Toward the Development of User-Centered Neurointegrated Lower Limb Prostheses.

The last few years witnessed radical improvements in lower-limb prostheses. Researchers have presented innovative solutions to overcome the limits of the first generation of prostheses, refining specific aspects which could be implemented in future prostheses designs. Each aspect of lower-limb prostheses has been upgraded, but despite these advances, a number of deficiencies remain and the most capable limb prostheses fall far short of the capabilities of the healthy limb. This article describes the current state of prosthesis technology; identifies a number of deficiencies across the spectrum of lower limb prosthetic components with respect to users' needs; and discusses research opportunities in design and control that would substantially improve functionality concerning each deficiency. In doing so, the authors present a roadmap of patients related issues that should be addressed in order to fulfill the vision of a next-generation, neurally-integrated, highly-functional lower limb prosthesis.

Progress in Dental Adhesive Materials.

There have been significant advances in adhesive dentistry in recent decades, with efforts being made to improve the mechanical and bonding properties of resin-based dental adhesive materials. Various attempts have been made to achieve versatility, introducing functional monomers and silanes into the materials' composition to enable the chemical reaction with tooth structure and restorative materials and a multimode use. The novel adhesive materials also tend to be simpler in terms of clinical use, requiring reduced number of steps, making them less technique sensitive. However, these materials must also be reliable and have a long-lasting bond with different substrates. In order to fulfill these arduous tasks, different chemical constituents and different techniques are continuously being developed and introduced into dental adhesive materials. This critical review aims to discuss the concepts behind novel monomers, bioactive molecules, and alternative techniques recently implemented in adhesive dentistry. Incorporating monomers that are more resistant to hydrolytic degradation and functional monomers that enhance the micromechanical retention and improve chemical interactions between adhesive resin materials and various substrates improved the performance of adhesive materials. The current trend is to blend bioactive molecules into adhesive materials to enhance the mechanical properties and prevent endogenous enzymatic degradation of the dental substrate, thus ensuring the longevity of resin-dentin bonds. Moreover, alternative etching materials and techniques have been developed to address the drawbacks of phosphoric acid dentin etching. Altogether, we are witnessing a dynamic era in adhesive dentistry, with advancements aiming to bring us closer to simple and reliable bonding. However, simplification and novelty should not be achieved at the expense of material properties.

Microbial contamination of resin composites inside their dispensers: An increased risk of cross-infection?

OBJECTIVES: To evaluate the effects of microorganisms' contamination inside the dispensing syringes of different types of resin-based composites (RBCs). METHODS: This study encompassed two sections. First, an anonymous electronic survey was submitted via Google forms to Italian dentists to acquire information about composite handling during clinical procedures. Then, a bench test was performed on nanohybrid RBCs differing in matrix chemistry and fillers [FiltekTM Supreme XTE (3MTM); Venus Pearl (Kulzer GmbH); Admira Fusion x-tra (Voco)] to evaluate the microbial viability on their surfaces with/out photocuring. Uncured RBCs were exposed to standardized inocula of Streptococcus Mutans, Candida Albicans, Lactobacillus Rhamnosus, or mixt plaque in an in vitro model reproducing clinical restorative procedures. Half of the RBC specimens were cured after exposure. Microbial viability was assessed using an MTT-based test. Statistical analysis included three-way ANOVA and Tukey's tests (p<0.05). RESULTS: Among 300 dentists completing the survey, the majority declared to use the spatula to carry the RBCs from the syringe to the dental cavity (50% same spatula; 35% two spatulas). However, 80% of respondents had personal feelings that using one spatula could be a source of cross-contamination. In vitro results using one spatula showed microbial contamination of all RBCs after one hour of storage. The contamination levels depended on the used strain and RBC type (p<0.0001), but photocuring did not reduce contamination (p = 0.2992). CONCLUSIONS: Microbial species' viability on uncured RBCs and after photocuring shows the existence of a considerable risk of cross-infection. Clinical procedures in Restorative Dentistry need to acknowledge and to reduce such risk during RBCs handling. CLINICAL SIGNIFICANCE: Dentists must be aware of the possibility of cross-infection during restorative procedures, especially when the same spatula is repeatedly used for placing RBC in the cavity.

Dentin Cross-linking Effect of Carbodiimide After 5 Years.

Carbodiimide (EDC)-based dentin primers preserve hybrid layer (HL) integrity. However, aging >1 y has not been investigated. The present study examined whether the cross-linking effect of EDC was reflected in dentin bond strength, endogenous enzymatic activity, and the chemical profile of the HL after 5-y aging in artificial saliva. Noncarious human third molars (N = 42) were cut to expose middle/deep coronal dentin and treated as follows: group 1, dentin etched with 35% H3PO4, pretreated with a 0.3M aqueous EDC primer for 1 min and restored with XP Bond (Dentsply Sirona); group 2, as in group 1 but without EDC pretreatment; group 3, Clearfil SE Bond (Kuraray-Noritake) primer applied to dentin surface, followed by EDC pretreatment as in group 1 and application of bond; group 4, as in group 3 without EDC pretreatment. After composite buildup, the specimens were cut into sticks or slabs, depending on the experiment. All tests were performed at baseline (T0) and after 5 y of aging (T5) in artificial saliva at 37 °C. Microtensile bond strength (µTBS) was tested at a crosshead speed of 1 mm/min until failure. Endogenous enzymatic activity was investigated with in situ zymography. The chemical profile of HL was determined via Raman spectroscopy. Three-way analysis of variance and post hoc Tukey test were used to analyze µTBS and in situ zymography data (α = 0.05). EDC pretreatment and aging significantly influenced µTBS and in situ zymography results (P < 0.05). Higher bond strength and lower gelatinolytic activity were identified in the EDC-treated groups at T5 (P < 0.05), especially in the etch-and-rinse groups. Raman spectra revealed less defined amide III peaks in control specimens at T5. The EDC cross-linking effect persisted in the HL for 5 y in terms of bond strength, collagen structure preservation, and dentinal enzyme silencing.

Direct activation of zebrafish neurons by ultrasonic stimulation revealed by whole CNS calcium imaging.

OBJECTIVE: Ultrasounds (US) use in neural engineering is so far mainly limited to ablation through high intensity focused ultrasound, but interesting preliminary results show that low intensity low frequency ultrasound could be used instead to modulate neural activity. However, the extent of this modulatory ability of US is still unclear, as in in vivo studies it is hard to disentangle the contribution to neural responses of direct activation of the neuron by US stimulation and indirect activation due either to sensory response to mechanical stimulation associated to US, or to propagation of activity from neighboring areas. Here, we aim to show how to separate the three effects and assess the presence of direct response to US stimulation in zebrafish. APPROACH: We observed in zebrafish larvae brain-wide US-induced activity patterns through calcium imaging microscopy. Sensory response to mechanical stimulation was assessed with a US shield. Activity propagation was assessed with inter-area latency evaluation. MAIN RESULTS: We prove that in selected brain regions the zebrafish's neural response is mainly due to direct activation, later spreading to the other regions. Shielding the neurons from direct US stimulation resulted in a significantly attenuated response, showing that sensory stimulation does not play a prominent role. SIGNIFICANCE: US non-invasive neuromodulatory approach might lead to novel ways to test and control neural activity, and hence to novel neuromodulatory therapies. Future studies will focus on the biophysical structure of directly responsive neurons to capture the mechanisms of US induced activity.

Intra-operative enteroscopy for the identification of obscure bleeding source caused by gastrointestinal angiodysplasias: through a balloon-tip trocar is better.

AIM: Intra-operative enteroscopy (IE) is a valid diagnostic tool which can be adopted in order to identify the precise location of bleeding gastrointestinal angiodysplasias (GIADs) of the small bowel. We describe a novel IE technique that may increase the diagnostic yield by maintaining a steady distension of the bowel and that prevents microtrauma to the intestinal mucosa and spillage of enteric content into the operative field. METHODS: After laparotomy, a centimetric transverse enterotomy is performed approximately at the middle of the small bowel. A 12-mm trocar with balloon is then introduced and insufflated. The small bowel is gently distended by carbon dioxide insufflation. Through the trocar, a paediatric colonscope is then inserted and the enteroscopy is performed either retrogradely to the duodenum or anterogradely to the caecum. Once located, surgery is tailored to the precise site of bleeding, with a consequent sparing of intestinal resection. RESULTS: IE with 12-mm trocar with balloon was adopted in four elderly patients undergoing surgery for bleeding GIADs. The length of small bowel resection ranged from 10 to 200 cm, depending on the number of GIADs. Operating time ranged from 210 to 275 min. Intra-operative blood loss was nil. No patient developed organ-space or wound infections. There was no recurrence of bleeding from the midgut. CONCLUSION: Performing IE through a balloon trocar may increase the diagnostic accuracy of the procedure with the benefit of reducing the risk of traumatic injury to the bowel and the risk of surgical site infection.

Progressive multifocal leukoencephalopathy in a patient post allo-HCT successfully treated with JC virus specific donor lymphocytes.

BACKGROUND: Progressive multifocal leukoencephalopathy is a demyelinating CNS disorder. Reactivation of John Cunningham virus leads to oligodendrocyte infection with lysis and consequent axonal loss due to demyelination. Patients usually present with confusion and seizures. Late diagnosis and lack of adequate therapy options persistently result in permanent impairment of brain functions. Due to profound T cell depletion, impairment of T-cell function and potent immunosuppressive factors, allogeneic hematopoietic cell transplantation recipients are at high risk for JCV reactivation. To date, PML is almost universally fatal when occurring after allo-HCT. METHODS: To optimize therapy specificity, we enriched JCV specific T-cells out of the donor T-cell repertoire from the HLA-identical, anti-JCV-antibody positive family stem cell donor by unstimulated peripheral apheresis [1]. For this, we selected T cells responsive to five JCV peptide libraries via the Cytokine Capture System technology. It enables the enrichment of JCV specific T cells via identification of stimulus-induced interferon gamma secretion. RESULTS: Despite low frequencies of responsive T cells, we succeeded in generating a product containing 20 000 JCV reactive T cells ready for patient infusion. The adoptive cell transfer was performed without complication. Consequently, the clinical course stabilized and the patient slowly went into remission of PML with JCV negative CSF and containment of PML lesion expansion. CONCLUSION: We report for the first time feasibility of generating T cells with possible anti-JCV activity from a seropositive family donor, a variation of virus specific T-cell therapies suitable for the post allo transplant setting. We also present the unusual case for successful treatment of PML after allo-HCT via virus specific T-cell therapy.

Comparison of linear frequency and amplitude modulation for intraneural sensory feedback in bidirectional hand prostheses.

Recent studies have shown that direct nerve stimulation can be used to provide sensory feedback to hand amputees. The intensity of the elicited sensations can be modulated using the amplitude or frequency of the injected stimuli. However, a comprehensive comparison of the effects of these two encoding strategies on the amputees' ability to control a prosthesis has not been performed. In this paper, we assessed the performance of two trans-radial amputees controlling a myoelectric hand prosthesis while receiving grip force sensory feedback encoded using either linear modulation of amplitude (LAM) or linear modulation of frequency (LFM) of direct nerve stimulation (namely, bidirectional prostheses). Both subjects achieved similar and significantly above-chance performance when they were asked to exploit LAM or LFM in different tasks. The feedbacks allowed them to discriminate, during manipulation through the robotic hand, objects of different compliances and shapes or different placements on the prosthesis. Similar high performances were obtained when they were asked to apply different levels of force in a random order on a dynamometer using LAM or LFM. In contrast, only the LAM strategy allowed the subjects to continuously modulate the grip pressure on the dynamometer. Furthermore, when long-lasting trains of stimulation were delivered, LFM strategy generated a very fast adaptation phenomenon in the subjects, which caused them to stop perceiving the restored sensations. Both encoding approaches were perceived as very different from the touch feelings of the healthy limb (natural). These results suggest that the choice of specific sensory feedback encodings can have an effect on user performance while grasping. In addition, our results invite the development of new approaches to provide more natural sensory feelings to the users, which could be addressed by a more biomimetic strategy in the future.

Multi-option therapy vs observation for small acoustic neuroma: hearing-focused management.

The current treatment options for acoustic neuromas (AN) - observation, microsurgery and radiotherapy - should assure no additional morbidity on cranial nerves VII and VIII. Outcomes in terms of disease control and facial function are similar, while the main difference lies in hearing. From 2012 to 2016, 91 of 169 patients (54%) met inclusion criteria for the present study, being diagnosed with unilateral, sporadic, intrameatal or extrameatal AN up to 1 cm in the cerebello-pontine angle; the remaining 78 patients (46%) had larger AN and were all addressed to surgery. The treatment protocol for small AN included observation, translabyrinthine surgery, hearing preservation surgery (HPS) and radiotherapy. Hearing function was assessed according to the Tokyo classification and the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) classification. Sixty-one patients (71%) underwent observation, 19 (22%) HPS and 6 (7%) translabyrinthine surgery; 5 patients were lost to follow-up. Median follow-up was 25 months. In the observation group, 24.6% of patients abandoned the wait-and-see policy for an active treatment; the risk of switching from observation to active treatment was significant for tumour growth (p = 0.0035) at multivariate analysis. Hearing deteriorated in 28% of cases without correlation with tumour growth; the rate of hearing preservation for classes C-D was higher than for classes A-B (p = 0.032). Patients submitted to HPS maintained an overall preoperative hearing class of Tokyo and AAO-HNS in 63% and 68% of cases, respectively. Hearing preservation rate was significantly higher for patients presenting with preoperative favourable conditions (in-protocol) (p = 0.046). A multi-option management for small AN appeared to be an effective strategy in terms of hearing outcomes.

Subthalamic Neural Activity Patterns Anticipate Economic Risk Decisions in Gambling.

Economic decision-making is disrupted in individuals with gambling disorder, an addictive behavior observed in Parkinson's disease (PD) patients receiving dopaminergic therapy. The subthalamic nucleus (STN) is involved in the inhibition of impulsive behaviors; however, its role in impulse control disorders and addiction is still unclear. Here, we recorded STN local field potentials (LFPs) in PD patients with and without gambling disorder during an economic decision-making task. Reaction times analysis showed that for all patients, the decision whether to risk preceded task onset. We compared then for both groups the STN LFP preceding high- and low-risk economic decisions. We found that risk avoidance in gamblers correlated with larger STN LFP low-frequency (<12-Hz) fluctuations preceding task onset. In particular, the amplitude of low-frequency LFP fluctuations carried significant information about future decisions. Decisions of patients not affected by gambling disorder were instead not correlated with pretask STN LFP. Our results suggest that STN activity preceding task onset affects risk decisions by preemptively inhibiting attraction to high but unlikely rewards in favor of a long-term payoff.

Zymography of Hybrid Layers Created Using Extrafibrillar Demineralization.

A chelate-and-rinse extrafibrillar calcium chelation dentin bonding concept has recently been developed and investigated for its effectiveness in improving resin-dentin bonding by bridging the gap between wet and dry dentin bonding. The objective of the present study was to evaluate the gelatinolytic activity of hybrid layers (HLs) created using the chelate-and-rinse bonding technique. Gelatinolytic activity within the HL was examined using in situ zymography and confocal laser-scanning microscopy after 24-h storage or after thermomechanical cycling. Dentin specimens were bonded with Prime&Bond NT (Dentsply Sirona) after conditioning with 15 wt% phosphoric acid for 15 s (control) or 15 wt% polymeric chelators (sodium salt of polyacrylic acid; PAAN) of 2 different molecular weights for 60 s. For each reagent, bonding was performed using dry-bonding and wet-bonding techniques ( n = 10). Slices containing the adhesive-dentin interface were covered with fluorescein-conjugated gelatin and examined with a confocal laser-scanning microscope. Fluorescence intensity emitted by the hydrolyzed fluorescein-conjugated gelatin was quantified. Gelatinolytic activity was expressed as the percentage of green fluorescence emitted within the HL. After storage for 24 h, enzymatic activity was only detected within the completely demineralized phosphoric acid-etched dentin, with values derived from dry bonding higher than those from wet bonding ( P < 0.05). Almost no fluorescence signals were detected within the HL when dentin was conditioned with PAANs compared with the controls ( P < 0.05). After thermomechanical cycling, enzymatic activities significantly increased for the phosphoric acid-conditioned, drying-bonding group compared with 24-h storage ( P < 0.05). The present study showed that the use of the chelate-and-rinse bonding concept for both dry-bonding and wet-bonding approaches results in the near absence of matrix-bound collagenolytic activities in the HL even after aging. This may be attributed to fossilization of endogenous proteases via preservation of intrafibrillar minerals within the dentin collagen matrix.

European Society of Endodontology position statement: the use of antibiotics in endodontics.

This position statement represents a consensus of an expert committee convened by the European Society of Endodontology (ESE) on Antibiotics in Endodontics. The statement is based on current scientific evidence as well as the expertise of the committee. The goal is to provide dentists and other healthcare workers with evidence-based criteria for when to use antibiotics in the treatment of endodontic infections, traumatic injuries of the teeth, revascularization procedures in immature teeth with pulp necrosis, and in prophylaxis for medically compromised patients. It also highlights the role that dentists and others can play in preventing the overuse of antibiotics. A recent review article provides the basis for this position statement and more detailed background information (International Endodontic Journal, 2017, https://doi.org/10.1111/iej.12741). Given the dynamic nature of research in this area, this position statement will be updated at appropriate intervals.

Endolymphatic sac tumour in von Hippel-Lindau disease: management strategies.

Endolymphatic sac tumour (ELST) is infrequent, as emerges from small series reported in the literature. It is a slow-growing malignancy with local aggressiveness and a low risk of distant metastases. It is often misdiagnosed because of the late onset of symptoms and difficulty in obtaining a biopsy. Its frequency is higher in von Hippel-Lindau (VHL) disease (a genetic systemic syndrome involving multiple tumours), with a prevalence of around 25%. The diagnosis is based on radiology, with specific patterns on contrast-enhanced MRI and typical petrous bone erosion on bone CT scan. Our experience of ELST in the years between 2012-2015 concerns 7 cases, one of which was bilateral, in patients with VHL disease. Four of the 7 patients underwent 5 surgical procedures at our institution. Each case is described in detail, including clinical symptoms, and the intervals between symptom onset, diagnosis and therapy. Postoperative morbidity was low after early surgery on small tumours, whereas extensive surgery for large tumours was associated with loss of cranial nerve function (especially VII, IX, X). The critical sites coinciding with loss of neurological function were the fallopian canal, jugular foramen, petrous apex and intradural extension into the posterior cranial fossa. Early surgery on small ELST is advocated for patients with VHL disease, in whom screening enables a prompt diagnosis and consequently good prognosis.

Substantivity of Carbodiimide Inhibition on Dentinal Enzyme Activity over Time.

The use of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide HCl (EDC) has recently been investigated for its effectiveness in the prevention of collagen degradation over time and the improvement of resin-dentin bond durability. The objective of the present study was to evaluate the effects of a 0.3 M EDC-containing conditioner on endogenous enzymatic activities within the hybrid layer (HL) created by a self-etch or an etch-and-rinse adhesive after 1 y. The activity within the HL was examined using in situ zymography and confocal laser scanning microscopy after 24 h or 1-y storage in artificial saliva. Dentin specimens were bonded with Clearfil SE Bond (CSE) or XP Bond (XPB). For CSE, the self-etching primer was applied and treated with 0.3 M EDC for 1 min, and then the bonding agent was applied. For XPB, dentin was etched and treated with 0.3 M EDC for 1 min and then bonded with the primer-bonding agent. Control specimens were prepared without EDC treatment. Slices containing the adhesive-dentin interface were covered with fluorescein-conjugated gelatin and observed with a multiphoton confocal microscope. Fluorescence intensity emitted by hydrolyzed fluorescein-conjugated gelatin was quantified, and the amount of gelatinolytic activity was represented by the percentage of green fluorescence emitted within the HL. After 24 h of storage, enzymatic activity was detected by in situ zymography within the HLs of both tested adhesives, with XPB higher than CSE ( P < 0.05). Almost no fluorescence signal was detected when specimens were pretreated with EDC compared to controls ( P < 0.05). After 1 y of storage, enzymatic activities significantly increased for all groups (excluding XPB control) compared to 24-h storage ( P < 0.05), with EDC pretreated specimens exhibiting significantly lower activity than controls ( P < 0.05). The present study showed, for the first time, that the use of EDC for both the self-etch and the etch-and-rinse approaches results in the reduction but not complete inhibition of matrix-bound collagenolytic enzyme activities over time in the HL.

Salvage of an Octogenarian Liver Graft Using Normothermic Perfusion: A Case Report.

Liver transplantation with very old donors is safe, but is associated with an increased incidence of ischemic-type biliary lesions and delayed graft function. Normothermic machine perfusion (NMP) is a novel technique for preservation of liver grafts and has the potential to reduce ischemia-reperfusion injury. A case is reported here of a liver transplantation (LT) with a graft from an 83-year-old brain-dead donor. Procurement was with dual perfusion and en bloc, modified fast technique. Donor kidneys were not transplanted due to severe atherosclerosis and poor perfusion. The liver was shipped to the transplantation center and underwent NMP with a blood-based perfusate. During machine perfusion lactates decreased, vascular flow was stable, and bile production restored, and the graft was considered suitable for transplantation. The postoperative course was uneventful and 4 months after surgery the patient is in good clinical condition with normal liver function. To date, few LTs have been performed with NMP in humans, but its preliminary results are promising. NMP allows functional evaluation of the graft and possibly reduction of post-transplantation complications when extended-criteria donor grafts are used.

Acoustic schwannoma with intracochlear extension and primary intracochlear schwannoma: removal through translabyrinthine approach with facial bridge cochleostomy and transcanal approach.

Intracochlear schwannomas can occur either as an extension of a larger tumor from the internal auditory canal, or as a solitary labyrinthine tumor. They are currently removed via a translabyrinthine approach extended to the basal turn, adding a transotic approach for tumors lying beyond the basal turn. Facial bridge cochleostomy may be associated with the translabyrinthine approach to enable the whole cochlea to be approached without sacrificing the external auditory canal and tympanum. We describe seven cases, five of which underwent cochlear schwannoma resection with facial bridge cochleostomy, one case with the same procedure for a suspect tumor and one, previously subjected to radical tympanomastoidectomy, who underwent schwannoma resection via a transotic approach. Facial bridge cochleostomy involved removing the bone between the labyrinthine and tympanic portions of the fallopian canal, and exposing the cochlea from the basal to the apical turn. Patients' recovery was uneventful, and long-term magnetic resonance imaging showed no residual tumor. Facial bridge cochleostomy can be a flexible extension of the translabyrinthine approach for tumors extending from the internal auditory canal to the cochlea. The transcanal approach is suitable for the primary exclusive intralabyrinthine tumor. The indications for the different approaches are discussed.

Engineering the Structural and Electronic Phases of MoTe2 through W Substitution.

MoTe2 is an exfoliable transition metal dichalcogenide (TMD) that crystallizes in three symmetries: the semiconducting trigonal-prismatic 2H- or α-phase, the semimetallic and monoclinic 1T'- or ß-phase, and the semimetallic orthorhombic γ-structure. The 2H-phase displays a band gap of ∼1 eV making it appealing for flexible and transparent optoelectronics. The γ-phase is predicted to possess unique topological properties that might lead to topologically protected nondissipative transport channels. Recently, it was argued that it is possible to locally induce phase-transformations in TMDs, through chemical doping, local heating, or electric-field to achieve ohmic contacts or to induce useful functionalities such as electronic phase-change memory elements. The combination of semiconducting and topological elements based upon the same compound might produce a new generation of high performance, low dissipation optoelectronic elements. Here, we show that it is possible to engineer the phases of MoTe2 through W substitution by unveiling the phase-diagram of the Mo1-xWxTe2 solid solution, which displays a semiconducting to semimetallic transition as a function of x. We find that a small critical W concentration xc ∼ 8% stabilizes the γ-phase at room temperature. This suggests that crystals with x close to xc might be particularly susceptible to phase transformations induced by an external perturbation, for example, an electric field. Photoemission spectroscopy, indicates that the γ-phase possesses a Fermi surface akin to that of WTe2.