Aesthetic satisfaction in lip and palate clefts: a comparative study between secondary and tertiary bone grafting

Lip and palate cleft represent one of the most frequently occurring congenital deformity, which includes dental anomalies, such as variation in tooth number and position. In case of hypodontia implant-prosthetic rehabilitation offers significant advantages in terms of function, aesthetics and quality of life and bone graft is usually needed. Secondary bone grafting, generally performed in the mixed dentition phase (years 8-11) seems to be the most successful method to allow for rehabilitation. It's often necessary to perform a tertiary bone grafting in adult age in order to achieve better bone quantity and quality before implant placement. Aim of this retrospective study was to evaluate the aesthetic perception that patients had of themselves comparing dental implants placed in tertiary grafted alveolar cleft sites with a previous secondary grafting to only secondary grafting. Between 2009 and 2012, fourteen alveolar cleft were treated with implant rehabilitation and eleven of them received tertiary bone grafting six months prior to implant placement. All patients were questioned to give a score from 1 to 10 their aesthetic satisfaction of their smile before and after implant rehabilitation and during pre-surgery provisional rehabilitation. At the end of their prosthesis rehabilitation patients who received tertiary bone grafting resulted more satisfied than those who had secondary bone grafting only (9.5 vs 8)

Frontal Functional Connectivity of Electrocorticographic Delta and Theta Rhythms during Action Execution Versus Action Observation in Humans

We have previously shown that in seven drug-resistant epilepsy patients, both reaching-grasping of objects and the mere observation of those actions did desynchronize subdural electrocorticographic (ECoG) alpha (8–13 Hz) and beta (14–30) rhythms as a sign of cortical activation in primary somatosensory-motor, lateral premotor and ventral prefrontal areas (Babiloni et al., 2016a). Furthermore, that desynchronization was greater during action execution than during its observation. In the present exploratory study, we reanalyzed those ECoG data to evaluate the proof-of-concept that lagged linear connectivity (LLC) between primary somatosensory-motor, lateral premotor and ventral prefrontal areas would be enhanced during the action execution compared to the mere observation due to a greater flow of visual and somatomotor information. Results showed that the delta-theta (<8 Hz) LLC between lateral premotor and ventral prefrontal areas was higher during action execution than during action observation. Furthermore, the phase of these delta-theta rhythms entrained the local event-related connectivity of alpha and beta rhythms. It was speculated the existence of a multi-oscillatory functional network between high-order frontal motor areas which should be more involved during the actual reaching-grasping of objects compared to its mere observation. Future studies in a larger population should cross-validate these preliminary results

Pharmacological control of the mevalonate pathway: Effect on arterial smooth muscle cell proliferation

The mevalonate (MVB) pathway is involved in cell proliferation. We investigated drugs acting at different enzymatic steps on rat aorta smooth muscle cell (SMC) proliferation. Competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (0.1-10 mu M) dose-dependently decreased (up to 90%) SMC proliferation. This effect was prevented by 100 mu M MVA, 10 mu M all-trans famesol (F-OH) and 5 mu M all-trans geranylgeraniol (GG-OH), precursors of protein prenyl groups, but not by 2-cis GG-OH, precursor of dolichols, squalene and ubiquinone. The same inhibitory effect was obtained with 6-fluoromevalonate (1-50 mu M), an inhibitor of MVA-pyrophosphate decarboxylase. Partial recovery of cell proliferation was possible by all-trans F-OH and all-trans GG-OH, but not MVA. Squalestatin 1 (1-25 mu M), a potent squalene synthase inhibitor, blocked cholesterol synthesis and slightly inhibited (21% decrease) SMC proliferation only at the highest tested concentration. NB-598 (1-10 mu M), a potent squalene epoxidase inhibitor, blocked cholesterol synthesis without affecting SMC proliferation. Finally, the benzodiazepine peptidomimetic BZA-5B (10-100 mu M), a specific inhibitor of protein famesyltransferase, time- and dose-dependently decreased SMC proliferation (up to 62%) after 9 days. This effect of BZA-5B was prevented by MVA and all-trans GG-OH, but not by all-trans F-OH. SMC proliferation was not affected by the closely related compound BZA-7B, which does not inhibit protein farnesyltransferase. Altogether, these findings focus the role of the MVA pathway in cell proliferation and call attention to the involvement of specific isoprenoid metabolites probably through farnesylated and geranylgeranylated proteins, in the control of this cellular event

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure\u2010freedom, seizure response ( 65&nbsp;50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45&nbsp;years (33\u201356) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p&nbsp;&lt;&nbsp;0.001); the corresponding values for 65&nbsp;50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p&nbsp;&lt;&nbsp;0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p&nbsp;=&nbsp;0.341) and seizure response (39.7% vs. 26.9%; p&nbsp;=&nbsp;0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p&nbsp;=&nbsp;0.017). Conclusion: The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations

Sustained seizure freedom with adjunctive brivaracetam in patients with focal onset seizures

The maintenance of seizure control over time is a clinical priority in patients with epilepsy. The aim of this study was to assess the sustained seizure frequency reduction with adjunctive brivaracetam (BRV) in real-world practice. Patients with focal epilepsy prescribed add-on BRV were identified. Study outcomes included sustained seizure freedom and sustained seizure response, defined as a 100% and a ≥50% reduction in baseline seizure frequency that continued without interruption and without BRV withdrawal through the 12-month follow-up. Nine hundred ninety-four patients with a median age of 45 (interquartile range = 32–56) years were included. During the 1-year study period, sustained seizure freedom was achieved by 142 (14.3%) patients, of whom 72 (50.7%) were seizure-free from Day 1 of BRV treatment. Sustained seizure freedom was maintained for ≥6, ≥9, and 12&nbsp;months by 14.3%, 11.9%, and 7.2% of patients from the study cohort. Sustained seizure response was reached by 383 (38.5%) patients; 236 of 383 (61.6%) achieved sustained ≥50% reduction in seizure frequency by Day 1, 94 of 383 (24.5%) by Month 4, and 53 of 383 (13.8%) by Month 7 up to Month 12. Adjunctive BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Background: In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective: This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods: The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure‐freedom, seizure response (≥&nbsp;50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results: A total of 1029 patients with a median age of 45&nbsp;years (33–56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p&nbsp;&lt;&nbsp;0.001); the corresponding values for ≥&nbsp;50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p&nbsp;&lt;&nbsp;0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p&nbsp;=&nbsp;0.341) and seizure response (39.7% vs. 26.9%; p&nbsp;=&nbsp;0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p&nbsp;=&nbsp;0.017). Conclusion: The BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Functional imaging of membrane potential at the single mitochondrion level: possible application for diagnosis of human diseases.

Functional biochemical tests are the gold standard for the diagnosis of mitochondria-related diseases. However, the availability of the biological samples from patients' tissues represents a severe limitation to the number of screenable enzymatic activities. In this study we developed a fluorescent probe-assisted microscopy protocol enabling to assess the δψm-generating capacity by mitochondria immobilized on a glass surface at the single organelle resolution-level. The advantage of this assay over others is to scale-down the amount of the biological sample required to test in a short time the functional activity of all the components of the oxidative phosphorylation system without loss of accuracy. Furthermore, the distribution of a given enzymatic activity can also be evaluated within the mitochondrial population enabling to measure the level of functional heterogeneity of the respiratory chain dysfunction. © 2011 Elsevier B.V. and Mitochondria Research Society