Dominant BIN1-related centronuclear myopathy (CNM) revealed by lower limb myalgia and moderate CK elevation

We report a BIN1-related CNM family with unusual clinical phenotype. The proband, a 56-year-old man suffered of lower limbs myalgia since the age of 52. Clinical examination showed short stature, mild symmetric eyelid ptosis without ophthalmoplegia, scapular winging and Achilles tendon retraction. A muscle weakness was not noted. CK levels were up to 350 UI/L. Deltoid muscle biopsy showed nuclear centralization and clustering, deep sarcolemmal invaginations and type 1 fiber hypotrophy. Whole body MRI revealed fatty infiltration of posterior legs compartments, lumbar paraspinal and serratus muscles. Myotonic dystrophy type1 and 2, Pompe disease and MTM1 and DNM2-related CNM were ruled out. By sequencing BIN1, we identified a heterozygous pathogenic mutation [c.107C > A (p.A36E)], and we demonstrate that the mutation strongly impairs the membrane tubulation property of the protein. One affected sister carried the same mutation. Her clinical examination and muscle MRI revealed a similar phenotype. Our findings expand the clinical and genetic spectrum of the autosomal dominant CNM associated with BIN1 mutations

Transcranial direct current stimulation improves the QT variability index and autonomic cardiac control in healthy subjects older than 60 years

Background: Noninvasive brain stimulation technique is an interesting tool to investigate the causal relation between cortical functioning and autonomic nervous system (ANS) responses. Objective: The objective of this report is to evaluate whether anodal transcranial direct current stimulation (tDCS) over the temporal cortex influences short-period temporal ventricular repolarization dispersion and cardiovascular ANS control in elderly subjects. Subjects and methods: In 50 healthy subjects (29 subjects younger than 60 years and 21 subjects older than 60 years) matched for gender, short-period RR and systolic blood pressure spectral variability, QT variability index (QTVI), and noninvasive hemodynamic data were obtained during anodal tDCS or sham stimulation. Results: In the older group, the QTVI, low-frequency (LF) power expressed in normalized units, the ratio between LF and high-frequency (HF) power, and systemic peripheral resistances decreased, whereas HF power expressed in normalized units and α HF power increased during the active compared to the sham condition (P,0.05). Conclusion: In healthy subjects older than 60 years, tDCS elicits cardiovascular and autonomic changes. Particularly, it improves temporal ventricular repolarization dispersion, reduces sinus sympathetic activity and systemic peripheral resistance, and increases vagal sinus activity and baroreflex sensitivity

Network abnormalities in generalized anxiety pervade beyond the amygdala-prefrontal cortex circuit: insights from graph theory

Generalized anxiety (GAD) has excessive anxiety and uncontrollable worry as core symptoms. Abnormal cerebral functioning underpins the expression and perhaps pathogenesis of GAD: Studies implicate impaired communication between the amygdala and the pre-frontal cortex (PFC). Our aim was to longitudinally investigate whether such network abnormalities are spatially restricted to this circuit or if the integrity of functional brain networks is globally disrupted in GAD. We acquired resting-state functional magnetic resonance imaging data from 16 GAD patients and 16 matched controls at baseline and after 1 year. Using network modelling and graph-theory, whole-brain connectivity was characterized from local and global perspectives. Overall lower global efficiency, indicating sub-optimal brain-wide organization and integration, was present in patients with GAD compared to controls. The amygdala and midline cortices showed higher betweenness centrality, reflecting functional dominance of these brain structures. Third, lower betweenness centrality and lower degree emerged for PFC, suggesting weakened inhibitory control. Overall, network organization showed impairments consistent with neurobiological models of GAD (involving amygdala, PFC, and cingulate cortex) and further pointed to an involvement of temporal regions. Such impairments tended to progress over time and predict anxiety symptoms. A graph-analytic approach represents a powerful approach to deepen our understanding of GAD

Intercomparison of Airborne Multi-Angle Polarimeter Observations from the Polarimeter Definition Experiment (PODEX)

In early 2013, three airborne polarimeters were flown on the high altitude NASA ER-2 aircraft in California for the Polarimeter Definition Experiment (PODEX). PODEX supported the pre-formulation NASA Aerosol-Cloud-Ecosystem (ACE) mission, which calls for an imaging polarimeter in polar orbit (among other instruments) for the remote sensing of aerosols, oceans and clouds. Several polarimeter concepts exist as airborne prototypes, some of which were deployed during PODEX as a capabilities test. Two of those instruments to date have successfully produced Level 1 (georegistered, calibrated radiance and polarization) data from that campaign: the Airborne Multiangle SpectroPolarimetric Imager (AirMSPI) and the Research Scanning Polarimeter (RSP). We compared georegistered observations of a variety of scene types by these instruments to test if Level 1 products agree within stated uncertainties. Initial comparisons found radiometric agreement, but polarimetric biases beyond measurement uncertainties. After subsequent updates to calibration, georegistration, and the measurement uncertainty models, observations from the instruments now largely agree within stated uncertainties. However, the 470nm reflectance channels have a roughly +6% bias of AirMSPI relative to RSP, beyond expected measurement uncertainties. We also find that observations of dark (ocean) scenes, where polarimetric uncertainty is expected to be largest, do not agree within stated polarimetric uncertainties. Otherwise, AirMSPI and RSP observations are consistent within measurement uncertainty expectations, providing credibility for subsequent creation of Level 2 (geophysical product) data from these instruments, and comparison thereof. The techniques used in this work can also form a methodological basis for other intercomparisons, such as of the data gathered during the recent Aerosol Characterization from Polarimeter and Lidar (ACEPOL) field campaign, carried out in October and November of 2017 with four polarimeters (including AirMSPI and RSP)

MULTIDISCIPLINARY APPROACH TO MEDICATION-RELATED OSTEONECROSIS OF THE JAW: REPORT OF A CASE

Nowadays the multidisciplinary team (MDT) plays a critical role in the treatment of patients with osteonecrosis of the oral cavity, in particular for the reconstructive-rehabilitation phase of complex cases. Among the objectives of the MDT we find the improvement of the quality of life of patients, the restoration of the anatomical defect following surgery, as well as the planning of an aesthetic-functional rehabilitation. The experience of the MDT composed of professionals belonging to the Medicine and Oral Pathology Outpatient Clinic of the Maggiore Hospital of Trieste and to the Department of Otolaryngology of the S. Maria degli Angeli Hospital in Pordenone is presented in relation to surgical-prosthetic rehabilitation in a patient with drug-induced osteonecrosis. The patient, suffering from right maxillary osteonecrosis induced by therapy with Zoledronic Acid, underwent a demolitive surgical intervention of right maxillectomy. At the same time, reconstruction was carried out using a microvascularized fibula flap and insertion of 5 implants. Subsequently, the patient was rehabilitated with a fixed prosthesis on implants. The rehabilitation of the treated patient allowed the resumption of functional activities such as chewing and phonation, guaranteeing the patient a good quality of life. Last but not least, it has allowed us to obtain a good result also from an aesthetic point of view. There are numerous studies in literature which confirm the success of planning by the MDT in treating MRONJ hat demonstrate how an effective and dynamic MDT positively influences the patient's therapeutic and rehabilitative path. The MDT must therefore be able to formulate a personalized therapeutic and rehabilitation plan for the individual patient

DEFB1 polymorphisms and salivary hBD-1 concentration in Oral Lichen Planus patients and healthy subjects

The aetiology of Oral Lichen Planus (OLP), a chronic inflammatory disease of oral mucosa, is not yet well understood. Since innate immunity may be hypothesized as involved in the susceptibility to OLP, we studied human beta defensin 1 (hBD-1) an antimicrobial peptide constitutively expressed in the saliva, looking at functional genetic variants possibly able to diminish hBD-1 production an consequently conferring major susceptibility to OLP

Ribavirin Impairs Salivary gland function During Combination Treatment With Pegylated Interferon Alfa-2a In HEpatitis C patients

Background: Xerostomia is a common adverse event of unknown etiology observed during pegylated interferon (PegIFN)/Ribavirin (Rbv) treatment. Objectives: To assess the frequency and mechanisms of xerostomia during PegIFN/Rbv therapy. Patients and Methods: Thirty-one naive patients with chronic hepatitis C consecutively received PegIFN-alpha 2a (180 mu g/week) plus Rbv (800-1200 mg/day). The controls were 10 patients with chronic hepatitis B who received PegIFN-alpha 2a (180 mu g/week). During treatment and follow-up, all patients underwent basal and masticatory stimulated sialometry, otorhinolaryngoiatric (ORL) examination, and a questionnaire survey to subjectively assess symptoms of oral dryness. Results: Twenty-seven patients on PegIFN/Rbv and 4 on PegIFN (87% vs. 40%, P = 0.006) reported xerostomia. Thirty patients on PegIFN/Rbv combination therapy and 2 patients on monotherapy had ORL signs of salivary gland hypofunction (97% vs. 20%, P < 0.0001). Mean basal (A) and stimulated (B) salivary flow rates (mL/min) progressively decreased during PegIFN/Rbv treatment (A, 0.49 at baseline vs. 0.17 at the end of treatment, P < 0.0001; B,1.24 at baseline vs. 0.53 at the end of treatment, P = 0.0004). At week 24 following PegIFN/Rbv treatment, salivary flow rates were similar to baseline (A, 0.53 at the end of follow-up vs. 0.49 at baseline; B,1.19 at the end of follow-up vs. 1.24 at baseline). Salivary function was unaffected in monotherapy patients. Conclusions: Rbv causes salivary gland hypofunction in hepatitis C patients receiving PegIFN/Rbv therapy, which promptly reverts to normal upon cessation of treatment

Knowledge and awareness of oral cancer: A cross-sectional survey in Trieste, Italy

The aim of the study was to verify the knowledge on oral cancer and to assess possible differences in awareness and information basing on different demographic and subject-related factors. An anonymous survey was provided to 750 random subjects using online-based questionnaires. Statistical analysis was performed in order to evaluate the influence of demographic variables (gender, age, education) on knowledge of oral cancer and its risk factors. 68.4% of individuals knew about the existence of oral cancer, mostly from media and family/friends. Awareness was significantly influenced by gender and higher education, but not by age. Most participants recognized smoking as a risk factor, but alcohol abuse and sunlight exposure are less known, especially among less educated subjects. On the contrary, our study shows a diffusion of false information: more than 30% of the participants indicated the possible role of amalgam fillings in oral cancer onset, independently of gender, age or education. The results of our study suggest the need for oral cancer awareness campaigns, where school and healthcare professionals should be actively involved in promoting, organizing and finding methods to monitor the medium and long-term efficacy with proper methodological quality

Impact of DEFB1 gene regulatory polymorphisms on hBD-1 salivary concentration

Human \u3b2-defensin 1 (hBD-1) is an antimicrobial peptide involved in epithelial defence of various tissues, also present in the saliva. Individual genetic variations within the DEFB1 gene, encoding for hBD-1, could influence gene expression and protein production