In vitro study of surface alterations to polyetheretherketone and titanium and their effect upon human gingival fibroblasts

Statement of problemSoft-tissue attachment to different surfaces may play a pivotal role in the long-term success of dental implants. However, studies on the issue, especially on newer materials, are sparse.PurposeThe purpose of this in vitro study was to evaluate the viability and adhesion of human gingival fibroblasts (HGFs) on different implant abutment materials with specific surface modifications.Material and methodsOne hundred and fifty specimens in 6 experimental groups were evaluated: smooth-machined titanium alloy (Ti), laser-modified titanium (TiL), smooth-machined polyetheretherketone (PEEK) (P), laser-modified PEEK (PL), plasma-treated PEEK (PP), laser- and plasma-treated PEEK (PLP). Machined Ti was considered as the control group. Surface roughness (S_a), water contact angle (WCA), and X-ray photoelectron spectroscopy (XPS) were measured. HGF attachment and proliferation were observed at 1, 3, and 7 days after cell seeding. Comparison of the means among the groups was performed with 1-way analysis of variance (ANOVA) with post hoc comparison using the Tukey test (α=.05).ResultsS_a values of the laser modified groups were significantly higher than those of the nonmodified (smooth-machined) groups (P<.001). WCAs were significantly different among PEEK groups, and plasma-sprayed groups had the lowest WCAs. XPS analysis of both Ti and PEEK groups showed laser treatment did not have any significant effect on the surface composition of the PEEK as the same bonds with similar ratio/fraction were detected in the spectrum of the modified specimens. Scanning electron microscopy (SEM) revealed more functionally oriented HGF cells on the laser-grooved surfaces. On the first, third, and seventh day of proliferation, the titanium groups showed no significant differences (P>.05). On the first and third days of proliferation, the plasma sprayed groups (PP, PLP) showed significantly greater proliferation than all experimental groups (P<.001). On the seventh day of proliferation, statistically significant differences were observed between all PEEK groups and between all PEEK groups and the Ti group (P<.001), with the exception of the PL and P groups and the PLP and Ti groups (P>.05).ConclusionsLaser-modified titanium and PEEK surfaces led to guided gingival fibroblast attachment. Plasma treatment of PEEK surfaces increased the wettability of this polymer and improved proliferation of HGF.     

Lengthier cryoablation and a bonus cryoapplication is associated with improved efficacy for cryothermal catheter ablation of supraventricular tachycardias in children

Introduction Cryoablation is an effective treatment for children with supraventricular tachycardias (SVT). The present study documents the effect of two different cryoablation protocols on acute and chronic success rates. Methods and results Fifty-three consecutive patients (age range, 5–20 years) were treated; patients 1 to 17 were treated by a standard ablation protocol and patients 18 to 53 were treated by a modified ablation protocol that required lengthier cryoablations plus delivery of a bonus cryoapplication to consolidate the acutely successful irreversible lesion created at intervention. Electrophysiological study (EPS) was performed with diagnostic catheters and cryoablations were performed with a 7FR 4 mm tip catheter (CryoCath Technologies). Acute endpoints for non-inducibility of atrioventricular nodal re-entrant tachycardia (AVNRT) by programmed atrial stimulation at baseline or during isoproterenol performed 30 min post procedure, as well as non-inducibility and conduction block over the accessory pathway (AP). The chronic endpoint was arrhythmia recurrence post intervention. No permanent cryo-related complications or adverse outcomes were reported. Acute success rates for patients 1 to 17 and 18 to 53 were 88 and 100%, respectively. The cumulative percentage of patients without arrhythmia recurrence at 12 month follow-up was significantly different at 73 and 90%, respectively. Conclusions Lengthier cryoablation delivery, approximating 7 min per cryoablation, increases the acute success rate at intervention. Moreover, these lengthier cryoablation deliveries plus a bonus cryoapplication to consolidate the acutely successful irreversible lesion created at intervention may also significantly improve the chronic success rate, while also maintaining an excellent safety profile for cryoablation treatment of children with SVT such as AVNRT and AP located near the AV junction.     

Altered striatal function in a mutant mouse lacking D1A dopamine receptors.

Of the five known dopamine receptors, D1A and D2 represent the major subtypes expressed in the striatum of the adult brain. Within the striatum, these two subtypes are differentially distributed in the two main neuronal populations that provide direct and indirect pathways between the striatum and the output nuclei of the basal ganglia. Movement disorders, including Parkinson disease and various dystonias, are thought to result from imbalanced activity in these pathways. Dopamine regulates movement through its differential effects on D1A receptors expressed by direct output neurons and D2 receptors expressed by indirect output neurons. To further examine the interaction of D1A and D2 neuronal pathways in the striatum, we used homologous recombination to generate mutant mice lacking functional D1A receptors (D1A-/-). D1A-/- mutants are growth retarded and die shortly after weaning age unless their diet is supplemented with hydrated food. With such treatment the mice gain weight and survive to adulthood. Neurologically, D1A-/- mice exhibit normal coordination and locomotion, although they display a significant decrease in rearing behavior. Examination of the striatum revealed changes associated with the altered phenotype of these mutants. D1A receptor binding was absent in striatal sections from D1A-/- mice. Striatal neurons normally expressing functional D1A receptors are formed and persist in adult homozygous mutants. Moreover, substance P mRNA, which is colocalized specifically in striatal neurons with D1A receptors, is expressed at a reduced level. In contrast, levels of enkephalin mRNA, which is expressed in striatal neurons with D2 receptors, are unaffected. These findings show that D1A-/- mice exhibit selective functional alterations in the striatal neurons giving rise to the direct striatal output pathway.     

Pharmacological and dietary prevention for colorectal cancer

Background

Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality. People at higher risk are those individuals with a family history of CRC and familial adenomatous polyposis. Prevention and screening are two milestones for this disease. The aim of this study is to evaluate the chemopreventive role of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclooxygenase 2 inhibitors, some micronutrients (folic acid, calcium, selenium, antioxidants) and probiotics.

Discussion

The studies on aspiring reported promising results, but it is debatable whether aspirin should be used as chemoprevention, because of its side effects and because of poor efficacy evident in subjects at high risk. Similar results were reported for other non-aspirin NSAIDs, such as sulindac and celecoxib, which the potential adverse effects limit their use. Selenium role in prevention of various types of cancer as well as in colon adenomas are often inconclusive or controversial. Several studies suggested that calcium may have a possible chemopreventive effect on colon adenomas and CRC, although contrasting results are reported for the latter. A recent meta-analysis including 13 randomized trial suggested that folic acid supplementation had not a chemiopreventive action on CRC. Several studies investigated the association between antioxidants, administered alone or in combination, and CRC risk, both among general and at risk population, but only few of them supported statistically significant results.

Conclusion

The results of this literature review showed an unclear role in CRC prevention of both pharmacological and dietary intervention. Despite several options are available to prevent colon cancer, it is challenging to identify a correct strategy to prevent CRC through pharmacological and dietary intervention due to the long latency of cancer promotion and development. Since some of the drugs investigated may have uncertain individual effects, it can be suggested to potentiate such effects by adding them together.

     

Validation of flavonoids as potential dipeptidyl peptidase III inhibitors: Experimental and computational approach

Fifteen flavonoids were studied for their inhibitory activity against human dipeptidyl peptidase III (hDPP III) combining an in vitro assay with an in silico molecular modeling study. All analyzed flavonoids showed inhibitory effects against hDPP III with the IC₅₀ values ranging from 22.0 to 437.2 μm . Our 3D QSAR studies indicate that the presence of hydrophilic regions at a flavonoid molecule increases its inhibitory activity, while the higher percentage of hydrophobic surfaces has negative impact on enzyme inhibition. Furthermore, molecular dynamics (MD) simulations of the complex of hDPP III with one of the most potent inhibitors, luteolin, were performed, and binding mode analysis revealed that the 3′ and 4′ hydroxyl group on B‐ring as well as 5 and 7 hydroxyl group on A‐ring helps luteolin to interact with the Asn391, Asn406, Tyr417, His450, Glu451, Val447, Glu512, Asn545, Gln566, and Arg572 residues. The MD results clearly provide valuable information explaining the importance of flavonoid hydroxyl groups in the mechanism for the binding pattern at the active site of hDPP III.     

Economic evaluation of Zepatier for the management of HCV in the Italian scenario

Background

Hepatitis C virus (HCV) is a major health issue worldwide. New generation of direct-active antiviral medications is an epoch-making turning point in the management of HCV infections.

Objective

Conducing a cost-effectiveness analysis comparing the combination of elbasvir/grazoprevir and sofosbuvir?+?pegylated interferon/ribavirin for the management of all HCV patients (even those in the initial stages of fibrosis).

Methods

A Markov model was built on the natural history of the disease to assess the efficacy of the alternatives. The outcomes are expressed in terms of quality adjusted life-years (QALYs) and result in terms of incremental cost-effectiveness ratio).

Results

Elbasvir/grazoprevir implies an expenditure of €21,104,253.74 with a gain of 19,287.90 QALYs and sofosbuvir?+?pegylated interferon/ribavirin implies an expenditure of €31,904,410.11 with a gain of 18,855.96 QALYs. Elbasvir/grazoprevir is thus a dominant strategy.

Conclusion

Consideration should be given to the opportunity cost of not treating patients with a lower degree of fibrosis (F0–F2).

     

3D Non-Fluoroscopic Cryoablation of Right-Sided Accessory Pathways in Children: Monocentric Study and Literature Review

Background: Cryoablation of accessory pathways (APs) is effective and very safe in children, as previously reported by our group. The aim of this retrospective study was to evaluate the current efficacy of 3D non-fluoroscopic cryoablation of right sided APs in children, comparing results obtained with the Ensite Velocity^TM and the more recent Ensite Precision^TM 3D mapping systems. Methods and Results: From January 2016 to December 2019, 102 pediatric patients [mean age 12.5 ± 2.8, 62 males (61% of total cohort)] with right APs underwent 3D non-fluoroscopic transcatheter cryoablation at our Institution. Fifteen (14.7%) patients had previously undergone catheter ablation. Acute procedural success rate was 95.1% (n = 97). No significant differences were detected in acute success rates achieved with Ensite Velocity^TM or Ensite PrecisionTM systems nor between manifest (94%) and concealed APs (100%). No permanent complications occurred. During follow-up (428 ± 286 days, median 396 days [interquartile range 179-713]), 19 patients (19.6%) had recurrences. Recurrences were more frequent for parahissian/anterior APs compared to midseptal/posterior and lateral APs (p = 0.043). Recurrences were not related to the Ensite system used. A redo ablation procedure was attempted in 13 cases, 11 cryoablation and 2 radiofrequency ablations: the former was successful in 10 cases out of 11 (90.9%). Conclusion: 3D cryoablation of right-sided APs is associated with a very high acute success rate with limited use of fluoroscopy, resulting in great benefit to the children. Recurrence rates are not high and patients can be retreated with cryo-energy with higher success rates.     

Clinical outcome of 193 extracardiac Fontan patients: the first 15 years.

OBJECTIVES: We sought to evaluate the mid-term outcome of hospital survivors with extracardiac Fontan circulation. BACKGROUND: Few data exist about the mid-term and long-term results of the extracardiac Fontan operation. METHODS: From November 1988 to November 2003, 221 patients underwent an extracardiac Fontan procedure as primary (9 patients) or secondary (212 patients) palliation, at a mean age of 72.2 months (range 13.1 to 131.3 months). A total of 165 of 193 early survivors underwent programmed noninvasive follow-up evaluations and at least one cardiac catheterization. RESULTS: The overall survival, including operative deaths, was 85% at 15 years. Freedom from late failure among hospital survivors is 92% at 15 years. A total of 127 of 165 survivors (77%) were in New York Heart Association functional class I. The incidence of late major problems was 24% (42 major problems in 36 of 165 patients): 19 patients had arrhythmias (11%), 5 patients had obstruction of the extracardiac conduit (3%) and 6 of the left pulmonary artery (3.5%), and 5 patients experienced ventricular failure (3%), leading to heart transplantation in 3 patients. Protein-losing enteropathy was found in two patients (1%). The incidence of late re-interventions was 12.7% (21 of 165 patients, including 15 epicardial pacemaker implantations). Four patients died (2.3%), two after heart transplantation. CONCLUSIONS: After 15 years of follow-up, the overall survival, the functional status, and the cardiopulmonary performance of survivors of the extracardiac Fontan procedure compare favorably with other series of patients who underwent the lateral tunnel approach. The incidence of late deaths, obstructions of the cavopulmonary pathway, re-interventions, and arrhythmias is lower than that reported late after other Fontan-type operations.     

Monitored atrial fibrillation duration predicts arterial embolic events in patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia pacemakers.

OBJECTIVES: The aim of our study was to evaluate arterial embolism (AE) occurrence rates and predictors in patients suffering from bradycardia and wearing a pacemaker with antitachycardia pacing therapies. BACKGROUND: Atrial fibrillation (AF) is associated with a high incidence of AE. METHODS: A total of 725 patients (360 men, age 71 +/- 11 years) were implanted with a DDDRP pacemaker (Medtronic AT500, Medtronic Inc., Minneapolis, Minnesota). At baseline 225 (31.0%) patients received antiplatelet therapy and 264 (36.4%) patients received anticoagulation agents. RESULTS: Over a median 22-month follow-up (25th to 75th interquartile range 16 to 30 months), AE occurred in 14 (1.9%) patients: 7 patients suffered a nonfatal ischemic stroke (0.6% per year), 4 patients had transient ischemic attack (0.34% per year), and 3 patients had embolic complications. Among baseline patients' characteristics, multivariate logistic analysis showed that embolic events are independently associated to ischemic heart disease (7.0 odds ratio [OR], 95% confidence interval [CI] 2.3 to 21.3, p = 0.001), prior embolic event (7.3 OR, 95% CI 1.2 to 43.9, p = 0.029), diabetes (5.0 OR, 95% CI 1.2 to 15.7, p = 0.032), and hypertension (4.1 OR, 95% CI 1.1 to 15.6, p = 0.036). The risk of embolism, adjusted for known risk factors, was 3.1 times increased (95% CI 1.1 to 10.5, p = 0.044) in patients with device-detected atrial fibrillation episodes longer than one day during follow-up. CONCLUSIONS: In a cohort of patients with bradycardia and AF, arterial embolism was common in patients with ischemic cardiopathy, hypertension, diabetes mellitus, and in patients with known stroke risk factors. Atrial fibrillation occurrences longer than one day were independently associated with embolic events.