Search

Background: Across the nation, growing numbers of individuals are exploring the use of cannabis for medical or recreational purposes, and the proportion of cannabis-positive drivers involved in fatal crashes increased from 8 percent in 2013 to 17 percent in 2014, raising concerns about the impact of cannabis use on driving. Previous studies have demonstrated that cannabis use is associated with impaired driving performance, but thus far, research has primarily focused on the effects of acute intoxication., Methods: The current study assessed the potential impact of cannabis use on driving performance using a customized driving simulator in non-intoxicated, heavy, recreational cannabis users and healthy controls (HCs) without a history of cannabis use., Results: Overall, cannabis users demonstrated impaired driving relative to HC participants with increased accidents, speed, and lateral movement, and reduced rule-following. Interestingly, however, when cannabis users were divided into groups based on age of onset of regular cannabis use, significant driving impairment was detected and completely localized to those with early onset (onset before age 16) relative to the late onset group (onset ≥16 years old). Further, covariate analyses suggest that impulsivity had a significant impact on performance differences., Conclusions: Chronic, heavy, recreational cannabis use was associated with worse driving performance in non-intoxicated drivers, and earlier onset of use was associated with greater impairment. These results may be related to other factors associated with early exposure such as increased impulsivity., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Visual processing and attention deficits are responsible for a substantial portion of the disability caused by schizophrenia, but the source of these deficits remains unclear. In 35 schizophrenia patients (SzP) and 34 healthy controls (HC), we used a rapid serial visual presentation (RSVP) visual search task designed to activate/deactivate the cortical components of the attentional control system (i.e. the dorsal and ventral attention networks, lateral prefrontal regions in the frontoparietal network, and cingulo-opercular/salience networks), along with resting state functional connectivity, to examine the integrity of these components. While we find that behavioral performance and activation/deactivation of the RSVP task are largely similar between groups, SzP exhibited decreased functional connectivity within late visual components and between prefrontal and other components. We also find that performance correlates with the deactivation of the ventral attention network in SzP only. This relationship is mediated by the functional connectivity of critical components of the attentional control system. In summary, our results suggest that the attentional control system is potentially used to compensate for visual cortex deficits. Furthermore, prefrontal deficits in SzP may interfere with this compensatory use of the attentional control system. In addition to highlighting focal deficits and potential compensatory mechanisms in visual processing and attention, our findings point to the attentional control system as a potential target for rehabilitation and neuromodulation-based treatments for visual processing deficits in SzP., Competing Interests: Declaration of Competing Interest GHP receives income and equity from Pfizer, Inc through family; DCJ has equity interest in Glytech, AASI, and NeuroRx. He serves on the board of Promentis. He holds intellectual property rights for the use of NMDAR agonists in the treatment of schizophrenia, NMDAR antagonists in the treatment of depression and PTSD, and has submitted disclosures for fMRI-based prediction of ECT and TMS response, and EEG-based diagnosis of neuropsychiatric disorders. Within the past 2 years, he has received consulting payments/honoraria from Cadence, Biogen, SK Life Science, Autifony, Glytech and Boehringer Ingelheim.  SCA, DRB, ECJ, RTS, NES, and CCK reported no biomedical financial interests or potential conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Predictors of risk of lethal arrhythmic events (LAE) is poorly understood and may differ from adults in children with hypertrophic cardiomyopathy (HCM)., Objective: The purpose of this study was to determine predictors of LAE in children with HCM., Methods: A retrospective data collection was performed on 446 children and teenagers 20 years and younger (290 [65%] male; mean age 10.1 ± 5.7 years) with idiopathic HCM from 35 centers. Patients were classified as group 1 (HCM with LAE) if having a secondary prevention implantable cardioverter-defibrillator (ICD) or primary prevention ICD with appropriate interventions or group 2 (HCM without LAE) if having a primary prevention ICD without appropriate interventions., Results: There were 152 children (34%) in group 1 and 294 (66%) in group 2. Risk factors for group 1 by univariate analysis were septal thickness, posterior left ventricular (LV) wall thickness, lower LV outflow gradient, and Q wave > 3 mm in inferior electrocardiographic leads. Factors not associated with LAE were family history of SCD, abnormal blood pressure response to exercise, and ventricular tachycardia on ambulatory electrocardiographic monitoring. Risk factors for SCD by multivariate analysis were age at ICD placement (hazard ratio [HR] 0.9; P = .0025), LV posterior wall thickness z score (HR 1.02; P < .005), and LV outflow gradient < 30 mm Hg (HR 2.0; P < .006). LV posterior wall thickness z score ≥ 5 was associated with LAE., Conclusion: Risk factors for LAE appear different in children compared to adults. Conventional adult risk factors were not significant in children. Further prospective studies are needed to improve risk stratification for LAE in children with HCM., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Autofluorescence is the emission of light by naturally occurring tissue components on the absorption of incident light. Autofluorescence within the eye is associated with several disorders, such as Age-related Macular Degeneration (AMD) which is a leading cause of central vision loss. Its pathogenesis is incompletely understood, but endogenous fluorophores in retinal tissue might play a role. Hyperspectral fluorescence microscopy of ex-vivo retinal tissue can be used to determine the fluorescence emission spectra of these fluorophores. Comparisons of spectra in healthy and diseased tissues can provide important insights into the pathogenesis of AMD. However, the spectrum from each pixel of the hyperspectral image is a superposition of spectra from multiple overlapping tissue components. As spectra cannot be negative, there is a need for a non-negative blind source separation model to isolate individual spectra. We propose a tensor formulation by leveraging multiple excitation wavelengths to excite the tissue sample. Arranging images from different excitation wavelengths as a tensor, a non-negative tensor decomposition can be performed to recover a provably unique low-rank model with factors representing emission and excitation spectra of these materials and corresponding abundance maps of autofluorescent substances in the tissue sample. We iteratively impute missing values common in fluorescence measurements using Expectation-Maximization and use L 2 regularization to reduce ill-posedness. Further, we present a framework for performing group hypothesis testing on hyperspectral images, finding significant differences in spectra between AMD and control groups in the peripheral macula. In the absence of ground truth, i.e. molecular identification of fluorophores, we provide a rigorous validation of chosen methods on both synthetic and real images where fluorescence spectra are known. These methodologies can be applied to the study of other pathologies presenting autofluorescence that can be captured by hyperspectral imaging., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Cannabis concentrates, including dabs, contain extremely high levels of Δ 9 -tetrahydrocannabinol (THC). Although these products appear to be gaining popularity among recreational cannabis consumers, little data exists regarding concentrate use in the US. We conducted a national web-based survey to examine patterns of concentrate use, specifically dabbing., Methods: 4077 respondents completed a survey designed to assess the use of conventional flower cannabis relative to dabs. Individuals provided information about frequency and magnitude of use, and also completed the Marijuana Motives Measure and Severity of Dependence Scale to examine whether dab users have different motives for use and/or demonstrate more severe consequences of use compared to those who only use conventional flower products., Results: 58% of respondents reported they had tried dabs at least once and 36.5% endorsed regular use (once a month or more). Those who use regularly use dabs were significantly more likely to report using for experimentation (feeling "curious") relative to reasons for using conventional flower products. Interestingly, motives reflecting positive effects (i.e., coping, sleep problems, relieving social anxiety) were endorsed more highly for flower use. In addition, regular dab users reported being more worried about their use of cannabis products relative to those who had tried dabs but did not use regularly., Conclusions: Results indicate that cannabis consumers do not necessarily choose dabs over flower products for positive effects, but rather appear to choose these highly potent products for experimentation. As concentrate use may lead to increased cannabis-related problems, studies directly assessing concentrate users are needed., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate whether the 2 subtypes of advanced age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) segregate separately in families and to identify which genetic variants are associated with these 2 subtypes., Design: Sibling correlation study and genome-wide association study (GWAS)., Participants: For the sibling correlation study, 209 sibling pairs with advanced AMD were included. For the GWAS, 2594 participants with advanced AMD subtypes and 4134 controls were included. Replication cohorts included 5383 advanced AMD participants and 15 240 controls., Methods: Participants had the AMD grade assigned based on fundus photography, examination, or both. To determine heritability of advanced AMD subtypes, a sibling correlation study was performed. For the GWAS, genome-wide genotyping was conducted and 6 036 699 single nucleotide polymorphisms (SNPs) were imputed. Then, the SNPs were analyzed with a generalized linear model controlling for genotyping platform and genetic ancestry. The most significant associations were evaluated in independent cohorts., Main Outcome Measures: Concordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes., Results: The difference between the observed and expected proportion of siblings concordant for the same subtype of advanced AMD was different to a statistically significant degree (P = 4.2 × 10(-5)), meaning that in siblings of probands with CNV or GA, the same advanced subtype is more likely to develop. In the analysis comparing participants with CNV to those with GA, a statistically significant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3 × 10(-9)), which was confirmed in the replication samples (OR, 1.38; P = 7.4 × 10(-14) for combined discovery and replication analysis)., Conclusions: Whether CNV versus GA develops in a patient with AMD is determined in part by genetic variation. In this large GWAS meta-analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD subtypes, but imparts greater risk for CNV than for GA. This locus explains a small proportion of the excess sibling correlation for advanced AMD subtype. Other loci were detected with suggestive associations that differ for advanced AMD subtypes and deserve follow-up in additional studies., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the risk of progression to advanced age-related macular degeneration (AMD) conferred by reticular pseudodrusen (RPD), an imaging presentation of reticular macular disease (RMD), in high-risk fellow eyes of subjects with AMD and unilateral choroidal neovascularization (CNV) in a large, prospective study., Design: Cohort study., Participants: Two hundred seventy-one subjects with AMD; 94 with RPD and 177 without RPD., Methods: Images from a cohort of 271 subjects with AMD in the Nutritional AMD treatment phase II (NAT 2) Study, a 3-year prospective study of subjects with unilateral CNV and large soft drusen in the fellow eye, were studied. The fellow eye, at high risk for advanced AMD developing, was the study eye. There were 5 visits per subject. Imaging at each visit consisted of color, red-free, and blue-light photography and fluorescein angiography. The images were analyzed for the presence of RPD, following disease progression throughout the 3-year study., Main Outcome Measures: The development of advanced AMD (CNV or geographic atrophy)., Results: For the 271 subjects who completed the full 3-year study, there was a significantly higher rate of advanced AMD (56% or 53/94) in fellow eyes with RPD at any visit compared with eyes without RPD (32% or 56/177; P < 0.0001, chi-square test; relative risk [RR], 1.8; 95% confidence interval [CI], 1.4-2.4). The chance of developing advanced AMD in the fellow eye in women with RPD (66%) was more than double that of women without RPD (30%; P < 0.00001; RR, 2.2; 95% CI, 1.6-3.1)., Conclusions: To the authors' knowledge, this is the first comprehensive prospective study of RMD, a distinct clinical phenotype of AMD that includes RPD. It provides strong confirmation that RMD, a disease entity with stereotypical presentations across imaging methods, is associated with a high risk of progression to advanced AMD, perhaps on an inflammatory or vascular basis. Reticular macular disease deserves wider recognition and consideration by clinicians caring for patients with AMD., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the association between variants in the complement component 5 (C5) gene and age-related macular degeneration (AMD)., Design: Separate and combined data from 3 large AMD case-control studies and a prospective population-based study (The Rotterdam Study)., Participants: A total of 2599 AMD cases and 3458 ethnically matched controls., Methods: Fifteen single nucleotide polymorphisms (SNPs) spanning the C5 gene were initially genotyped in 375 cases and 199 controls from The Netherlands (The Amsterdam/Rotterdam-Netherlands [AMRO-NL] study population). Replication testing of selected SNPs was performed in the Rotterdam Study (NL) and study populations from Southampton, United Kingdom (UK), and New York, United States (US)., Main Outcome Measures: Early and late stages of prevalent and incident AMD, graded according to (a modification of) the international grading and classification system of AMD., Results: Significant allelic or genotypic associations between 8 C5 SNPs and AMD were found in the AMRO-NL study and this risk seemed to be independent of CFH Y402H, LOC387715 A69S, age, and gender. None of these findings could be confirmed consistently in 3 replication populations., Conclusions: Although the complement pathway, including C5, plays a crucial role in AMD, and the C5 protein is present in drusen, no consistent significant associations between C5 SNPs and AMD were found in any of these studies. The implications for genetic screening of AMD are discussed., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

In in vivo tolerance induction, the dose of tolerogen injected is generally linearly correlated to the length of tolerance induced. Small, medium and large doses are related to no, partial and long-term tolerance, respectively. However, even with injection of substantially large doses of tolerogen, the length of tolerance induced varies over a wide range. Most of the recipients can still reject donor grafts. In this study, it is shown that the linear dose-response can be altered into an all or nothing response in a H-Y antigen-specific TCR transgenic (Tg) mouse model. In thymectomized female Tg mice, injection of 3, 30 and 100 x 10(6) male spleen cells was correlated to no, partial and massive deletion of Tg (alpha T beta T) CD8 cells, respectively. When the thymectomized Tg mice were injected with 9 x 10(6) T cell-enriched (T+) male cells, one half of the recipients showed no deletion of alpha T beta T cells, and in the other half massive deletion occurred. In complete correlation with deletion, all male skin grafts were rejected in the undeleted group as PBS-injected controls, whereas with massive deletion they were indefinitely tolerized. Thus, partial deletion and partial tolerance can be avoided. Injection of 18 x 10(6) male T+ cells induced long-term tolerance in all the recipients. The all or none T cell deletion and long-term tolerance induction has not only significant implications in understanding the mechanism of peripheral tolerance induction, but also in tolerance induction in transplantation, gene therapy and the prevention and treatment of autoimmune diseases.

Mice carrying a rearranged TCR Vbeta 8.2 transgene express the Vbeta protein on the vast majority of peripheral T-cells. The bone marrow and peripheral blood, as well as other lymphoid organs of both untreated animals and animals depleted of T-cells by neonatal thymectomy and/or injection from birth of monoclonal anti-TCR antibodies, contain a small population of cells that express low levels of the Vbeta transgene product, but no T-cell or other detectable lineage-specific phenotypic markers. When such TG-bearing BM cells are purified and injected directly into the non-TG thymus, they show the phenotypic maturation sequences of intrathymic T-cell development and, subsequently, mature TG-bearing peripheral T-cells. However, this population failed to support long-term recovery from lethal irradiation. Both Vbeta 8.2 TG and CD3delta mRNA transcripts are strongly expressed in the cell population, but no CD3gamma, CD3epsilon, CD3zeta, CD4, CD8beta, pre-Talpha, or RAG-1 transcript was detected. The transgene-encoded TCR component is not bound to the cell membrane exclusively by a phosphatidylinositol linkage. The data show that the fully rearranged TCR transgene and transcripts for at least one of the associated CD3 components, CD3delta, can be expressed on a subpopulation of BM and PBL cells that has not passed through the thymus. The phenotypic characteristics of this cell population resemble those described for the earliest thymocyte described by others. The TG protein molecule in this model may provide a specific developmental marker for a prothymocyte lineage subset that lacks pluripotential properties., (Copyright 1997 Academic Press.)

Dual-cement resins are composite resins that are both light activated and chemically cured. They can be cured completely with a visible light source or by the catalyst and base reaction of the material. With the control of setting time, dual cements appear to offer clinicians advantages in orthodontic bonding. The purposes of the present research are to compare various dual cements in regard to orthodontic bonding and to evaluate them in relation to currently used chemically cured and light-cured composite resins for bonding stainless steel mesh-backed orthodontic brackets. Seven currently available orthodontic bonding systems (three light cured and four chemically cured) and three dual cements were evaluated. Each of the 10 groups contained 15 noncarious mandibular incisors. Mandibular incisor brackets were bonded to the teeth in accordance with the manufacturer's recommendation. After bonding, the teeth were stored for 5 days in water at 37 degrees C. An Instron machine (Instron Corp., Canton, Mass.) was used to test samples. All samples were compared with Concise orthodontic bonding composite (3M, St. Paul, Minn.). The results of this investigation show that it is possible to bond solid, mesh-backed metal orthodontic brackets to teeth with a dual cement. The shear bond strengths of the dual cements, as tested in the laboratory, should be adequate to withstand normal orthodontic forces. Increased control of the setting time of the dual cements will allow the clinician more time to correctly position brackets and to remove excess resin before curing. In addition, the clinician can be assured of complete polymerization with the chemical properties of the dual cement resins.

The distribution of fluorescein between the anterior chamber and the anterior vitreous was measured in two groups of patients after oral administration: group I, extracapsular cataract extraction (ECCE) patients with intact capsule and posterior chamber intraocular lens (PC IOL) (n = 12); group II, intracapsular cataract extraction (ICCE) patients with anterior chamber IOL (AC IOL) (n = 13). The fluorescein concentrations were measured by fluorophotometry and the penetration ratios were calculated. The penetration of fluorescein into the anterior vitreous was significantly less in the ECCE group (group I, penetration ratio = 2.03 +/- 1.00 X 10(-3) min-1; group II, penetration ratio = 5.99 +/- 4.89, X 10(-3) min-1, P less than 0.01). The authors concluded that in ECCE versus ICCE a significantly smaller proportion of fluorescein is found in the anterior vitreous relative to the aqueous after passage through the blood-aqueous barrier. This suggests a barrier to posterior movement of other molecules that may initially gain access to the eye in the anterior segment (e.g., prostaglandins).

Of 175 patients treated surgically for potentially lethal or refractory cardiac tachyarrhythmias, 53 underwent mapping and definitive operation using cryoablative techniques as the primary or adjunctive method. Included were 16 patients with supraventricular tachycardia caused by accessory pathways (Kent bundle) in the right anterior or posterior paraseptal location. Cryoablation was successful in abolishing tachycardia in 93.7% (15 of 16). Six patients (100%) with permanent junctional reciprocating tachycardia were cured by cryoablation. Eighteen of 19 patients with atrial ectopic tachycardia were treated by cryoablation alone or in combination with excision of the atrial appendage, with success in 15 (83.3%). Five of these were left atrial foci cured by cryoablation. Fourteen right atrial foci were treated by excision of the appendage only (1 patient), excision of the appendage and local cryoablation (8 patients), and cryoablation alone (5 patients). Three of these underwent partial (2 patients) or complete (1 patient) atrial disconnection after excisional and cryoablative techniques failed to control the tachycardia. Multiple ectopic atrial foci were common (9 patients), and successful cryoablation was accomplished in 100% of the patients with a single atrial ectopic focus (10 patients) but in only 66% of those with multiple foci. Thirteen of 19 infants with critical ventricular tachycardia were treated by cryoablation at the site of the ectopic focus, either alone or in combination with excision of the area. Elimination of tachycardia was accomplished in 13 patients (100%). Myocardial hamartoma (Purkinje cell tumor) was the histological diagnosis in 11 of the infants with ventricular tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Pars plana vitrectomy can be combined with injection of fluorosilicone oil to treat complex retinal detachments. We describe three cases to illustrate the technique, which is adapted according to the type and location of the retinal breaks.

Although the technique of performing invasive electrophysiologic studies is similar in children and adults, the indications, interpretation, and management based on the studies are different. The major indications in children are determination of the specific diagnosis of an unknown arrhythmia and mapping prior to surgical treatment; chronic drug studies are performed for severely symptomatic patients, but technical considerations in the child limit the routine use of repeated drug trials. The greatest potential indication for invasive studies is in prognostication of symptomatic arrhythmias; this has not been possible in sinus node dysfunction and AV block, and the role in ventricular arrhythmias is under investigation. In the area of therapeutics, although drugs may have a similar effect in adults and children, the mechanism for the underlying arrhythmias may differ. The ventricular arrhythmias after congenital heart disease may have as their underlying cause the hypertrophic ventricle, not the pediatric substrate. Thus, some of the investigations originally performed in children eventually may contribute to a better understanding of arrhythmias in patients of all ages.

An enzyme-linked immunosorbent assay (ELISA) using murine spermatozoa and thymocytes is described for the detection of anti-H-Y antibodies. ELISA is more sensitive and reproducible than cytotoxicity and the PA-SRBC test. It is particularly useful for the rapid screening of a large number of samples.

We investigated the retinal toxicity of various combinations of four antiviral agents in intravitreal injection and vitrectomy infusion solutions in the rabbit. The nontoxic concentration of each individual agent for intravitreal injection and for vitrectomy infusion has previously been described. Our results support the concept that concentrations of 200 micrograms/0.1 mL of trifluridine, 400 micrograms/0.1 mL of hydroxyacyclovir, 200 micrograms/0.1 mL of acyclovir and 30 micrograms/0.1 mL of vidarabine can be combined for intravitreal injection without toxic retinal effects. Moreover, 60 micrograms/mL of trifluridine, 20 micrograms/mL of hydroxyacyclovir, 40 micrograms/mL of acyclovir and 8 micrograms/mL of vidarabine can be combined in vitrectomy infusion solutions without retinal damage. Further study is needed to determine the full potential of such combinations.

A method of curing light-cured composite resins by transillumination to cement acid-etched fixed partial dentures was adapted to bond solid mesh-backed lingual orthodontic brackets. Results of this investigation showed that the bond strengths of the orthodontic brackets bonded with light-cured composite resins were significantly less (P less than 0.05) than the bond strengths of the orthodontic brackets cemented with traditional adhesives and orthodontic composite resins. Notwithstanding, the bond strengths achieved with the transilluminated light-cured composite resins should be adequate to withstand the forces of mastication and orthodontic movements. There was no correlation of bond strengths of the brackets cemented with the transilluminated light-cured composite resins when compared to the faciolingual widths of the teeth.

The in vitro mitogenic effects of endotoxin (LPS), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and staphylococcal enterotoxin B (SEB) on mouse spleen cells were studied by light and electron microscopy. By light microscopy, LPS was found to "transform" a culture largely composed of small lymphocytes into "large lymphocytes" which did not synthesize DNA and into blast cells which did synthesize DNA. The blast cells were morphologically similar to those transformed by PHA, PWM and SEB. By electron microscopy, a large percentage of the endotoxin-transformed cells developed extensive dilated rough ER. Their appearance was similar to that reported by others for cells stimulated by PWM, but in our hands the development of rough ER was more conspicuous in LPS-stimulated cells. In contrast, PHA and SEB produced few blast cells which contained significant rough ER. The morphologic observations are consistent with the hypothesis that the mitogenic effect of endotoxin is on bone-marrow-derived lymphocytes. This effect may relate to the known adjuvant effect of endotoxin in vivo.