OSAS: valutazione della patologia e patente professionale

La sindrome delle apnee ostruttive del sonno è una patologia che colpisce indistintamente maschi e femmine. La OSAS (Obstructive Sleep Apnea Syndrome) è determinata da episodi ripetuti di ostruzione parziale o completa delle vie aeree superiori.I disturbi del sonno non solo si ripercuotono negativamente sulla salute e sulla qualità della vita di chi ne soffre, ma aumentano anche i rischi sulle strade. Il 19 febbraio 2016 è stato pubblicato sulla Gazzetta Ufficiale n. 41 il decreto dirigenziale 3 febbraio 2016 del Ministero della Salute, che fornisce gli indirizzi medico-legali da osservare per l’accertamento dell’idoneità psico-fisica alla guida per coloro che sono affetti, o che si sospetta possano essere affetti, da OSAS. The syndrome of obstructive sleep apneee is a condition that affects males and females without distinction. OSAS (Obstructive sleep apnea syndrome) is advanced by Repeated episodes of partial or complete obstruction of the upper airway.Sleep disorders not only have a negative effect on the health and quality of life of those who suffer, but also increase the risks on the roads.On February 19, 2016 it was published in the Official Gazette no. 41 of the Ministry of Health Decree of 3 February 2016, which contains the medical-legal guidelines to be observed for the assessment of the psycho-physical fitness to guide those who are affected, or who are suspected of being affected, by OSA

Hepatocytes undergo punctuated expansion dynamics from a periportal stem cell niche in normal human liver

Background & Aims: While normal human liver is thought to be generally quiescent, clonal hepatocyte expansions have been observed, though neither their cellular source nor their expansion dynamics have been determined. Knowing the hepatocyte cell of origin, and their subsequent dynamics and trajectory within the human liver will provide an important basis to understand disease-associated dysregulation. Methods: Herein, we use in vivo lineage tracing and methylation sequence analysis to demonstrate normal human hepatocyte ancestry. We exploit next-generation mitochondrial sequencing to determine hepatocyte clonal expansion dynamics across spatially distinct areas of laser-captured, microdissected, clones, in tandem with computational modelling in morphologically normal human liver. Results: Hepatocyte clones and rare SOX9+ hepatocyte progenitors commonly associate with portal tracts and we present evidence that clones can lineage-trace with cholangiocytes, indicating the presence of a bipotential common ancestor at this niche. Within clones, we demonstrate methylation CpG sequence diversity patterns indicative of periportal not pericentral ancestral origins, indicating a portal to central vein expansion trajectory. Using spatial analysis of mitochondrial DNA variants by next-generation sequencing coupled with mathematical modelling and Bayesian inference across the portal-central axis, we demonstrate that patterns of mitochondrial DNA variants reveal large numbers of spatially restricted mutations in conjunction with limited numbers of clonal mutations. Conclusions: These datasets support the existence of a periportal progenitor niche and indicate that clonal patches exhibit punctuated but slow growth, then quiesce, likely due to acute environmental stimuli. These findings crucially contribute to our understanding of hepatocyte dynamics in the normal human liver. Impact and implications: The liver is mainly composed of hepatocytes, but we know little regarding the source of these cells or how they multiply over time within the disease-free human liver. In this study, we determine a source of new hepatocytes by combining many different lab-based methods and computational predictions to show that hepatocytes share a common cell of origin with bile ducts. Both our experimental and computational data also demonstrate hepatocyte clones are likely to expand in slow waves across the liver in a specific trajectory, but often lie dormant for many years. These data show for the first time the expansion dynamics of hepatocytes in normal liver and their cell of origin enabling the accurate measurment of changes to their dynamics that may lead to liver disease. These findings are important for researchers determining cancer risk in human liver

Clonal transitions and phenotypic evolution in Barrett esophagus

BACKGROUND & AIMS: Barrett's esophagus (BE) is a risk factor for esophageal adenocarcinoma but our understanding of how it evolves is poorly understood. We investigated BE gland phenotype distribution, the clonal nature of phenotypic change, and how phenotypic diversity plays a role in progression. METHODS: Using immunohistochemistry and histology, we analyzed the distribution and the diversity of gland phenotype between and within biopsy specimens from patients with nondysplastic BE and those who had progressed to dysplasia or had developed postesophagectomy BE. Clonal relationships were determined by the presence of shared mutations between distinct gland types using laser capture microdissection sequencing of the mitochondrial genome. RESULTS: We identified 5 different gland phenotypes in a cohort of 51 nondysplastic patients where biopsy specimens were taken at the same anatomic site (1.0-2.0 cm superior to the gastroesophageal junction. Here, we observed the same number of glands with 1 and 2 phenotypes, but 3 phenotypes were rare. We showed a common ancestor between parietal cell-containing, mature gastric (oxyntocardiac) and goblet cell-containing, intestinal (specialized) gland phenotypes. Similarly, we have shown a clonal relationship between cardiac-type glands and specialized and mature intestinal glands. Using the Shannon diversity index as a marker of gland diversity, we observed significantly increased phenotypic diversity in patients with BE adjacent to dysplasia and predysplasia compared to nondysplastic BE and postesophagectomy BE, suggesting that diversity develops over time. CONCLUSIONS: We showed that the range of BE phenotypes represents an evolutionary process and that changes in gland diversity may play a role in progression. Furthermore, we showed a common ancestry between gastric and intestinal-type glands in BE

OSAS : valutazione della patologia e patente professionale

La sindrome delle apnee ostruttive del sonno è una patologia che colpisce indistintamente maschi e femmine. La OSAS (Obstructive Sleep Apnea Syndrome) è determinata da episodi ripetuti di ostruzione parziale o completa delle vie aeree superiori. I disturbi del sonno non solo si ripercuotono negativamente sulla salute e sulla qualità della vita di chi ne soffre, ma aumentano anche i rischi sulle strade. Il 19 febbraio 2016 è stato pubblicato sulla Gazzetta Ufficiale n. 41 il d ecreto dirigenziale 3 febbraio 2016 del Ministero della Salute, che fornisce gli indirizzi medico -legali da osservare per l’accertamento dell’idoneità psico -fisica alla guida per coloro che sono affetti, o che si sospetta possano essere affetti, da OSAS

Prevalenza di OSAS nella provincia di Pesaro-Urbino : dati derivati da uno screening su titolari di patente superiore e /o professionale afferenti alla CML dell'Area Vasta 1

none6norestrictedVittoria, Emanuela; Sisti, Davide; Pascucci, Paolo; Cappelli, Giorgio; Carlotti, Eugenio; Grossi, PaolaVittoria, Emanuela; Sisti, Davide; Pascucci, Paolo; Cappelli, Giorgio; Carlotti, Eugenio; Grossi, Paol

Stage I/II follicular lymphoma: Spread of bcl-2/IgH+ cells in blood and bone marrow from primary site of disease and possibility of clearance after involved field radiotherapy

Stage I/IIA follicular lymphoma (FL) is considered a localised disease that can be adequately treated with radiotherapy alone. Bone marrow (BM) and peripheral blood (PB) involvement in FL was investigated by polymerase chain reaction (PCR) in a series of 24 consecutive patients with histologically revised diagnosis and treated with involved field radiotherapy. Despite the limited stage, Bcl-2/IgH+ cells were found at diagnosis in PB and/or BM of 16 patients (66·6%). After treatment, in 9/15 Bcl-2/IgH positive evaluable patients, a disappearance of Bcl-2/IgH+ cells was observed, which persisted after a median follow-up of 43·5 months (range 11-70) in all but one patient. Quantitative PCR demonstrated the feasibility of clearing PB and BM Bcl-2+ cells after local irradiation of the primary site of the disease only when the basal number of lymphoma cells was <1:100 000. Patients with Bcl-2/IgH+ cells at diagnosis or after treatment had a higher likelihood of relapse. Thus, despite a negative BM biopsy, the majority of localised FL Bcl-2/IgH+ cells were found in the PB and BM. Lymphoma cells can reversibly spread from the affected lymph node to PB and BM and, in a proportion of cases, durably disappear after irradiation. The possibility of a persistent lymphoma cell clearance is proportional to the amount of cells detected at presentation by quantitative PCR. © 2007 The Authors

Transformation of follicular lymphoma to diffuse large B cell lymphoma may occur by divergent evolution from a common progenitor cell or by direct evolution form the follicular lymphoma clone

To investigate the cell of origin linking follicular (FL) and transformed (t-FL) lymphomas, we analyzed the somatic hypermutation (SHM) pattern of the variable region of the immunoglobulin heavy gene (IgH-VH) in 18 sequential FL/t-FL samples and a father (donor) and son (recipient), who developed FL and t-FL, after transplantation. Genealogic trees showed a pattern compatible with a common progenitor cell (CPC) origin in 13 cases. The identification of the t-FL clonotype in the previous FL sample and of the putative CPC sequence in both the FL/t-FL biopsies showed that the intraclonal diversity of FL and t-FL germinal centers (GCs) is more intricate than previously described, and all 3 clonotypes (CPC, FL, t-FL) may occur simultaneously within the same lymph node. On the basis of the father/son model, this CPC must be long-lived, providing a possible explanation for the incurable nature of this disease