Intra-islet insulin synthesis defects are associated with endoplasmic reticulum stress and loss of beta cell identity in human diabetes

Aims/hypothesis: Endoplasmic reticulum (ER) stress and beta cell dedifferentiation both play leading roles in impaired insulin secretion in overt type 2 diabetes. Whether and how these factors are related in the natural history of the disease remains, however, unclear. Methods: In this study, we analysed pancreas biopsies from a cohort of metabolically characterised living donors to identify defects in in situ insulin synthesis and intra-islet expression of ER stress and beta cell phenotype markers. Results: We provide evidence that in situ altered insulin processing is closely connected to in vivo worsening of beta cell function. Further, activation of ER stress genes reflects the alteration of insulin processing in situ. Using a combination of 17 different markers, we characterised individual pancreatic islets from normal glucose tolerant, impaired glucose tolerant and type 2 diabetic participants and reconstructed disease progression. Conclusions/interpretation: Our study suggests that increased beta cell workload is accompanied by a progressive increase in ER stress with defects in insulin synthesis and loss of beta cell identity. Graphical abstract: [Figure not available: see fulltext.

Health self-perception in patient with Crohn’s disease. a web survey

Background. Crohn’s Disease (CD) has an incidence on the physical and psychological autonomy of the patient, such as to alter their daily life. The impact of the disease on the daily life of the patients is related to the symptoms and complications of the disease. Patient autonomy and participation in social and work life are the goals that nurses must reach for patients with CD to improve their quality of life. Aim. To measure the perception of the health of people with a diagnosis of CD. Method. Review of the literature on PubMed, and internet sites. Administration on the web of the standardised questionnaire Short Form Health Survey (SF-12). Results. A total of 228 patients with CD completed valid questionnaires and were enrolled. The SF-12 questionnaire scores make it possible to build a physical health index (PCS) with a median value of 36,10 (min 33,8; max 42,4) and mental health index (MCS) with a median value of 36,04 (min 28.5; max 38,4). There were statistically significant data related to the achievement of the degree with median 41.9 (min 35,1; max 48,4) compared to non-graduates with a p<0.001 and in relation to the employment level (median 37.9 min/max 34,7/46,7) compared to unemployed and inactive with a p = 0.03. Conclusion. Despite the inevitable complications of the disease (intestinal and extra-intestinal symptoms), most of our sample did not exhibit significant physical limitations (surgical intervention, stomach packaging which generally causes a decrease in libido in both male and female patients ). The nurse cares for a patient with CD must have not only technical skills and specialist skills, but a holistic vision of the patient. Despite some findings in this study, this research orientation deserves more attention

Evidence of SARS-CoV-2-Specific Memory B Cells Six Months After Vaccination With the BNT162b2 mRNA Vaccine

SARS-CoV-2 mRNA vaccines have demonstrated high efficacy and immunogenicity, but limited information is currently available on memory B cell generation and long-term persistence. Here, we investigated spike-specific memory B cells and humoral responses in 145 subjects, up to 6 months after the BNT162b2 vaccine (Comirnaty) administration. Spike-specific antibodies peaked 7 days after the second dose and significant antibody titers and ACE2/RBD binding inhibiting activity were still observed after 6 months, despite a progressive decline over time. Concomitant to antibody reduction, spike-specific memory B cells, mostly IgG class-switched, increased in the blood of vaccinees and persisted 6 months after vaccination. Following the in vitro restimulation, circulating memory B cells reactivated and produced spike-specific antibodies. A high frequency of spike-specific IgG+ plasmablasts, identified by computational analysis 7 days after boost, positively correlated with the generation of IgG+ memory B cells at 6 months. These data demonstrate that mRNA BNT162b2 vaccine elicits strong B cell immunity with spike-specific memory B cells that still persist 6 months after vaccination, playing a crucial role for a rapid response to SARS-CoV-2 virus encounter

The slower antibody response in myelofibrosis patients after two doses of MRNA sars-COV-2 vaccine calls for a third dose

Immunization with mRNA SARS-CoV-2 vaccines has been highly recommended and prioritized in fragile subjects, including patients with myelofibrosis (MF). Available data on the vaccine immune response developed by MF patients and the impact of ruxolitinib treatment are still too fragmented to support an informed decision on a third dose for this category of subjects. Here, we show that 76% of MF patients develop spike-specific IgG after the second mRNA SARS-CoV-2 vaccine dose, but the response has a slower kinetics compared to healthy subjects, suggesting a reduced capability of their immune system to promptly react to vaccination. A reduced ACE2/RBD binding inhibition activity of spike-specific antibodies was also observed, especially in ruxolitinibtreated patients. Our results, showing slow kinetics of antibody responses in MF patients following vaccination with mRNA SARS-CoV-2 vaccines, support the need for a third vaccine dose

Gestione avanzata delle vie aeree. un’overview sull’intubazione orotracheale Airways advanced management. An overview about orotracheal intubation

Introduzione. L’ampia produzione scientifica relativa al trattamento del paziente critico mette in risalto la forte eterogeneità organizzativa dei sistemi di emergenza sanitaria presenti nel panorama internazionale, evidenziando come gli operatori sanitari impegnati in questo setting siano in possesso di livelli di competenza e responsabilità operativa differenti. Obiettivo. L’obiettivo della revisione è quello di analizzare le competenze e responsabilità dell’infermiere nella manovra di intubazione orotracheale (IOT) e i principali strumenti tecnologici in uso. Materiali e Metodi. È stata effettuata una revisione della letteratura mediante interrogazione di banche dati di interesse infermieristico (Cinahl Complete, Cochrane Library, PubMed e Scopus). Non sono stati posti limiti temporali. Risultati. Gli articoli reperiti hanno permesso l’esplorazione di tre ambiti: le tecnologie e gli strumenti a disposizione del professionista; le conoscenze e competenze del professionista abilitato all’intubazione; le responsabilità dell’infermiere nella gestione delle vie aeree in Italia. Sebbene, infatti, in Italia l’IOT sia appannaggio della sola professione medica, in ambito internazionale suddetta manovra rientra tra le competenze del personale infermieristico e non, previa opportuna e adeguata formazione. Studi dimostrano che le percentuali di intubazioni riuscite, eseguite da personale non medico si avvicinano molto a quelle dei medici e, inoltre, per la gestione avanzata delle vie aeree in rapidità e sicurezza, è stato dimostrato di uguale efficacia l’utilizzo dei dispositivi sovraglottici (SG), sebbene il tubo endotracheale sia indicato come gold standard nel management delle vie respiratorie. Conclusioni. L’appropriatezza ed efficacia del trattamento, specie in ambito extra ospedaliero, richiede una fattiva e consolidata collaborazione multiprofessionale e multidisciplinare. Nel contempo, le strategie d’intervento attuate e la qualità delle cure prestate risultano fortemente condizionate da fattori quali competenze cliniche del personale sanitario, abilità tecniche ed esperienza degli operatori e abilità non tecniche (esempio, capacità di lavoro in team).Introduction. The wide scientific production related to the critical patient treatment, underlines the strong organizational heterogeneity of the health emergency systems in the international scene, highlighting how the health workers involved in this setting have different levels of competence and operational responsibilities. Objective. The aim of the review is to analyze skills and responsibilities of nurse in the orotracheal intubation (OTI) and the main used technological tools. Materials and Methods. A literature review was performed by querying nursing databases (Cinahl Complete, Cochrane Library, PubMed and Scopus). No time limits were set. Results. The articles found, allowed the exploration of three areas: the technologies and tools available to the professional; the knowledge and skills of the professional enabled to intubation; the responsibilities of nurse in the airway management in Italy. In fact, although in Italy the OTI is a prerogative of medical profession, in the international sphere this procedure, after an appropriate and adequate training, is part of nursing, and not, skills. Specific studies show that the percentage of successful intubations performed by non-medical staff is very close to the ones performed by doctors. Moreover, for the quickly and safely advanced airway management, has been shown that the use of the supraglottic airway devices (SAD) is equally effective compared to the endotracheal intubation, referred as the gold standard in respiratory management. Conclusions. The treatment’s appropriateness and effectiveness, especially in the extra-hospital setting, requires an effective and consolidated multi-professional and multidisciplinary collaboration. At the same time, the implemented intervention strategies and the quality of provided care are strongly influenced by: healthcare staff clinical skills, operators technical skills and experience and non-technical skills (example, ability to work in a team)

Intra-islet insulin synthesis defects are associated with endoplasmic reticulum stress and loss of beta cell identity in human diabetes

Aims/hypothesis: Endoplasmic reticulum (ER) stress and beta cell dedifferentiation both play leading roles in impaired insulin secretion in overt type 2 diabetes. Whether and how these factors are related in the natural history of the disease remains, however, unclear. Methods: In this study, we analysed pancreas biopsies from a cohort of metabolically characterised living donors to identify defects in in situ insulin synthesis and intra-islet expression of ER stress and beta cell phenotype markers. Results: We provide evidence that in situ altered insulin processing is closely connected to in vivo worsening of beta cell function. Further, activation of ER stress genes reflects the alteration of insulin processing in situ. Using a combination of 17 different markers, we characterised individual pancreatic islets from normal glucose tolerant, impaired glucose tolerant and type 2 diabetic participants and reconstructed disease progression. Conclusions/interpretation: Our study suggests that increased beta cell workload is accompanied by a progressive increase in ER stress with defects in insulin synthesis and loss of beta cell identity. Graphical abstract: [Figure not available: see fulltext.