L'anatomia endodontica dei secondi molari superiori: ricerca ex vivo

Aim: of the present study was to deter- mine anatomic complexities which can be seen in maxillary second molars, with a specific attention to the presence of MB2 (second mesio-buccal) canals. Methodology: 50 maxillary second molars, which had been extracted for periodontal reasons, were selected for the study, following strict exclusion cri- teria. After determining the different roots, only the mesio-buccal one was examined. Location and number of canals were determined (i) after a normal access cavity, (ii) after a wider removal of dentine from the chamber floor, and (iii) after sectioning the root 4 mm be- low the cementum-enamel junction. Data were collected and analyzed. Results: MB2 canals were present in 44% of the examined teeth (20% of ca- ses showed Weine 2 configuration, while the remaining 24% showed Weine 3 configuration). It was possible to estabilish patency in MB2 canals only in 28% of cases. Conclusions: MB2 canals are often present in maxillary second molars, being individuated in nearly half cases. This possibility and the presence of an indipendent apex make the research of MB2 canals mandatory during the endodontic treatment

Primary and malignant cholangiocytes undergo CD40 mediated Fas dependent Apoptosis, but are insensitive to direct activation with exogenous fas ligand

Introduction Cholangiocarcinoma is a rare malignancy of the biliary tract, the incidence of which is rising, but the pathogenesis of which remains uncertain. No common genetic defects have been described but it is accepted that chronic inflammation is an important contributing factor. We have shown that primary human cholangiocyte and hepatocyte survival is tightly regulated via co-operative interactions between two tumour necrosis family (TNF) receptor family members; CD40 and Fas (CD95). Functional deficiency of CD154, the ligand for CD40, leads to a failure of clearance of biliary tract infections and a predisposition to cholangiocarcinoma implying a direct link between TNF receptor-mediated apoptosis and the development of cholangiocarcinoma. Aims To determine whether malignant cholangiocytes display defects in CD40 mediated apoptosis. By comparing CD40 and Fas-mediated apoptosis and intracellular signalling in primary human cholangiocytes and three cholangiocyte cell lines. Results Primary cholangiocytes and cholangiocyte cell lines were relatively insensitive to direct Fas-mediated killing with exogenous FasL when compared with Jurkat cells, which readily underwent Fas-mediated apoptosis, but were extremely sensitive to CD154 stimulation. The sensitivity of cells to CD40 activation was similar in magnitude in both primary and malignant cells and was STAT-3 and AP-1 dependent in both. Conclusions 1) Both primary and malignant cholangiocytes are relatively resistant to Fas–mediated killing but show exquisite sensitivity to CD154, suggesting that the CD40 pathway is intact and fully functional in both primary and malignant cholangiocytes 2) The relative insensitivity of cholangiocytes to Fas activation demonstrates the importance of CD40 augmentation of Fas dependent death in these cells. Agonistic therapies which target CD40 and associated intracellular signalling pathways may be effective in promoting apoptosis of malignant cholangiocytes

Role of interface/border traps on the threshold voltage instability of SiC power transistors

In this paper the role of interface/border defects on the threshold voltage drift (ΔVTH) of SiC power MOSFETs has been investigated by means of slow and fast positive bias temperature instability (PBTI), hysteresis and conductance tests. Results have shown an opposite temperature (T) dependency based on the level of the applied gate bias (VG) and on the adopted stress technique. With VG > 30 V and a slow-PBTI procedure, the creation of new oxide defects and/or the charge trapping in deep states occurs, showing a positive T-dependency. On the contrary, with a lower VG and a fast-PBTI test, the ΔVTH shows a negative T-dependency, associated to dominant role of pre-existing interface and/or border traps

Alternative Splicing of RNA Triplets Is Often Regulated and Accelerates Proteome Evolution

Thousands of human genes contain introns ending in NAGNAG (N any nucleotide), where both NAGs can function as 3′ splice sites, yielding isoforms that differ by inclusion/exclusion of three bases. However, few models exist for how such splicing might be regulated, and some studies have concluded that NAGNAG splicing is purely stochastic and nonfunctional. Here, we used deep RNA-Seq data from 16 human and eight mouse tissues to analyze the regulation and evolution of NAGNAG splicing. Using both biological and technical replicates to estimate false discovery rates, we estimate that at least 25% of alternatively spliced NAGNAGs undergo tissue-specific regulation in mammals, and alternative splicing of strongly tissue-specific NAGNAGs was 10 times as likely to be conserved between species as was splicing of non-tissue-specific events, implying selective maintenance. Preferential use of the distal NAG was associated with distinct sequence features, including a more distal location of the branch point and presence of a pyrimidine immediately before the first NAG, and alteration of these features in a splicing reporter shifted splicing away from the distal site. Strikingly, alignments of orthologous exons revealed a ~15-fold increase in the frequency of three base pair gaps at 3′ splice sites relative to nearby exon positions in both mammals and in Drosophila. Alternative splicing of NAGNAGs in human was associated with dramatically increased frequency of exon length changes at orthologous exon boundaries in rodents, and a model involving point mutations that create, destroy, or alter NAGNAGs can explain both the increased frequency and biased codon composition of gained/lost sequence observed at the beginnings of exons. This study shows that NAGNAG alternative splicing generates widespread differences between the proteomes of mammalian tissues, and suggests that the evolutionary trajectories of mammalian proteins are strongly biased by the locations and phases of the introns that interrupt coding sequences.Damon Runyon Cancer Research Foundation (DRG 2032-09)National Science Foundation (U.S.). (no. 0821391)United States. National Institutes of Healt

Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies

sem informaçãoThe epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant91sem informaçãosem informaçãosem informaçã

Fc receptor-like 5 and anti-CD20 treatment response in granulomatosis with polyangiitis and microscopic polyangiitis

BACKGROUND. Baseline expression of FCRL5, a marker of naive and memory B cells, was shown to predict response to rituximab (RTX) in rheumatoid arthritis. This study investigated baseline expression of FCRL5 as a potential biomarker of clinical response to RTX in granulomatosis with polyangiitis (CPA) and microscopic polyangiitis (MPA). METHODS. A previously validated quantitative PCR-based (qPCR-based) platform was used to assess FCRL5 expression in patients with GPA/MPA (RAVE trial, NCT00104299). RESULTS. Baseline FCRL5 expression was significantly higher in patients achieving complete remission (CR) at 6,12, and 18 months, independent of other clinical and serological variables, among those randomized to RTX but not cyclophosphamide-azathioprine (CYC/AZA). Patients with baseline FCRL5 expression >= 0.01 expression units (termed FCRL5(hi)) exhibited significantly higher CR rates at 6,12, and 18 months as compared with FCRL5(lo) subjects (84% versus 57% [P = 0.016], 68% versus 40% [P = 0.02], and 68% versus 29% [P = 0.0009], respectively). CONCLUSION. Our data taken together suggest that FCRL5 is a biomarker of B cell lineage associated with increased achievement and maintenance of complete remission among patients treated with RTX and warrant further investigation in a prospective manner

Risk and resilience factors for specific and general psychopathology worsening in people with Eating Disorders during COVID-19 pandemic: a retrospective Italian multicentre study

Purpose: The COVID-19 pandemic restrictions had negative impact on the psychopathology of people with Eating Disorders (EDs). Factors involved in the vulnerability to stressful events have been under-investigated in this population. We aimed to assess which factors contributed to COVID-19-induced worsening in both general and specific psychopathology. Methods: Three-hundred and twelve people with a clinically defined diagnosis of an ED and undergoing a specialist ED treatment in different Italian ED services before the spreading of COVID-19 pandemic filled in an online survey. ED specific and general psychopathology changes after COVID-19 quarantine were retrospectively evaluated. Factors related to COVID-19 concerns (financial condition, fear of contagion, perceived social isolation/support, satisfaction in peer, family or sentimental relationships), illness duration and treatment-related variables (type of treatment provided, type of access to care, satisfaction with therapeutic relationships) were included as predicting factors in a structural equational model, which included latent variables consisting of general and ED psychopathology items as outcomes. Results: A perceived low quality of therapeutic relationships, fear of contagion and increased isolation were positively associated with psychopathology worsening. Reduced satisfaction with family and with friends’ relationships and reduced perceived social support were associated with ED and general symptoms deterioration, respectively. No significant effect emerged for intimate relationships, illness duration, economic condition and type of treatment. Conclusions: This study provides a comprehensive evaluation of clinical variables associated with psychopathological changes during the COVID-19 lockdown period highlighting potential risk and resilience factors and, possibly, informing treatment as well as prevention strategies for EDs. Level of evidence IV: Evidence obtained from multiple time series analysis such as case studies

Lateralizing Value of Interictal Spikes on Overnight Sleep-EEG Studies in Temporal Lobe Epilepsy

Purpose: To determine the lateralizing value of interictal epileptiform discharges (IEDs) recorded during overnight sleep-EEG studies in temporal lobe epilepsy. Because IEDs are more prevalent in non-rapid eye movement (NREM) sleep than in wakefulness, overnight sleep-EEG recordings may contribute additional lateralizing information to the epilepsy surgery evaluation beyond daytime EEGs. Methods: Twenty-four subjects with medically refractory temporal lobe epilepsy underwent continuous overnight sleep-EEG recordings. Subjects were seizure free ≤24 h before study and receiving stable doses of medication. The IED foci recorded on overnight studies were compared with daytime EEGs, interictal samples, and ictal recordings during long-term monitoring, brain magnetic resonance images (MRIs), and surgical outcome. Results: (a) In all 24 subjects, including 13 without IEDs on daytime EEGs, temporal IEDs were present during NREM sleep and were exclusively or predominantly (<95%) unilateral in 15 and bitemporal in nine. (b) Unilateral NREM IEDs were concordant with surface or depth ictal-onset regions in 14 subjects, even if MRIs were normal (three subjects) or surface ictal-onset regions were bilateral (five subjects). Eleven of 12 subjects with unilateral concordant NREM IEDs who have undergone surgery are seizure free. (c) Bitemporal IEDs were associated with postoperative seizures in all subjects with normal MRIs or widespread MRI abnormalities. However, all subjects with bitemporal IEDs and MRI hippocampal abnormalities concordant with ictal-onset regions had good to excellent surgical outcomes. Conclusions: When combined with other investigations, IEDs recorded on overnight studies add prognostic data to the epilepsy surgery evaluation not provided by daytime EEGs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66154/1/j.1528-1157.1999.tb02044.x.pd

Risk and resilience factors for specific and general psychopathology worsening in people with Eating Disorders during COVID-19 pandemic: a retrospective Italian multicentre study

Purpose: The COVID-19 pandemic restrictions had negative impact on the psychopathology of people with Eating Disorders (EDs). Factors involved in the vulnerability to stressful events have been under-investigated in this population. We aimed to assess which factors contributed to COVID-19-induced worsening in both general and specific psychopathology. Methods: Three-hundred and twelve people with a clinically defined diagnosis of an ED and undergoing a specialist ED treatment in different Italian ED services before the spreading of COVID-19 pandemic filled in an online survey. ED specific and general psychopathology changes after COVID-19 quarantine were retrospectively evaluated. Factors related to COVID-19 concerns (financial condition, fear of contagion, perceived social isolation/support, satisfaction in peer, family or sentimental relationships), illness duration and treatment-related variables (type of treatment provided, type of access to care, satisfaction with therapeutic relationships) were included as predicting factors in a structural equational model, which included latent variables consisting of general and ED psychopathology items as outcomes. Results: A perceived low quality of therapeutic relationships, fear of contagion and increased isolation were positively associated with psychopathology worsening. Reduced satisfaction with family and with friends\u2019 relationships and reduced perceived social support were associated with ED and general symptoms deterioration, respectively. No significant effect emerged for intimate relationships, illness duration, economic condition and type of treatment. Conclusions: This study provides a comprehensive evaluation of clinical variables associated with psychopathological changes during the COVID-19 lockdown period highlighting potential risk and resilience factors and, possibly, informing treatment as well as\ua0prevention strategies for EDs. Level of evidence IV: Evidence obtained from multiple time series analysis such as case studies