Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related ...to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m
) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety.
RSNA, 2017.
The OH+ cation is a well‐known diatomic for which the triplet (3Σ−) ground state is 50.5 kcal mol−1 more stable than its corresponding singlet (1Δ) excited state. However, the singlet forms a strong ...donor–acceptor bond to argon with a bond energy of 66.4 kcal mol−1 at the CCSDT(Q)/CBS level, making the singlet ArOH+ cation 3.9 kcal mol−1 more stable than the lowest energy triplet complex. Both singlet and triplet isomers of this molecular ion were prepared in a cold molecular beam using different ion sources. Infrared photodissociation spectroscopy in combination with messenger atom tagging shows that the two spin isomers exhibit completely different spectral signatures. The ground state of ArOH+ is the predicted singlet with a covalent Ar−O bond.
Singlet and triplet ArOH+ cations were both generated in a cold molecular beam experiment and their infrared spectra were measured. The singlet displays a strong donor–acceptor‐type chemical bond, making this species the global minimum of this molecular system at the highest levels of theory.
In proximity to seismic operations, bowhead whales (Balaena mysticetus) decrease their calling rates. Here, we investigate the transition from normal calling behavior to decreased calling and ...identify two threshold levels of received sound from airgun pulses at which calling behavior changes. Data were collected in August-October 2007-2010, during the westward autumn migration in the Alaskan Beaufort Sea. Up to 40 directional acoustic recorders (DASARs) were deployed at five sites offshore of the Alaskan North Slope. Using triangulation, whale calls localized within 2 km of each DASAR were identified and tallied every 10 minutes each season, so that the detected call rate could be interpreted as the actual call production rate. Moreover, airgun pulses were identified on each DASAR, analyzed, and a cumulative sound exposure level was computed for each 10-min period each season (CSEL10-min). A Poisson regression model was used to examine the relationship between the received CSEL10-min from airguns and the number of detected bowhead calls. Calling rates increased as soon as airgun pulses were detectable, compared to calling rates in the absence of airgun pulses. After the initial increase, calling rates leveled off at a received CSEL10-min of ~94 dB re 1 μPa2-s (the lower threshold). In contrast, once CSEL10-min exceeded ~127 dB re 1 μPa2-s (the upper threshold), whale calling rates began decreasing, and when CSEL10-min values were above ~160 dB re 1 μPa2-s, the whales were virtually silent.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
Backsplash galaxies are galaxies that once resided inside a cluster, and have migrated back outside as they move towards the apocentre of their orbit. The kinematic properties of these ...galaxies are well understood, thanks to the significant study of backsplashers in dark matter-only simulations, but their intrinsic properties are not well-constrained due to modelling uncertainties in subgrid physics, ram pressure stripping, dynamical friction, and tidal forces. In this paper, we use the IllustrisTNG300-1 simulation, with a baryonic resolution of Mb ≈ 1.1 × 107 M⊙, to study backsplash galaxies around 1302 isolated galaxy clusters with mass 1013.0 < M200,mean/M⊙ < 1015.5. We employ a decision tree classifier to extract features of galaxies that make them likely to be backsplash galaxies, compared to nearby field galaxies, and find that backsplash galaxies have low gas fractions, high mass-to-light ratios, large stellar sizes, and low black hole occupation fractions. We investigate in detail the origins of these large sizes, and hypothesize their origins are linked to the tidal environments in the cluster. We show that the black hole recentring scheme employed in many cosmological simulations leads to the loss of black holes from galaxies accreted into clusters, and suggest improvements to these models. Generally, we find that backsplash galaxies are a useful population to test and understand numerical galaxy formation models due to their challenging environments and evolutionary pathways that interact with poorly constrained physics.
Phosphorothioate nucleotides have emerged as powerful pharmacological substitutes of their native phosphodiester analogs with important translational applications in antisense oligonucleotide (ASO) ...therapeutics and cyclic dinucleotide (CDN) synthesis. Stereocontrolled installation of this chiral motif has long been hampered by the systemic use of phosphorus(III) P(III)-based reagent systems as the sole practical means of oligonucleotide assembly. A fundamentally different approach is described herein: the invention of a P(V)-based reagent platform for programmable, traceless, diastereoselective phosphorus-sulfur incorporation. The power of this reagent system is demonstrated through the robust and stereocontrolled synthesis of various nucleotidic architectures, including ASOs and CDNs, via an efficient, inexpensive, and operationally simple protocol.
Huntington disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. Although the length of this repeat is inversely correlated with age of onset (AOO), it does not fully explain ...the variability in AOO. We assessed the sequence downstream of the CAG repeat in HTT reference: (CAG)n-CAA-CAG, since variants within this region have been previously described, but no study of AOO has been performed. These analyses identified a variant that results in complete loss of interrupting (LOI) adenine nucleotides in this region (CAG)n-CAG-CAG. Analysis of multiple HD pedigrees showed that this LOI variant is associated with dramatically earlier AOO (average of 25 years) despite the same polyglutamine length as in individuals with the interrupting penultimate CAA codon. This LOI allele is particularly frequent in persons with reduced penetrance alleles who manifest with HD and increases the likelihood of presenting clinically with HD with a CAG of 36–39 repeats. Further, we show that the LOI variant is associated with increased somatic repeat instability, highlighting this as a significant driver of this effect. These findings indicate that the number of uninterrupted CAG repeats, which is lengthened by the LOI, is the most significant contributor to AOO of HD and is more significant than polyglutamine length, which is not altered in these individuals. In addition, we identified another variant in this region, where the CAA-CAG sequence is duplicated, which was associated with later AOO. Identification of these cis-acting modifiers have potentially important implications for genetic counselling in HD-affected families.
This study determines the extent of deposition in gadolinium-based contrast agent–exposed pediatric population and whether prior observations were related to age-dependent breakdown of the blood ...blood-brain barrier.
PURPOSETo evaluate the safety and effectiveness of the LipiFlow System compared to the iHeat Warm Compress (WC) for adults with meibomian gland dysfunction (MGD).
METHODSThis was a non-significant ...risk, prospective, open-label, randomized, crossover multicenter clinical trial. One hundred thirty-nine subjects were randomized between LipiFlow (n=69) and WC control (n=70). Subjects in the LipiFlow group received a 12-minute LipiFlow treatment and were reexamined at 1 day, 2 weeks and 4 weeks. Control subjects received a 5-minute iHeat treatment with instructions to perform the same treatment daily for 2 weeks. At 2 weeks, they crossed over (LipiFlow Crossover) and received the LipiFlow treatment. Effectiveness parametersmeibomian gland (MG) assessment, tear break-up time (TBUT) and dry eye symptoms. Safety parametersadverse events, ocular health exam, ocular surface staining, intraocular pressure, visual acuity and discomfort.
RESULTSLipiFlow resulted in significant improvement (P < 0.05) in MG secretion at 2 and 4 weeks (mean ± standard deviation at baseline = 6.3 ± 3.5; 2 weeks = 14.3 ± 8.7; 4 weeks = 16.7 ± 8.7); and TBUT at 2 and 4 weeks(at baseline = 5.5 ± 2.9; 2 weeks = 6.9 ± 5.0; 4 weeks = 7.4 ± 5.5). There was no significant change in MG secretion or TBUT in the control group. LipiFlow resulted in a greater significant reduction in dry eye symptoms than the iHeat WC. The crossover group demonstrated similar significant improvement 2 weeks post-treatment with the LipiFlow. There was no significant difference between groups in the incidence of non-serious, device-related adverse events.
CONCLUSIONThe LipiFlow System was significantly more effective than iHeat WC. These results support its safety and effectiveness in the treatment of MGD and dry eye symptoms.
Fish are the most diverse and widely distributed vertebrates, yet little is known about the microbial ecology of fishes nor the biological and environmental factors that influence fish microbiota. To ...identify factors that explain microbial diversity patterns in a geographical subset of marine fish, we analyzed the microbiota (gill tissue, skin mucus, midgut digesta and hindgut digesta) from 101 species of Southern California marine fishes, spanning 22 orders, 55 families and 83 genera, representing ~25% of local marine fish diversity. We compare alpha, beta and gamma diversity while establishing a method to estimate microbial biomass associated with these host surfaces. We show that body site is the strongest driver of microbial diversity while microbial biomass and diversity is lowest in the gill of larger, pelagic fishes. Patterns of phylosymbiosis are observed across the gill, skin and hindgut. In a quantitative synthesis of vertebrate hindguts (569 species), we also show that mammals have the highest gamma diversity when controlling for host species number while fishes have the highest percent of unique microbial taxa. The composite dataset will be useful to vertebrate microbiota researchers and fish biologists interested in microbial ecology, with applications in aquaculture and fisheries management.
Since the inception of the Canadian Cardiovascular Society heart failure (HF) guidelines in 2006, much has changed in the care for patients with HF. Over the past decade, the HF Guidelines Committee ...has published regular updates. However, because of the major changes that have occurred, the Guidelines Committee believes that a comprehensive reassessment of the HF management recommendations is presently needed, with a view to producing a full and complete set of updated guidelines. The primary and secondary Canadian Cardiovascular Society HF panel members as well as external experts have reviewed clinically relevant literature to provide guidance for the practicing clinician. The 2017 HF guidelines provide updated guidance on the diagnosis and management (self-care, pharmacologic, nonpharmacologic, device, and referral) that should aid in day-to-day decisions for caring for patients with HF. Among specific issues covered are risk scores, the differences in management for HF with preserved vs reduced ejection fraction, exercise and rehabilitation, implantable devices, revascularization, right ventricular dysfunction, anemia, and iron deficiency, cardiorenal syndrome, sleep apnea, cardiomyopathies, HF in pregnancy, cardio-oncology, and myocarditis. We devoted attention to strategies and treatments to prevent HF, to the organization of HF care, comorbidity management, as well as practical issues around the timing of referral and follow-up care. Recognition and treatment of advanced HF is another important aspect of this update, including how to select advanced therapies as well as end of life considerations. Finally, we acknowledge the remaining gaps in evidence that need to be filled by future research.
Depuis la parution des Lignes directrices sur l’insuffisance cardiaque (IC) de la Société canadienne de cardiologie en 2006, les soins aux patients atteints de ce trouble ont connu d’importants changements. Au cours de la dernière décennie, le Comité des lignes directrices sur l’IC a publié des mises à jour périodiques. Toutefois, en raison des changements importants qui sont survenus, le Comité des lignes directrices a jugé qu’il était nécessaire de procéder à une réévaluation exhaustive des recommandations sur la prise en charge de l’IC afin de produire un ensemble complet de lignes directrices à jour. Les membres des comités primaire et secondaire sur l’IC de la Société canadienne de cardiologie, ainsi que des spécialistes externes, ont passé en revue la littérature pertinente afin d’indiquer aux cliniciens la marche à suivre. Les lignes directrices de 2017 donnent des indications sur le diagnostic et la prise en charge (autosoins, traitements pharmacologiques et non pharmacologiques, dispositifs et orientation des patients) destinées à faciliter la prise de décisions quotidiennes en matière de soins aux patients atteints d’IC. Parmi les questions abordées figurent notamment les cotes de risque, les différences de prise en charge selon qu’il s’agit d’IC à fraction d’éjection préservée ou réduite, l’activité physique et la réadaptation, les dispositifs implantables, la revascularisation, la dysfonction ventriculaire droite, l’anémie et la carence en fer, le syndrome cardiorénal, l’apnée du sommeil, les cardiomyopathies, l’IC pendant la grossesse, la cardio-oncologie et la myocardite. Le comité a apporté une attention particulière aux stratégies et aux traitements visant à prévenir l’IC, à l’organisation des soins aux patients atteints d’IC, à la prise en charge des comorbidités, ainsi qu’à des questions pratiques concernant les délais d’orientation du patient et les soins de suivi. La reconnaissance et le traitement de l’IC au stade avancé, et notamment le choix des thérapies à ce stade et les considérations en matière de fin de vie, représentent un autre aspect important de cette mise à jour. Enfin, le comité reconnaît les lacunes dans les données probantes qui subsistent et devront être comblées par les recherches futures.