Aseptic Silk Ligatures Induce Bone Resorption Around Titanium Implants: A 12-week Pilot Study in Rabbits.

PURPOSE: Marginal bone resorption (MBR) around oral implants may sometimes be a selflimiting condition due to balancing immunological reactions against the utilized materials, rather than a progressive bacterial infection. Contrary to previous assumptions from ligature induced experimental peri-implantitis studies, our recent 8-week experiment showed that marginal ligatures per se trigger an inflammatory immune response, resulting in bone resorption around implants in absence of a plaque. The present study aims to investigate whether this inflammatory/immunological reaction attenuates or progresses toward implant failure after a longer healing time, 12 weeks. MATERIALS AND METHODS: Sterile silk ligatures were placed around the top of titanium (Ti) implants and compressed against the femoral cortical bone plate of 6 rabbits. A non-ligated implant was used as control. After 12 weeks of submerged healing, ground sections of implants and surrounding tissues were investigated with light microscopy. The marginal soft tissues were also analyzed using selected qPCR markers. RESULTS: Histologically, the ligatures were outlined by immune cells, including multinucleated giant cells (MNGC), with adjacent fibrous encapsulation and resorbed peripheral bone that contrasted from the osseointegrated non-ligated control implants. The difference in expression of qPCR markers was not significant, but >2-fold upregulation of markers CD11b, IL1b, ARG1, NCF1, CD4 and >2-fold downregulation of CD8 indicated a mild, focal inflammatory/immune response against the ligatures compared to controls, with upregulation of M1 and M2 macrophages, neutrophils and helper T-cells and downregulation of killer T cells. Further, the bone formation markers OC and ALPL were >2 fold down regulated, consistent with the lack of osseointegration of the ligatures, compared to control implants. CONCLUSIONS: Marginal silk ligatures per se trigger an inflammatory/immune response and aseptic bone resorption around oral implants. Compared to our previous 8-week study, the inflammatory reaction against the silk appears to attenuate with time, with only a mild persisting inflammation that may block osseointegration and instead maintains a fibrous tissue encapsulation type reaction. This may explain why traditional ligature experiments have required regular exchange of ligatures in order for the bone resorption to progress.

Four Days Are Enough to Provide a Reliable Daily Step Count in Mild to Moderate Parkinson's Disease through a Commercial Smartwatch.

Daily steps could be a valuable indicator of real-world ambulation in Parkinson's disease (PD). Nonetheless, no study to date has investigated the minimum number of days required to reliably estimate the average daily steps through commercial smartwatches in people with PD. Fifty-six patients were monitored through a commercial smartwatch for 5 consecutive days. The total daily steps for each day was recorded and the average daily steps was calculated as well as the working and weekend days average steps. The intraclass correlation coefficient (ICC) (3,k), standard error of measurement (SEM), Bland-Altman statistics, and minimum detectable change (MDC) were used to evaluate the reliability of the step count for every combination of 2-5 days. The threshold for acceptability was set at an ICC ≥ 0.8 with a lower bound of CI 95% ≥ 0.75 and a SAM < 10%. ANOVA and Mann-Whitney tests were used to compare steps across the days and between the working and weekend days, respectively. Four days were needed to achieve an acceptable reliability (ICC range: 0.84-0.90; SAM range: 7.8-9.4%). In addition, daily steps did not significantly differ across the days and between the working and weekend days. These findings could support the use of step count as a walking activity index and could be relevant to developing monitoring, preventive, and rehabilitation strategies for people with PD.

Effect of Drilling Preparation on Immediately Loaded Implants: An In Vivo Study in Sheep.

PURPOSE: To determine the biologic and biomechanical effects of two implant drilling protocols on the cortical bone around implants subjected to immediate loading. MATERIALS AND METHODS: A total of 48 implants were inserted into the mandibles of six sheep following one of two drilling protocols: undersized preparation (US; n = 24) and nonundersized preparation (NUS; n = 24). Immediately after implant insertion, an abutment was placed on each implant and 36 implants were subjected to 10 sessions of dynamic vertical loads (1,500 cycles, 1 Hz) of 25 N or 50 N. Insertion torque value (ITV) was recorded at implant installation. Resonance frequency analysis (RFA) was measured at implant insertion and at each loading session. Fluorochrome was administered at day 17, and the animals were euthanized after 5 weeks. The removal torque values (RTVs) were measured, and samples underwent histomorphometric, µCT (microcomputed tomography), and fluorescence image acquisition analyses. The bone volume density (BV/TV), bone-to-implant contact (BIC), bone area fraction occupancy (BAFO), and fluorochrome stained bone surface (MS) were calculated. A linear mixed model analysis was performed, and Pearson paired correlation was calculated. RESULTS: Five implants from the NUS group failed, with a mean ITV of 8.8 Ncm and an RFA value of 57. The mean ITVs for US group and NUS group were 80.5 (± 14) Ncm and 45.9 (± 25) Ncm, respectively (P < .001). No differences were noted in the RFA values from the time of implant insertion until the end of the study. No differences in RTV, BV/TV, BAFO, or MS were observed between the groups. Intense new bone formation took place in the NUS group implants that were subjected to load. CONCLUSIONS: Undersized preparation of cortical bone ensured a greater BIC compared to a nonundersized preparation. Moreover, this study demonstrated that immediate loading did not interfere with the osseointegration process, but loading induced intense new bone formation in the NUS group. It is not recommended to immediately load the implants when the clinically perceived primary stability is lower than an ITV of 10 Ncm and an RFA value of 60. Int J Oral Maxillofac Implants 2023;38:607-618. doi: 10.11607/jomi.9949.

On the material dependency of peri-implant morphology and stability in healing bone.

The microstructural architecture of remodeled bone in the peri-implant region of screw implants plays a vital role in the distribution of strain energy and implant stability. We present a study in which screw implants made from titanium, polyetheretherketone and biodegradable magnesium-gadolinium alloys were implanted into rat tibia and subjected to a push-out test four, eight and twelve weeks after implantation. Screws were 4 mm in length and with an M2 thread. The loading experiment was accompanied by simultaneous three-dimensional imaging using synchrotron-radiation microcomputed tomography at 5 µm resolution. Bone deformation and strains were tracked by applying optical flow-based digital volume correlation to the recorded image sequences. Implant stabilities measured for screws of biodegradable alloys were comparable to pins whereas non-degradable biomaterials experienced additional mechanical stabilization. Peri-implant bone morphology and strain transfer from the loaded implant site depended heavily on the biomaterial utilized. Titanium implants stimulated rapid callus formation displaying a consistent monomodal strain profile whereas the bone volume fraction in the vicinity of magnesium-gadolinium alloys exhibited a minimum close to the interface of the implant and less ordered strain transfer. Correlations in our data suggest that implant stability benefits from disparate bone morphological properties depending on the biomaterial utilized. This leaves the choice of biomaterial as situational depending on local tissue properties.

Levodopa/carbidopa intestinal gel via percutaneous endoscopic transgastric jejunostomy in advanced Parkinson's disease: hitting two birds with one stone?

Here we focus on people with advanced PD undergoing percutaneous endoscopic transgastric jejunostomy (PEG-J) ("one stone") for LCIG infusion therapy for managing severe motor fluctuations ("first bird") and discuss its implications for improving accompanying symptoms of cardiovascular, urinary, and gastrointestinal autonomic failure ("second bird").

The impact of dysphagia in Parkinson's disease patients treated with levodopa/carbidopa intestinal gel.

BACKGROUND: Dysphagia is common in advanced phases of Parkinson disease (PD), and is a risk factor for aspiration pneumonia. Nonetheless, dysphagia has been poorly investigated in PD patients treated with levodopa-carbidopa intestinal gel (LCIG). We aimed to analyze the impact of dysphagia on mortality in LCIG treated patients and its relationship with other PD disability milestones. METHODS: We retrospectively evaluated 95 consecutive PD patients treated with LCIG. Kaplan-Meier and log-rank test were used to compare mortality in patients with dysphagia from others. Cox regression was used to estimate the impact of dysphagia, age, disease duration, and Hoehn and Yahr (H&Y) on mortality in the entire cohort. Finally, univariate and multivariate regression analyses were used to estimate the association between dysphagia and age, disease duration, H&Y, hallucinations, and dementia. RESULTS: A significantly higher mortality rate was observed in patients with dysphagia. In the Cox model, dysphagia was the only feature significantly associated with mortality (95%CI 2.780-20.609; p < 0.001). Univariate analyses showed a significant correlation between dysphagia and dementia (OR: 0.387; p:0.033), hallucinations (OR: 0.283; p:0.009), and H&Y score (OR: 2.680; p < 0.001); in the multivariate analysis, only the H&Y stage was associated with the presence of dysphagia (OR: 2.357; p:0.003). CONCLUSION: Dysphagia significantly increased the risk of death in our cohort of LCIG-treated patients, independently from other relevant features such as age, disease duration, dementia, and hallucinations. These findings support the management of this symptom as a priority in the advanced PD stages, even in people treated with LCIG.

Age at Onset Influences Progression of Motor and Non-Motor Symptoms during the Early Stage of Parkinson's Disease: A Monocentric Retrospective Study.

The interactions between the age at onset with other pathogenic mechanisms and the interplays between the disease progression and the aging processes in Parkinson's disease (PD) remain undefined, particularly during the first years of illness. Here, we retrospectively investigated the clinical presentation and evolution of the motor and non-motor symptoms and treatment-related complications during the first 5 years of illness in subjects categorized according to age at onset. A total of 131 subjects were divided into "Early-Onset-PD" (EOPD; onset ≤49 years), "Middle-Onset-PD" (MOPD; onset 50-69 years) and "Late-Onset-PD" (LOPD; onset ≥70 years). The T0 visit was set at the time of the clinical diagnosis; the T1 visit was 5 years (±5 months) later. At T0, there were no significant differences in the motor features among the groups. At T1, the LOPD patients displayed a significantly higher frequency of gait disturbances and a higher frequency of postural instability. Moreover, at T1, the LOPD subjects reported a significantly higher frequency of non-motor symptoms; in particular, cardiovascular, cognitive and neuropsychiatric domains. The presented results showed a significantly different progression of motor and non-motor symptoms in the early course of PD according to the age at onset. These findings contribute to the definition of the role of age at onset on disease progression and may be useful for the pharmacological and non-pharmacological management of PD.

Monoamine-oxidase Type B Inhibitors and Cognitive Functions in Parkinson's Disease: Beyond the Primary Mechanism of Action.

Symptoms of cognitive impairment are rather common since the early stage of Parkinson's disease (PD); they aggravate with disease progression and may lead to dementia in a significant proportion of cases. Worsening of cognitive symptoms in PD patients depends on the progression of subcortical dopaminergic damage as well as the involvement of other brain neurotransmitter systems in cortical and subcortical regions. Beyond the negative impact on disability and quality of life, the presence and severity of cognitive symptoms may limit adjustments of dopamine replacement therapy along the disease course. This review focuses on the consequences of the administration of monoamine-oxidase type Binhibitors (MAOB-I) on cognition in PD patients. Two drugs (selegiline and rasagiline) are available for the treatment of motor symptoms of PD as monotherapy or in combination with L-DOPA or dopamine agonists in stable and fluctuating patients; a further drug (safinamide) is usable in fluctuating subjects solely. The results of available studies indicate differential effects according to disease stage and drug features. In early, non-fluctuating patients, selegiline and rasagiline ameliorated prefrontal executive functions, similarly to other dopaminergic drugs. Benefit on some executive functions was maintained in more advanced, fluctuating patients, despite the tendency of worsening prefrontal inhibitory control activity. Interestingly, high-dose safinamide improved inhibitory control in fluctuating patients. The benefit of high-dose safinamide on prefrontal inhibitory control mechanisms may stem from its dual mechanism of action, allowing reduction of excessive glutamatergic transmission, in turn secondary to increased cortical dopaminergic input.

DNA G-Quadruplex Recognition In Vitro and in Live Cells by a Structure-Specific Nanobody.

G-quadruplexes (G4s) are four-stranded DNA secondary structures that occur in the human genome and play key roles in transcription, replication, and genome stability. G4-specific molecular probes are of vital importance to elucidate the structure and function of G4s. The scFv antibody BG4 has been a widely used G4 probe but has various limitations, including relatively poor in vitro expression and the inability to be expressed intracellularly to interrogate G4s in live cells. To address these considerations, we describe herein the development of SG4, a camelid heavy-chain-only derived nanobody that was selected against the human Myc DNA G4 structure. SG4 exhibits low nanomolar affinity for a wide range of folded G4 structures in vitro. We employed AlphaFold combined with molecular dynamics simulations to construct a molecular model for the G4-nanobody interaction. The structural model accurately explains the role of key amino acids and Kd measurements of SG4 mutants, including arginine-to-alanine point mutations that dramatically diminish G4 binding affinity. Importantly, predicted amino acid-G4 interactions were subsequently confirmed experimentally by biophysical measurements. We demonstrate that the nanobody can be expressed intracellularly and used to image endogenous G4 structures in live cells. We also use the SG4 protein to positionally map G4s in situ and also on fixed chromatin. SG4 is a valuable, new tool for G4 detection and mapping in cells.

Review of PEEK implants and biomechanical and immunological responses to a zirconium phosphate nano-coated PEEK, a blasted PEEK, and a turned titanium implant surface.

PURPOSE: To investigate the biomechanical and immunological reactions to coated and non-coated blasted PEEK implants in vivo after 12 weeks and review the associated literature. METHODS: Two osteotomy sites were performed in each proximal tibia of 10 lop-eared rabbits (n= 4 per rabbit). Each rabbit received a randomly placed (1) blasted zirconium phosphate nano-coated PEEK- (nano-ZrP), (2) blasted PEEK- (PEEK) and (3) titanium implant (Ti) and an empty sham site. At 12 weeks, removal torque of all implants and biological investigation with qPCR was performed. The implant surfaces were analyzed prior to insertion with interferometry, SEM and XPS. RESULTS: The interferometry analysis showed that there was no difference in roughness for the uncoated PEEK compared to the ZrP coated PEEK implants. The titanium implants were considerably smoother (Sa= 0.23 µm) than the uncoated Sa= 1.11 µm) and ZrP coated PEEK implants (Sa= 1.12 µm). SEM analysis on the PEEK implants corroborated the interferometry results; no difference in structure between the uncoated vs. the ZrP coated PEEK was visible on the micrometer level. At higher magnifications, the ZrP coating was visible in the SEM as a thin, porous network. All tested implants displayed osseointegration with the highest RTQ for nano-ZrP (18.4 Ncm) followed by PEEK (14.5 Ncm) and Ti (11.5 Ncm). All implants activated the immune system, with elevated macrophage and M2 macrophage qPCR markers at 12 weeks compared to the sham site. CLINICAL SIGNIFICANCE: Nano-ZrP coating improves osseointegration of blasted PEEK implants at 12 weeks of follow-up. Osseointegration of titanium, PEEK and nano-ZrP PEEK is not a normal bone healing process, but rather a shield-off mechanism that appears to be regulated by the innate immune system.

Evaluation of pregenomic HBV RNA in HBeAg-negative patients.

The distinction between chronic HBeAg-negative hepatitis (CHB) and chronic HBeAg-negative infection (CIB) can be challenging and important for providing advice on prognosis, as well as determining need for treatment. The aim of the present study was to evaluate pgRNA levels in treatment-naïve HBeAg-negative chronic HBV-infected patients. In addition, pgRNA levels were compared to traditional markers in order to assess their clinical utility. A retrospective study was carried out, including 85 cases of CHBs and 74 CIBs. Globally, when the virological markers (pgRNA, qHBsAg, and HBV DNA) were analyzed, significant differences were found between the CHB and CIB groups (P<0.001). Overall, positive correlations were demonstrated, as follows: between pgRNA levels and qHBsAg (Spearman r=0.30, P<0.001), between pgRNA and HBV DNA (Spearman r=0.73, P<0.001), and between pgRNA and ALT (Spearman r=0.67, P<0.001). Out of the 85 CHB patients, 82 (96.5%) agreed to start treatment. At baseline, 38/82 patients, as well as the 3 untreated CHB patients, had undetectable pgRNA levels. The 74 CIB carriers also had undetectable pgRNA levels. During the follow-up period, no patients experienced viral reactivation or progression of liver disease. These results suggest that the addition of plasmatic HBV-pgRNA levels to the traditional diagnostic flowchart of HBeAg-negative patients may improve the correct identification of cases at risk, especially patients with occasional increases in HBV viremia.

High-resolution ex vivo analysis of the degradation and osseointegration of Mg-xGd implant screws in 3D.

Biodegradable magnesium (Mg) alloys can revolutionize osteosynthesis, because they have mechanical properties similar to those of the bone, and degrade over time, avoiding the need of removal surgery. However, they are not yet routinely applied because their degradation behavior is not fully understood. In this study we have investigated and quantified the degradation and osseointegration behavior of two biodegradable Mg alloys based on gadolinium (Gd) at high resolution. Mg-5Gd and Mg-10Gd screws were inserted in rat tibia for 4, 8 and 12 weeks. Afterward, the degradation rate and degradation homogeneity, as well as bone-to-implant interface, were studied with synchrotron radiation micro computed tomography and histology. Titanium (Ti) and polyether ether ketone (PEEK) were used as controls material to evaluate osseointegration. Our results showed that Mg-5Gd degraded faster and less homogeneously than Mg-10Gd. Both alloys gradually form a stable degradation layer at the interface and were surrounded by new bone tissue. The results were correlated to in vitro data obtained from the same material and shape. The average bone-to-implant contact of the Mg-xGd implants was comparable to that of Ti and higher than for PEEK. The results suggest that both Mg-xGd alloys are suitable as materials for bone implants.

The use of implant-level connection in screw-retained fixed partial dentures: A 3-year randomised clinical trial.

OBJECTIVES: This randomised controlled trial compares the 3-year outcomes, that is, marginal bone-level (MBL) changes and clinical parameters, between an abutment-level (AL) and implant-level (IL) connection for implants with an internal conical connection (ICC) supporting a screw-retained fixed partial denture. MATERIAL AND METHODS: Fifty patients with 119 implants were randomly allocated to either the AL or IL group. Radiographic and clinical examinations were performed after one, two, and 3 years. A linear mixed model was used to evaluate the differences between groups. RESULTS: The MBL change was not significantly different between the groups at any point. The MBL was 0.12 ± 0.31 mm (AL) and 0.23 ± 0.26 mm (IL) after 1 year; 0.15 ± 0.34 mm (AL) and 0.17 ± 0.22 mm (IL) after 2 years; 0.18 ± 0.39 mm (AL) and 0.15 ± 0.21 mm (IL) after 3 years. The bleeding on probing was 43.44 ± 39.24% (AL) and 58.19 ± 41.20% (IL) after 1 year; 35.78 ± 39.22% (AL) and 50.43 ± 41.49% (IL) after 2 years; 51.27 ± 44.63% (AL) and 49.57 ± 37.31% (IL) after 3 years and was significantly different (p = .025) between 1 and 2 years. The probing depth showed a significant difference at each time point while the plaque was not significant between the groups. The overall technical, biological and prosthetic complication rates were 5.04%, 3.36%, and 16.00%, respectively. CONCLUSIONS: The MBL change was similar in the groups. The slight differences in the soft tissue complications between the groups are likely not of clinical relevance. An IL connection is considered to be a valid alternative to an AL set-up in ICC implants.

Multimodal ex vivo methods reveal that Gd-rich corrosion byproducts remain at the implant site of biodegradable Mg-Gd screws.

Extensive research is being conducted on magnesium (Mg) alloys for bone implant manufacturing, due to their biocompatibility, biodegradability and mechanical properties. Gadolinium (Gd) is among the most promising alloying elements for property control in Mg alloy implants; however, its toxicity is controversial. Investigating Gd behavior during implant corrosion is thus of utmost importance. In this study, we analyzed the degradation byproducts at the implant site of biodegradable Mg-5Gd and Mg-10Gd implants after 12 weeks healing time, using a combination of different imaging techniques: histology, energy-dispersive x-ray spectroscopy (EDX), x-ray microcomputed tomography (µCT) and neutron µCT. The main finding has been that, at the healing time in exam, the corrosion appears to have involved only the Mg component, which has been substituted by calcium and phosphorus, while the Gd remains localized at the implant site. This was observed in 2D by means of EDX maps and extended to 3D with a novel application of neutron tomography. X-ray fluorescence analysis of the main excretory organs also did not reveal any measurable accumulation of Gd, further reinforcing the conclusion that very limited or no removal at all of Gd-alloy happened during degradation. STATEMENT OF SIGNIFICANCE: Gadolinium is among the most promising alloying elements for property control in biodegradable magnesium alloy implants, but its toxicity is controversial and its behavior during corrosion needs to be investigated. We combine 2D energy dispersive x-ray spectroscopy and 3D neutron and x-ray tomography to image the degradation of magnesium-gadolinium implants after 12 weeks of healing time. We find that, at the time in exam, the corrosion has involved only the magnesium component, while the gadolinium remains localized at the implant site. X-ray fluorescence analysis of the main excretory organs also does not reveal any measurable accumulation of Gd, further reinforcing the conclusion that very limited or no removal at all of Gd-alloy has happened during degradation.

Hepatitis C Virus Core Antigen (HCVAg): an affordable assay to monitor the efficacy of treatment in DAAs era.

Hepatitis C virus (HCV) Core Antigen (HCVAg) and HCV-RNA were tested in 962 plasma/serum samples from 180 patients during Direct Antiviral Agents (DAAs) treatment and at follow-up. One hundred and eighty individuals were included: 71% carried advanced fibrosis and 43% were treatment-experienced. A Sustained Virological Response (SVR) was achieved in 166/180 (92%) individuals: 96/102 (94.1%) na ve and 70/78 (89.7%) treatment-experienced (p=0.20). The baseline median levels of HCV-RNA and HCVAg were not significantly different between individuals achieving SVR (5.92 x 105 IU/mL, IQR 5.4-6.4, and 3,417 fmol/L, 2,900-3,795) and those without SVR (6.06 x 105 IU/mL, 5.63-6.57, and 3,391 fmol/L, 2,828-4,077). The HCV-RNA vs. HCVAg assays results showed a fair correlation with an overall moderate qualitative agreement (kappa=0.52). Among treatment-failed individuals, at failure 100% of the assays results were positive for both techniques, with HCV-RNA median value 3.09 x 105 IU/mL (2.10-29.09) and HCVAg median value 1570.28 fmol/L (360.15-9317.67). Undetectable HCV-RNA at EOT showed sensitivity 54%, specificity 100%, negative predictive value (NPV) 93% and positive predictive value (PPV) 100%. Undetectable HCVAg at EOT showed sensitivity 74%, specificity 100%, NPV 97% and PPV 100%. The operative and economic advantages of the HCVAg support the alternative use of HCVAg to monitor DAAs treatment outcome.

A Role for Human DNA Polymerase λ in Alternative Lengthening of Telomeres.

Telomerase negative cancer cell types use the Alternative Lengthening of Telomeres (ALT) pathway to elongate telomeres ends. Here, we show that silencing human DNA polymerase (Pol λ) in ALT cells represses ALT activity and induces telomeric stress. In addition, replication stress in the absence of Pol λ, strongly affects the survival of ALT cells. In vitro, Pol λ can promote annealing of even a single G-rich telomeric repeat to its complementary strand and use it to prime DNA synthesis. The noncoding telomeric repeat containing RNA TERRA and replication protein A negatively regulate this activity, while the Protection of Telomeres protein 1 (POT1)/TPP1 heterodimer stimulates Pol λ. Pol λ associates with telomeres and colocalizes with TPP1 in cells. In summary, our data suggest a role of Pol λ in the maintenance of telomeres by the ALT mechanism.

Osseointegration and antibacterial effect of an antimicrobial peptide releasing mesoporous titania implant.

Medical devices such as orthopedic and dental implants may get infected by bacteria, which results in treatment using antibiotics. Since antibiotic resistance is increasing in society there is a need of finding alternative strategies for infection control. One potential strategy is the use of antimicrobial peptides, AMPs. In this study, we investigated the antibiofilm effect of the AMP, RRP9W4N, using a local drug-delivery system based on mesoporous titania covered titanium implants. Biofilm formation was studied in vitro using a safranine biofilm assay and LIVE/DEAD staining. Moreover, we investigated what effect the AMP had on osseointegration of commercially available titanium implants in vivo, using a rabbit tibia model. The results showed a sustained release of AMP with equal or even better antibiofilm properties than the traditionally used antibiotic Cloxacillin. In addition, no negative effects on osseointegration in vivo was observed. These combined results demonstrate the potential of using mesoporous titania as an AMP delivery system and the potential use of the AMP RRP9W4N for infection control of osseointegrating implants.

Impact of a Hydrophilic Dental Implant Surface on Osseointegration: Biomechanical Results in Rabbit.

This study aimed to evaluate the effect of surface hydrophilicity on the biomechanical aspects of osseointegration of dental implants in the tibia and femur of rabbits. Forty-eight mature female New Zealand White rabbits were included, and 96 commercially pure, Grade 4, titanium dental implants (control group), and 96 implants of same macro geometry with the hydrophilic surface (test group) were used in this study. One osteotomy was performed in each tibia and femur on both sides of the rabbit, and four implants were placed in each rabbit. Control and test groups were randomly allocated on the left and right sides. During surgery, insertion torque (ITQ) value of the complete implant placement was recorded. After healing periods of 0, 2, 4, and 8 weeks after surgery, implant stability quotient (ISQ) value, and removal torque (RTQ) values were measured. No statistical difference was observed for ITQ, for ISQ and for RTQ between the control group and test group in tibia/femur for all time periods. The effect of hydrophilic properties on moderately roughened surfaces has no impact in terms of biomechanical outcomes (ISQ values and RTQ values) after a healing period of 2 to 8 weeks in rabbit tibias /femurs.

The tolerability, safety and efficacy of safinamide in elderly Parkinson's disease patients: a retrospective study.

Safinamide (SF) is a third-generation monoamine-oxidase-B inhibitor that proved efficacy as add-on to levodopa in fluctuating Parkinson's disease (PD) patients. Despite the high prevalence of complicated PD in older population, the data on the tolerability, safety and efficacy of SF in elderly patients are rather poor. Here we studied retrospectively the consequences of add-on with SF in PD patients older than 65 years. Fifty-three fluctuating PD patients were included (30 subjects aged between 65 and 75 years, the remaining 23 subjects aged > 75 years). Patients were treated with either 50 (n = 27) or 100 mg (n = 26) SF for at least 6 months. In all patients, fluctuations were identified by the report of a Wearing-Off-Questionnaire-19 (WOQ-19) score ≥ 3 at baseline. Add-on with SF was well tolerated and safe. Adverse events occurred in 30% of patients and led to drug discontinuation in 11% of cases. At follow-up visits, 60% of patients reported lowering of the WOQ-19 score to ≤ 2. There were no significant differences related to age or daily drug dose in tolerability, safety or efficacy. The results of this study provide evidence of the efficacy, tolerability and safety of SF in elderly PD patients.