégulations de l’homéostasie métabolique ont été mises en évidence, ce qui rend très difficile l’établissement du rôle exact de l’obésité dans la morbidité d’organe liée au SAOS. Aucune étude n’a jusqu’à présent réussi à démontrer que l’obésité était associée à une « sur-morbidité d’organe » dans le SAOS de l’enfant. Elle est toutefois associée à une efficacité moindre des traitements du SAOS et, en particulier, de l’adéno-amygdalectomie. Les complications per- et postopératoires sont plus fréquentes et plus sévères chez l’enfant obèse. Le recours à un traitement par pression positive continue (PPC) est donc plus fréquent chez l’enfant obèse mais la compliance de celui-ci à la PPC est moins bonne que chez l’enfant non obèse. En conclusion, l’obésité de l’enfant constituant un problème de santé publique à l’échelle mondiale, sa prévention constitue une des mesures les plus efficaces pour diminuer l’incidence et la morbidité associée au SAOS de l’enfant.

Autosomal dominant polycystic kidney disease (APDKD) is the most relevant hereditary disease in Nephrology being commonin patients with renal failure or in hemodialysis. The disease has significant comorbidities complicating the everyday life of patients, and is characterized by a disabling set of symptoms: acute or chronic pain, abdominal obstruction, and gastrointestinal disorders.The natural history of the disease is still unknown, thus making it hard to plan and design the appropriate clinical approaches.A modern information network as well as a web database, aimed at gathering a variety of patient information (clinical and epidemiological), could be a valuable tool to identify more easily patients suffering from the disease and, thus, improve clinical management.

Since the introduction of the cytological screening programs, a significant reduction in the incidence of cervical cancer has been achieved. Almost all of these cancers are related to high-risk (HR) Human Papillomavirus (HPV) cervical infections. However, the natural history of HPV infection seems to be different in younger patients, resulting in a higher rate of regression. There is, therefore, the need to identify HPV-related biomarkers in order to enhance the effectiveness of screening of high-risk cytological lesions, in particular in women over 35 years of age. This study aims to evaluate the prognostic value of the HR HPV E6 and E7 mRNA expression in women with intraepithelial lesions of the cervix, older or younger than 35 years of age. One hundred and eighty-four HR HPV DNA positive patients with a low squamous intraepithelial lesion (LSIL) were tested for mRNA expressions, included in an observational study, and evaluated at follow-up with standard cytology up to 24 months from the mRNA test. The frequency of HSIL/LSIL cytology in the older cohort of mRNA positive patients was significantly higher compared to mRNA-negative patients, both at 1 and 2 years of follow-up (Chi-square: p 0.007 and p 0.009), but this difference was not found in the younger cohort. According to our results, the E6/E7 mRNA test could be a biomarker for viral activity, useful in identifying patients at higher risk of abnormal cytology, and in implementing the management of HR HPV DNA-positive women over 35 years of age.

During haemodialysis blood membrane contact causes the release of the content of platelet alpha-granules, which contain platelet-derived growth factor (PDGF). In view of its possible role in accelerated atherosclerotic processes, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during haemodialysis sessions performed using a cellulosic membrane.

Abstract: The size of a pancreatic ductal carcinoma is one of the factors that has the greatest impact on the prognosis of the disease. Precise measurement of tumor size in such cases can obviously be achieved only by the pathologist, but, as a result of the increasingly widespread use and refinement of imaging procedures, a fairly accurate preoperative estimate now appears feasible for identifying those lesions which measure ≤2 m in size and which are conventionally defined as “small tumors.” At tomography, 15/72 patients (20.8%) with cancer of the head of the pancreas observed in our department over the period 1991 to 1994 were prospectively identified as having tumors measuring ≤2 cm. Histology subsequently confirmed that the growths measured 2 cm or less in size in only 4 of these patients, thus revealing that the imaging technique tended to underestimate the tumor diameters. If we exclude the mean time elapsing from onset of symptoms to diagnosis, which was found to be significantly shorter in small than in non-small tumors (6.3 vs 34.2 days,P <0.01), no statistically significant differences were observed in any of the clinical and blood chemistry data evaluated (including CA 19-9 values) in patients with small vs non-small tumors who underwent radical resection. Small tumors of the pancreas are still rare and their diagnosis is often incidental (2/4 in this case series) and can only be confirmed by pathology findings. The radiological detection of a small tumor, however, is strongly suggestive of resectability (more than 70% in this series). This should prompt the surgeon to adopt an aggressive approach, even though the topographical location and biological nature of tumors measuring ≤2 cm are known to be capable of substantially undermining their potentially better prognosis.

Cystinuria is an autosomal recessive amino-aciduria where three urinary phenotypes have been described (I, II, and III). An amino acid transporter gene, SLC3A1 (formerly rBAT), was found to be responsible for this disorder. To assess whether mutations in SLC3A1 are involved in different cystinuria phenotypes, linkage with this gene and its nearest marker (D2S119) was analyzed in 22 families with type I and/or type III cystinuria. Linkage with heterogeneity was proved (alpha = 0.45; P < 0.008). Type I/I families showed homogeneous linkage to SLC3A1 (Zmax > 3.0 at theta = 0.00; alpha = 1), whereas types I/III and III/III were not linked. Our data suggest that type I cystinuria is due to mutations in the SLC3A1 gene, whereas another locus is responsible for type III. This result establishes genetic heterogeneity for cystinuria, classically considered as a multiallelic monogenic disease.

Flow cytometry (FC) may be considered as a fundamental technique in studying cell biology and pathology. It combines the quantitative character of biochemical methods with the multiparametric capacities of microscope analysis in a high‐precision process for rapid analysis of individual cell characteristics. Three original FC techniques routinely applied in the field of renal transplantation are reported in the present study. They concern the donor‐recipient cross‐match test, the morphological analysis of urinary sediment and the modulation of the density of various membrane antigens on the lymphocyte surface. A common factor underlies all these methods: they aim to provide the physician with a reliable diagnostic tool in clinical renal transplantation.

The present study reports on a biological model based on fibroblast proliferation applied to 3 different types of flat-plate dialysis membrane, in order to ascertain whether the artificial materials currently used in hemodialysis cause in vitro cellular proliferation. The study plan we followed involved plate membrane isolation from non-used dialyzers and used dialyzers, observed through scanning electron microscopy (SEM) both before and after testing with human fibroblasts by means of cell culture. Fibroblast growth was assessed by phase contrast light microscopy examination and cytometric DNA content evaluation. Our investigations proved that the artificial materials we considered interact with fibroblast cultures. Noticeable proliferative response was observed both after contact with unused material and on mediation by the protein layer absorbed on the membrane surface at the end of dialysis sessions. In this last case fibroblast proliferative activity appeared higher than that observed with unused membranes, showing that the soluble molecules entrapped in the protein layer appeared able to exert a biological activity even in in vitro tests

Annular shaped pile groups are a very common foundation layout for onshore wind turbines and other slender structures. In this study, their performance under vertical loads of moderate to high eccentricity, including moment rotation response and bearing capacity, was investigated by centrifuge testing on small scale physical models embedded in kaolin clay. To identify experimentally the capacity of the examined pile groups under different load paths, the model foundations were loaded monotonically until a clear collapse mechanism was achieved. The testing procedure and the proposed interpretation methodology can be easily adapted to load paths or pile layouts other than those considered in the current study. The experimental data can be adopted as a useful benchmark for mathematical models aimed at predicting the response of pile groups to complex load paths. The results of this testing program can also be used to assess the degree of conservatism of current methods adopted by industry for the design of piled foundations subjected to eccentric loads.

Les parents d’enfants ayant un trouble respiratoire du sommeil (TRS) peuvent avoir une qualité de vie et un sommeil perturbés. Le but de notre étude était d’évaluer la qualité de vie et du sommeil des parents d’enfants appareillés par une pression positive continue (PPC) ou une ventilation non invasive (VNI).

Le syndrome de Rett est caractérisé par une altération du développement du système nerveux central avec des troubles respiratoires à l’éveil et pendant le sommeil et des réveils fréquents. Les altérations polysomnographiques (PSG) ont été très peu décrites dans ce syndrome.

Les pathologies qui se manifestent par une résistance à l’action de la parathormone sont appelées pseudohypoparathyroïdies (PHP). Ce terme désigne un groupe de maladies rares dont les causes sont hétérogènes, génétiques ou épigénétiques. La classification actuelle de ces pathologies repose sur la présence de signes cliniques comme la brachydactylie, l’obésité et la petite taille (l’ostéodystrophie d’Albright), sur l’absence de réponse à la PTH endogène et exogène, et sur la mesure de l’activité biologique de la protéine G. Cependant, cette classification exclue les pathologies telles que l’acrodysostose ou l’hétéroplasie osseuse progressive, de même que les bases (epi)génétiques des différents sous-types de PHP. Le réseau EuroPHP a entrepris de proposer une nouvelle classification qui englobe toutes les pathologies caractérisées par une anomalie de la voie de signalisation PTH/PTHrP.

Background: Gastroesophageal reflux disease (GERD) in newborn is characterized by a protean symptomatology that includes excessive irritability and crying, frequent vomiting and regurgitations, feeding problems, rumination, apnea, aspiration pneumonia, failure to thrive and anemia. The aim of this study was to investigate the relationship between symptoms and gastroesophageal activity in infants with gastroesophageal reflux.Methods: To evaluate gastroesophageal tract activity we have combined multichannel intraluminal electrical impedance (MII) and pH monitoring with epigastric impedance (EGI) in 30 neonates with suspected GERD. This combination of three methods provides complementary, simultaneous data from the esophagus and stomach. MII detected reflux episodes were characterized by time of occurrence, duration, height, pH, gastric filling state and gastric emptying velocity. Relations between GER features, gastric emptying data and symptoms observed during the trial were statistically evaluated.Results: During 90 hours of combined recording 248 reflux events (15.3% acid) were detected in 30 neonates. 99 episodes were associated to symptoms. The average (SD) gastric emptying time was 148.2(21.9) minutes with a T½ of 56.2(15.1) minutes. The main gastric emptying velocity was 0.69(0.12) radians. The number of GER and acid GER per tracing were respectively 8.3(1.0) and 1.3(0.8). Crying(24) was associated to long and acid reflux events. Regurgitations(13) and vomiting(8) were associated to high level of GER and gastric filling level. Rumination(31) was increased during high level GERs. Irritability(20) was observed in both: low level and high duration reflux episodes. In the end a correlation between apnea(3) and acid refluxes was observed.Conclusions: Our data suggest a relationship between GER symptoms and gastroesophageal activity. These findings could be relevant to practice of giving neonatal GERD therapeutic treatments on the grounds of infants symptoms. Further studies are necessary to establish the impact of our results and a possible clinical utilization.

Background: Gastroesophageal reflux (GER) is a common and relevant clinical problem in infants. Relationships between GER and gastric emptying are still unclear. The multiple intraluminal impedance (MII) technique is based on the intraluminal measurement of electrical impedance between 6 electrodes during a bolus passage. On the basis of the temporal sequence of impedance changes, it can be identified whether a change in impedance is caused by a bolus moving in an antegrade (swallow) or a retrograde (reflux) direction. Epigastric impedance (EGI) is a technique to evaluate gastric emptying by measuring modifications in the impedance value in the gastric area by means of 4 skin electrodes. Aim of this study was to investigate the relationship between GER and gastric emptying by multiple intraluminal impedance and epigastric impedance in infants.Methods: 9 term infants with GER simptoms were evaluated by MII (Sleuth Recorder Sandhill) connected to an intraluminal 6 channel probe and by EGI (Akern) simultaneously. Data were collected for 180 min after the ingestion of a milk meal for two time for each patient. Refluxate events were detected by MII as impedance changes in the distal channels proceeded sequentially to the more proximal channels. From the epigastric impedance emptying curve was calculated for each refluxate event the level of gastric emptying and the emptying velocity (figure). Data were compared by using Pearson correlation.Results: 18 simultaneously analysis were performed for a total of 54 hours recording. 163 refluxate events were detected. The average emptying time and the number of reflux events were respectively 132±34(minutes), 9.1±3.3(events/ analysis). The frequency of refluxate events was significantly correlated with the emptying velocity (r=0.93; p<0.05). No correlations were found between GER and gastric emptying time or level of gastric emptying.Conclusion: Gastric emptying in GER infants has not a linear trend. Delayed emptying periods with an increasing of refluxate events are followed by fast emptying periods with decreasing of refluxate events. This variability suggests that a dismotility disorder interesting all the gastroesophageal tract might be relevant in infants affected by GER.