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Epilepsies have numerous specific mechanisms. The understanding of neural dynamics leading to seizures is important for disclosing pathological mechanisms and developing therapeutic approaches. We investigated electrographic activities and neural dynamics leading to convulsive seizures in patients and mouse models of Dravet syndrome (DS), a developmental and epileptic encephalopathy in which hypoexcitability of GABAergic neurons is considered to be the main dysfunction. We analyzed EEGs from DS patients carrying a SCN1A pathogenic variant, as well as epidural electrocorticograms, hippocampal local field potentials, and hippocampal single-unit neuronal activities in Scn1a+/- and Scn1aRH/+ DS mice. Strikingly, most seizures had low-voltage-fast onset in both patients and mice, which is thought to be generated by hyperactivity of GABAergic interneurons, the opposite of the main pathological mechanism of DS. Analyzing single-unit recordings, we observed that temporal disorganization of the firing of putative interneurons in the period immediately before the seizure (preictal) precedes the increase of their activity at seizure onset, together with the entire neuronal network. Moreover, we found early signatures of the preictal period in the spectral features of hippocampal and cortical field potential of Scn1a mice and of patients' EEG, which are consistent with the dysfunctions that we observed in single neurons and that allowed seizure prediction. Therefore, the perturbed preictal activity of interneurons leads to their hyperactivity at the onset of generalized seizures, which have low-voltage-fast features that are similar to those observed in other epilepsies and are triggered by hyperactivity of GABAergic neurons. Preictal spectral features may be used as predictive seizure biomarkers. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is the branch of science aiming at creating algorithms able to carry out tasks that typically require human intelligence. In medicine, there has been a tremendous increase in AI applications thanks to increasingly powerful computers and the emergence of big data repositories. Multiple sclerosis (MS) is a chronic autoimmune condition affecting the central nervous system with a complex pathogenesis, a challenging diagnostic process strongly relying on magnetic resonance imaging (MRI) and a high and largely unexplained variability across patients. Therefore, AI applications in MS have the great potential of helping us better support the diagnosis, find markers for prognosis to eventually design more powerful randomised clinical trials and improve patient management in clinical practice and eventually understand the mechanisms of the disease. This topical review aims to summarise the recent advances in AI applied to MRI data in MS to illustrate its achievements, limitations and future directions. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common malignant primary bone cancer, but it is infrequently reported in cats. Feline appendicular osteosarcoma typically exhibits good prognosis when treated with surgery alone. A retrospective multi‐institutional study was conducted to identify possible prognostic factors. Cats diagnosed with appendicular osteosarcoma were included if initial staging and follow‐up information were available. Data including signalment, tumour characteristics, treatment modalities, and survival outcomes were collected and analysed. Fifty‐six cats were included; the femur was the most frequently affected bone. Eight cats had distant metastasis at admission and an additional 9 developed metastatic disease during follow‐up, resulting in an overall metastatic rate of 30%. Forty‐nine (87.5%) cats underwent surgery, and 4 also received adjuvant chemotherapy. Among operated cats, median time to local progression (TTLP), time to distant progression and tumour‐specific survival (TSS) were not reached. One‐ and 2‐year survival rates were 66% and 55%, respectively. Seven (12.5%) cats received no treatment; 1‐ and 2‐year survival rates were 25% and 0%, respectively. Operated cats had significantly longer TTLP (P <.001) and TSS (P =.001) compared with non‐operated cats. Among operated cats, young age negatively impacted local tumour progression, while the presence of distant metastasis at diagnosis was associated with a higher risk of tumour‐related death. This study reaffirms the good prognosis for cats with appendicular osteosarcoma undergoing surgery, but sheds light on some additional factors to consider. Accurate initial staging is recommended, as the metastatic rate may exceed many previous estimations. Surgery substantially extends survival time, whereas the role of chemotherapy remains uncertain. [ABSTRACT FROM AUTHOR]

Digital impression provides several advantages in implant prosthodontics; however, its use in full-arch rehabilitations, especially immediately after surgery, has yet to be validated. The aim of this study was to retrospectively analyse the fit of immediate full-arch prostheses, fabricated using conventional or digital impressions. Patients requiring a full-arch immediate loading rehabilitation were divided into three groups: T1 (digital impression taken immediately after surgery), T2 (Preoperative digital impression, guided surgery—prefabricated temporary bridge) and C (conventional impression taken immediately after surgery). Immediate temporary prostheses were delivered within 24 h after surgery. X-rays were obtained at the time of prosthesis delivery and at the 2-year follow-up. Primary outcomes were cumulative survival rate (CSR) and prosthesis fit. Secondary outcomes were marginal bone level (MBL) and patient satisfaction. One hundred and fifty patients were treated from 2018 to 2020, with 50 in each group. Seven implants failed during the observation period. The CSR was 99% for T1, 98% for T2 and 99.5% for C. A statistically significant difference in prosthesis fit was found among T1 and T2 vs. C. A statistically significant difference was found in the MBL between T1 and C. The outcomes of the present study suggest that digital impression is a viable alternative to conventional protocols for the realisation of full-arch immediate loading prostheses. [ABSTRACT FROM AUTHOR]

Small molecules in solution may interfere with mechanistic investigations, as they can affect the stability of catalytic states and produce off-cycle states that can be mistaken for catalytically relevant species. Here we show that the hydride state (Hhyd), a proposed central intermediate in the catalytic cycle of [FeFe]-hydrogenase, can be formed in wild-type [FeFe]-hydrogenases treated with H2 in absence of other, non-biological, reductants. Moreover, we reveal a new state with unclear role in catalysis induced by common low pH buffers. [ABSTRACT FROM AUTHOR]

Hydrogenases are metalloenzymes that catalyze the reversible oxidation of molecular hydrogen into protons and electrons. For this purpose, [FeFe]-hydrogenases utilize a hexanuclear iron cofactor, the H-cluster. This biologically unique cofactor provides the enzyme with outstanding catalytic activities, but it is also highly oxygen sensitive. Under in vitro conditions, oxygen stable forms of the H-cluster denoted Htrans and Hinact can be generated via treatment with sulfide under oxidizing conditions. Herein, we show that an Htrans-like species forms spontaneously under intracellular conditions on a time scale of hours, concurrent with the cells ceasing H2 production. Addition of cysteine or sulfide during the maturation promotes the formation of this H-cluster state. Moreover, it is found that formation of the observed Htrans-like species is influenced by both steric factors and proton transfer, underscoring the importance of outer coordination sphere effects on H-cluster reactivity. [ABSTRACT FROM AUTHOR]

his multicenter retrospective clinical study aimed to evaluate the clinical performance of zirconia abutments in anterior and posterior regions, focusing on implant-abutment connections and restoration vertical height (RVH). Six experienced prosthodontists used 965 computer-aided design/computer-assisted manufacture zirconia abutments in 601 patients. Different surgical approaches were taken according to the needs of each patient. The final restorations were all-ceramic single crowns and short-span fixed dental prostheses. Screw-retained restorations were mainly used in anterior areas, whereas cemented prostheses were chosen in cases where the implant position was not ideal. Different types of implant-abutment connections were compared: external, internal with metal components, and internal full-zirconia conical connection. All the restorations were followed up for 4 to 10 years. Technical and biologic complications were assessed in relation to several biomechanical variables, such as RVH. Differences between groups were statistically analyzed, and longevity of abutments was evaluated according to Kaplan-Meier survival analysis. Zirconia abutments resulted in overall survival and success rates of 98.9% and 94.8%, respectively. External connections reported survival and success rates of 99.7% and 94.5%, internal metal connections 99.8% and 95.5%, and internal zirconia connections 93.1% and 93.1%, respectively. Overall complication rates of 1.14%, 3.42%, and 0.62% were reported for fractures, chipping, and unscrewing, respectively. The external connection showed the longest survival while the internal zirconia connection showed the highest fracture incidence over the observation period. The clinical risk limit of RVH was identified as 14 mm. Zirconia abutments showed satisfactory clinical performance in anterior and posterior regions after 4 to 10 years. RVH and connection type influenced the clinical longevity of restorations; in particular, internal connections with secondary metallic components reduced the incidence of complications. [ABSTRACT FROM AUTHOR]

The purpose of this case series was to report the clinical outcomes and histologic findings of vertical ridge augmentation using a combination of titanium mesh and recombinant human platelet-derived growth factor BB (rhPDGF-BB). Two patients were included, and anorganic bovine bone particles were used. The bone graft was mixed with rhPDGF-BB and loaded onto the bony defect up to the level of the adjacent alveolar crest. A preadapted titanium mesh was placed over the grafted region; no areas of the grafted region were exposed. Postoperative healing was without complications. During reentry surgery for removal of the titanium mesh, all implants could be placed according to the prosthetic design. This report demonstrates the remarkable efficacy of guided bone regeneration using a combination of titanium mesh and rhPDGF for vertical ridge augmentation, thus expanding the indications for implant therapy and allowing recovery of the three-dimensional esthetic architecture in a severely resorbed alveolar ridge. [ABSTRACT FROM AUTHOR]

This study aimed to assess the clinical performance of lithium disilicate restorations supported by natural teeth or implants. Eight hundred sixty lithium disilicate adhesive restorations, including crowns on natural teeth and implant abutments, veneers, and onlays, were made in 312 patients. Parafunctional patients were included, but subjects with uncontrolled periodontitis and gingival inflammation were excluded. Veneers up to 0.5 mm thick were luted with flowable composite resin or light curing cements, while dual-curing composite systems were used with veneers up to 0.8 mm thick. Onlays up to 2 mm in thickness were luted with flowable composite resins or dual-curing composite cements. Crowns up to 1 mm in thickness were cemented with self-adhesive or dual-curing resin cements. The observational period ranged from 12 to 72 months, with a mean follow-up of 3 years. The mechanical and esthetic outcomes of the restorations were evaluated according to the modified California Dental Association (CDA) criteria. Data were analyzed with descriptive statistics. Twenty-six mechanical complications were observed: 17 porcelain chippings, 5 fractures, and 4 losses of retention. Structural drawbacks occurred mainly in posterior segments, and monolithic restorations showed the lowest number of mechanical complications. The clinical ratings of the successful restorations, both monolithic and layered, were satisfactory according to the modified CDA criteria for color match, porcelain surface, and marginal integrity. The cumulative survival rates of lithium disilicate restorations ranged from 95.46% to 100%, while cumulative success rates ranged from 95.39% to 100%. All restorations recorded very high survival and success rates. The use of lithium disilicate restorations in fixed prosthodontics proved to be effective and reliable in the short- and medium-term. [ABSTRACT FROM AUTHOR]