Influence of carbonated acid beverage on fracture resistance and marginal gap formation in different restorative approaches to non-carious cervical lesions.

OBJECTIVE: This study is to evaluate fracture resistance, failure mode, and gap formation at the restorative interface of unrestored or restored non-carious cervical lesions (NCCLs) submitted to a short-term erosive environment. MATERIALS AND METHODS: Artificial NCCLs were produced in vitro in bovine incisors, and were randomly divided into four restorative resins groups (n = 22): nanohybrid-NR; bulk-fill-BR; flow with a nanohybrid layer-FNR; bulk-fill with a nanohybrid layer-BNR; and a group unrestored-UR (n = 16). Half of the specimens were submitted to an erosive challenge (per 5 min, 3 × a day for 7 days, before and after restoration), and the other half, was immersed in artificial saliva. After, all teeth undergone thermal (5 ºC, 37 ºC, and 55 ºC, 3600 cycles) and mechanical (50 N, 2 Hz, 300,000 cycles) aging. Eighty teeth were subjected to compressive loading, and resistance and failures were analyzed, while 24 teeth were evaluated for gaps by microcomputed tomography. Statistical tests were performed (p < 0.05). RESULTS: The restorative approaches affected fracture resistance (η2p = 0.14, p = 0.023), and gap formation (η2 = 0.18, p = 0.012) and so did the immersion medium (fracture η2p = 0.09, p = 0.008; gap η2 = 0.09, p = 0.017). BNR showed the highest resistance, while UR the lowest. FNR showed the highest gaps in both immersion media. Neither the resin groups nor the immersion media were associated with failure mode. CONCLUSIONS: The erosive immersion medium based in acid beverages has been shown to affect NCCLs with or without restoration, but when Bulk-Fill resin is covered by nanohybrid resin, the performance is good. CLINICAL RELEVANCE: Erosion negatively affects restorations, but unrestored NCCL shows worse biomechanical performance in stress-bearing situations.

Proteomics Reveals mRNA Regulation and the Action of Annexins in Thyroid Cancer.

Differentiated thyroid cancer is the most common malignancy of the endocrine system. Although most thyroid nodules are benign, given the high incidence of thyroid nodules in the population, it is important to understand the differences between benign and malignant thyroid cancer and the molecular alterations associated with malignancy to improve detection and signal potential diagnostic, prognostic, and therapeutic targets. Proteomics analysis of benign and malignant human thyroid tissue largely revealed changes indicating modifications in RNA regulation, a common cancer characteristic. In addition, changes in the immune system and cell membrane/endocytic processes were also suggested to be involved. Annexin A1 was considered a potential malignancy biomarker and, similarly to other annexins, it was found to increase in the malignant group. Furthermore, a bioinformatics approach points to the transcription factor Sp1 as being potentially involved in most of the alterations seen in the malignant thyroid nodules.

Peptidomics Unveils Distinct Acetylation Patterns of Histone and Annexin A1 in Differentiated Thyroid Cancer.

Thyroid cancer is a common malignancy of the endocrine system. Nodules are routinely evaluated for malignancy risk by fine needle aspiration biopsy (FNAB), and in cases such as follicular lesions, differential diagnosis between benign and malignant nodules is highly uncertain. Therefore, the discovery of new biomarkers for this disease could be helpful in improving diagnostic accuracy. Thyroid nodule biopsies were subjected to a precipitation step with both the insoluble and supernatant fractions subjected to proteome and peptidome profiling. Proteomic analysis identified annexin A1 as a potential biomarker of thyroid cancer malignancy, with its levels increased in malignant samples. Also upregulated were the acetylated peptides of annexin A1, revealed by the peptidome analysis of the supernatant fraction. In addition, supernatant peptidomic analysis revealed a number of acetylated histone peptides that were significantly elevated in the malignant group, suggesting higher gene transcription activity in malignant tissue. Two of these peptides were found to be robust malignancy predictors, with an area under the receiver operating a characteristic curve (ROC AUC) above 0.95. Thus, this combination of proteomics and peptidomics analyses improved the detection of malignant lesions and also provided new evidence linking thyroid cancer development to heightened transcription activity. This study demonstrates the importance of peptidomic profiling in complementing traditional proteomics approaches.

Effect of different materials for conventional and 3D-printed models on the mechanical properties of ethylene-vinyl acetate utilized for fabricating custom-fit mouthguards.

BACKGROUND/AIM: The interaction between the ethylene-vinyl acetate (EVA) with distinct materials utilized for obtaining dental models can affect the performance of resulting mouthguards. This study attempted to evaluate the effect of different materials for conventional (dental stone) or 3D-printed (resin) models on EVA's physical and mechanical properties and surface characteristics. MATERIAL AND METHODS: EVA sheets (Bioart) were laminated over four model types: GIV, conventional Type IV dental stone model (Zhermak); ReG, resin-reinforced Type IV dental stone model (Zero Stone); 3DnT, 3D resin printed model (Anycubic) without surface treatment; 3DT, 3D-printed model (Anycubic) with water-soluble gel (KY Jelly Lubricant, Johnson & Johnson) coating during post-curing process. The EVA specimens were cut following the ISO 37-II standard (n = 30). Shore A hardness was measured before and after plasticization on the contact (internal) or opposite (external) surfaces with the model. The breaking force (F, N), elongation (EL, mm), and ultimate tensile strength (UTS, MPa) were measured using a universal testing machine. Macro-photography and scanning electron microscopy were adopted for classifying the EVA surface alteration. Data were analyzed by one-way ANOVA with repeated measures, followed by Tukey's test (α = .05). RESULTS: Plasticization significantly decreased Shore A values for the tested EVA regardless of the model type (p < .001). Higher F, El, and UTS values were verified for the EVA with 3DT and GIV models compared to ReG and 3DnT (p < .001). 3DnT models resulted in severe surface alteration and a greater reduction of the mechanical properties of the EVA. CONCLUSION: The interaction of EVA with 3D resin-printed models without surface treatment or resin-reinforced Type IV dental stone models significantly affected the physical and mechanical properties of this material. The utilization of water-soluble gel coating during the post-curing process of 3D resin printed models improved the mechanical properties of the EVA, similarly when this material was plasticized over conventional Type IV dental stone model.

Platinum(II) and Copper(II) complexes of asymmetric halogen-substituted [NN'O] ligands: Synthesis, characterization, structural investigations and antiproliferative activity.

In order to better understand the effect of structure, halogen substitution, metal ions and ligand flexibility on antiproliferative activity, eight Cu(II) complexes and eight Pt(II) complexes were obtained of 2,4-X1,X2-6-((pyridine-2-ylmethylamino)methyl)phenol and 2,4-X1,X2-6-((pyridine-2-ylmethylamino)ethyl)phenol (where X is Cl, Br, or I) ligands. The compounds were characterized with various techniques, such as FT-IR, NMR, elemental analysis and single-crystal X-ray diffraction (SCXRD). The X-ray structures showed that ligand acts as a bidentate and tridentate donor in Cu(II) and Pt(II) complexes, respectively. This difference in structures is due to the use or non-use of base in the preparation of complexes. Also, complexation of Cl2-H2L1 with CuCl2·2H2O gives two different types of structures: polymer (Cl2-H2L1-Cupolymer) and dimer (Cl2-H2L1-Cudimer), according to the crystal color. In addition, 1H NMR spectrum for platinum complexes display two set of signals that can be attributed to the presence of two isomers in solution. All complexes induced moderate to high reduction in A2780 and HCT116 cancer cell viability. However, only complexes bearing iodo- substituted in ligands exhibited significantly low cytotoxicity in normal fibroblasts when compared with cancer cell lines. The antiproliferative effect exhibited by I2-H2L2-Cu complex in A2780 cell line was due to induction of cell death mechanisms, namely by apoptosis and autophagy. I2-H2L2-Cu complex does not cause DNA cleavage but a slight delay in cell cycle was observed for the first 24 h of exposition. High cytotoxicity was related with the induction of intracellular ROS. This increase in intracellular ROS was not accompanied by destabilization of the mitochondrial membrane which is an indication that ROS are being triggered externally by I2-H2L2-Cu complex and in agreement with an extrinsic apoptosis activation. I2-H2L2-Cu complex has a pro-angiogenic effect, increasing the vascularization of the CAM in chicken embryos. This is also a very important characteristic in cancer treatment since the increased vascularization in tumors might facilitate the delivery of therapeutic drugs. Taken together, these results support the potential therapeutic of the I2-H2L2-Cu complex.

Malignancy risk of thyroid nodules: quality assessment of the thyroid ultrasound report.

BACKGROUND: Thyroid nodules are a challenge in clinical practice and thyroid ultrasonography is essential for assessing the risk of malignancy. The use of ultrasound-based malignancy risk classification systems has been recommended by several scientific societies but radiologist's adherence to these guidelines may vary. The authors aimed to analyze the quality of the information provided by the thyroid ultrasound report, to assess the malignancy risk of thyroid nodules, in Portugal. METHODS: Multicenter and retrospective study, conducted in three of the five Portuguese NUTS2 corresponding to about 88.3% of the mainland population. We included 344 consecutive unselected participants aged ≥ 18 years who underwent thyroid ultrasonography in 2019. The description of six features of the dominant thyroid nodule was analyzed: maximum size, shape, margins, composition, echogenicity and echogenic foci. A utility score, including these six features, was used as an indicator of the report's quality. A score of 4 was considered as a minimum value. RESULTS: Maximum diameter was reported for all nodules. Shape, margins, composition, echogenicity and echogenic foci were reported in 8.1%, 25.0%, 76.5%, 53.2% and 20.9%, respectively. Only 21.8% of the nodules had a score ≥ 4. At least one of four suspicious features, including marked hypoechogenicity, microcalcifications, irregular margins and non-oval shape, was identified in 8.7% of the nodules. Cervical lymph nodes' status was reported in 93% of the exams. The risk category was only reported in 7.8% of the participants. CONCLUSION: The adherence of Portuguese radiologists to a standardized reporting model and to an ultrasound-based malignancy risk stratification system is still low and has implications for the correct characterization of the malignancy risk of nodules and the decision to perform fine-needle aspiration biopsy.

Human umbilical cord tissue-derived mesenchymal stromal cells as adjuvant therapy for myocardial infarction: a review of current evidence focusing on pre-clinical large animal models and early human trials.

Although biologically appealing, the concept of tissue regeneration underlying first- and second-generation cell therapies has failed to translate into consistent results in clinical trials. Several types of cells from different origins have been tested in pre-clinical models and in patients with acute myocardial infarction (AMI). Mesenchymal stromal cells (MSCs) have gained attention because of their potential for immune modulation and ability to promote endogenous tissue repair, mainly through their secretome. MSCs can be easily obtained from several human tissues, the umbilical cord being the most abundant source, and further expanded in culture, making them attractive as an allogeneic "of-the-shelf" cell product, suitable for the AMI setting. The available evidence concerning umbilical cord-derived MSCs in AMI is reviewed, focusing on large animal pre-clinical studies and early human trials. Molecular and cellular mechanisms as well as current limitations and possible translational solutions are also discussed.

Surgical versus transcatheter aortic valve replacement in low-risk patients: A long-term propensity score-matched analysis.

BACKGROUND: Recent studies suggest the use of transcatheter aortic valve implantation (TAVI) as an alternative to surgical aortic valve replacement (SAVR) in lower risk populations, but real-world data are scarce. METHODS: Single-center retrospective study of patients undergoing SAVR (between June 2009 and July 2016, n = 682 patients) or TAVI (between June 2009 and July 2017, n = 400 patients). Low surgical risk was defined as EuroSCORE II (ES II) < 4% for single noncoronary artery bypass graft procedure. TAVI patients were propensity score-matched in a 1:1 ratio with SAVR patients, paired by age, New York Heart Association class, diabetes mellitus, chronic obstructive pulmonary disease, atrial fibrillation, creatinine clearance, and left ventricular ejection fraction < 50%. RESULTS: A total of 158 patients (79 SAVR and 79 TAVI) were matched (mean age 79 ± 6 years, 79 men). TAVI patients had a higher incidence of permanent pacemaker implantation (0% vs. 19%, p < 0.001) and more than mild paravalvular leak (4% vs. 18%, p = 0.009), but comparable rates of stroke, major or life-threatening bleeding, emergent cardiac surgery, new-onset atrial fibrillation, and need for renal replacement therapy. Hospital length-of-stay and 30-day mortality were similar. At a median follow-up of 4.5 years (IQR 3.0-6.9), treatment strategy did not influence all-cause mortality (HR 1.19, 95% CI 0.77-1.83, log rank p = 0.43) nor rehospitalization (crude subdistribution HR 1.56, 95% CI 0.71-3.41, p = 0.26). ES II remained the only independent predictor of long-term all-cause mortality (adjusted HR 1.40, 95% CI 1.04-1.90, p = 0.029). CONCLUSION: In this low surgical risk severe aortic stenosis population, we observed similar rates of 30-day and long-term all-cause mortality, despite higher rates of permanent pacemaker implantation and more than mild paravalvular leak in TAVI patients. The results of this small study suggest that both procedures are safe and effective in the short-term, while the Heart Team remains essential to assess both options on the long-term.

In Vitro and In Vivo Effect of Palladacycles: Targeting A2780 Ovarian Carcinoma Cells and Modulation of Angiogenesis.

Palladacycles are versatile organometallic compounds that show potential for therapeutic use. Here are described the synthesis and characterization of mono- and dinuclear palladacycles bearing diphosphines. Their biological effect was investigated in A2780, an ovarian-derived cancer line, and in normal dermal fibroblasts. The compounds displayed selective cytotoxicity toward the A2780 cell line. Compound 3 decreased the cell viability through cell cycle retention in G0/G1, triggered apoptosis through the intrinsic pathway, and induced autophagy in A2780 cells. Compound 9 also induced cell cycle retention, apoptosis, and cellular detachment. Notably, compound 9 induced the production of intracellular reactive oxygen species (ROS). Our work demonstrated that compound 3 enters A2780 cells via active transport, which requires energy, while compound 9 enters A2780 cells mostly passively. The potential effect of palladacycles in angiogenesis was investigated for the first time in an in vivo chorioallantoic membrane model, showing that while compound 3 displayed an antiangiogenic effect crucial to fighting cancer progression, compound 9 promoted angiogenesis. These results show that palladacycles may be used in different clinical applications where pro- or antiangiogenic effects may be desirable.

Exploiting the antiproliferative potential of spiropyrazoline oxindoles in a human ovarian cancer cell line.

Cancer is still one of the deadliest diseases worldwide despite the efforts in its early detection and treatment strategies. However, most chemotherapeutic agents still present side effects in normal tissues and acquired resistance that limit their efficacy. Spiropyrazoline oxindoles might be good alternatives as they have shown antiproliferative activity in human breast and colon cancer cell lines, without eliciting cytotoxicity in healthy cells. However, their potential for ovarian cancer was never tested. In this work, the antiproliferative activity of five spiropyrazoline oxindoles was assessed in ovarian cancer cells A2780 and the biological targets and mechanism of action of the most promising compound evaluated. Compound 1a showed the highest antiproliferative effect, as well as the highest selectivity for A2780 cells compared to healthy fibroblasts. This antiproliferative effect results from the induction of cell death by mitochondria-mediated apoptosis and autophagy. In vitro DNA interaction studies demonstrated that 1a interacts with DNA by groove-binding, without triggering genotoxicity. In addition, 1a showed a strong affinity to bovine serum albumin that might be important for further inclusion in drug delivery platforms. Proteomic studies reinforced 1a role in promoting A2780 endoplasmatic reticulum (ER) stress by destabilizing the correct protein folding which triggers cell death via apoptosis and autophagy.

Influence of material and loading location on stress distribution of inlays.

PURPOSE: To evaluate the stress distribution of inlays fabricated with restorative materials of different elastic moduli under two functional loading conditions by using three-dimensional (3D) finite element analysis (FEA) models of a second maxillary premolar. METHODS: A 3D model of a sound maxillary left second premolar and its supporting bone was generated in a previous study and reutilized under permission of the authors for the present study. Inlay models obtained from the sound tooth were then assigned according to the type and inherent elastic modulus of the restorative material used, as follows: microhybrid composite (Filtek Z250); indirect resin composite (Paradigm); lithium disilicate reinforced glass ceramic (IPS e.max Press); and type III gold alloy. The geometric models were then exported for 3D FEA. All materials were considered isotropic, homogeneous, and linear-elastic. A static load of 100 N was applied in two conditions: axially at both cusps (axial loading) and at the mesial marginal ridge (proximal loading). Maximum principal and von Mises stresses were used to analyze the stress distribution pattern in inlays and sound premolar models. RESULTS: Under axial loading condition, either resin composite, ceramic or type III gold alloy inlays generated a similar biomechanical behavior, especially in terms of stress distribution in the remaining tooth structure and cusp deflection. However, higher tensile stresses were observed along the proximal gingival margin of the preparation under proximal loading in the Z250 and Paradigm models, as well as a greater cusp deflection. In contrast, a deflection like the sound model was observed in the ceramic and gold inlay models. CLINICAL SIGNIFICANCE: Restorative materials with higher elastic modulus, such as dental ceramics and type III gold alloys, seem to be the best choice for maxillary premolars restored with inlays in the presence of occlusal contact on the marginal ridge.

Vanadium(IV) Complexes with Methyl-Substituted 8-Hydroxyquinolines: Catalytic Potential in the Oxidation of Hydrocarbons and Alcohols with Peroxides and Biological Activity.

Methyl-substituted 8-hydroxyquinolines (Hquin) were successfully used to synthetize five-coordinated oxovanadium(IV) complexes: [VO(2,6-(Me)2-quin)2] (1), [VO(2,5-(Me)2-quin)2] (2) and [VO(2-Me-quin)2] (3). Complexes 1-3 demonstrated high catalytic activity in the oxidation of hydrocarbons with H2O2 in acetonitrile at 50 °C, in the presence of 2-pyrazinecarboxylic acid (PCA) as a cocatalyst. The maximum yield of cyclohexane oxidation products attained was 48%, which is high in the case of the oxidation of saturated hydrocarbons. The reaction leads to the formation of a mixture of cyclohexyl hydroperoxide, cyclohexanol and cyclohexanone. When triphenylphosphine is added, cyclohexyl hydroperoxide is completely converted to cyclohexanol. Consideration of the regio- and bond-selectivity in the oxidation of n-heptane and methylcyclohexane, respectively, indicates that the oxidation proceeds with the participation of free hydroxyl radicals. The complexes show moderate activity in the oxidation of alcohols. Complexes 1 and 2 reduce the viability of colorectal (HCT116) and ovarian (A2780) carcinoma cell lines and of normal dermal fibroblasts without showing a specific selectivity for cancer cell lines. Complex 3 on the other hand, shows a higher cytotoxicity in a colorectal carcinoma cell line (HCT116), a lower cytotoxicity towards normal dermal fibroblasts and no effect in an ovarian carcinoma cell line (order of magnitude HCT116 > fibroblasts > A2780).

The Potential of Metabolomics in the Diagnosis of Thyroid Cancer.

Thyroid cancer is the most common endocrine system malignancy. However, there is still a lack of reliable and specific markers for the detection and staging of this disease. Fine needle aspiration biopsy is the current gold standard for diagnosis of thyroid cancer, but drawbacks to this technique include indeterminate results or an inability to discriminate different carcinomas, thereby requiring additional surgical procedures to obtain a final diagnosis. It is, therefore, necessary to seek more reliable markers to complement and improve current methods. "Omics" approaches have gained much attention in the last decade in the field of biomarker discovery for diagnostic and prognostic characterisation of various pathophysiological conditions. Metabolomics, in particular, has the potential to identify molecular markers of thyroid cancer and identify novel metabolic profiles of the disease, which can, in turn, help in the classification of pathological conditions and lead to a more personalised therapy, assisting in the diagnosis and in the prediction of cancer behaviour. This review considers the current results in thyroid cancer biomarker research with a focus on metabolomics.

Vitamin D, parathyroid hormone and metabolic syndrome - the PORMETS study.

BACKGROUND: Vitamin D (VitD) and parathyroid hormone (PTH) play important roles in calcium metabolism and skeletal homeostasis. Estimates of the VitD status in several European countries show large variations between them. In addition, no national population-based estimate has been published. VitD and PTH may also play important roles in cardiovascular risk, which has been suggested to be associated with metabolic syndrome (MetS) and is very prevalent in Portugal. The goal of our study was to evaluate the prevalence of hypovitaminosis D and its determinants as well as PTH serum level determinants and associations of the 25-hydroxyvitamin D and PTH serum levels with MetS and its individual components in a sample of the Portuguese mainland population. METHODS: PORMETS is a national cross-sectional study that includes a total sample of 4095 adults. A subsample, including 500 participants, was randomly selected for the present study. A structured questionnaire was administered to collect information on personal medical histories and socio-demographic and behavioral characteristics. Blood pressure and anthropometrics measurements were performed. Fasting venous samples were collected and PTH and 25-hydroxyvitamin D were measured. VitD adequacy was classified according to the Institute of Medicine, and MetS was classified according to the Joint Interim Statement recommendations. Multiple linear regression and unconditional logistic regression models were used to estimate the associations between the levels of PTH and 25-hydroxyvitamin D and with MetS and its individual components. RESULTS: The prevalence of VitD deficiency was 37.7%, and MetS was present in 191 participants (38.4%). The serum PTH levels showed a positive association (OR: 1.014; 95%CI: 1.002, 1.026) with the waist circumference component of MetS. The serum 25-hydroxyvitamin D levels were negatively associated with MetS (OR: 0.957; 95%CI: 0.922, 0.993) as well as with its blood pressure (OR: 0.949; 95%CI: 0.912, 0.987) and triglycerides (OR: 0.930; 95%CI: 0.892, 0.969) components. CONCLUSION: This study showed a high national prevalence of hypovitaminosis D. The PTH levels showed a significant positive association with the WC component of MetS, and the VitD levels were negatively associated with the BP and triglycerides components as well as with the MetS.

The prevalence of the metabolic syndrome in Portugal: the PORMETS study.

BACKGROUND: The PORMETS study was designed to estimate the prevalence of metabolic syndrome and its determinants in the overall and administrative regions of the Portuguese mainland. METHODS: A cross-sectional study of a representative sample of non-institutionalized Portuguese adults selected from primary health care centres lists including 1695 men and 2309 women was conducted from February 2007 to July 2009. A structured questionnaire was administered, collecting information on personal medical history and socio-demographic and behavioural characteristics. Anthropometrics, blood pressure, and venous blood samples were obtained. Metabolic syndrome was defined according to three operational definitions. The prevalence ratios and their respective 95% confidence intervals were calculated using binomial generalized linear regression, with the log link function. RESULTS: The prevalence rates of metabolic syndrome in this sample of Portuguese adults were 36.5%, 49.6%, and 43.1%, using the Adult Treatment Panel III, International Diabetes Federation and Joint Interim Statement definitions, respectively. The most prevalent feature of metabolic syndrome in this sample was high blood pressure (64.3%) and the lowest was high fasting glucose (24.9%). After adjustment for age and gender, significant differences were observed for the 18 districts of the Portugal mainland. Additionally, metabolic syndrome was significantly more frequent in non-urban areas than in urban ones (p = 0.001). The prevalence of metabolic syndrome was significantly higher in women (p˂0.001) and older participants (p˂0.001), as well as in those who reported being housewives (p = 0.010), retired (p = 0.046) or unemployed (p = 0.024). CONCLUSIONS: This study showed that metabolic syndrome is highly prevalent in the Portuguese adult population. Regional differences in the prevalence of this syndrome were observed, and this condition was more common in non-urban areas and less favoured socio-economic categories.

Tumor Microenvironment Modulation via Gold Nanoparticles Targeting Malicious Exosomes: Implications for Cancer Diagnostics and Therapy.

Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes' release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs' properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs' role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression.

Safety and Long-Term Outcomes of Catheter Ablation of Atrial Fibrillation Using Magnetic Navigation versus Manual Conventional Ablation: A Propensity-Score Analysis.

INTRODUCTION: Whether or not the potential advantages of using a magnetic navigation system (MNS) translate into improved outcomes in patients undergoing atrial fibrillation (AF) ablation is a question that remains unanswered. METHODS AND RESULTS: In this observational registry study, we used propensity-score matching to compare the outcomes of patients with symptomatic drug-refractory AF who underwent catheter ablation using MNS with the outcomes of those who underwent catheter ablation using conventional manual navigation. Among 1,035 eligible patients, 287 patients in each group had similar propensity scores and were included in the analysis. The primary efficacy outcome was the rate of AF relapse after a 3-month blanking period. At a mean follow-up of 2.6 ± 1.5 years, AF ablation with MNS was associated with a similar risk of AF relapse as compared with manual navigation (18.4% per year and 22.3% per year, respectively; hazard ratio 0.81, 95% CI 0.63-1.05; P = 0.108). Major complications occurred in two patients (0.7%) using MNS, and in six patients (2.1%) undergoing manually navigated ablation (P = 0.286). Fluoroscopy times were 21 ± 10 minutes in the manual navigation group, and 12 ± 9 minutes in the MNS group (P < 0.001), whereas total procedure times were 152 ± 52 minutes and 213 ± 58 minutes, respectively (P < 0.001). CONCLUSIONS: In this propensity-score matched comparison, magnetic navigation and conventional manual AF ablations seem to have similar relapse rates and a similar risk of complications. AF ablations with magnetic navigation take longer to perform but expose patients to significantly shorter fluoroscopy times.

Neurologic complications after transradial or transfemoral approach for diagnostic and interventional cardiac catheterization: A propensity score analysis of 16,710 cases from a single centre prospective registry.

BACKGROUND AND AIM: Transradial approach (TRA) is being used increasingly as the preferential vascular access site for both diagnostic and interventional procedures. However, concerns have risen about the risk of clinically meaningful neurologic complications. We aimed to assess the association between the risk of stroke/transient ischemic attack (TIA) and the transradial (vs. transfemoral) approach. METHODS AND RESULTS: Data from 16,710 cases included in a single centre prospective registry between January 2006 and November 2012 was analyzed. Radial procedures were considered as those in which the radial access was used either primarily (n = 4,195) or after conversion (n = 36). Potential cases with neurologic events were targeted by cross-referencing patients who underwent both cardiac catheterization and cranial-computed tomography (cranial-CT) during the same admission episode (n = 67). Procedure-related events were defined as a definitive non-CABG related stroke/TIA occurring within 48 hr of the procedure. TRA increased from 0.7% in 2006 to 75% in 2012. Total incidence of stroke/TIA was 0.16% and did not change over the study period (P = 0.26). There was no significant difference in stroke/TIA rates between groups (0.165% vs. 0.160%; P = 1.0). After correction for baseline differences and propensity score matching, TRA was not an independent predictor of stroke/TIA (OR 1.21; 95% CI 0.49-2.98 and 1.3; 95% CI 0.55-3.54, respectively). Results were consistent in pre-specified sub-groups according to age (≥65 y.o. vs. younger), gender, interventional vs. diagnostic and ACS vs. stable. CONCLUSION: Rates of documented stroke/TIA were low. Our observational study suggests that widening the use of the TRA is not associated with an increased risk of clinically relevant procedure-related neurologic complications.

Effect of joint design and welding type on the flexural strength and weld penetration of Ti-6Al-4V alloy bars.

STATEMENT OF PROBLEM: Framework longevity is a key factor for the success of complete-arch prostheses and commonly depends on the welding methods. However, no consensus has been reached on the joint design and welding type for improving framework resistance. PURPOSE: The purpose of this study was to assess the effect of different joint designs and welding methods with tungsten inert gas (TIG) or laser to join titanium alloy bars (Ti-6Al-4V). MATERIAL AND METHODS: Seventy titanium alloy bar specimens were prepared (3.18 mm in diameter × 40.0 mm in length) and divided into 7 groups (n=10): the C-control group consisting of intact specimens without joints and the remaining 6 groups consisting of specimens sectioned perpendicular to the long-axis and rejoined using an I-, X30-, or X45-shaped joint design with TIG welding (TI, TX30, and TX45) or laser welding (LI, LX30, and LX45). The specimens were tested with 3-point bending. The fracture surfaces were first evaluated with stereomicroscopy to measure the weld penetration area and then analyzed with scanning electron microscopy (SEM). The data were statistically analyzed with 2-way ANOVA and the Tukey post hoc test, 1-way ANOVA and the Dunnett test, and the Pearson correlation test (α=.05). RESULTS: Specimens from the X30 and X45 groups showed higher flexural strength (P<.05) and welded area (P<.05) than specimens from the I groups, regardless of the welding type. TIG welded groups showed significantly higher flexural strength than the laser groups (P<.05), regardless of the joint design. TIG welding also resulted in higher welded areas than laser welding for the I-shaped specimens. No significant differences were found for the weld penetration area in the X45 group, either for laser or TIG welding. SEM analysis showed more pores at the fracture surfaces of the laser specimens. Fracture surfaces indicative of regions of increased ductility were detected for the TIG specimens. CONCLUSIONS: TIG welding resulted in higher flexural strength for the joined titanium specimens than laser welding. For both welding methods, X30- and X45-shaped joint designs resulted in higher flexural strength and welding penetration than the I-shaped joint design.

Heterocyclic Anticancer Compounds: Recent Advances and the Paradigm Shift towards the Use of Nanomedicine's Tool Box.

The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles.