A new mutation in GJC2 associated with subclinical leukodystrophy

Recessive mutations in GJC2, the gene-encoding connexin 47 (Cx47), cause Pelizaeus–Merzbacher-like disease type 1, a severe dysmyelinating disorder. One recessive mutation (p.Ile33Met) has been associated with a much milder phenotype––hereditary spastic paraplegia type 44. Here, we present evidence that a novel Arg98Leu mutation causes an even milder phenotype––a subclinical leukodystrophy. The Arg98Leu mutant forms gap junction plaques in HeLa cells comparable to wild-type Cx47, but electrical coupling was 20-fold lower in cell pairs expressing Arg98Leu than for cell pairs expressing wild-type Cx47. On the other hand, coupling between Cx47Arg98Leu and Cx43WT expressing cells did not show such reductions. Single channel conductance and normalized steady-state junctional conductance–junctional voltage (G _j–V _j) relations differed only slightly from those for wild-type Cx47. Our data suggest that the minimal phenotype in this patient results from a reduced efficiency of opening of Cx47 channels between oligodendrocyte and oligodendrocyte with preserved coupling between oligodendrocyte and astrocyte, and support a partial loss of function model for the mild Cx47 associated disease phenotypes.     

Multi-Technique Diagnostic Analysis of Plasters and Mortars from the Church of the Annunciation (Tortorici,Sicily)

Plasters and mortars of the Church of the Annunciation (Tortorici, Sicily) were characterized, for the first time, both at the elemental and molecular levels, by means of portable X-ray fluorescence (XRF) and Raman spectroscopy, to achieve information on the “state of health” of the whole structure. The understanding of their degradation mechanisms and the identification of consequent degradation patterns can define the environmental factors responsible for interpreting the potential pathological forms that can impact the general building vulnerability. In this sense, the results obtained in this article provide relevant information to identify and address both the characterization of building materials and the fundamental causes of their deterioration. At the same time, if coupled with the attempt to supply a chronological order of the major restoration interventions carried out on the investigated site, they provide new insights to calibrate the models for building vulnerability studies.     

A comparison between stereophotogrammetry and smartphone structured light technology for three-dimensional face scanning

ObjectivesTo compare three-dimensional facial scans obtained by stereophotogrammetry with two different applications for smartphone supporting the TrueDepth system, a structured light technology.Materials and MethodsFacial scans of 40 different subjects were acquired with three different systems. The 3dMDtrio Stereophotogrammetry System (3dMD, Atlanta, Ga) was compared with a smartphone (iPhone Xs; Apple, Cupertino, Calif) equipped with the Bellus3D Face Application (version 1.6.11; Bellus3D Inc, Campbell, Calif) or Capture (version 1.2.5; Standard Cyborg Inc, San Francisco, Calif). Times of image acquisition and elaboration were recorded. The surface-to-surface deviation and the distance between 18 landmarks from 3dMD reference images to those acquired with Bellus3D or Capture were measured.ResultsCapturing and processing times with the smartphone applications were considerably longer than with the 3dMD system. The surface-to-surface deviation analysis between the Bellus3D and 3dMD showed an overlap percentage of 80.01% ± 5.92% and 56.62% ± 7.65% within the ranges of 1 mm and 0.5 mm discrepancy, respectively. Images from Capture showed an overlap percentage of 81.40% ± 9.59% and 56.45% ± 11.62% within the ranges of 1 mm and 0.5 mm, respectively.ConclusionsThe face image acquisition with the 3dMD device is fast and accurate, but bulky and expensive. The new smartphone applications combined with the TrueDepth sensors show promising results. They need more accuracy from the operator and more compliance from the patient because of the increased acquisition time. Their greatest advantages are related to cost and portability.     

Cardiotoxicity from Capecitabine Chemotherapy: Prospective Study of Incidence at Rest and During Physical Exercise

BackgroundPhysical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine.Patients and MethodsOne hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout.ResultsCardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44).ConclusionCapecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended.Clinical Trials registration numberCRO-2010-17.     

Side-to-side esophagojejunostomy during totally laparoscopic total gastrectomy for malignant disease: a multicenter study

Background  

Esophagojejunostomy (EJS) represents the most difficult steps during totally laparoscopic total gastrectomy (TLTG). Over the past few years, several techniques have been developed. This study aimed to evaluate the feasibility and surgical outcomes of the laparoscopic intracorporeal side-to-side EJS during TLTG used to treat malignant disease of the stomach.     

Metachromatic leukodystrophy with late adult-onset: diagnostic clues and differences from other genetic leukoencephalopathies with dementia

Journal of Neurology -     

Survival and prognostic indicators in compensated and decompensated cirrhosis

Six-year survival of cirrhosis was assessed in a series of 1155 consecutive patients (751 men, 404 women). Among the men, 33% were alcoholics and 18% were HB_sAg positive; corresponding figures for the women were 15% and 6%, respectively. Features of decompensation at first presentation were observed in 63% of the patients. Six-year survival was 54% in compensated and 21% in decompensated patients. No significant differences in survival were found between alcoholics and nonalcoholics. Leading causes of death were liver failure (49%), hepatocellular carcinoma (22%), and bleeding (13%). The prognostic role of 21 variables was evaluated separately in compensated and decompensated patients by the Cox's regression model. The following variables were found to be significant predictors of death risk in compensated patients: male sex, HB_sAg positivity, age, prothrombin time prolongation, and esophageal varices. In decompensated disease the significant indicators of death risk were: hepatocellular carcinoma, encephalopathy, hemorrhage, SGOT, esophageal varices, gamma globulins, prothrombin time prolongation, continued abuse of alcohol, HB_sAg positivity, gamma glutamyl transpeptidase, and cholinesterase. A simple prognostic index based upon the relative risk coefficient of the significant variables is suggested.Members of the Liver Study Group are: Maria Caltagirone, Gabriella Filippazzo, Giovanni Gatto, Gandolfo Giannuoli, Silvio Margin, Guiseppe Malizia, Lorenzo Maniaci, Maria Pia Marcenó, Alberto Maringhini, Rocco Micciolo, Salvatore Orsini, Fabio Pace, Ugo Palazzo, Linda Pasta, Giuseppina Russo, Rosa Giovanna Simonetti, Mario Spinello, Mario Traina, Mario Valenza, Maria Vinci, Giovanni Vizzini.