Abstract
Lymphedema (LD) is characterized by the accumulation of interstitial fluid, lipids and inflammatory cell infiltrate in the limb. Here, we find that LD tissues from women who developed LD ...after breast cancer exhibit an inflamed gene expression profile. Lipidomic analysis reveals decrease in specialized pro-resolving mediators (SPM) generated by the 15-lipoxygenase (15-LO) in LD. In mice, the loss of SPM is associated with an increase in apoptotic regulatory T (T
reg
) cell number. In addition, the selective depletion of 15-LO in the lymphatic endothelium induces an aggravation of LD that can be rescued by Treg cell adoptive transfer or ALOX15-expressing lentivector injections. Mechanistically, exogenous injections of the pro-resolving cytokine IFN−β restores both 15-LO expression and Treg cell number in a mouse model of LD. These results provide evidence that lymphatic 15-LO may represent a therapeutic target for LD by serving as a mediator of T
reg
cell populations to resolve inflammation.
Vapor-phase adsorption of the C8 alkylaromatic components p-xylene (p-x), m-xylene (m-x), o-xylene (o-x), and ethylbenzene (eb) on the three-dimensional microporous metal−organic framework (MOF) ...Zn(BDC)(Dabco)0.5 (BDC = 1,4-benzenedicarboxylate, Dabco = 1,4-diazabicyclo2.2.2octane) was investigated. Single- and multicomponent fixed-bed experiments were carried out at temperatures ranging from 125 to 175 °C and total hydrocarbon pressures up to 0.10 bar. At high pressure, the adsorption capacity for all the components varies from 35 to 26 g/100 gads at 125 and 175 °C. Henry’s constants are slightly different for all C8 alkylaromatics, except for o-xylene, which is significantly higher. The adsorption enthalpies at zero coverage for the different isomers ranges from 77.40 (eb) to 79.84 kJ/mol (o-x), indicating that the C8 alkylaromatics have comparable interactions with the framework at the low coverage. On the basis of binary and quaternary breakthrough experiments performed at different hydrocarbon pressures and temperatures, MOF Zn(BDC)(Dabco)0.5 was realized for the efficient and feasible separation of o-xylene from other C8 alkylaromatic components with the selectivity up to 1.88 because of the stronger interactions between o-xylene molecules and the framework and their differential pore-filling and molecular-packing effects confined within nanopores of MOFs.
•Molecular drivers related to advanced OPSCC remain undetermined.•HPV-positive cases were enriched with inhibitory T-cells immune response genes.•Integrated genomic-transcriptomic analysis revealed ...driver genes in 11q13.•PPFIA1 overexpression and HPV status are independent prognostic markers.•SHANK2 overexpression was related to incomplete therapy response.
To identify potential molecular drivers associated with prognosis and response to treatment in advanced oropharyngeal squamous cell carcinomas (OPSCC).
Thirty-three OPSCC biopsies from untreated Brazilian patients were evaluated for human papilloma virus genotyping, genome wide copy number alterations and gene expression profiling. Data were integrated using CONEXIC algorithm. Validation with TCGA dataset and confirmation by RT-qPCR of candidate genes were performed.
High-risk HPV positive cases, detected in 55% of advanced OPSCC, were associated with better outcome. Losses of 8p11.23-p11.22, 14q11.1-q11.2 and 15q11.2, and gains of 11q13.2 and 11q13.2-q13.3 were detected as recurrent alterations. Gains of 3q26.31 and 11q13.2 and losses of 9p21.3 were exclusively detected in HPV-negative tumors. Two clusters of expression profiles were observed, being one composed mostly by HPV positive cases (83%). HPV-positive enriched cluster showed predominantly immune response-related pathways. Integrative analysis identified 10 modulators mapped in 11q13, which were frequently cancer-related. These 10 genes showed copy number gains, overexpression and an association with worse survival, further validated by TCGA database analyses. Overexpression of four genes (ORAOV1, CPT1A, SHANK2 and PPFIA1) evaluated by RT-qPCR confirmed their association with poor survival. Multivariate analysis showed that PPFIA1 overexpression and HPV status are independent prognostic markers. Moreover, SHANK2 overexpression was significantly associated with incomplete response to treatment.
The integrative genomic and transcriptomic data revealed potential driver genes mapped in 11q13 associated with worse prognosis and response to treatment, giving fundamentals for the identification of novel therapeutic targets in OPSCC.
Study design, and results of the primary efficacy hierarchical endpoints.
The win ratio was calculated using an unmatched non-parametric pairwise comparison for each endpoint. The win ratio given as ...the total number of winner pairs by the total number of the loser pairs. In the present study, a win ratio > 1 indicates benefit of double-dose in-hospital influenza vaccination.
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•The first 45 days after an ACS is the period with the more risk for CV events.•Double-dose influenza vaccination following an ACS did not reduce cardiorespiratory.•Similar results were found for only to hierarchical cardiovascular endpoints.•COVID-19 hospitalizations and death did not impact hierarchical endpoints.
Influenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain.
The VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization).
The trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70–––1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71–––1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48–––1.39; P = 0.46). No serious adverse events were observed.
In patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization.
Highlights • Evidence on the role of sexual behaviours in head and neck cancer (H&NC) aetiology is inconsistent. • This is the first meta-analysis assessing the association between sexual behaviours ...and H&NC. • We noted an increased risk of H&NC for a higher number of sexual and oral sex partners. • No effect for oral sex practice and age at first intercourse on H&NC risk was observed. • Observed associations might be attributed to confounding effects of socio-demographic and behavioural factors.
We assessed soil fungal and fungal‐like diversity using metabarcoding in ornithogenically influenced soils around nests of the bird species Phalacrocorax atriceps, Macronectes giganteus, Pygoscelis ...antarcticus, and Pygoscelis adelie on the South Shetland Islands, maritime Antarctic. A total of 1,392,784 fungal DNA reads was obtained and assigned to 186 amplicon sequence variants (ASVs). The dominant fungal phylum was Ascomycota, followed by Basidiomycota, Chytridiomycota, Blastocladiomycota, Rozellomycota, Mortierellomycota, Monoblepharomycota, Aphelidiomycota, Basidiobolomycota, Mucoromycota, and the fungal‐like Oomycota (Stramenopila), in rank order. Antarctomyces sp., Blastocladiomycota sp., Pseudogymnoascus pannorum, Microascaceae sp., Mortierella sp., Lobulomycetales sp., Sordariomycetes sp., Fungal sp., Rhizophydiales sp., Pseudeurotiaceae sp., Chytridiomycota sp. 1, Filobasidiella sp., Tausonia pullulans, Betamyces sp., and Leucosporidium sp. were the most abundant assigned taxa. The fungal assemblages present in the different ornithogenically influenced soils displayed different diversity indices. However, in general, we detected high fungal diversity and few taxa shared between the samples. Despite the polyextreme environmental conditions experienced in these Antarctic soils, the metabarcoding approach detected a rich and complex fungal community dominated by saprophytes, but with some pathogenic taxa also present. The community was dominated by psychrophilic and psychrotolerant taxa, some apparently endemic to Antarctica, and those identified only at higher taxonomic levels, which may represent currently undescribed fungi. The mycobiome detected included taxa characterized by different ecological roles, including saprotrophic, human‐ and animal‐associated, phytopathogenic, mutualistic, and cosmopolitan. These fungi may potentially be dispersed by birds or in the air column over great distances, including between different regions within Antarctica and from South America, Africa, and Oceania.
High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density lipoprotein particles may be cardioprotective and reduce infarct size in the setting of ...myocardial injury. Lecithin-cholesterol acyltransferase is a rate-limiting enzyme in reverse cholesterol transport. MEDI6012 is a recombinant human lecithin-cholesterol acyltransferase that increases high-density lipoprotein cholesterol. Administration of lecithin-cholesterol acyltransferase has the potential to reduce infarct size and regress coronary plaque in acute ST-segment-elevation myocardial infarction.
REAL-TIMI 63B (A Randomized, Placebo‑controlled Phase 2b Study to Evaluate the Safety and Efficacy of MEDI6012 in Acute ST Elevation Myocardial Infarction) was a phase 2B multinational, placebo-controlled, randomized trial. Patients with ST-segment-elevation myocardial infarction within 6 hours of symptom onset and planned for percutaneous intervention were randomly assigned 2:1 to MEDI6012 (2- or 6-dose regimen) or placebo and followed for 12 weeks. The primary outcome was infarct size as a percentage of left ventricular mass by cardiac MRI at 10 to 12 weeks, with the primary analysis in patients with TIMI Flow Grade 0 to 1 before percutaneous intervention who received at least 2 doses of MEDI6012. The secondary outcome was change in noncalcified plaque volume on coronary computed tomographic angiography from baseline to 10 to 12 weeks with the primary analysis in patients who received all 6 doses of MEDI6012.
A total of 593 patients were randomly assigned. Patients were a median of 62 years old, 77.9% male, and 95.8% statin naive. Median time from symptom onset to randomization was 146 (interquartile range IQR, 103-221) minutes and from hospitalization to randomization was 12.7 (IQR, 6.6-24.0) minutes, and the first dose of drug was administered a median of 8 (IQR, 3-13) minutes before percutaneous intervention. The index myocardial infarction was anterior in 69.6% and TIMI Flow Grade 0 to 1 in 65.1% of patients. At 12 weeks, infarct size did not differ between treatment groups (MEDI6012: 9.71%, IQR 4.79-16.38; placebo: 10.48%, IQR, 4.92-16.61, 1-sided
=0.79. There was also no difference in noncalcified plaque volume (geometric mean ratio, 0.96 95% CI, NA-1.10, 1-sided
=0.30). There was no significant difference in treatment emergent serious adverse events.
Administration of MEDI6012 in patients with acute ST-segment-elevation myocardial infarction did not result in a significant reduction in infarct size or noncalcified plaque volume at 12 weeks. MEDI6012 was well tolerated with no excess in overall serious adverse events.
URL: https://www.
gov; Unique identifier: NCT03578809.
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► We study single and multicomponent sorption of xylene isomers in MOF 1. ► We describe the sorption of xylene isomers in MOF 1 using DSL model. ► The calculation of isosteric heats ...of sorption validate the DSL model. ► MOF 1 can be used to separate o-xylene from the other isomers.
Single and multicomponent adsorption equilibria of xylene isomers: o-xylene (o-x), m-xylene (m-x), p-xylene (p-x) and ethylbenzene (eb) was investigated on the three dimensional microporous metal–organic framework Zn(BDC)(Dabco)0.5 (BDC=1,4-benzenedicarboxylate, Dabco=1,4-diazabicyclo2.2.2-octane), MOF 1, in the range of temperatures between 398 and 448K and partial pressures up to 0.1bar. The equilibrium data show that a significant amount (around 34g/100gads at 398K) of xylene isomers can be adsorbed in MOF 1. The affinity to the adsorbent measured by the Henry’s constants to decreases in the order o-x>m-x>eb>p-x for all temperatures. The zero coverage adsorption enthalpies are all similar and range from 77.4 (eb) to 79.8kJ/mol (o-x). The Dual-Site Langmuir model (DSL) was used for the interpretation and correlation of the experimental data. The parameters obtained from the pure component isotherms fitting were also used to predict the multicomponent equilibrium data by an extended DSL model. A good agreement was obtained between the predictions and the experimental data. It was also demonstrated that the DSL model is also capable to explain the increase in the isosteric heat of sorption with increasing coverage.
Increased risk of new-onset diabetes with statins challenges the long-term safety of this drug class. However, few reports have analyzed this issue during acute coronary syndromes (ACS).
To explore ...the association between early initiation of statin therapy and blood glucose levels in patients admitted with ACS.
This was a retrospective analysis of patients hospitalized with ACS. Statin-naïve patients were included and divided according to their use or not of statins within the first 24 hours of hospitalization. The primary endpoint was incidence of in-hospital hyperglycemia (defined as peak blood glucose > 200 mg/dL). Multivariable linear and logistic regression models were used to adjust for confounders, and a propensity-score matching model was developed to further compare both groups of interest. A p-value of less than 0.05 was considered statistically significant.
A total of 2,357 patients were included, 1,704 of them allocated in the statin group and 653 in the non-statin group. After adjustments, statin use in the first 24 hours was associated with a lower incidence of in-hospital hyperglycemia (adjusted OR=0.61, 95% CI 0.46-0.80; p < 0.001) and lower need for insulin therapy (adjusted OR = 0.56, 95% CI 0.41-0.76; p < 0.001). These associations remained similar in the propensity-score matching models, as well as after several sensitivity analyses, such as after excluding patients who developed cardiogenic shock, severe infection or who died during index-hospitalization.
Among statin-naïve patients admitted with ACS, early statin therapy was independently associated with lower incidence of in-hospital hyperglycemia. (Arq Bras Cardiol. 2021; 116(2):285-294).
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