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Increased expression of interleukin-6 (IL-6) both in cerebrospinal fluid (CSF) and plasma is closely associated with convulsive epilepsy and symptom severity of depression. By comparison, at present, little is known about the role of this cytokine in childhood (non-convulsive) absence epilepsy. The aim of this work was to investigate the potential effects of acute and chronic treatment with tocilizumab (TCZ, 10 and 30 mg/kg/day), on absence seizures, their development, and related psychiatric comorbidity in WAG/Rij rats. It is known that lipopolysaccharide (LPS)-induced changes in inflammatory processes increase absence epileptic activity. In order to study the central effects of TCZ, we investigated whether administration of this anti-IL-6R antibody could modulate the lipopolysaccharide (LPS) or IL-6-evoked changes in absence epileptic activity in WAG/Rij rats. Our results demonstrate that TCZ, at both doses, significantly reduced the development of absence seizures in adult WAG/Rij rats at 6 months of age (1 month after treatment suspension) compared with untreated controls, thus showing disease-modifying effects. Decreased absence seizure development at 6 months of age was also accompanied by reduced comorbid depressive-like behavior, whereas no effects were observed on anxiety-related behavior. Acute treatment with TCZ, at 30 mg/kg, had anti-absence properties lasting ~25 h. The co-administration TCZ with i.c.v. LPS or IL-6 showed that TCZ inhibited the worsening of absence seizures induced by both proinflammatory agents in the WAG/Rij rats, supporting a central anti-inflammatory-like protective action. These results suggest the possible role of IL-6 and consequent neuroinflammation in the epileptogenic process underlying the development and maintenance of absence seizures in WAG/Rij rats. Accordingly, IL-6 signaling could be a promising pharmacological target in absence epilepsy and depressive-like comorbidity. [ABSTRACT FROM AUTHOR]

Abstract In this paper, we show that the transient waveforms arising from several localised pulses in a micro-structured material can be reproduced by a corresponding generalised continuum of the relaxed micromorphic type. Specifically, we compare the dynamic response of a bounded micro-structured material to that of bounded continua with special kinematic properties: (i) the relaxed micromorphic continuum and (ii) an equivalent Cauchy linear elastic continuum. We show that, while the Cauchy theory is able to describe the overall behaviour of the metastructure only at low frequencies, the relaxed micromorphic model goes far beyond by giving a correct description of the pulse propagation in the frequency band-gap and at frequencies intersecting the optical branches. In addition, we observe a computational time reduction associated with the use of the relaxed micromorphic continuum, compared to the sensible computational time needed to perform a transient computation in a micro-structured domain. [ABSTRACT FROM AUTHOR]

Objective Older patients with cancer suffer from chemotherapy-related toxicities more frequently than younger patients. As novel agents are being used more commonly in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), toxicities of these agents in older patients have not been well studied. Further, impact of these toxicities on outcomes in the elderly is unknown. This study aimed to answer both questions. Patients and Methods We reviewed 14 Alliance for Clinical Trials in Oncology trials that enrolled CLL and/or NHL patients between 2004–2014. Toxicity was assessed per the NCI-CTCAE (version 3–5). Probabilities of experiencing grade three or four hematologic and non-hematologic toxicities were modeled as a function of clinical and disease-related factors using logistic regression. Results 1199 patients (409 age ≥ 65; 790 age < 65) were analyzed; 438 received only biologic therapy (145 age ≥ 65; 293 age < 65), and 761 received biologic + chemotherapy (264 age ≥ 65; 497 age < 65). The odds of grade three or four hematologic [odds ratio (OR) 1.70; p  = 0.009: 95% CI (1.57–1.84)] and non-hematologic toxicities [OR 1.47; p  = 0.022; 95% CI (1.39–1.55)] were increased in older patients with CLL, as well as odds of grade three or four non-hematologic toxicities [OR 1.89; p  = 0.017; 95% CI (1.64–2.17)] in older patients with NHL. Grade three or four hematologic toxicities were associated with inferior OS and PFS in older patients with NHL [HR 3.14; p  = 0.006; 95% CI (2.25–4.39) for OS and 3.06; p  = 0.011; 95% CI (2.10–4.45) for PFS], though not in CLL. A prognostic model predicting grade three or four toxicities was also developed. Conclusions CLL and NHL patients ≥ 65 year encounter more toxicities than younger patients even when treated with novel biologic agents. Development of grade three or four hematologic toxicities lead to inferior PFS and OS in NHL but not in CLL. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether repeated abutment disconnections and reconnections have any impact on peri-implant bone resorption and soft tissue healing.Materials and Methods: Electronic and manual searches were conducted for English-language articles published up to March 2017 that identified a relation between repeated disconnections of implant abutments (PA group) and prosthetic or implant failures, complications, marginal bone loss (MBL), soft tissue healing, and esthetic evaluation (pink esthetic score [PES]) after at least 1 year of function compared with implants receiving a final abutment at the time of implant placement (DA group).Results: Fourteen articles (535 patients with 994 implants) were selected for qualitative analysis. Six of these were included in the meta-analysis. Five prostheses failed in the PA group and 1 failed in the DA group (P = .1047). Seven biologic complications occurred in the PA group and 6 occurred in the DA group (P = .8121). MBL was significantly less in the DA group (difference, 0.279 mm; P = .000). Greater buccal recession occurred in the PA group (difference, 0.198 mm; P = .0004). The PES evaluation showed no differences between groups (P = .289).Conclusions: Repeated abutment disconnections and reconnections considerably increased MBL and buccal recession. Further studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

In this paper, we report a combined experimental/simulation analysis of the degradation induced by hot carrier mechanisms, under ON-state stress, in silicon-based LDMOS transistors. In this regime, electrons can gain sufficient kinetic energy necessary to create interface states, hence inducing device degradation. In particular, the ON-resistance degradation in linear regime has been experimentally characterized by means of different stress conditions and temperatures. The hot-carrier stress regime has been fully reproduced in the frame of TCAD simulations by using physics-based models able to provide the degradation kinetics. A thorough investigation of the spatial interface trap distribution and its gate-bias and temperature dependences has been carried out achieving a quantitative understanding of the degradation effects in the device. [ABSTRACT FROM AUTHOR]

The aim of this research was to evaluate the effect of grape probiotic fermented beverages made of goat milk, with or without added grape pomace on gut microbiota in a Simulator of Human Intestinal Microbial Ecosystem (SHIME®). SHIME® model was used to investigate to assess changes in microbial composition and fermentation metabolites (short- and branched-chain fatty acids and ammonium), as well as under the antioxidant capacity. The results demonstrated that the beverages formulated, with or without grape pomace extract, exhibited high dietary fiber, oleic acid, phenolic compounds content and antioxidant activity. Both beverages also kept L. rhamnosus and S. thermophilus viable during their passage through the intestinal tract and had a positive effect on gut microbiota metabolism, increasing the antioxidant capacity and the production of short-chain fatty acids, and decreasing the ammonium concentration. Therefore, the multifunctional beverages formulated in this study can offer a new perspective for the production of foods with positive potential effects on human health. [ABSTRACT FROM AUTHOR]

Statement of problem In patients with an altered skeletal maxillomandibular relationship and bone resorption, the rehabilitation of edentulous jaws by combining 4 implants, 2 straight medially and 2 tilted distally, may be preferred to avoid a bone augmentation procedure. Purpose The purpose of this single cohort 1-year prospective study was to evaluate the clinical performance of a 4-implant overdenture fully supported by a computer-aided designed and computer-aided manufactured (CAD-CAM) titanium bar. Material and methods This single cohort prospective study included edentulous participants rehabilitated with a 4-implant overdenture in 1 of the 2 jaws. The outcomes were implant and prosthetic survival and success rates, any biologic and technical complications, periimplant marginal bone loss, changes in the oral health impact profile (OHIP), bleeding on probing, and the plaque index. Results Eighteen participants received 72 implants. One year after implant placement, no implants or prosthesis had failed, and no biologic or technical complications had been observed. At the 1-year follow-up, the mean marginal bone loss was 0.29 ±0.16 mm. The OHIP summary scores demonstrated a significant improvement in oral health-related quality of life. At the 1-year follow-up, positive bleeding was found in 2 participants (11.1%) around 3 implants (4.1%). Three participants (16.6%), accounting for 5 implants (6.9%), showed a slight amount of plaque. Conclusions A 4-implant overdenture supported by a CAD-CAM titanium bar may be a reliable option for the treatment of the edentulous mandible and maxilla over a 1-year period. Oral health-related quality of life significantly improved in all treated participants. [ABSTRACT FROM AUTHOR]

Purpose To evaluate clinical and radiographic performance of a novel implant system that allows for hydraulic Schneiderian membrane elevation and simultaneously bone graft augmentation. Materials and methods Sixty-two consecutive patients with a mean age of 53.1 years and a severe atrophy of the posterior maxilla (3.0 to 7.0 mm) underwent 64 transcrestal sinus floor elevations and submerged implant placement. The following clinical and radiographic parameters were assessed: implant failure, any complications and bone gain measured using cone beam computed tomography. Results No patient dropped out. No implants failed and all the prostheses were uneventful at the last follow-up examination (mean 23.0 months; range 12–45). All the procedures were completed successfully, with elevation of the sinus membrane and insertion of bone graft and the dental implant at the planned site. No intraoperative or postoperative adverse events were observed, such as membrane tears or facial hematoma. The mean residual alveolar ridge height was 5.2 ± 1 mm (range 3.3–7.0 mm). Mean bone gain was 10.9 ± 2.43 mm (range 5.3–16.5) after an average healing period of 8 months. Conclusions Hydraulic elevation of the Schneiderian membrane using the iRaise sinus-lift system (Maxillent Ltd) can be considered a valuable treatment option for the rehabilitation of atrophic edentulous posterior maxillae. [ABSTRACT FROM AUTHOR]

Pathological accumulation of Aβ oligomers has been linked to neuronal networks hyperexcitability, potentially underpinned by glutamatergic AMPA receptors (AMPARs) dysfunction. We aimed to investigate whether the non-competitive block of AMPARs was able to counteract the alteration of hippocampal epileptic threshold, and of synaptic plasticity linked to Aβ oligomers accumulation, being this glutamate receptor a valuable specific therapeutic target. In this work, we showed that the non-competitive AMPARs antagonist perampanel (PER) which, per se , did not affect physiological synaptic transmission, was able to counteract Aβ-induced hyperexcitability. Moreover, AMPAR antagonism was able to counteract Aβ-induced hippocampal LTP impairment and hippocampal-based cognitive deficits in Aβ oligomers-injected mice, while retaining antiseizure efficacy. Beside this, AMPAR antagonism was also able to reduce the increased expression of proinflammatory cytokines in this mice model, also suggesting the presence of an anti-inflammatory activity. Thus, targeting AMPARs might be a valuable strategy to reduce both hippocampal networks hyperexcitability and synaptic plasticity deficits induced by Aβ oligomers accumulation. • AMPAR modulation by PER reduces neuronal hyperactivity and synchronization. • AMPAR modulation ameliorates cognitive functions and performances in Aβ mice models. • PER reduces the levels of pro-inflammatory cytokines in Aβ oligomers-injected mice. [ABSTRACT FROM AUTHOR]

Aim The aim of this prospective clinical study is to assess the 4-year outcomes of implant-supported restorations performed using a computer-guided template-assisted flapless implant surgery approach in patients reconstructed with fibula or iliac crest free flaps. Materials and methods Twelve jaws in 10 patients were reconstructed with osteomyocutaneous free flap after tumour resection or gunshot wound, after complete healing computer-assisted template-based flapless implant placement, based on prosthetic and aesthetic analysis, was performed using a customized protocol. Treatment success was evaluated using the following parameters: survival of implants/prostheses, prosthetic and biologic complications, marginal bone remodelling, soft tissue parameters and patient satisfaction. Results A total of 56 implants were placed; the implants ranged between 8 and 16 mm in length and were either 3.5, 4.3 or 5 mm wide. All the patients have reached the 4-year follow-up. Three implants were lost accounting for an overall implant survival rate of 94.6%. No prosthesis were lost. Some complications were recorded. Four years after loading the mean marginal bone loss was 1.43 ± 0.49 mm at the palatal/lingual site and 1.48 ± 0.46 mm at the vestibular site. All the patients showed healthy soft tissues with stable probing depth (4 .93 ± 0.75%) and successful bleeding on probing values (12 ± 5.8%); 90% of patients were satisfied of the treatment at the 4-year follow-up. Conclusions Computer-guided template-assisted flapless implant surgery seems to be a viable option for patients undergoing reconstruction with free flaps after tumour resection or gunshot trauma, although many challenges remain. A high degree of patient satisfactorily was reported. [ABSTRACT FROM AUTHOR]

In this paper, we present an analysis of the degradation and recovery mechanisms in p-channel power U-MOSFETs due to Negative Bias Temperature Instability (NBTI). In particular, we study the influence of NBTI on threshold voltage and sub-threshold slope, which are the main figures of merit affected by charge trapping in the oxide and by interface state generation. The temperature and bias dependence of NBTI phenomena have been investigated. As a result, we report a higher degradation with the temperature and gate bias increase. On the other hand, by monitoring the recovery phase in different conditions, we found out similar behaviors heavily reported in CMOS technology, which are: (i) recovery mechanism is mainly due to oxide detrapping charge; (ii) higher temperatures allow a faster and larger recovery, hence it is an accelerator factor also for this mechanism; (iii) the oxide defects, involved in the detrapping phase, have an energy position confined in the band-gap of the silicon. [ABSTRACT FROM AUTHOR]

Background context Transforaminal lumbar interbody fusion (TLIF) is an increasingly used alternative fusion method over anterior and posterior lumbar interbody fusions. There are conflicting results on the optimal positioning of interbody devices. No study has addressed the lumbosacral segment, L5–S1, where the lordotic configuration presents unique challenges. Purpose To determine if there are biomechanical and/or anatomical advantages related to the positioning of an interbody device at L5–S1, either anterior or posterior to the neutral axis. Study design An in vitro biomechanical study using human cadaveric lumbar specimens. Methods Lumbar specimens were biomechanically tested using pure moments with and without compressive axial loading. Testing was performed in intact and after TLIF with the implant posterior (TLIF-post) and anterior (TLIF-ant) to neutral axis. Segmental range of motion (ROM) and stiffness were analyzed at the L5–S1 surgical level and the adjacent L4–L5 level. Neuroforaminal height measurements of L5–S1 were analyzed in neutral and end range positions. Results Compared with the intact condition, ROM decreased more than 75% at L5–S1 and stiffness increased up to 270% with TLIF. There was no significant difference between anterior or posterior placement for ROM and stiffness. There was a change in L5–S1 neuroforaminal height based on the placement, with posterior placement showing a significant increase compared with anterior placement. There were no relative changes in neuroforaminal height under loading after TLIF. Compressive load did not affect the magnitudes or resulting significance of outcome measures at L5–S1 after either TLIFs. Conclusions An interbody spacer with the addition of posterior instrumentation significantly enhances the mechanical stability of L5–S1 regardless of interbody position. There were noticeable increases in terms of construct stability and stiffness after both TLIF-ant and TLIF-post in comparison with the intact condition. A posteriorly placed interbody implant did result in the distraction of the neuroforamin. Positioning an interbody implant at L5–S1 for TLIF with posterior instrumentation should be at the discretion of the surgeon without consequence to biomechanical stability. [ABSTRACT FROM AUTHOR]