Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To ...constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42<L<117 MeV. This value is slightly lower but consistent with the L values deduced from a recent measurement of the neutron skin thickness of ^{208}Pb.
The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This ...Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.
Aliment Pharmacol Ther 31, 548–552
Summary
Background Confocal laser endomicroscopy (CLE) is rapidly emerging as a valuable tool for gastrointestinal endoscopic imaging. Fluorescent contrast agents ...are used to optimize imaging with CLE, and intravenous fluorescein is the most widely used contrast agent. Fluorescein is FDA‐cleared for diagnostic angiography of the retina. For these indications, the safety profile of fluorescein has been well‐documented; however, to date, fluorescein is not cleared for use with CLE.
Aims To estimate the rate of serious and total adverse events attributable to intravenous fluorescein when used for gastrointestinal CLE.
Methods We performed a cross sectional survey of 16 International Academic Medical Centres with active research protocols in CLE that involved intravenous fluorescein. Centres using i.v. fluorescein for CLE who were actively monitored for adverse events were included.
Results Sixteen centres performed 2272 gastrointestinal CLE procedures. The most common dose of contrast agent was 2.5–5 mL of 10% sodium fluorescein. No serious adverse events were reported. Mild adverse events occurred in 1.4% of individuals, including nausea/vomiting, transient hypotension without shock, injection site erythema, diffuse rash and mild epigastric pain. The limitation is that only immediate post procedure events were actively monitored.
Conclusions Use of intravenous fluorescein for gastrointestinal CLE appears to be safe with few acute complications.
Using the dcQMD transport model, the isoscalar and isovector in-medium potentials of the
Δ
(1232) baryon are studied and information regarding their effective strength is obtained from a comparison ...to experimental pion production data in heavy-ion collisions below 800 MeV/nucleon impact energy. The best description is achieved for an isoscalar potential moderately more attractive than the nucleon optical potential and a rather small isoscalar relative effective mass
m
Δ
∗
≈
0.45. For the isovector component only a constraint between the potential’s strength at saturation and the isovector effective mass difference can be extracted, which depends on quantities such as the slope of the symmetry energy and the neutron-proton effective mass difference. These results are incompatible with the usual assumption, in transport models, that the
Δ
(1232) and nucleon potentials are equal. The density dependence of symmetry energy can be studied using the high transverse momentum tail of pion multiplicity ratio spectra. Results are however correlated with the value of neutron-proton effective mass difference. This region of spectra is shown to be affected by uncertain model ingredients such as the pion potential or in-medium correction to inelastic scattering cross-sections at levels smaller than 10%. Extraction of precise constraints for the density dependence of symmetry energy above saturation will require experimental data for pion production in heavy-ion collisions below 800 MeV/nucleon impact energy and experimental values for the high transverse momentum tail of pion multiplicity ratio spectra accurate to better than 5%.
Aims/hypothesis
MicroRNAs regulate a broad range of biological mechanisms. To investigate the relationship between microRNA expression and type 2 diabetes, we compared global microRNA expression in ...insulin target tissues from three inbred rat strains that differ in diabetes susceptibility.
Methods
Using microarrays, we measured the expression of 283 microRNAs in adipose, liver and muscle tissue from hyperglycaemic (Goto–Kakizaki), intermediate glycaemic (Wistar Kyoto) and normoglycaemic (Brown Norway) rats (
n
= 5 for each strain). Expression was compared across strains and validated using quantitative RT-PCR. Furthermore, microRNA expression variation in adipose tissue was investigated in 3T3-L1 adipocytes exposed to hyperglycaemic conditions.
Results
We found 29 significantly differentiated microRNAs (
p
adjusted
< 0.05): nine in adipose tissue, 18 in liver and two in muscle. Of these, five microRNAs had expression patterns that correlated with the strain-specific glycaemic phenotype. MiR-222 (
p
adjusted
= 0.0005) and miR-27a (
p
adjusted
= 0.006) were upregulated in adipose tissue; miR-195 (
p
adjusted
= 0.006) and miR-103 (
p
adjusted
= 0.04) were upregulated in liver; and miR-10b (
p
adjusted
= 0.004) was downregulated in muscle. Exposure of 3T3-L1 adipocytes to increased glucose concentration upregulated the expression of miR-222 (
p
= 0.008), miR-27a (
p
= 0.02) and the previously reported miR-29a (
p
= 0.02). Predicted target genes of these differentially expressed microRNAs are involved in pathways relevant to type 2 diabetes.
Conclusion
The expression patterns of miR-222, miR-27a, miR-195, miR-103 and miR-10b varied with hyperglycaemia, suggesting a role for these microRNAs in the pathophysiology of type 2 diabetes, as modelled by the Gyoto–Kakizaki rat. We observed similar patterns of expression of miR-222, miR-27a and miR-29a in adipocytes as a response to increased glucose levels, which supports our hypothesis that altered expression of microRNAs accompanies primary events related to the pathogenesis of type 2 diabetes.
Tissue-resident innate lymphoid cells (ILCs) help sustain barrier function and respond to local signals. ILCs are traditionally classified as ILC1, ILC2 or ILC3 on the basis of their expression of ...specific transcription factors and cytokines
. In the skin, disease-specific production of ILC3-associated cytokines interleukin (IL)-17 and IL-22 in response to IL-23 signalling contributes to dermal inflammation in psoriasis. However, it is not known whether this response is initiated by pre-committed ILCs or by cell-state transitions. Here we show that the induction of psoriasis in mice by IL-23 or imiquimod reconfigures a spectrum of skin ILCs, which converge on a pathogenic ILC3-like state. Tissue-resident ILCs were necessary and sufficient, in the absence of circulatory ILCs, to drive pathology. Single-cell RNA-sequencing (scRNA-seq) profiles of skin ILCs along a time course of psoriatic inflammation formed a dense transcriptional continuum-even at steady state-reflecting fluid ILC states, including a naive or quiescent-like state and an ILC2 effector state. Upon disease induction, the continuum shifted rapidly to span a mixed, ILC3-like subset also expressing cytokines characteristic of ILC2s, which we inferred as arising through multiple trajectories. We confirmed the transition potential of quiescent-like and ILC2 states using in vitro experiments, single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) and in vivo fate mapping. Our results highlight the range and flexibility of skin ILC responses, suggesting that immune activities primed in healthy tissues dynamically adapt to provocations and, left unchecked, drive pathological remodelling.
Assessment of Neuropathic Pain in Primary Care Haanpää, Maija L., MD, PhD; Backonja, Misha-Miroslav, MD, PhD; Bennett, Michael I., MB, ChB ...
The American journal of medicine,
10/2009, Letnik:
122, Številka:
10
Journal Article
Recenzirano
Abstract Management of patients presenting with chronic pain is a common problem in primary care. Essentially, the classification of chronic pain falls into 3 broad categories: (1) pain owing to ...tissue disease or damage (nociceptive pain), (2) pain caused by somatosensory system disease or damage (neuropathic pain), and (3) pain without a known somatic background. Key challenges in developing a targeted holistic approach to treatment include appropriate diagnosis of the cause or causes of pain; identifying the type of pain and assessing the relative importance of its various components; and determining appropriate treatment. In clinical examination, sensory abnormalities are the crucial findings leading to a diagnosis of neuropathic pain, for which pharmacotherapy with antidepressants and anticonvulsants represents the cornerstone of medical treatment. Chronic neuropathic pain is underrecognized and undertreated, yet primary care physicians are uniquely placed on the frontlines of patient management, where they can play a pivotal role in treatment and prevention through diagnosis, therapy, follow-up, and referral. This review provides guidance in understanding and identifying the neuropathic contribution to pain presenting in primary care; assessing its severity through patient history, physical examination, and appropriate diagnostic tests; and establishing a rational treatment plan.
•Environmental benefits of JB blends were found but adverse impact on NOx.•Addition of 0.15% (m) DPPD in JB20, average reduction in NO up to 16.54%.•In some cases, engine power is reduced with DPPD ...additive.•Emissions of HC and CO for JB blends with DPPD were lower compared to diesel.•Addition of DPPD in JB blends reduction of EGT was found.
Energy requirements are increasing rapidly due to fast industrialization and the increased number of vehicles on the road. The use of biodiesel in diesel engines instead of diesel results in the proven reduction of harmful exhaust emissions. However, most researchers have reported that they produce higher NOx emissions compared to diesel, which is a deterrent to the expansion of the market for these fuels. Several proposed pathways try to account for NOx formation during the combustion process. Among them, the Fenimore mechanism explains that fuel radicals formed during the combustion process react with nitrogen from the air to form NOx. It could be proposed that if these radical reactions could be terminated, the NOx formation rate for biodiesel combustion would decrease. An experimental study was conducted on a four-cylinder diesel engine to evaluate the performance and emission characteristics of Jatropha biodiesel blends (JB5, JB10, JB15 and JB20) with and without the addition of N,N′-diphenyl-1,4-phenylenediamine (DPPD) antioxidant. For each tested fuel, the engine performance and emissions were measured at engine speeds 1000–4000rpm at an interval of 500rpm under the full throttle condition. The results showed that this antioxidant additive could reduce NOx emissions significantly with a slight penalty in terms of engine power and Brake Specific Fuel Consumption (BSFC) as well as CO and HC emissions. However, when compared to diesel combustion, the emissions of HC and CO with the addition of the DPPD additive were found to be nearly the same or lower. By the addition of 0.15% (m) DPPD additive in JB5, JB10, JB15 and JB20, the reduction in NOx emissions were 8.03%, 3.503%, 13.65% and 16.54% respectively, compared to biodiesel blends without the additive under the full throttle condition. Moreover, the addition of DPPD additive to all biodiesel blend samples reduced the exhaust gas temperature.
Soil Transmitted Helminths (STH) infect over 1.5 billion people globally and are associated with anemia and stunting, resulting in an annual toll of 1.9 million Disability-Adjusted Life Years ...(DALYs). School-based deworming (SBD), via mass drug administration (MDA) campaigns with albendazole or mebendazole, has been recommended by the World Health Organization to reduce levels of morbidity due to STH in endemic areas. DeWorm3 is a cluster-randomized trial, conducted in three study sites in Benin, India, and Malawi, designed to assess the feasibility of interrupting STH transmission with community-wide MDA as a potential strategy to replace SBD. This analysis examines data from the DeWorm3 trial to quantify discrepancies between school-level reporting of SBD and gold standard individual-level survey reporting of SBD.
Population-weighted averages of school-level SBD calculated at the cluster level were compared to aggregated individual-level SBD estimates to produce a Mean Squared Error (MSE) estimate for each study site. In order to estimate individual-level SBD coverage, these MSE values were applied to SBD estimates from the control arm of the DeWorm3 trial, where only school-level reporting of SBD coverage had been collected. In each study site, SBD coverage in the school-level datasets was substantially higher than that obtained from individual-level datasets, indicating possible overestimation of school-level SBD coverage. When applying observed MSE to project expected coverages in the control arm, SBD coverage dropped from 89.1% to 70.5% (p-value < 0.001) in Benin, from 97.7% to 84.5% (p-value < 0.001) in India, and from 41.5% to 37.5% (p-value < 0.001) in Malawi.
These estimates indicate that school-level SBD reporting is likely to significantly overestimate program coverage. These findings suggest that current SBD coverage estimates derived from school-based program data may substantially overestimate true pediatric deworming coverage within targeted communities.
NCT03014167.
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