Thermodynamic Assessment on the Integration of Thermo-Electric Modules in a Wood Fireplace

The growing demand for electricity produced from renewable sources and the development of new technologies for the combustion of biomass, arose a growing interest on the possible coupling of thermoelectric modules with stove-fireplaces. The current thermoelectric generators have a solid structure, do not produce noise, do not require maintenance and can be used for the recovery of waste heat or excess, at the same time they hold a very low conversion efficiency and they need an adequate cooling system. Nevertheless, they still hold a cost, which is still too high to make them attractive. Nonetheless, if the modules are applied to a heat source which otherwise would be wasted, the attractiveness of the solution certainly rises. In this study, a thermodynamic analysis of a stove-fireplace is presented, considering both combustion process and the flame – walls heat transfer of the. A design solution for a concentrator device to funnel the wasted heat from the fireplace to the thermo-electric modules is also presented

In silico analysis and theratyping of an ultra-rare CFTR genotype (W57G/A234D) in primary human rectal and nasal epithelial cells

Mutation targeted therapy in cystic fibrosis (CF) is still not eligible for all CF subjects, especially for cases carrying rare variants such as the CFTR genotype W57G/A234D (c.169T>G/c.701C>A). We performed in silico analysis of the effects of these variants on protein stability, which we functionally characterized using colonoids and reprogrammed nasal epithelial cells. The effect of mutations on cystic fibrosis transmembrane conductance regulator (CFTR) protein was analyzed by western blotting, forskolin-induced swelling (FIS), and Ussing chamber analysis. We detected a residual CFTR function that increases following treatment with the CFTR modulators VX661±VX445±VX770, correlates among models, and is associated with increased CFTR protein levels following treatment with CFTR correctors. In vivo treatment with VX770 reduced sweat chloride concentration to non-CF levels, increased the number of CFTR-dependent sweat droplets, and induced a 6% absolute increase in predicted FEV1% after 27 weeks of treatment indicating the relevance of theratyping with patient-derived cells in CF

Italia: un paese troppo poco digitale?

Keynote lecture con Luca Attias, commissario straordinario per l'attuazione dell'Agenda Digitale. A seguire, dialogo con Massimo Cerofolini, giornalista Eta Beta Radio Rai

Thermodynamic Assessment on the Integration of Thermo-Electric Modules in a Wood Fireplace

The growing demand for electricity produced from renewable sources and the development of new technologies for the combustion of biomass, arose a growing interest on the possible coupling of thermoelectric modules with stove-fireplaces

L’endometriosi inguinale. Case report e revisione della letteratura

L’endometriosi è una patologia relativamente frequente che colpisce donne in età fertile ed è caratterizzata dalla presenza di tessuto endometriale ectopico che risponde agli stimoli ormonali del normale ciclo mestruale. L’etiologia è tuttora sconosciuta e la sintomatologia è piuttosto aspecifica. La diagnosi si basa sull’utilizzo dell’esame ultrasonografico, caratterizzato da elevata sensibilità e specificità, e della RMN. L’approccio laparoscopico, associato o meno alla terapia medica pre- e post-chirurgica, rappresenta il trattamento terapeutico di scelta. Viene presentato un caso di una giovane donna giunta alla nostra osservazione per la presenza di una massa in regione inguinale, rivelatasi poi sede di focolaio endometriosico. Tale caso ha suggerito la revisione della letteratura scientifica internazionale, con particolare attenzione alle metodiche diagnostiche e alla relazione esistente fra endometriosi tumore ovarico, soprattutto con i sottotipi endometrioide (EAC) e a cellule chiare (CCC)

Cystic fibrosis transmembrane conductance regulator functional evaluations in a G542X+/- IVS8Tn:T7/9 patient with acute recurrent pancreatitis

BACKGROUND: Acute recurrent pancreatitis (ARP) is characterized by episodes of acute pancreatitis in an otherwise normal gland. When no cause of ARP is identifiable, the diagnosis of "idiopathic" ARP is given. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene increase the risk of ARP by 3- to 4-times compared to the general population, while cystic fibrosis (CF) patients present with a 40- to 80-times higher risk of developing pancreatitis. CASE SUMMARY: In non-classical CF or CFTR-related disorders, CFTR functional tests can help to ensure a proper diagnosis. We applied an individualized combination of standardized and new CFTR functional bioassays for a patient referred to the Verona CF Center for evaluation after several episodes of acute pancreatitis. The CFTR genotype was G542X+/- with IVS8Tn:T7/9 polymorphism. The sweat (Cl-) values were borderline. Intestinal current measurements were performed according to the European Cystic Fibrosis Society Standardized Operating Procedure. Recent nasal surgery for deviated septum did not allow for nasal potential difference measurements. Lung function and sputum cultures were normal; azoospermia was excluded. Pancreas divisum was excluded by imaging but hypoplasia of the left hepatic lobe was detected. Innovative tests applied in this case include sweat rate measurement by image analysis, CFTR function in monocytes evaluated using a membrane potential-sensitive fluorescent probe, and the intestinal organoids forskolin-induced swelling assay. CONCLUSION: Combination of innovative CFTR functional assays might support a controversial diagnosis when CFTR-related disorders and/or non-classical CF are suspected

WS18.3 A combination of CFTR functional tests supporting drug development and diagnosis: the contribution of intestinal epithelial organoids

CFTR functional test

ePS01.7 Supporting diagnosis with a combination of standardized and new CFTR functional tests

Cystic Fibrosi

Cerebrospinal fluid lipoproteins inhibit α-synuclein aggregation by interacting with oligomeric species in seed amplification assays

Abstract Background Aggregation of α-synuclein (α-syn) is a prominent feature of Parkinson’s disease (PD) and other synucleinopathies. Currently, α-syn seed amplification assays (SAAs) using cerebrospinal fluid (CSF) represent the most promising diagnostic tools for synucleinopathies. However, CSF itself contains several compounds that can modulate the aggregation of α-syn in a patient-dependent manner, potentially undermining unoptimized α-syn SAAs and preventing seed quantification. Methods In this study, we characterized the inhibitory effect of CSF milieu on detection of α-syn aggregates by means of CSF fractionation, mass spectrometry, immunoassays, transmission electron microscopy, solution nuclear magnetic resonance spectroscopy, a highly accurate and standardized diagnostic SAA, and different in vitro aggregation conditions to evaluate spontaneous aggregation of α-syn. Results We found the high-molecular weight fraction of CSF (> 100,000 Da) to be highly inhibitory on α-syn aggregation and identified lipoproteins to be the main drivers of this effect. Direct interaction between lipoproteins and monomeric α-syn was not detected by solution nuclear magnetic resonance spectroscopy, on the other hand we observed lipoprotein-α-syn complexes by transmission electron microscopy. These observations are compatible with hypothesizing an interaction between lipoproteins and oligomeric/proto-fibrillary α-syn intermediates. We observed significantly slower amplification of α-syn seeds in PD CSF when lipoproteins were added to the reaction mix of diagnostic SAA. Additionally, we observed a decreased inhibition capacity of CSF on α-syn aggregation after immunodepleting ApoA1 and ApoE. Finally, we observed that CSF ApoA1 and ApoE levels significantly correlated with SAA kinetic parameters in n = 31 SAA-negative control CSF samples spiked with preformed α-syn aggregates. Conclusions Our results describe a novel interaction between lipoproteins and α-syn aggregates that inhibits the formation of α-syn fibrils and could have relevant implications. Indeed, the donor-specific inhibition of CSF on α-syn aggregation explains the lack of quantitative results from analysis of SAA-derived kinetic parameters to date. Furthermore, our data show that lipoproteins are the main inhibitory components of CSF, suggesting that lipoprotein concentration measurements could be incorporated into data analysis models to eliminate the confounding effects of CSF milieu on α-syn quantification efforts