Outcomes Among Diabetic Patients Undergoing Percutaneous Coronary Intervention With Contemporary Drug-Eluting Stents: Analysis From the BIONICS Randomized Trial

Objectives

The authors sought to investigate the impact of diabetes mellitus (DM) on outcomes following contemporary drug-eluting stent (DES) implantation in the BIONICS (BioNIR Ridaforolimus Eluting Coronary Stent System in Coronary Stenosis) trial.

Convection‐Enhanced Drug Delivery to the Brain: Therapeutic Potential and Neuropathological Considerations

Convection‐enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods—bypass of the blood–brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease. Substantial research effort has been dedicated to optimize the technology for CED and identify the parameters, which govern successful drug distribution. It seems likely that successful clinical translation of CED will depend on suitable catheter technology being used in combination with drugs with optimal physicochemical characteristics, and on neuropathological analysis in appropriate preclinical models. In this review, we consider the factors most likely to influence the success or failure of CED, and review its application to the treatment of high‐grade glioma, Parkinson's disease (PD) and Alzheimer's disease (AD).     

Changes in physical activity,diet, and body weight across the education and employment transitions of early adulthood: A systematic review and meta‐analysis

Early adulthood is a time when individuals go through important life transitions, such as moving from high school into higher education or employment, but the impact of these life transitions on changes in body weight, diet, and physical activity is not known. We searched six electronic databases to July 2019 for longitudinal observational studies providing data on adiposity, diet, and/or physical activity across education or employment transitions in young people aged between 15 and 35 years. We found 19 studies, of which 17 assessed changes in physical activity, three body weight, and five diet or eating behaviours. Meta‐analysis (n=9) found that leaving high school was associated with a decrease of ?7.04 (95% CI, ?11.26, ?2.82) min/day of moderate‐to‐vigorous physical activity. Three studies reported increases in body weight on leaving high school. A small number of studies suggested decreases in diet quality on leaving high school (n=2/4 papers) and leaving university (n=1) but not on starting employment (n=1). Studies suggested no change in physical activity on leaving university (n=4) but decreases in physical activity on starting employment (n=2/3). The transition of leaving high school is an important time to support individuals to prevent decreases in physical activity and gains in body weight.     

Coenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetes

Aims/hypothesis  

An increase in the production of reactive oxygen species is commonly thought to contribute to the development of diabetic cardiomyopathy. This study aimed to assess whether administration of the antioxidant coenzyme Q₁₀ would protect the diabetic heart against dysfunction and remodelling, using the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the efficacy of coenzyme Q₁₀ to that of the ACE inhibitor ramipril.     

Association of vitamin D receptor gene polymorphisms with insulin resistance and response to vitamin D

The objectives of the study were to determine associations between single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene and insulin resistance and the effects of these SNPs on changes in insulin sensitivity in response to vitamin D supplementation. The research described here was an extension of the Surya study. Genotyping of the Cdx-2, FokI, BsmI, ApaI, and TaqI SNPs was carried out on 239 South Asian women in New Zealand using polymerase chain reaction-based techniques. Associations of these genotypes and 3' end haplotypes with insulin resistance were determined using multiple regression analysis. Associations between SNP genotypes and responses in insulin sensitivity to vitamin D supplementation (4000 IU vitamin D(3) per day) were also determined for a subset (81) of these women. BsmI BB, ApaI AA, and TaqI tt genotypes were significantly associated with lower insulin resistance compared with BsmI bb, ApaI aa, and TaqI TT, respectively, in the cohort of 239 women. Furthermore, homozygosity of the haplotypes baT and BAt was associated with higher and lower insulin resistance, respectively, compared with no copies of their respective alleles. Of the 81 subjects who were supplemented with vitamin D, women with the FokI Ff genotype showed a significantly greater improvement in insulin sensitivity (increase of 29.4 [2.9, 38.1]) compared with women with the FokI FF genotype (increase of 2.3 [-11.5, 10.1]). This study has highlighted the association of vitamin D responsiveness and insulin resistance with VDR gene polymorphisms. This is the first study to determine associations between all three. Genotyping of the VDR gene may provide a predictive measure for insulin resistance in response to vitamin D intervention.     

Association between smoking and outcomes in older adults with atrial fibrillation

Tobacco smoking is a risk factor for atrial fibrillation (AF), but little is known about the impact of smoking in patients with AF. Of the 4060 patients with recurrent AF in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 496 (12%) reported having smoked during the past two years. Propensity scores for smoking were estimated for each of the 4060 patients using a multivariable logistic regression model and were used to assemble a matched cohort of 487 pairs of smokers and nonsmokers, who were balanced on 46 baseline characteristics. Cox and logistic regression models were used to estimate the associations of smoking with all-cause mortality and all-cause hospitalization, respectively, during over 5 years of follow-up. Matched participants had a mean age of 70 ± 9 years (± S.D.), 39% were women, and 11% were non-white. All-cause mortality occurred in 21% and 16% of matched smokers and nonsmokers, respectively (when smokers were compared with nonsmokers, hazard ratio=HR=1.35; 95% confidence interval=95%CI=1.01-1.81; p=0.046). Unadjusted, multivariable-adjusted and propensity-adjusted HR (95% CI) for all-cause mortality associated with smoking in the pre-match cohort were: 1.40 (1.13-1.72; p=0.002), 1.45 (1.16-1.81; p=0.001), and 1.39 (1.12-1.74; p=0.003), respectively. Smoking had no association with all-cause hospitalization (when smokers were compared with nonsmokers, odds ratio=OR=1.21; 95%CI=0.94-1.57, p=0.146). Among patients with AF, a recent history of smoking was associated with an increased risk of all-cause mortality, but had no association with all-cause hospitalization.     

Sensitivity and Specificity of MMPI-2 Validity Scales and Indicators to Malingered Neurocognitive Dysfunction in Traumatic Brain Injury

The present study used a known-groups design to determine the classification accuracy of 10 MMPI-2 validity scales and indicators in the detection of cognitive malingering in traumatic brain injury. Participants were 259 traumatic brain injury and 133 general clinical patients seen for neuropsychological evaluation. The TBI patients were subdivided into groups based on a comprehensive examination of effort following Slick, Sherman, and Iverson's (1999 Slick , D. J. , Sherman , E. M. S. , & Iverson , G. L. ( 1999 ). Diagnostic criteria for malingering neurocognitive dysfunction: Proposed standards for clinical practice and research . The Clinical Neuropsychologist , 13 , 545 – 561 . [INFOTRIEVE] [CSA] [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]) criteria. More extreme scores demonstrated excellent specificity; often impressive sensitivity was seen even while maintaining a low false positive error rate. Specificity was good even in stroke, memory disorder, and psychiatric patients without incentive. The results of this study are presented in frequency tables that can be easily referenced in clinical practice.     

Development of polymorphic microsatellite markers for the North American porcupine, Erethizon dorsatum, using paired-end Illumina sequencing

We isolated and characterized a total of 19 microsatellite loci from the North American porcupine, Erethizon dorsatum. Loci were screened in 22 individuals from St. Lawrence and Franklin Counties in northern New York State. The number of alleles per locus ranged from 4 to 14, observed heterozygosity ranged from 0.316 to 1.000, and the probability of identity values ranged from 0.028 to 0.243. These new loci will provide tools for examination of the effects of habitat fragmentation, for instance by roads and other infrastructure, on gene flow and population subdivision in this species.     

Human tooth germ stem cell response to calcium-silicate based endodontic cements

Objective

The aim of this study was to compare the cytotoxic effects of endodontic cements on human tooth germ stem cells (hTGSCs). MTA Fillapex, a mineral trioxide aggregate (MTA)-based, salicylate resin containing root canal sealer, was compared with iRoot SP, a bioceramic sealer, and AH Plus Jet, an epoxy resin-based root canal sealer.

Material and Methods

To evaluate cytotoxicity, all materials were packed into Teflon rings (4 mmµ3 mm) and co-cultured with hTGSCs with the aid of 24-well Transwell permeable supports, which had a pore size of 0.4 µm. Coverslips were coated with MTA Fillapex, iRoot SP and AH Plus Jet and each coverslip was placed onto the bottom of one well of a six-well plate for scanning electron microscopy (SEM) analysis. Before the cytotoxicity and SEM analysis, all samples were stored at 37ºC and at 95% humidity and 5% CO₂ for 24 hours to set. The cellular viability was analyzed using MTS test (3-(4,5-dimethyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium). The cytotoxic effects and SEM visualization of the tested materials were analyzed at 24-hour, 72-hour, one-week and two-week periods.

Results

On the 1^st day, only MTA Fillapex caused cytotoxicity compared to negative control (NC) group (p<0.008). No significant difference was observed between the other tested materials at this period (p>0.05). After 14 days of incubation with the test materials, MTA Fillapex exhibited significantly higher cytotoxicity compared with iRoot SP, AH Plus Jet and the NC group (P<0.008). In the SEM analysis, the highest levels of cell attachment were observed for iRoot SP and the control group. After 24 hours, MTA Fillapex reduced the number of cells attached to the surface.

Conclusions

Within the limitations of this study, sealers exerted different cytotoxic effects on hTGSCs. Although all materials have exerted cellular toxicity, iRoot SP and AH Plus Jet may promote better attachment to hTGSCs.     

Feasibility of using multivector impedance to monitor pulmonary congestion in heart failure patients

Purpose

Pulmonary edema (PE) is associated with fluid accumulation in the lungs. Device-based impedance measurements have been used to detect fluid overload prior to hospitalization. However, studies have reported a high false positive rate (FPR). The objective of this study was to develop and test a new multivector impedance-based algorithm that reliably tracks PE clinical events.

Methods

We enrolled patients with implanted CRT-Ds in 23 US centers within 2 weeks of device implant. Six-vector impedance data was collected automatically by the CRT-Ds every 30 min during emergency department visits/hospitalizations and every 2 h at all other times. Detection algorithms for cardiac resynchronization therapy defibrillator (CRT-D) and implantable cardiac defibrillator (ICD) devices were developed using those impedance vectors that would be available in corresponding devices and retrospectively evaluated.

Results

There were 75 patients (69 % male), mean age 66?±?12 years, with a LVEF of 23?±?6 % and QRS of 149?±?25 ms. Twenty-one major clinical events occurred over 8.2?±?2.6 months of follow-up time. CRT-D vector combinations resulted in a sensitivity of 71.4 % (95 % confidence interval 47.8–88.7) and a FPR of 0.56 (0.30–0.94) false positives per patient-year (FPs/pt-yr); ICD vector combinations resulted in a sensitivity of 61.9 % (38.4–81.9) and a FPR of 0.63 (0.36–0.90) FPs/pt-yr. In comparison, the single-vector RVCoil-Can implementation of this algorithm resulted in a sensitivity of 57.1 % (34.0–78.2) and a FPR of 0.74 (0.44–1.12) FPs/pt-yr.

Conclusions

This multivector impedance algorithm was effective in tracking PE clinical events in this patient population. Additional studies are needed to prospectively evaluate the performance of this algorithm in a larger population.