RECENSIONI

- Massimo Baldacci, Franco Frabboni, Umberto Margiotta,Longlife/Longwide learning. Per un Trattato Europeo della Formazione di Chiara Urbani;- Pier Giuseppe Rossi, Didattica enattiva. Complessità, teorie dell’azione, professionalità docente di Francesca Coin;- Stefano Calabrese (a cura di), Neuronarratologia. Il futuro dell’analisi del racconto di Luisa Salmaso.

RECENSIONI

- Massimo Baldacci, Franco Frabboni, Umberto Margiotta, Longlife/Longwide learning. Per un Trattato Europeo della Formazione di Chiara Urbani; - Pier Giuseppe Rossi, Didattica enattiva. Complessità, teorie dell’azione, professionalità docente di Francesca Coin; - Stefano Calabrese (a cura di), Neuronarratologia. Il futuro dell’analisi del racconto di Luisa Salmaso.

Hepatic adrenal rest tumor in a patient with multifactorial liver cirrhosis: a case report with CT and MRI findings and pathologic correlation

AbstractBackgroundAdrenal rest tumor is an ectopic collection of adrenocortical cells in an extra-adrenal site, more frequently located around the kidney, retroperitoneum, spermatic cord, para-testicular region and broad ligament, but very rarely occurring also in the liver. Hepatic adrenal rest tumor poses a diagnostic challenge in differentiating it from hepatocellular carcinoma, particularly in a cirrhotic liver.Case presentationAn 83-years-old male was referred to our hospital by his family doctor for hepatological evaluation due to multifactorial liver cirrhosis. Ultrasound revealed a centimetric hypoechoic nodule in the VI hepatic segment in the context of a liver with signs of cirrhosis and steatosis. The patient first underwent MRI and then CT, which showed a fat containing focal liver lesion in the subcapsular location of the right lobe, strictly adjacent to the homolateral adrenal gland. The nodule was hypervascular in the arterial phase, washed out in the portal-venous and transitional phases, resulting hypointense in the hepato-biliary phase at MR imaging. In the suspicion of a hepatocellular carcinoma, the nodule was surgically removed, and the patient's postoperative course was unremarkable. The final histopathological diagnosis was of adrenal rest tumor of the liver.ConclusionsHepatic adrenal rest tumor is an extremely rare hepatic tumor, often without any clinical manifestation, that can also occur in the cirrhotic liver as in our case. Although there are not specific imaging findings, the possible diagnosis of HART should be considered when we observe a well-defined lesion in the subcapsular location of the right lobe, with fat containing, hypervascularity after contrast medium injection and vascular supply from the right hepatic artery

Quantitative analysis of the seminal plasma proteome in secondary hypogonadism

In the grey zone of testosterone levels between 8 and 12 nmol/L, the usefulness of therapy is controversial; as such, markers of tissue action of androgens may be helpful in adjusting clinical decisions. To better understand the effect of the hypothalamic-pituitary-testicular axis on male accessory secretion, we performed a proteomic quantitative analysis of seminal plasma in patients with secondary hypogonadism, before and after testosterone replacement therapy (TRT). Ten male patients with postsurgical hypogonadotrophic hypogonadism were enrolled in this study, and five of these patients were evaluated after testosterone treatment. Ten men with proven fertility were selected as a control group. An aliquot of seminal plasma from each individual was subjected to an in-solution digestion protocol and analyzed using an Ultimate 3000 RSLC-nano HPLC apparatus coupled to a LTQ Orbitrap Elite mass spectrometer. The label-free quantitative analysis was performed via Precursor Ions Area Detector Node. Eleven proteins were identified as decreased in hypogonadic patients versus controls, which are primarily included in hydrolase activity and protein binding activity. The comparison of the proteome before and after TRT comes about within the discovery of six increased proteins. This is the primary application of quantitative proteomics pointed to uncover a cluster of proteins reflecting an impairment not only of spermatogenesis but of the epididymal and prostate epithelial cell secretory function in male hypogonadism. The identified proteins might represent putative clinical markers valuable within the follow-up of patients with distinctive grades of male hypogonadism

LIMPIC: a computational method for the separation of protein MALDI-TOF-MS signals from noise

BACKGROUND: Mass spectrometry protein profiling is a promising tool for biomarker discovery in clinical proteomics. However, the development of a reliable approach for the separation of protein signals from noise is required. In this paper, LIMPIC, a computational method for the detection of protein peaks from linear-mode MALDI-TOF data is proposed. LIMPIC is based on novel techniques for background noise reduction and baseline removal. Peak detection is performed considering the presence of a non-homogeneous noise level in the mass spectrum. A comparison of the peaks collected from multiple spectra is used to classify them on the basis of a detection rate parameter, and hence to separate the protein signals from other disturbances. RESULTS: LIMPIC preprocessing proves to be superior than other classical preprocessing techniques, allowing for a reliable decomposition of the background noise and the baseline drift from the MALDI-TOF mass spectra. It provides lower coefficient of variation associated with the peak intensity, improving the reliability of the information that can be extracted from single spectra. Our results show that LIMPIC peak-picking is effective even in low protein concentration regimes. The analytical comparison with commercial and freeware peak-picking algorithms demonstrates its superior performances in terms of sensitivity and specificity, both on in-vitro purified protein samples and human plasma samples. CONCLUSION: The quantitative information on the peak intensity extracted with LIMPIC could be used for the recognition of significant protein profiles by means of advanced statistic tools: LIMPIC might be valuable in the perspective of biomarker discovery

Use of acellular intact fish skin grafts in treating acute paediatric wounds during the COVID-19 pandemic : A case series

Publisher Copyright: © 2022 MA Healthcare Ltd. All rights reserved.OBJECTIVE: More specific strategies are needed to support children requiring skin grafting. Our goal was to identify procedures that reduce operating times, post-operative complications, pain and length of hospital stay. Patient safety, optimal wound bed support and quick micro-debridement with locoregional anaesthesia were prioritised. Ultimately, a novel acellular fish skin graft (FSG) derived from north Atlantic cod was selected for use. METHOD: We admitted consecutive paediatric patients with various lesions requiring skin grafting for definitive wound closure. All FSGs were applied and bolstered in the operating room following debridement. RESULTS: In a cohort of 15 patients, the average age was 8 years and 9 months (4 years 1 month-13 years 5 months). Negative pressure wound therapy (NPWT) was given to 12 patients. Rapid wound healing was observed in all patients, with a wound area coverage of 100% and complete healing in 95% of wounds. Time until engraftment in patients receiving NPWT was reduced by about a half (to an average 12 days) from our standard experience of 21 days. Ten patients received locoregional anaesthesia and were discharged after day surgery. The operating time was <60 minutes, and no complications or allergic reactions were reported. Excellent pliability of the healed wound was achieved in all patients, without signs of itching and scratching in the postoperative period. This case series is the first and largest using FSG to treat paediatric patients with different wound aetiologies. We attribute the rapid transition to acute wound status and the good pliability of the new epidermal-dermal complex to the preserved molecular components of the FSG, including omega-3. CONCLUSION: FSG represents an innovative and sustainable solution for paediatric wound care that results in shorter surgery time and reduced hospital stays, with accelerated wound healing times.Peer reviewe

Mutational and large deletion study of genes implicated in hereditary forms of primary hyperparathyroidism and correlation with clinical features

The aim of this study was to carry out genetic screening of the MEN1, CDKN1B and AIP genes, both by direct sequencing of the coding region and multiplex ligation-dependent probe amplification (MLPA) assay in the largest monocentric series of Italian patients with Multiple Endocrine Neoplasia type 1 syndrome (MEN1) and Familial Isolated Hyperparathyroidism (FIHP). The study also aimed to describe and compare the clinical features of MEN1 mutation-negative and mutation-positive patients during long-term follow-up and to correlate the specific types and locations of MEN1 gene mutations with onset and aggressiveness of the main MEN1 manifestations. A total of 69 index cases followed at the Endocrinology Unit in Pisa over a period of 19 years, including 54 MEN1 and 15 FIHP kindreds were enrolled. Seven index cases with MEN1 but MEN1 mutation-negative, followed at the University Hospital of Cagliari, were also investigated. FIHP were also tested for CDC73 and CaSR gene alterations. MEN1 germline mutations were identified in 90% of the index cases of familial MEN1 (F-MEN1) and in 23% of sporadic cases (S-MEN1). MEN1 and CDC73 mutations accounted for 13% and 7% of the FIHP cohort, respectively. A CDKN1B mutation was identified in one F-MEN1. Two AIP variants of unknown significance were detected in two MEN1-negative S-MEN1. A MEN1 positive test best predicted the onset of all three major MEN1-related manifestations or parathyroid and gastro-entero-pancreatic tumors during follow-up. A comparison between the clinical characteristics of F and S-MEN1 showed a higher prevalence of a single parathyroid disease and pituitary tumors in sporadic compared to familial MEN1 patients. No significant correlation was found between the type and location of MEN1 mutations and the clinical phenotype. Since all MEN1 mutation-positive sporadic patients had a phenotype resembling that of familial MEN1 (multiglandular parathyroid hyperplasia, a prevalence of gastro-entero-pancreatic tumors and/or the classic triad) we might hypothesize that a subset of the sporadic MEN1 mutation-negative patients could represent an incidental coexistence of sporadic primary hyperparathyroidism and pituitary tumors or a MEN1 phenocopy, in our cohort, as in most cases described in the literature

Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal β cells and human pancreatic islets

Type 2 diabetes is characterized by progressive β cell dysfunction, with lipotoxicity playing a possible pathogenetic role. Palmitate is often used to examine the direct effects of lipotoxicity and it may cause mitochondrial alterations by activating protein acetylation. However, it is unknown whether palmitate influences protein acetylation in β cells. We investigated lysine acetylation in mitochondrial proteins from INS-1E β cells (INS-1E) and in proteins from human pancreatic islets (HPI) after 24 h palmitate exposure. First, we confirmed that palmitate damages β cells and demonstrated that chemical inhibition of deacetylation also impairs INS-1E function and survival. Then, by 2-D gel electrophoresis, Western Blot and Liquid Chromatography-Mass Spectrometry we evaluated the effects of palmitate on protein acetylation. In mitochondrial preparations from palmitate-treated INS-1E, 32 acetylated spots were detected, with 13 proteins resulting over-acetylated. In HPI, 136 acetylated proteins were found, of which 11 were over-acetylated upon culture with palmitate. Interestingly, three proteins, glutamate dehydrogenase, mitochondrial superoxide dismutase, and SREBP-1, were over-acetylated in both INS-1E and HPI. Therefore, prolonged exposure to palmitate induces changes in β cell protein lysine acetylation and this modification could play a role in causing β cell damage. Dysregulated acetylation may be a target to counteract palmitate-induced β cell lipotoxicity

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