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.

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.

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.

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.

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.

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.

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.

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.

An alternative procedure to leukapheresis for peripheral hematopoietic progenitor cell collection in very-low-weight children: A single pediatric center experience.

BACKGROUND: PBSC collection using a blood cell separator in very low weight patients can be frequently complicated by severe adverse effects and technical difficulties. MATERIAL AND METHODS: From March 2013 to January 2017, 14 PBSC collections were performed in 12 children weighing less than 10 kg, affected by different solid tumours. PBSC collection was performed with a "homemade" aseptically assembled circuit. The circuit is composed by a 150 mL collection bag connected with a 4 stopcock ramp, perfused with ACD. This circuit allows collection of a specific total blood amount from CVC, depending on CD34+ /kg target. RESULTS: Mean CD34+ cell performance per collection was 9.3 × 106 /kg. Tolerance to the procedure was very good as none of the patients experienced complications, with the exception of a patient who showed mild cyanosis and pallor after collection. Moreover, no bleeding or thrombotic complications have been observed. To date, 16 PBSC reinfusions have been performed in 7 children with a mean CD34+ cells viability of 98.1% ± 2.7 and mean WBC viability of 57% ± 10. Cell recovery after thawing was 87% ± 10.8. A rapid graft intake for both neutrophils and platelets, between day 7 and 20 after reinfusion was observed. DISCUSSION: The procedure of total blood collection without the use of a cell separator is feasible and allows a good PBSC collection without significant side effects in very low-weight children. Moreover, this method could represent a valid and safe alternative to leukapheresis in patients where classic procedure could be difficult to apply.

Serum hepatitis B core-related antigen is an effective tool to categorize patients with HBeAg-negative chronic hepatitis B.

The discrimination between active chronic hepatitis B (CHB) and the clinically quiescent infection (CIB) is not always easy, as a significant portion of patients falls in a "grey" zone. Hepatitis B core-related antigen (HBcrAg) is a now quantifiable serological marker with potential applications in diagnosis and therapy monitoring. The aim of the present study was to evaluate the HBcrAg serum levels in HBeAg-negative HBV infection, and its ability in identifying the clinical profile, in comparison with HBsAg serum levels. HBcrAg was retrospectively assessed on serum samples from a population of treatment-naive HBeAg-negative patients by ChemiLuminescent Enzyme Immunoassay (CLEIA). HBsAg and HBV-DNA data were collected. Serological data were associated to clinical profile, defined in the subsequent follow-up of at least 1 year. In the overall population of 160 HBeAg-negative patients, HBcrAg results weakly correlated with qHBsAg levels (Spearman r = 0.471, P < 0.0001) and correlated closely with HBV-DNA (Spearman r = 0.746, P < 0.0001). HBcrAg levels were significantly higher in 85 CHB patients relative to 75 CIB carriers. A value of 2.5 logU/mL produced the optimal cut-off to identify CIB patients, with diagnostic accuracy comparable to HBsAg levels. In long-term clinical evaluation, a single measurement of HBcrAg at the established cut-off was optimally consistent with clinical outcome. Conversely, the HBsAg cut-off performed well in the true quiescent phase and less in more difficult-to-categorize patients. In conclusion, single-point use of HBcrAg serum levels provides an accurate identification of CIB and represents a useful tool for patient classification.

Osseointegration effects of local release of strontium ranelate from implant surfaces in rats.

BACKGROUND: Numerous studies have reported the beneficial effects of strontium on bone growth, particularly by stimulating osteoblast proliferation and differentiation. Thus, strontium release around implants has been suggested as one possible strategy to enhance implant osseointegration. AIM: This study aimed to evaluate whether the local release of strontium ranelate (Sr-ranelate) from implants coated with mesoporous titania could improve bone formation around implants in an animal model. MATERIALS AND METHODS: Mesoporous titania (MT) thin coatings were formed utilizing the evaporation induced self-assembly (EISA) method using Pluronic (P123) with or without the addition of poly propylene glycol (PPG) to create materials with two different pore sizes. The MT was deposited on disks and mini-screws, both made of cp Ti grade IV. Scanning electron microscopy (SEM) was performed to characterize the MT using a Leo Ultra55 FEG instrument (Zeiss, Oberkochen, Germany). The MT was loaded with Sr-ranelate using soaking and the drug uptake and release kinetics to and from the surfaces were evaluated using quartz crystal microbalance with dissipation monitoring (QCM-D) utilizing a Q-sense E4 instrument. For the in vivo experiment, 24 adult rats were analyzed at two time points of implant healing (2 and 6 weeks). Titanium implants shaped as mini screws were coated with MT films and divided into two groups; supplied with Sr-ranelate (test group) and without Sr-ranelate (control group). Four implants (both test and control) were inserted in the tibia of each rat. The in vivo study was evaluated using histomorphometric analyses of the implant/bone interphase using optical microscopy. RESULTS: SEM images showed the successful formation of evenly distributed MT films covering the entire surface with pore sizes of 6 and 7.2 nm, respectively. The QCM-D analysis revealed an absorption of 3300 ng/cm2 of Sr-ranelate on the 7.2 nm MT, which was about 3 times more than the observed amount on the 6 nm MT (1200 ng/cm2). Both groups showed sustained release of Sr-ranelate from MT coated disks. The histomorphometric analysis revealed no significant differences in bone implant contact (BIC) and bone area (BA) between the implants with Sr-ranelate and implants in the control groups after 2 and 6 weeks of healing (BIC with a p-value of 0.43 after 2 weeks and 0.172 after 6 weeks; BA with a p-value of 0.503 after 2 weeks, and 0.088 after 6 weeks). The mean BIC and BA values within the same group showed significant increase among all groups between 2 and 6 weeks. CONCLUSION: This study could not confirm any positive effects of Sr-ranelate on implant osseointegration.

Efficacy, Safety, and Predictors of Direct-acting antivirals in Hepatitis C Virus Patients with Heterogeneous Liver Diseases.

Safety, efficacy, and predictor factors of sustained-virological-response after 24 weeks of new direct-acting antivirals were evaluated in hepatitis C virus patients with different stages of hepatic disease. 260 patients, median age 60 years, of whom 48.1% cirrhotics, 17.7% liver transplant recipients, and 45.7% naïve were treated with Sofosbuvir+Ribavirine, Sofosbuvir+Simeprevir±Ribavirine, Sofosbuvir+Daclatasvir± Ribavirine, Sofosbuvir+Ledispavir±Ribavirine, Ombitasvir/Paritaprevir/Ritonavir+Ribavirine and Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir±Ribavirine. Therapy outcomes, hematochemical parameters, viral replication, genotype, and resistance-associated-mutations were analyzed retrospectively. Sustained virological response was 90.4% in the whole population, 83.2% in cirrhotics, 85% in patients with previous virological failure, 93.6% in patients >60 years, and 95.6% in liver transplant recipients. SVR24 for each drug regimen was 75% Sofosbuvir+Ribavirine, 80.4% Sofosbuvir+Simeprevir±Ribavirine, 94.3% Sofosbuvir+Daclatasvir±Ribavirine, 98.7% Sofosbuvir+Ledispavir±Ribavirine, 100% Ombitasvir/ Paritaprevir/Ritonavir+Ribavirine and Ombitasvir/Paritaprevir/Ritonavir+Dasabuvir±Ribavirine. The highest sustained virological response rates were obtained with genotype-1b (95.9%). Twenty-five patients, mostly cirrhotics or suffering from severe liver complications, manifested relapse (84%), breakthrough (12%), or non-response (4%). Mild side effects were observed in 41.1% of patients. Model-for-End-Liver- Disease score <10 and alanine aminotransferase ≤20 U/L at week 8 of therapy proved positive predictors of sustained virological response. Direct-acting antiviral therapy is efficacious and safe even in patients with advanced liver disease and/ or previous virological failure; Model-for-End-Liver-Disease <10 and alanine aminotransferase reduction during therapy were found to be reliable predicting markers of sustained-virological-response.

Syphilis in a high-density urban area in the North of Italy.

Although far less common now than in the past, syphilis continues to pose a danger to public health and should not be overlooked. In this study, we evaluated the presence and characteristics of syphilis in a group of patients attending an STI Clinic in the North of Italy. A retrospective study was carried out, analysing the data from the 5609 subjects who attended the STI Clinic of St. Orsola-Malpighi Hospital (Bologna) for syphilis screening from January 2016 to December 2017. Globally, 692 patients (12.3%) were found positive for treponemal tests, with a significant difference between males and females (16.6% vs 4.1%; P<0.0001). Moreover, positive women were more likely foreign (63.3%), in contrast to men, who were more likely Italian (86.1%; P<0.0001). A total of 306 patients (44.2%), mainly males (47% vs 25%; P=0.0003), received a diagnosis of early syphilis. These cases peaked among patients 35-44 years (31%) and 25-34 years (26.8%). Overall, 32.9% of the women found positive for treponemal tests were pregnant. Among them, 84.6% were foreign (mainly from Eastern Europe) and 38.4% received a diagnosis of early syphilis. No cases of mother-to-child syphilis were found. The presence of an HIV-syphilis co-infection was found in 21.5% of patients with early syphilis, with a significant association with the male sex (P<0.009). In-depth knowledge of the characteristics of syphilis could help set up effective strategies for its control.

Prevalence and antimicrobial resistance of genital Mollicutes in Italy over a two-year period.

Knowledge of the prevalence and antimicrobial susceptibility of genital Mollicutes is crucial to offer guidelines for empirical treatments. The aim of this study was to investigate the prevalence and the resistance profile of Mycoplasma hominis (MH) and Ureaplasma urealyticum/Ureaplasma parvum (UU/UP) in genital samples over a two-year period in Bologna, Italy. From January 2015 to December 2016, data on all the subjects providing uro-genital specimens for Mollicutes detection by culture were analyzed. A total of 4660 subjects (84.4% females) were enrolled and an overall Mollicutes prevalence of 30.9% was found. Women turned positive for Mollicutes infection twice as often as men (33.3% vs 17.8%) and the detection rate progressively decreased with increasing age. Ureaplasmas represented the commonest species isolated (overall prevalence: 24.2%), whereas mixed infections (6.5%) and MH single infections (3.9%) were far less common. Ureaplasma species showed significant levels of quinolone resistance, especially to ciprofloxacin (77%), whereas MH strains were non-susceptible to azithromycin and roxithromycin in about 90% of cases. Mollicutes co-infections showed a more severe resistance pattern than single infections. Over time, the resistance rate for azithromycin and roxithromycin increased significantly. Globally, our results revealed that minocycline and doxycycline can still be first-line drugs for Mollicutes treatment.

Vitamin E for the treatment of E-antigen-positive chronic hepatitis B in paediatric patients: results of a randomized phase 2 controlled study.

BACKGROUND & AIMS: The treatment of chronic hepatitis B infection (CHB) in children is still an area of great uncertainty. Vitamin E is an immunostimulating/antioxidant compound proven to be safe and effective for the treatment of adult CHB. The aim of this phase 2 controlled study was to evaluate the safety and efficacy of vitamin E for the treatment of paediatric HBeAg-positive CHB. METHODS: Forty-six children were randomized in a 1:1 ratio to receive vitamin E at a dose of 15 mg/kg/day (in galenic preparation) or no treatment for 12 months and were monitored for the subsequent 12 months. Clinical, biochemical, haematological and serovirological evaluations were carried out every 3 months. RESULTS: No significant side effects were associated with the vitamin E treatment. At the end of the study, anti-HBe seroconversion was obtained in 7 of 23 (30.4%) of vitamin E-treated versus 1 of 23 (4.3%) of the control patients (P = 0.05), while a virological response (≥2 log decrease in HBV-DNA from baseline) was observed in 9 of 23 (39.1%) vs. 2 of 23 (8.7%) respectively (P = 0.035). CONCLUSIONS: Vitamin E administration for the treatment of paediatric CHB at the tested dosage has no significant side effects and may induce anti-HBe seroconversion. Vitamin E could represent a tool for the treatment of paediatric CHB.

Chemically modified titanium-zirconium implants in comparison with commercially pure titanium controls stimulate the early molecular pathways of bone healing.

OBJECTIVES: Titanium-zirconium (TiZr) has been proposed as a mechanically stronger alternative to commercially pure titanium for oral and orthopaedic implants. However, not much is known on the osseointegration kinetics of TiZr surfaces. In this study, we aimed to identify the genetic response of bone around TiZr implants compared to pure Ti. MATERIAL AND METHODS: Microtextured and hydrophilic TiZr implants (tests) and cpTi implants grade IV (controls) were placed in the tibia of 30 New Zealand white rabbits. At 2, 4 and 12 weeks, the implants were subjected to removal torque test (RTQ). The expression of a panel of genes involved in the process of osseointegration was measured in the bone around the test and control implants by means of quantitative real-time polymerase chain reaction (PCR) and compared to the control samples. RESULTS: The controls yielded statistically significant higher RTQ at 4 weeks, but the RTQ of the tests had a larger increase between 4 and 12 weeks, when both groups reached similar values. The gene expression analysis showed that all selected markers for bone formation, bone remodelling and cytokines were significantly upregulated around TiZr implants after 2 weeks. After 4 weeks of healing, two bone formation markers were significantly more expressed in the test samples, while at 12 weeks, the expression of all genes was similar in the two groups. CONCLUSIONS: TiZr implants showed comparable biomechanical outcomes to cpTi up to 12 weeks of healing. However, at early healing stages, they showed a significant upregulation of osteogenesis and osteoclastogenesis markers.

Implant stability and bone remodeling up to 84 days of implantation with an initial static strain. An in vivo and theoretical investigation.

OBJECTIVES: When implants are inserted, the initial implant stability is dependent on the mechanical stability. To increase the initial stability, it was hypothesized that bone condensation implants will enhance the mechanical stability initially and that the moderately rough surface will further contribute to the secondary stability by enhanced osseointegration. It was further hypothesized that as the healing progresses the difference in removal torque will diminish. In addition, a 3D model was developed to simulate the interfacial shear strength. This was converted to a theoretical removal torque that was compared to the removal torque obtained in vivo. MATERIAL AND METHODS: Condensation implants, inducing bone strains of 0.015, were installed into the left tibia of 24 rabbits. Non-condensation implants were installed into the right tibia. All implants had a moderately rough surface. The implants had an implantation time of 7, 28, or 84 days before the removal torque was measured. The interfacial shear strength at different healing time was estimated by the means of finite element method. RESULTS: At 7 days of healing, the condensation implant had an increased removal torque compared to the non-bone-condensation implant. At 28 and 84 days of healing, there was no difference in removal torque. The simulated interfacial shear strength ratios of bone condensation implants at different implantation time were in line with the in vivo data. CONCLUSIONS: Moderately rough implants that initially induce bone strain during installation have increased stability during the early healing period. In addition, the finite element method may be used to evaluate differences in interlocking capacity.

Modified protocol of the intraoral welding technique for immediate implant-supported rehabilitation of the edentulous maxilla.

PURPOSE: The aim of this study was to report the outcomes of a treatment option of immediate loading with intraoral welding on only 4 implants for the restoration of patients with maxillary edentulism. MATERIALS AND METHODS: Seventeen consecutive patients were rehabilitated with 2 parallel and 2 tilted implants in the maxilla. Immediately after implant placement, angulated abutments were screwed on the implants to create better parallelism among the implants; thereafter, a titanium bar was intraorally welded to the welding pins to create a superstructure that rigidly splinted the implants. A fixed full-arch durable prosthesis was delivered on the same day of the surgery. The patients were followed for 26.5 months on average. RESULTS: During the follow-up time, 2 implants were lost giving an implant survival rate of 97%. Nonetheless, all the prostheses remained in function and the prosthetic success was 100%. CONCLUSIONS: The rehabilitation of the edentulous maxilla with an immediately loaded full-arch prosthesis, obtained through intraoral welding on only 4 implants, is a functionally and esthetically successful treatment.

Increase of ribavirin dose improves sustained virological response in HCV-genotype 1 patients with a partial response to peg-interferon and ribavirin.

BACKGROUND AND AIM: In patients with chronic hepatitis C receiving Peg interferon/ribavirin (PEG-IFN/RBV) who do not achieve ≥ 2 log-reduction in HCV-RNA at week 12 (null responders, NR) and in those with ≥ 2 log-decrease but detectable at week 24 (partial responders, PR) the probability to achieve the sustained virological response (SVR) is almost null. The aim of this study was to investigate the efficacy of individualized schedule of progressively increased RBV doses in the setting of PEG-IFN/RBV treatment. MATERIAL AND METHODS: PR or NR to PEG-IFN/RBV instead of discontinuing treatment were enrolled to receive increasing doses of RBV until a target theoretical concentration ([tRBV]) of ≥ 15 µmol/L (by pharmacokinetic formula based on glomerular filtration rate). HCV-RNA was assessed every 4 weeks and, if detectable, RBV dose was gradually increased until negativization. Twelve weeks later, patients with detectable HCV-RNA discontinued therapy while those with undetectable HCV-RNA continued for further 48 weeks. RESULTS: Twenty genotype-1 patients (8 NR and 12 PR) were enrolled. After 12 weeks 9 (45%) were still HCV-RNA positive and were discontinued, while remaining 11 had undetectable HCV-RNA. One stopped treatment for side effects. Ten completed treatment. Five (all PR) achieved SVR. Side effects incidence was similar to that observed during PEG-IFN/RBV. CONCLUSIONS: In conclusion, RBV high doses, according to individualized schedule, increase SVR in PR on a similar extent to that of triple therapy but without increase of side effects. Such treatment should be considered in PR with no access or intolerant to protease inhibitors (PI).