Indicazioni chirurgiche e sopravvivenza nei tumori neuroendocrini pancreatici

La prognosi e le indicazioni al trattamento chirurgico dei tumori neuroendocrini pancreatici vengono attualmente valutati sulla base di sistemi classificativi di recente introduzione, e sono pertanto ancora dibattuti nella letteratura scientifica. Viene presentato un gruppo di settantasette pazienti con tumori neuroendocrini pancreatici trattati chirurgicamente, analizzando i principali paramentri istologici, clinici e biologici in relazione alla prognosi e la sopravvivenza riscontrata nel successivo follow up. Si propone, sulla base dei risultati di questo studio e di precedenti attinenti pubblicazizoni, una revisione delle indicazioni chirurgiche al trattamento di lesioni pancreatiche sospette per neoplasie neuroendocrine

Homozygous FVII deficiencies with different reactivity towards tissue thromboplastins of different origin.

The reagents most frequently used for FVII activity assay are obtained by rabbit brain or human placenta. In recent years, human recombinant thromboplastins have received great attention. FVII activity in FVII deficiency is usually low, regardless of the thromboplastin used. There are a few exceptions to this rule. These are represented by FVII Padua (Arg304Gln), FVII Nagoya (Arg304Trp), and FVII (Arg79Gln). In these three instances, clear discrepancies were noted in the FVII activity depending on the thromboplastin used. This indicates that at least two areas of FVII are involved in tissue binding, namely an epidermal growth factor domain of the light chain (Arg79Gln) and the catalytic domain (Arg304), controlled by exons 4 and 8, respectively. Since these three variants are cross reactive material positive, namely they are Type 2 defects, all other variants with normal antigen should be investigated by a panel of at least three tissue thromboplastins (rabbit brain, human tissue or human recombinant, and ox brain derived) in order to obtain a satisfactory classification

Il digitale e la formazione dei docenti di sostegno. Digital and training of support teachers

The introductory part of this article will deal with the evolution of the training of teachers, planned in Italy, for the achievement of specialization on support following the pandemic crisis due to Covid-19. The analysis will make particular reference to the introduction of innovative teaching and learning methodologies, underscoring how the use of Information and Communication Technologies (ICT) has had a positive impact in guaranteeing the right to training of students, becoming more pervasive than the time and space of use. In the second section, using a comparative method, the reactions of other European training systems in the preparation and education of their teachers will be analysed. In particular, the analysis will focus on the strategies adopted by other countries to address the critical issues caused by the crisis, and then analyze the advantages in today’s teaching. In the final part, the paper will focus on the future prospects of the teacher training course, starting from well-proven teaching methods implemented by means of contemporary technologies

Anatomically reduced fixation should always be considered when treating B and C proximal epiphyseal humeral fractures

Background Proximal humeral fractures are commonly observed in elderly patients. Management of these injuries is controversial. Literature comparing locking plate fixation, arthroplasty, and conservative treatments show no clear advantages for any of these management strategies. Thus far, no study has considered anatomically reduced fractures obtained after locking plate treatment. To clarify the best surgical procedure in middle-aged patients, we considered outcomes and major complications leading to surgical revision following an anatomically reduced fracture fixed with locking plate and reverse shoulder arthroplasty (RSA) in the treatment of type B/C fractures in patients between 50 and 75 years of age. Methods This is a retrospective study including 59 patients between 50 and 75 years of age with type B/C proximal humeral fracture treated with RSA or with locking plate fixation (resulting in an anatomical reduction) between January 2010 and December 2018. Preoperative radiographs and computed tomography (CT) were evaluated in all patients. Clinical and radiologic follow-up was performed using range of motion (ROM), the Constant-Murley Score (CMS), the Oxford Shoulder Score (OSS), the Simple Shoulder Test (SST), the Subjective Shoulder Value (SSV), and visual analog scale (VAS). Major complications were considered. Results In the plate fixation group, ROM, CMS, SST, and VAS were higher than in the RSA group. Lower complication rates compared with the literature were observed in both groups. Anatomically reduced fracture fixed with plate and screw could outperform RSA in terms of outcome. In second-level centers where traumatology is performed by surgeons with great expertise in upper limb trauma, the choice between plate fixation and reverse arthroplasty should be made during surgery. Conclusion Anatomically reduced fractures showed better outcomes compared with RSA in type B/C fractures. Surgeons should always try to perform a reduction of the fracture in order to understand if a plate fixation could be feasible. If it is impossible to perform an anatomical reduction, we suggest to consider RSA. This is a retrospective observational study

Study of the preanalytical variables affecting the measurement of clinically relevant free-circulating microRNAs: focus on sample matrix, platelet depletion, and storage conditions

Introduction: Circulating microRNAs (miRNAs) are emerging as potential biomarkers. However, the lack of preanalytical and analytical standardization limits their use. The aim of this study was to determine the expression of different miRNAs in plasma according to different collection and storage conditions. Materials and methods: Venous blood from 10 volunteers was collected in tubes spray-coated with dipotassium salt of ethylendiaminetetraacetic acid, either with (plasma-preparation tube, PPT) or without (K2EDTA) gel separator. Platelet-poor plasma (PPP) was also obtained from K2EDTA plasma. After storage under different conditions, miRNA-enriched total RNA was isolated from plasma and reverse transcribed. A panel of 179 miRNAs was assayed by quantitative polymerase chain reaction and the results were analysed by GenEx software. Detectability and stability of miRNAs were determined. Results: The number of undetected miRNAs was: 18, 24, and 22 in PPT; 83, 43, and 20 in K2EDTA; and 76, 106, and 104 in PPP samples, for plasma immediately frozen at - 80°C and plasma stored for 24h at room temperature or 4°C, respectively. Circulating miRNA expression in PPT samples was not affected by storage delay or temperature, while the percentage of up- and down-regulated miRNA in K2EDTA and PPP samples ranged from 2%, and 1% to 7%, and 5%, respectively. Conclusions: Sample matrix, temperature and delay in storage strongly influence the expression level of plasma miRNAs. Our results indicate PPT tubes as the most suitable matrix to improve total miRNA detectability and stability, independently of temperature

Myocardial structural, perfusion and metabolic correlates of left bundle branch block mechanical derangement in patient with dilated cardiomyopathy

Background-Left bundle branch block (LBBB) influences upon regional left ventricular (LV) structure, perfusion and metabolism were not thoroughly investigated in dilated cardiomyopathy (DCM) patients. Methods and Results-Eleven DCM patients with LBBB (69?11 years, LV ejection fraction[EF]: 35?8%) and 7 DMC patients without LBBB (58?9 years, LV EF: 37?10%) were studied by cardiac magnetic resonance (CMR) and positron emission tomography (PET). Left ventricle was divided in 3 regions: septum, adjacent (anterior-inferior) and lateral. Regional midwall circumferential strain, maximum shortening (&#1013;peak) and strain rate were obtained from tagged CMR. Systolic stretch index (SSI) was calculated as positive strain rate (stretching) divided by total strain rate. Myocardial metabolic rate of glucose (MMRG), resting and hyperemic myocardial blood flow (MBF) were quantitated using 2-[18F]fluoro-2-deoxyglucose and [13N]ammonia PET, respectively. Conversely from non LBBB patients, LBBB patients showed highly inhomogeneous systolic deformation pattern which changed gradually moving from discoordinate [(SSI: 0.485 (0.284)] and poorly contracting (&#1013;peak: -1.14?0.96%) septum to coordinate [SSI: 0.002 (0.168)] and strongly contracting (&#1013;peak: -13.63?2.58%) lateral region (both P<0.0001). This pattern was closely matched to MMRG distribution disclosing lowest, intermediate and highest values respectively in the septum, adjacent and lateral regions (P<0.0001). Septal-to-lateral thickness ratio was lower in LBBB than non LBBB patients (P=0.03). In both groups, LV distribution of resting and hyperemic MBF and MBF reserve did not differ significantly. Conclusions-In DCM patients, the extensive LV contraction abnormalities induced by LBBB caused regional myocardial metabolic and structural remodeling without consistent changes in blood flows.-

The histone demethylase PHF8 regulates astrocyte differentiation and function

Astrocyte differentiation; Chromatin transcription; SynapseDiferenciación de astrocitos; Transcripción de la cromatina; SinapsisDiferenciació d'astròcits; Transcripció de la cromatina; SinapsiEpigenetic factors have been shown to play a crucial role in X-linked intellectual disability (XLID). Here, we investigate the contribution of the XLID-associated histone demethylase PHF8 to astrocyte differentiation and function. Using genome-wide analyses and biochemical assays in mouse astrocytic cultures, we reveal a regulatory crosstalk between PHF8 and the Notch signaling pathway that balances the expression of the master astrocytic gene Nfia. Moreover, PHF8 regulates key synaptic genes in astrocytes by maintaining low levels of H4K20me3. Accordingly, astrocytic-PHF8 depletion has a striking effect on neuronal synapse formation and maturation in vitro. These data reveal that PHF8 is crucial in astrocyte development to maintain chromatin homeostasis and limit heterochromatin formation at synaptogenic genes. Our studies provide insights into the involvement of epigenetics in intellectual disability.This study was supported by grants from the Spanish Ministry of Economy (Ministerio de Economía, Industria y Competitividad, Gobierno de España; BFU2015-69248-P and PGC2018-096082-B-I00 to M.A.M.-B.) and Ministerio de Ciencia e Innovación (PID2019-111217RB-I00 to X.C) and a Travelling Fellowship from Boehringer Ingelheim to S.I. Open access funding provided by Consejo Superior de Investigaciones Científicas. Deposited in PMC for immediate release

Comparison of the effects of primary somatostatin analogue therapy and pituitary adenomectomy on survival in patients with acromegaly: a retrospective cohort study

Objective: Acromegalic patients have an increased risk of mortality. The objective of this study was to compare the effect of different therapies for acromegaly on mortality. Design and methods: The mortality rate of 438 consecutive acromegalic patients was compared with that of the general population using the standardized mortality ratio (SMR); the effect of different therapies on survival was evaluated using Cox regression analysis. Results: Twenty patients (4.5%) died between 1999 and 2009. Age- and sex-adjusted SMR was 0.70 (95% CI 0.43–1.08). The Cox regression analysis revealed that, in the whole population, both general risk factors (age and physical status) and specific factors for acromegaly (macroadenoma, hypopituitarism and uncontrolled disease) were associated with death. The most compromised patients at diagnosis had a higher mortality rate (PZ0.001), which also occurred in patients with controlled acromegaly. Death occurred in 2.4% (adenomectomy), 2.6% (adenomectomy followed by somatostatin analogue (SSA) therapy) and 11.4% (SSA therapy as the primary therapy) of the patients. The risk of death was higher in patients receiving SSA therapy as the primary therapy (hazard ratio (HR) 5.52, 95% CI 1.06–28.77, PZ0.043) than in all patients submitted to adenomectomy; however, a higher risk of death occurred only in diabetic patients treated with SSAs alone (HR 21.94, 95% CI 1.56–309.04, PZ0.022). Radiotherapy was associated with an increased risk of mortality, which occurred in patients with the more locally advanced disease. Conclusions: Therapies for acromegaly and comorbidities have lowered the risk of mortality to the level of the general population; the effect of SSA therapy alone or that following pituitary adenomectomy was comparable to that of curative neurosurgery on survival in non-diabetic patients; on the contrary, SSA therapy as the primary therapy may be less effective than adenomectomy in reducing mortality rate in diabetic patients

Growth Hormone Is Necessary for the p53-Mediated, Obesity-Induced Insulin Resistance in Male C57BL/6J × CBA Mice

Insulin resistance is a key marker of both obesity and GH excess. The purpose of the study was to assess the role of GH on p53-mediated insulin resistance of male mice with obesity due to a high-fat diet. C57BL/6J CBA male mice fed on a high-fat diet (Obe) were studied; male mice fed a normal diet (Lean) or transgenic mice for bovine GH under the same genetic background (Acro) served as controls. The convergence of p53 and GH pathways was evaluated by Western blot. Obe mice had insulin resistance, which was sustained by a selective increased expression of p53 in adipose tissue. Normal insulin sensitivity was restored, and adipose p53 expression normalized when the GH pathway was blocked. Only the adipose p53 expression was sensitive to the GH blockage, which occurred through the p38 pathway. Adipose tissue of Obe mice had a coordinate overexpres- sion of suppressors of cytokine signal 1–3 and signal transducers and activators of transcrip- tion-1, -3, and -5b, not different from that of Acro mice, suggesting an increased sensitivity of adipose tissue to GH. On the contrary, Lean mice were unaffected by changes of GH action. GH seems to be necessary for the increased adipose p53 expression and for insulin resistance of obese mice