Identification of D179H, a novel missense GJB2 mutation in a Western Sicily family

The main purpose of this study was to describe a novel missense mutation (p.D179H) found in a Western Sicily family and to examine the genetic and audiologic profiles of all family members by performing a GJB2 and GJB6 mutations analysis and a complete audiologic assessment. The proband was a 3-month-old infant with a congenital profound sensorineural hearing loss; direct sequencing of the GJB2 revealed the presence of a c.35delG mutation in the heterozygous state and a heterozygous G[C transition at nucleotide 535 in trans; this novel mutation, called p.D179H, resulted in an aspartic acid to histidine change at codon 179. It was also evidenced in the heterozygous state in two members of this family, both with normal hearing. No GJB6 mutations were evidenced in all subjects studied. Considering the genotypic and phenotypic analysis of all family members, we suggest, differently from the p.D179 N mutation previously reported, a recessive mode of inheritance. Functional studies on p.D179H have to be performed to confirm our hypothesis

Oxidative stress neuroinflammation and cellular stress response in sensorineural hearing loss: novel nutritional therapeutical approaches

This study is intended to validate the hypothesis that changes in the redox state of glutathione, the major endogenous antioxidant, associated with the abnormal expression and activity of cytoprotective vitagenes, which in normal conditions are expressed only at low level may represent a critical factor, involved in the physiopathological changes associated to degenerative damage occurring in cochlear diseases. Moreover modulation of stress responsive vitagenes by nutritional antioxidants can be an effective therapeutic strategy to minimize consequences of oxidative stress associated to the pathogenesis and course of sensorineural hearing loss. One therapeutic approach can be antioxidant substances, as cisteina and superoxide dismutase supplementation to burst vitagenes and confer neuroprotection. The damage caused in the inner ear by oxidative stress can induce apoptosis and necrosis of both the hair cells as neurons of the spiral ganglion. Reactive oxygen species (ROS) and free radicals are formed not only as by-products of various metabolic pathways but also for exposure to ototoxic substances such as aminoglycosides and cisplatin, for hypoxia/ischemia and to exposure to noise. Although the mechanism of production of ROS within the cochlea has not yet been precisely identified, it is conceivable that mitochondrial dysfunction and consequent burst in oxidative stress are major causative factors. Consistent with this notion, it is known that the base of the cochlea is more vulnerable to oxidative damage resulted from exposure to ototoxic substances than the apical portions. The difference in survival between the basal outer hair cells and the apical ones appear to be due to a significantly lower level of glutathione in the basal outer hair cells than the apical, a phenomenon that makes it easier basal cells vulnerable to damage from free radicals. © Mattioli 188

Hollow core waveguide for simultaneous laser plastic welding

Welding of plastics is a very important process in many industrial fields such as electronic packaging, medical applications, textile joining and automotive. It is often used when finished structure is too large to mold, for cost effectiveness or when dissimilar materials have to be joined. It is also employed in MEMs and Bio-MEMs applications, for example for microfluidic devices, where joint areas are very small, and need an amount of precision that other techniques can’t provide. This work focuses on description of transparent laser plastic welding technique, comparing simultaneous and quasi-simultaneous welding, and the development of an experimental setup for an automotive application. There are different laser welding methods, like simultaneous welding, where all the joining interface is irradiated at the same time and often includes a hollow guide to direct laser beam, and quasi-simultaneous welding, for example contour welding or scanning welding, where the laser spot is driven on joining interface via movement of the source or changing the path of the laser beam. An innovative tool end experimental setup was made to evaluate the simultaneous versus quasi-simultaneous welding to join polymeric material for an automotive application. A DFSS design of experiment was used. A LIMO laser bar diode @808nm with a maximum output power of 50 Watts, was coupled to a multi-mode 400 μm glass core optical fiber (Boscottica) with a numerical aperture of 0.22, by a LIMO Beam Transformation System HOC 150/500 (1401.612). The beam at the output of the fiber was guided through two different optical systems to the welding joint to test the two methods. A SANYO stepper motor was used for the quasi-simultaneous welding. Different kind of plastic materials were joined, Hostacom TRC 787N and THERMORUN TT875NE/BE. We performed static pull tests and dynamic pull test, and found optimum and baseline configuration

PEDOT:PSS Morphostructure and ion-to-electron transduction and amplification mechanisms in organic electrochemical transistors

Organic electrochemical transistors (OECTs) represent a powerful and versatile type of organic-based device, widely used in biosensing and bioelectronics due to potential advantages in terms of cost, sensitivity, and system integration. The benchmark organic semiconductor they are based on is poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), the electrical properties of which are reported to be strongly dependent on film morphology and structure. In particular, the literature demonstrates that film processing induces morphostructural changes in terms of conformational rearrangements in the PEDOT:PSS in-plane phase segregation and out-of-plane vertical separation between adjacent PEDOT-rich domains. Here, taking into account these indications, we show the thickness-dependent operation of OECTs, contextualizing it in terms of the role played by PEDOT:PSS film thickness in promoting film microstructure tuning upon controlled-atmosphere long-lasting thermal annealing (LTA). To do this, we compared the LTA-OECT response to that of OECTs with comparable channel thicknesses that were exposed to a rapid thermal annealing (RTA). We show that the LTA process on thicker films provided OECTs with an enhanced amplification capability. Conversely, on lower thicknesses, the LTA process induced a higher charge carrier modulation when the device was operated in sensing mode. The provided experimental characterization also shows how to optimize the OECT response by combining the control of the microstructure via solution processing and the effect of postdeposition processing

Nanomolar detection of the antitumor drug tamoxifen by flexible organic electrochemical devices

Organic Electrochemical Transistors (OECTs) represent a versatile tool successfully exploited in the field of Bioelectronics. In particular, OECTs have been used for the detection of a wide set of bioanalytes, often showing superior performance compared to that of commonly used sensors. In this study, we propose a flexible, disposable OECT, based on poly (3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) channels and few layers graphene (FLG) sheets gate electrodes, for the detection of Tamoxifen (TAM), an important antitumor drug widely used in breast cancer therapy. The optimal device operation conditions in terms of sensitivity and limit of detection (LOD) have been investigated too

Therapeutic approaches to pediatric pseudotumor cerebri: new insights from literature data

The pseudotumor cerebri syndrome (PTCS), also known as idiopathic intracranial hypertension (IIH), is characterized by signs and symptoms of increased intracranial pressure such as headache and cranial nerve palsies, in the absence of any space-occupying mass. This condition commonly affects overweight women of childbearing age, even if it is also frequent in men and children. Children with PTCS may present with atypical signs and symptoms, with a different prognosis compared to adults. However, the treatment is the same for both children and adults, even if there are no strict treatment guidelines in regards. All treatment strategies in children are based on retrospective studies and none has been evaluated in prospective or randomized controlled trial studies. This review focuses on literature data on PTCS treatment in children

Incorporating dose–volume histogram parameters of swallowing organs at risk in a videofluoroscopy-based predictive model of radiation-induced dysphagia after head and neck cancer intensity-modulated radiation therapy

Purpose: To develop a videofluoroscopy-based predictive model of radiation-induced dysphagia (RID) by incorporating DVH parameters of swallowing organs at risk (SWOARs) in a machine learning analysis. Methods: Videofluoroscopy (VF) was performed to assess the penetration-aspiration score (P/A) at baseline and at 6 and 12 months after RT. An RID predictive model was developed using dose to nine SWOARs and P/A-VF data at 6 and 12 months after treatment. A total of 72 dosimetric features for each patient were extracted from DVH and analyzed with linear support vector machine classification (SVC), logistic regression classification (LRC), and random forest classification (RFC). Results: 38 patients were evaluable. The relevance of SWOARs DVH features emerged both at 6 months (AUC 0.82 with SVC; 0.80 with LRC; and 0.83 with RFC) and at 12 months (AUC 0.85 with SVC; 0.82 with LRC; and 0.94 with RFC). The SWOARs and the corresponding features with the highest relevance at 6 months resulted as the base of tongue (V65 and Dmean), the superior (Dmean) and medium constrictor muscle (V45, V55; V65; Dmp; Dmean; Dmax and Dmin), and the parotid glands (Dmean and Dmp). On the contrary, the features with the highest relevance at 12 months were the medium (V55; Dmin and Dmean) and inferior constrictor muscles (V55, V65 Dmin and Dmax), the glottis (V55 and Dmax), the cricopharyngeal muscle (Dmax), and the cervical esophagus (Dmax). Conclusion: We trained and cross-validated an RID predictive model with high discriminative ability at both 6 and 12 months after RT. We expect to improve the predictive power of this model by enlarging the number of training datasets

Aerosol Jet Printed Organic Memristive Microdevices Based on a Chitosan:PANI Composite Conductive Channel

In this study we show a chitosan:polyaniline (CPA)-based ink, responding to eco-biofriendly criteria, specifically developed for the manufacturing of the first organic memristive device (OMD) with an aerosol jet printed conductive channel. Our contribution is in the context of bioelectronics, where there is an increasing interest in emulating neuro-morphic functions. In this framework, memristive devices and systems have been shown to be well suited. In particular organic-based devices are envisaged as very promising in some applications, such as brain-machine interfacing, owing to specific properties of organics (e.g., biocompatibility, mixed ionic-electronic conduction). On the other hand, the research activities on flexible organic (bio)electronic devices and direct writing (DW) noncontact techniques increasingly overlap in the effort of achieving reliable applications benefiting from the rapid prototyping to accomplish a fast device optimization. In this context, ink-based techniques, such as aerosol jet printing (AJP), although particularly well suited to implement 3D-printed electronics due to advantages it offers in terms of a wide set of allowed printable materials, still require research efforts aimed at conferring printability to the desired precursors. The developed CPA composite was characterized by FTIR, DLS, and MALDI-TOF techniques, while the related aerosol jet printed films were studied by SEM and profilometry. Taking advantage of the intrinsic and stable electrical conductivity of CPA films, which do not necessarily require any acidic treatment to promote a sustained charge carrier conduction, 10 mu m short-channel OMDs were hence manufactured by interfacing the printed CPA layers with a solid polyelectrolyte (SPE). We accordingly demonstrated prototypes of stable and best performing OMD devices with downscaled features, showing well-defined counterclockwise hysteresis/rectification and an enhanced durability. These properties pave the way to further improving performance, as well as to realizing a direct integration of the devices into hardware neural networks by in-line fabrication routes