Single Versus Double Hadad-Bassagasteguy Flap in Expanded Endoscopic Skull-Base Surgery

The reconstruction of dural defects, after endoscopic removal of skull-base lesions, remains challenging when a large defect or a high flow intraoperative cerebrospinal fluid (CSF) leak is observed. The aim of this study is to describe our preliminary experience with a double Hadad-Bassagasteguy (H-B) flap technique for skull-base repair, comparing its efficacy with the use of a single H-B flap in our series. A retrospective chart review was conducted on patients who underwent exclusive endoscopic endonasal skull-base surgery at our Referral Skull Base Center from December 2014 to January 2018. Data on patient demographics, pathology, preoperative and postoperative imaging, intraoperative findings, surgical route, defect size, reconstruction techniques and repair materials, were analyzed. Patients were divided into double and single H-B flap groups. In the single and double H-B groups, the postoperative CSF leak rates were 37.5% (6 of 16 patients) and 4.5% (1 of 22 patients), respectively. The difference between the two groups was statistically significant (p = 0.0470). In patients with defects > 4 cm or high-flow intraoperative CSF leakage related to the opening of the third ventricle, the double H-B flap was successfully placed with no occurrence of postoperative CSF leakage. The double H-B flap significantly reduced the postoperative CSF leakage rate after expanded transnasal skull-base surgery. Particularly in challenging cases, where a large skull-base defect or a high-flow intraoperative CSF leak was observed, this reconstructive method proved to be very effective, with no evidence of postoperative CSF fistulas

Garnet‐rich veins in an ultrabasic amphibolite from NE Sardinia, Italy: An example of vein mineralogical re‐equilibration during the exhumation of a granulite terrane

A complex system of mono‐ and polymineralic centimeter‐thick veins occurs within the ultrabasic amphibolites of Montigiu Nieddu hill in northeastern Sardinia, and they are filled with garnet, amphibole, chlorite, and epidote. Some garnet‐rich veins are margined by an amphibole layer at the interface with the host rock and/or show replacement of epidote concentrated in the vein core. Together with homogeneous matrix garnet (Grt1), millimetric, euhedral, and strongly zoned garnet porphyroblasts occur within these veins. The estimated pressure–temperature conditions (P = 1.0–1.7 GPa, T = 650–750 °C) for the formation of Grt1 match the metamorphic peak and early exhumation derived previously for the host rocks and confirm that the garnet veins also formed under high‐pressure (HP) conditions. The igneous protolith of the host rocks experienced HP metamorphism in a subduction zone and underwent exhumation in an exhumation channel. The vein system in the ultrabasic amphibolites formed by cyclic hydrofracturing as rapid and transient events such as crack‐seal veining. The growth of multiple vein‐filling mineral assemblages indicates the formation of separate vein‐producing cycles

Aortic stenosis and aortic regurgitation express different titin isoforms: Differences and relationships with functional and geometric characteristics

Background-Titin represents an important biomechanical sensor which determines compliance and diastolic/ systolic function of the left ventricle (LV). To assess the different titin-isoform expression and the relationships with functional and geometric patterns, we analyzed titin-isoform expression and cardiomyocytes contractile functioninmyocardialbiopsysamplesofpatientsundergoingaorticvalvereplacement(AVR)foraorticstenosis (AS)and for aorticregurgitation (AR). Method-Specimens,collectedfromtheLVof35withASand35withARundergoingAVRwereanalyzedfortitinisoform expression and cardiomyocytes force measurement. Ten donor hearts were analyzed as controls for normal values. Results were implemented with preoperative geometry and function assessed by Doppler echocardiography. Results-Comparedtocontrols,N2BA/N2Btitin-isoformsratiowasreducedto0.24inAS(p b 0.001)butincreased to 0.51 in AR (p b 0.001). N2BA/N2B titin-isoforms ratio was further reduced in 8 patients with severe (restrictive) diastolic dysfunction (0.17 ± 0.03, p b 0.001) but was increased in patients with severe systolic dysfunction (0.58 ± 0.07, p b 0.001). As compared to controls, Fpasive was higher in AS (6.7 ± 0.2 vs 4.4 ± 0.4kN/m2,p b 0.001)butwaslowerinAR(3.7±0.2vs4.4±0.4kN/m2,p b 0.001).Totalforcewascomparable. FpassivewassignificantlyhigherinAS patientswithseverethanwithmoderateLVdiastolicdysfunction(7.1± 0.5 vs 6.6.±0.6,p=0.004). Conclusions-titin-isoform expression differs in AS and AR as adaptive response to different pathophysiologic scenarios. Co-expressing isoforms at varying ratios results in modulation of the passive mechanical behavior of the LV at different degree of dysfunction and allows for compensative adjustment of the diastolic/systolic properties of the myocardium

Primary mitochondrial myopathy: Clinical features and outcome measures in 118 cases from Italy

Objective: To determine whether a set of functional tests, clinical scales, patient-reported questionnaires, and specific biomarkers can be considered reliable outcome measures in patients with primary mitochondrial myopathy (PMM), we analyzed a cohort of Italian patients. Methods: Baseline data were collected from 118 patients with PMM, followed by centers of the Italian network for mitochondrial diseases. We used the 6-Minute Walk Test (6MWT), Timed Up-and-Go Test (x3) (3TUG), Five-Times Sit-To-Stand Test (5XSST), Timed Water Swallow Test (TWST), and Test of Masticating and Swallowing Solids (TOMASS) as functional outcome measures; the Fatigue Severity Scale and West Haven-Yale Multidimensional Pain Inventory as patient-reported outcome measures; and FGF21, GDF15, lactate, and creatine kinase (CK) as biomarkers. Results: A total of 118 PMM cases were included. Functional outcome measures (6MWT, 3TUG, 5XSST, TWST, and TOMASS) and biomarkers significantly differed from healthy reference values and controls. Moreover, functional measures correlated with patients' perceived fatigue and pain severity. Patients with either mitochondrial or nuclear DNA point mutations performed worse in functional measures than patients harboring single deletion, even if the latter had an earlier age at onset but similar disease duration. Both the biomarkers FGF21 and GDF15 were significantly higher in the patients compared with a matched control population; however, there was no relation with severity of disease. Conclusions: We characterized a large cohort of PMM by evaluating baseline mitochondrial biomarkers and functional scales that represent potential outcome measures to monitor the efficacy of treatment in clinical trials; these outcome measures will be further reinvestigated longitudinally to define the natural history of PMM

TrkB modulates fear learning and amygdalar synaptic plasticity by specific docking sites

Understanding the modulation of the neural circuitry of fear is clearly one of the most important aims in neurobiology. Protein phosphorylation in response to external stimuli is considered a major mechanism underlying dynamic changes in neural circuitry. TrkB (Ntrk2) neurotrophin receptor tyrosine kinase potently modulates synaptic plasticity and activates signal transduction pathways mainly through two phosphorylation sites [Y515/Shc site; Y816/PLCgamma (phospholipase Cgamma) site]. To identify the molecular pathways required for fear learning and amygdalar synaptic plasticity downstream of TrkB, we used highly defined genetic mouse models carrying single point mutations at one of these two sites (Y515F or Y816F) to examine the physiological relevance of pathways activated through these sites for pavlovian fear conditioning (FC), as well as for synaptic plasticity as measured by field recordings obtained from neurons of different amygdala nuclei. We show that a Y816F point mutation impairs acquisition of FC, amygdalar synaptic plasticity, and CaMKII signaling at synapses. In contrast, a Y515F point mutation affects consolidation but not acquisition of FC to tone, and also alters AKT signaling. Thus, TrkB receptors modulate specific phases of fear learning and amygdalar synaptic plasticity through two main phosphorylation docking sites

Distribution of Exonic Variants in Glycogen Synthesis and Catabolism Genes in Late Onset Pompe Disease (LOPD)

Pompe disease (PD) is a monogenic autosomal recessive disorder caused by biallelic pathogenic variants of the GAA gene encoding lysosomal alpha-glucosidase; its loss causes glycogen storage in lysosomes, mainly in the muscular tissue. The genotype-phenotype correlation has been extensively discussed, and caution is recommended when interpreting the clinical significance of any mutation in a single patient. As there is no evidence that environmental factors can modulate the phenotype, the observed clinical variability in PD suggests that genetic variants other than pathogenic GAA mutations influence the mechanisms of muscle damage/repair and the overall clinical picture. Genes encoding proteins involved in glycogen synthesis and catabolism may represent excellent candidates as phenotypic modifiers of PD. The genes analyzed for glycogen synthesis included UGP2, glycogenin (GYG1-muscle, GYG2, and other tissues), glycogen synthase (GYS1-muscle and GYS2-liver), GBE1, EPM2A, NHLRC1, GSK3A, and GSK3B. The only enzyme involved in glycogen catabolism in lysosomes is alpha-glucosidase, which is encoded by GAA, while two cytoplasmic enzymes, phosphorylase (PYGB-brain, PGL-liver, and PYGM-muscle) and glycogen debranching (AGL) are needed to obtain glucose 1-phosphate or free glucose. Here, we report the potentially relevant variants in genes related to glycogen synthesis and catabolism, identified by whole exome sequencing in a group of 30 patients with late-onset Pompe disease (LOPD). In our exploratory analysis, we observed a reduced number of variants in the genes expressed in muscles versus the genes expressed in other tissues, but we did not find a single variant that strongly affected the phenotype. From our work, it also appears that the current clinical scores used in LOPD do not describe muscle impairment with enough qualitative/quantitative details to correlate it with genes that, even with a slightly reduced function due to genetic variants, impact the phenotype

Lipomatosis Incidence and Characteristics in an Italian Cohort of Mitochondrial Patients.

Lipomas have often been associated with mtDNA mutations and were mainly observed in patients with mutation in mitochondrial tRNAlysine which is also the most frequent mutation associated with MERRF. Up to date, no systematic studies have been developed in order to assess the incidence of lipomas in large cohorts of mitochondrial patients.The aim of this study is to analyze the incidence and characteristics of lipomas among an Italian cohort of patients with mitochondrial diseases. A retrospective, database-based study (Nation-wide Italian Collaborative Network of Mitochondrial Diseases) of patients with lipomas was performed. A total of 22 (1.7%) patients with lipomas have been identified among the 1,300 mitochondrial patients, enrolled in the Italian database. In about 18% multiple systemic lipomatosis (MSL) was the only clinical manifestation; 54% of patients showed a classical MERRF syndrome. Myopathy, alone or in association with other symptoms, was found in 27% of patients. Lactate was elevated in all the 12 patients in which was measured. Muscle biopsy was available in 18/22 patients: in all of them mitochondrial abnormalities were present. Eighty six percent had mutations in mtDNA coding for tRNA lysine. In most of patients, lipomas were localized along the cervical-cranial-thoracic region. In 68% of the patients were distributed symmetrically. Only two patients had lipomas in a single anatomical site (1 in right arm and 1 in gluteus maximum). MSL is often overlooked by clinicians in patients with mitochondrial diseases where the clinical picture could be dominated by a severe multi-systemic involvement. Our data confirmed that MSL is a rare sign of mitochondrial disease with a strong association between multiple lipomas and lysine tRNA mutations. MSL could be considered, even if rare, a red flag for mitochondrial disorders, even in patients with an apparently isolated MSL

Congenital myopathies: Clinical phenotypes and new diagnostic tools

Congenital myopathies are a group of genetic muscle disorders characterized clinically by hypotonia and weakness, usually from birth, and a static or slowly progressive clinical course. Historically, congenital myopathies have been classified on the basis of major morphological features seen on muscle biopsy. However, different genes have now been identified as associated with the various phenotypic and histological expressions of these disorders, and in recent years, because of their unexpectedly wide genetic and clinical heterogeneity, next-generation sequencing has increasingly been used for their diagnosis. We reviewed clinical and genetic forms of congenital myopathy and defined possible strategies to improve cost-effectiveness in histological and imaging diagnosis

NEMO-SN1 Abyssal Cabled Observatory in the Western Ionian Sea

The NEutrinoMediterranean Observatory—Submarine Network 1 (NEMO-SN1) seafloor observatory is located in the central Mediterranean Sea, Western Ionian Sea, off Eastern Sicily (Southern Italy) at 2100-m water depth, 25 km from the harbor of the city of Catania. It is a prototype of a cabled deep-sea multiparameter observatory and the first one operating with real-time data transmission in Europe since 2005. NEMO-SN1 is also the first-established node of the European Multidisciplinary Seafloor Observatory (EMSO), one of the incoming European large-scale research infrastructures included in the Roadmap of the European Strategy Forum on Research Infrastructures (ESFRI) since 2006. EMSO will specifically address long-term monitoring of environmental processes related to marine ecosystems, marine mammals, climate change, and geohazards