The efficient delivery of nanomaterials to specific targets for in vivo biomedical imaging is hindered by rapid sequestration by the reticuloendothelial system (RES) and consequent short circulation ...times. To overcome these two problems, we have prepared a new stealth PEG polymer conjugate containing a terminal 1,1-bisphosphonate (BP) group for strong and stable binding to the surface of ultrasmall-superparamagnetic oxide nanomaterials (USPIOs). This polymer, PEG(5)-BP, can be used to exchange the hydrophobic surfactants commonly used in the synthesis of USPIOs very efficiently and at room temperature using a simple method in 1 h. The resulting nanoparticles, PEG(5)-BP-USPIOs are stable in water or saline for at least 7 months and display a near-zero ζ-potential at neutral pH. The longitudinal (r 1) and transverse (r 2) relaxivities were measured at a clinically relevant magnetic field (3 T), revealing a high r 1 of 9.5 mM–1 s–1 and low r 2/r 1 ratio of 2.97, making these USPIOs attractive as T1-weighted MRI contrast agents at high magnetic fields. The strong T1-effect was demonstrated in vivo, revealing that PEG(5)-BP-USPIOs remain in the bloodstream and enhance its signal 6-fold, allowing the visualization of blood vessels and vascular organs with high spatial definition. Furthermore, the optimal relaxivity properties allow us to inject a dose 4 times lower than with other USPIOs. PEG(5)-BP-USPIOs can also be labeled using a radiolabeled-BP for visualization with single photon emission computed tomography (SPECT), and thus affording dual-modality contrast. The SPECT studies confirmed low RES uptake and long blood circulation times (t 1/2 = 2.97 h). These results demonstrate the potential of PEG(5)-BP-USPIOs for the development of targeted multimodal imaging agents for molecular imaging.
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IJS, KILJ, NUK, PNG, UL, UM
What factors influence mucocele recurrence? Himelfarb, Melissa; Britt, Michael C.; Flanagan, Sarah ...
Oral surgery, oral medicine, oral pathology and oral radiology,
20/May , Volume:
137, Issue:
5
Journal Article
Peer reviewed
The purpose of this study was to identify whether age is associated with mucocele recurrence after excision.
This retrospective cohort study consisted of 492 patients who underwent oral mucocele ...excision at Boston Children's Hospital from 2010 to 2022. Fisher's exact tests were used to assess the association between age and mucocele recurrence. An adjusted logistic regression model was run to evaluate the effect of age on mucocele recurrence while controlling for confounders. A P value < .05 was considered significant.
Mucocele recurrence was observed in 24 cases (4.9%). There was a significant association between age and mucocele recurrence (2.2% for <7 years vs. 2.9% for 7 to <13 years vs. 9.2% for 13 to <18 years vs. 8.9% for >18 years; P = .005). Sex; history of behavioral disorders; mucocele size, duration, and location; suture technique; and type of anesthesia were not significantly associated with recurrence (P > .135). An adjusted logistic regression model verified a significant association between age and mucocele recurrence (odds ratio, 1.053; 95% confidence interval, 1.019-1.088; P = .035).
Mucocele recurrence occurs infrequently in patients younger than 7 years and is most prevalent in the teenage to young adult patient population. For every year increase in age, the odds of mucocele recurrence increase by 5.3%.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Contamination of their carrion food supply with the non-steroidal anti-inflammatory drug diclofenac has caused rapid population declines across the Indian subcontinent of three species of Gyps ...vultures endemic to South Asia. The governments of India, Pakistan and Nepal took action in 2006 to prevent the veterinary use of diclofenac on domesticated livestock, the route by which contamination occurs. We analyse data from three surveys of the prevalence and concentration of diclofenac residues in carcasses of domesticated ungulates in India, carried out before and after the implementation of a ban on veterinary use. There was little change in the prevalence and concentration of diclofenac between a survey before the ban and one conducted soon after its implementation, with the percentage of carcasses containing diclofenac in these surveys estimated at 10.8 and 10.7%, respectively. However, both the prevalence and concentration of diclofenac had fallen markedly 7-31 months after the implementation of the ban, with the true prevalence in this third survey estimated at 6.5%. Modelling of the impact of this reduction in diclofenac on the expected rate of decline of the oriental white-backed vulture (Gyps bengalensis) in India indicates that the decline rate has decreased to 40% of the rate before the ban, but is still likely to be rapid (about 18% year(-1)). Hence, further efforts to remove diclofenac from vulture food are still needed if the future recovery or successful reintroduction of vultures is to be feasible.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The role of ecological theory in microbial ecology Prosser, James I; Bohannan, Brendan J. M; Curtis, Tom P ...
Nature reviews. Microbiology,
200705, 2007-May, 2007-5-00, 20070501, Volume:
5, Issue:
5
Journal Article
Peer reviewed
Open access
Microbial ecology is currently undergoing a revolution, with repercussions spreading throughout microbiology, ecology and ecosystem science. The rapid accumulation of molecular data is uncovering ...vast diversity, abundant uncultivated microbial groups and novel microbial functions. This accumulation of data requires the application of theory to provide organization, structure, mechanistic insight and, ultimately, predictive power that is of practical value, but the application of theory in microbial ecology is currently very limited. Here we argue that the full potential of the ongoing revolution will not be realized if research is not directed and driven by theory, and that the generality of established ecological theory must be tested using microbial systems.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Materials that combine magnetic order with other desirable physical attributes could find transformative applications in spintronics, quantum sensing, low-density magnets and gas separations. Among ...potential multifunctional magnetic materials, metal-organic frameworks, in particular, bear structures that offer intrinsic porosity, vast chemical and structural programmability, and the tunability of electronic properties. Nevertheless, magnetic order within metal-organic frameworks has generally been limited to low temperatures, owing largely to challenges in creating a strong magnetic exchange. Here we employ the phenomenon of itinerant ferromagnetism to realize magnetic ordering at T
= 225 K in a mixed-valence chromium(II/III) triazolate compound, which represents the highest ferromagnetic ordering temperature yet observed in a metal-organic framework. The itinerant ferromagnetism proceeds through a double-exchange mechanism, which results in a barrierless charge transport below the Curie temperature and a large negative magnetoresistance of 23% at 5 K. These observations suggest applications for double-exchange-based coordination solids in the emergent fields of magnetoelectrics and spintronics.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Oxidative stress is a central part of innate immune-induced neurodegeneration. However, the transcriptomic landscape of central nervous system (CNS) innate immune cells contributing to oxidative ...stress is unknown, and therapies to target their neurotoxic functions are not widely available. Here, we provide the oxidative stress innate immune cell atlas in neuroinflammatory disease and report the discovery of new druggable pathways. Transcriptional profiling of oxidative stress-producing CNS innate immune cells identified a core oxidative stress gene signature coupled to coagulation and glutathione-pathway genes shared between a microglia cluster and infiltrating macrophages. Tox-seq followed by a microglia high-throughput screen and oxidative stress gene network analysis identified the glutathione-regulating compound acivicin, with potent therapeutic effects that decrease oxidative stress and axonal damage in chronic and relapsing multiple sclerosis models. Thus, oxidative stress transcriptomics identified neurotoxic CNS innate immune populations and may enable discovery of selective neuroprotective strategies.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma, have among the highest mortality rates of all childhood cancers, despite recent advancements in cancer therapeutics. This ...is partly because, unlike some CNS tumors, the blood-brain barrier (BBB) of DMG tumor vessels remains intact. The BBB prevents the permeation of many molecular therapies into the brain parenchyma, where the cancer cells reside. Focused ultrasound (FUS) with microbubbles has recently emerged as an innovative and exciting technology that non-invasively permeabilizes the BBB in a small focal region with millimeter precision. In this review, current treatment methods and biological barriers to treating DMGs are discussed. State-of-the-art FUS-mediated BBB opening is then examined, with a focus on the effects of various ultrasound parameters and the treatment of DMGs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background and aims
Excessive alcohol consumption has a substantial impact on public health services. A key element determining alcohol availability is alcohol outlet density. This study investigated ...the relationship between on‐trade and off‐trade outlets and hospital admission rates in local neighbourhoods.
Design
National small‐area level ecological study.
Setting and participants
All 32 482 lower layer super output census areas (LSOAs) in England (42 227 108 million people aged 15+ years). Densities for six outlet categories (outlets within a 1‐km radius of residential postcode centroids, averaged for all postcodes within each LSOA) were calculated.
Measurements
Main outcome measures were admissions due to acute or chronic conditions wholly or partially attributable to alcohol consumption from 2002/03 to 2013/14.
Findings
There were 1 007 137 admissions wholly, and 2 153 874 admissions partially, attributable to alcohol over 12 years. After adjustment for confounding, higher densities of on‐trade outlets (pubs, bars and nightclubs; restaurants licensed to sell alcohol; other on‐trade outlets) and convenience stores were associated with higher admission rate ratios for acute and chronic wholly attributable conditions. For acute wholly attributable conditions, admission rate ratios were 13% (95% confidence interval = 11–15%), 9% (7–10%), 12% (10–14%) and 10% (9–12%) higher, respectively, in the highest relative to the lowest density categories by quartile. For chronic wholly attributable conditions, rate ratios were 22% (21–24%), 9% (7–11%), 19% (17–21%) and 7% (6–9%) higher, respectively. Supermarket density was associated with modestly higher acute and chronic admissions but other off‐trade outlet density was associated only with higher admissions for chronic wholly attributable conditions. For partially attributable conditions, there were no strong patterns of association with outlet densities.
Conclusions
In England, higher densities of several categories of alcohol outlets appear to be associated with higher hospital admission rates for conditions wholly attributable to alcohol consumption.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Cellular senescence has been associated with the structural and functional decline observed during physiological lung aging and in chronic obstructive pulmonary disease (COPD). Airway epithelial ...cells are the first line of defense in the lungs and are important to COPD pathogenesis. However, the mechanisms underlying airway epithelial cell senescence, and particularly the role of telomere dysfunction in this process, are poorly understood. We aimed to investigate telomere dysfunction in airway epithelial cells from patients with COPD, in the aging murine lung and following cigarette smoke exposure. We evaluated colocalization of γ-histone protein 2A.X and telomeres and telomere length in small airway epithelial cells from patients with COPD, during murine lung aging, and following cigarette smoke exposure in vivo and in vitro. We found that telomere-associated DNA damage foci increase in small airway epithelial cells from patients with COPD, without significant telomere shortening detected. With age, telomere-associated foci increase in small airway epithelial cells of the murine lung, which is accelerated by cigarette smoke exposure. Moreover, telomere-associated foci predict age-dependent emphysema, and late-generation Terc null mice, which harbor dysfunctional telomeres, show early-onset emphysema. We found that cigarette smoke accelerates telomere dysfunction via reactive oxygen species in vitro and may be associated with ataxia telangiectasia mutated-dependent secretion of inflammatory cytokines interleukin-6 and -8. We propose that telomeres are highly sensitive to cigarette smoke-induced damage, and telomere dysfunction may underlie decline of lung function observed during aging and in COPD.
Abstract
Background
Policy responses to the Global Financial Crisis emphasized wide-ranging fiscal austerity measures, many of which have been found to negatively impact health outcomes. This paper ...investigates change in patterns of mortality at local authority level in England (2010–11 to 2017–18) and the relation with fiscal austerity measures.
Methods
Data from official local authority administrative records are used to quantify the gap between observed deaths and what was anticipated in the 2010-based subnational population projections. Regression analyses are used to explore the relation between excess deaths, austerity and wider process of population change at local authority level.
Results
We estimate 231 707 total excess deaths, the majority of which occurred since 2014–15 (89%) across the majority of local authorities (91%). Austerity is positively associated with excess deaths. For working age adults, there is a clear gradient to the impact of austerity, whereas for older adults, the impact is more uniform.
Conclusions
Fiscal austerity policies contributed to an excess of deaths for older people and widened social inequalities for younger populations. These results call for an end to all austerity measures and require further research into areas with the highest total excess deaths as a priority following the COVID-19 pandemic.
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NUK, OILJ, UL, UM, UPUK, VSZLJ
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