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Sickle cell disease (SCD) is characterized by frequent, unpredictable pain episodes and other vaso-occlusive crises (VOCs) leading to significant healthcare utilization. VOC frequency is often an endpoint in clinical trials investigating novel therapies for this devastating disease.

The Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaboration investigating clinical severity in SCD using a validated questionnaire and medical chart review standardized across four countries (United States, United Kingdom, Italy and Ghana).

This study, focused on pain crisis incidence and healthcare utilization, included 868 patients, equally represented according to age and gender. HgbSS was the most common genotype. Patients from Ghana used the Emergency Room/Day Hospital for pain more frequently (annualized mean 2.01) than patients from other regions (annualized mean 1.56 U.S.; 1.09 U.K.; 0.02 Italy), while U.K. patients were hospitalized for pain more often (annualized mean U.K. 2.98) than patients in other regions (annualized mean 1.98 U.S.; 1.18 Ghana; Italy 0.54). Italy's hospitalization rate for pain (annualized mean 0.57) was nearly 20 times greater than its emergency room/day hospital only visits for pain (annualized mean 0.03). When categorized by genotype and age, similar results were seen.

Geographic differences in pain crisis frequency and healthcare utilization may correlate with variable organization of healthcare systems among countries and should be considered regarding trial design, endpoints, and analysis of results when investigating novel agents for clinical benefit.

Geographic differences in pain crisis frequency and healthcare utilization may correlate with variable organization of healthcare systems among countries and should be considered regarding trial design, endpoints, and analysis of results when investigating novel agents for clinical benefit.

Fractional exhaled nitric oxide (FE

) is a marker of type 2 airway inflammation used in clinical practice in asthma. However, reference values are needed to broaden the clinical use of FE

and this is within the scope of a newly started Global Lung Function Initiative task force. We aim to study FE

levels with special emphasis on the upper limit of normal (ULN) in relation to the type and degree of IgE sensitisation.

FE

was measured in 1855 non-smoking, respiratory healthy subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Atopic subjects (n=424), defined as being IgE-sensitised to aeroallergens (ImmunoCAP Phadiatop™, ≥0.35 PAU/l) were compared to non-atopic subjects (<0.35 PAU/l, n=1431). Atopic subjects were further characterised according to their grade of IgE sensitisation (IgE antibody tertiles (T1<1.16, T2 1.16-3.72 and T3 >3.72 PAU/l) and sensitisation to perennial (cat or mite) or seasonal (birch) allergens.

Subjects IgE-sensitised to cat or mite had higher FE

compared to non-atopic subjects (FE

(ppb) median 20.0 vs. 15.0, and ULN 50.4 vs. 33.0, p<0.001). This was seen to a lesser extent for subjects IgE-sensitised to birch only (median 18.0 vs. 15.0, and ULN 38.0 vs. 33.0, p=0.048). Atopic subjects with a high degree of IgE sensitisation (Phadiatop >3.72 PAU/l) had the highest FE

compared to non-atopic subjects (median 20.0 vs. 15.0, and ULN 56.0 vs. 33.0, p<0.001).

The type and degree of IgE sensitisation should be considered in generating FE

reference values.

The type and degree of IgE sensitisation should be considered in generating FENO reference values.

After aortic coarctation (CoA) repair, patients still suffer from cardiovascular complications. The aim of this study was to measure cardiovascular markers, intima-media thickness (IMT) and plaques in controls and patients with CoA.

Sixty-four patients with CoA (66% male, mean age 48±15 years) and controls (54% men, mean age 47±16 years) underwent ultrasound of their arteries. A multiplex platform to analyze circulating blood levels biomarkers reflecting inflammation, tissue remodeling and repair was used.

In men following CoA repair, a significantly increased carotid bulb IMT was observed in comparison to the control group (1.05 [0.72-1.24] vs. 0.67 [0.59-0.95] mm; p=0.003). Median common carotid artery (CCA) IMT was increased in men compared to controls (0.82 [0.61-0.97] mm vs. 0.58 [0.53-0.76] mm, p<0.003) and in women compared to controls (0.83 [0.70-0.92] vs. 0.60 [0.55-0.69], p<0.004). selleckchem CoA demonstrated an independent association with IMT in both men and women. Men with CoA were also more likely to have a plaque in their carotid arteries (p=0.010). In women with CoA, we observed significantly lower levels of stem cell factor (SCF, p=0.004) while in men with CoA we observed significantly lower levels of matrix metalloproteinase-3 (MMP-3, p=0.048), tumor necrosis factor receptor 1 (TNF-R1, p=0.032), tumor necrosis factor receptor superfamily member 10B (TRAIL-R2, p=0.019) and monocyte chemotactic protein 1 (MCP-1, p=0.015).

This is the first study to show that despite successful CoA repair, patients have more carotid atherosclerosis than can be explained by changes in tissue remodeling and repair.

This is the first study to show that despite successful CoA repair, patients have more carotid atherosclerosis than can be explained by changes in tissue remodeling and repair.Mycobacterial infections cause a reasonable burden of morbidity and mortality in global feline populations, many of which are 'Vulnerable' or 'Endangered'. Identifying these infections may facilitate efforts to protect these animals. An interferon-gamma (IFNγ) release assay (IGRA) to diagnose mycobacteriosis in domestic cats has been adapted for use in lions; however, the development of species-specific antibodies may be laborious. Therefore, we investigated whether anti-cat IFNγ antibodies can bind to recombinant IFNγ (rIFNγ) from other Felidae species, permitting use of the feline IGRA in a wider range of felids. Unique Felidae IFNγ protein sequences and their corresponding coding nucleotide sequence were identified from online databases; plasmids with an IFNγ-gene insert were synthesised to transform E. coli-DH5α and subsequently transfect HEK 293 T cells to secrete rIFNγ. Enzyme-linked immunosorbent assay using a commercial anti-cat IFNγ kit was performed to detect rIFNγ from Felidae, the domestic dog and cattle. Five unique rIFNγ Felidae proteins were synthesised; anti-cat IFNγ antibodies were able to bind to all five proteins, while cross-reactivity with canine and bovine rIFNγ was negligible. This suggests that anti-cat IFNγ antibodies are sufficient for detection of IFNγ across other Felidae species, namely the lion, tiger, cheetah, cougar, Iberian lynx and the Canadian lynx.Utilization of natural clay minerals for the treatment of heavy metal cadmium contamination is appealing as the affordable and readily accessible raw materials. However, the low reactivity of natural serpentine limits its practical application for Cd removal. In the present study, mechanochemical activation of antigorite-type serpentine (SP) as example was introduced to enhance its removal capacity for heavy metal of cadmium high enough for practical use. It was found ball-milling at 600 rpm for 60 min for antigorite resulted in the increased release of hydroxyl group to facilitate the precipitation of Cd2+, giving a capacity of 27.4 mg/g for the treatment of 100 mg/L Cd2+ for 120 min at room temperature, which was 10 times higher than that of the pristine antigorite (2.5 mg/g). More significantly, magnesium sulfate (MgSO4, MS) was introduced for the first time to process antigorite, thus to form MgSO4-incorporated antigorite. As a result, the removal capacity for Cd2+ was dramatically increased to 239.7 mg/gmetal contamination may be expected.Microplastics (MPs) pollution is increasingly appreciated as a significant environmental issue, however, the large-scale pattern of MPs in farmland soils and its associated environmental impacts are unknown. This study investigated a national-scale distribution of micro(meso)plastics (MMPs) in the soil of 30 farmlands across China. The abundance of MMPs in soils was 25.56-2067.78 items kg-1, with a mean of 358.37 items kg-1, i.e. 6.79 mg kg-1 or 0.0007% after mass conversion. MPs accounted for 93.1% of MMPs, the abundance varied greatly among different regions, high in arid or semi-arid north but relatively low in mild southwest regions. Major MPs included polypropylene, polyethylene, and polyester, tending to decrease in abundance from surface to deeper soil layers. Further, meta-analysis revealed that MPs exposure influenced bulk density, soil enzymes including fluorescein diacetate hydrolase (FDAse) and urease, and crop biomass, and minimum effective concentrations (MEC) were in the range of 0.0040-10%. We found that actual abundance in the national-scale soils was lower than MEC, but partly overlapped or close, which implies various degrees of environmental impacts. These findings disclose the national-scale pollution pattern of MPs in farmlands and its latent risks to soil environments and crop growth.Efficient catalysts for oxygen (O2) activation under room condition are required for effective wet air oxidation (WAO) technology. Here, we report a novel manganese-cobalt-based composite (MnO-CoO@Co) fabricated on a graphite felt (GF) support for catalyzing the electro-activation of O2 under room condition. Abundant Co-MnO and CoO-MnO heterointerfaces are formed in the composite. In comparison to the single-metal counterparts, i.e. CoO@Co/GF (16.99 wt% Co) and MnO/GF (26.83 wt% Mn), the bimetal MnO-CoO@Co/GF (5.29 wt% Co and 8.79 wt% Mn) displays an improved oxygen storage capacity and provides more active sites to accommodate surface adsorbed oxygen species. Notably, the strong synergy derived from bimetal heterointerfaces enhances the electron transfer and oxygen mobilization during the electro-activation of O2, thereby significantly reducing the reaction barrier. MnO-CoO@Co/GF exhibits excellent efficiency and stability in electrocatalytic WAO (ECWAO) towards the removal of pharmaceuticals and personal care products (PPCPs) over a wide pH range from 4.0 to 10.0. link2 A model pollutant sulfamethoxazole (SMX) acquires mineralization efficiency of 78.4 ± 2.1% and mineralization current efficiency of 157.89% at +1.0 V of electrode potential. link3 The toxicity of PPCPs can be totally eliminated after the ECWAO treatment. This work highlights the synergy derived from bimetal heterointerfaces in O2 electrocatalysis, and provides a promising approach for advanced WAO catalysts in PPCPs pollution control.

Combinations of PD-1/PD-L1 immune checkpoint inhibitors (ICI) with VEGFR-TKIs as first-line therapy significantly improve outcomes of metastatic renal cell carcinoma (mRCC) patients. The benefit of these combinations is well evident in the IMDC intermediate- and poor-risk population, but remains unclear in the subgroup of patients with favorable prognosis. Our meta-analysis aims at evaluating whether the addition of ICIs to VEGFR-TKIs is able to improve the outcome compared to VEGFR-TKIs alone in mRCC patients with favorable prognosis.

This meta-analysis searched MEDLINE/PubMed, the Cochrane Library and ASCO Meeting abstracts for randomized clinical trials (RCTs) testing the combination of VEGFR-TKI+ICI in mRCC. Data extraction was conducted according to the PRISMA statement. Summary hazard ratio (HR) was calculated using random- or fixed-effects models, depending on studies heterogeneity.

Four RCTs were selected. VEGFR-TKI+ICI combinations improved PFS compared to sunitinib (fixed-effect, HR=0.63; p<0.