Background
A high proportion of COVID‐19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for ...SARS‐CoV‐2 and the renin‐angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. ACE2 is abundant in the gut and associated with gut microbiota composition. We hypothesized that gut leakage of microbial products, and subsequent inflammasome activation could contribute to cardiac involvement in COVID‐19 patients.
Methods
Plasma levels of a gut leakage marker (LPS‐binding protein, LBP), a marker of enterocyte damage (intestinal fatty acid binding protein, IFABP), a gut homing marker (CCL25, ligand for chemokine receptor CCR9) and markers of inflammasome activation (IL‐1β, IL‐18 and their regulatory proteins) were measured at three time points (day 1, 3–5 and 7–10) in 39 hospitalized COVID‐19 patients and related to cardiac involvement.
Results
Compared to controls, COVID‐19 patients had elevated plasma levels of LBP and CCL25 but not IFABP, suggesting impaired gut barrier function and accentuated gut homing of T cells without excessive enterocyte damage. Levels of LBP were twice as high at baseline in patients with elevated cardiac markers compared with those without and remained elevated during hospitalization. Also, markers of inflammasome activation were moderately elevated in patients with cardiac involvement. LBP was associated with higher NT‐pro‐BNP levels, whereas IL‐18, IL‐18BP and IL‐1Ra were associated with higher troponin levels.
Conclusion
Patients with cardiac involvement had elevated markers of gut leakage and inflammasome activation, suggestive of a potential gut‐heart axis in COVID‐19.
Background. Clinical data on the association of diabetes mellitus with common infections are virtually lacking, not conclusive, and often biased. We intended to determine the relative risks of common ...infections in patients with type 1 and type 2 diabetes mellitus (DM1 and DM2, respectively). Methods. In a 12-month prospective cohort study conducted as part of the Second Dutch National Survey of General Practice, we compared 705 adult patients who had DM1 and 6712 adult patients who had DM2 with 18,911 control patients who had hypertension without diabetes. Outcome measures were medically attended episodes of infection of the respiratory tract, urinary tract, and skin and mucous membranes. We applied multivariable and polytomous logistic regression analysis to determine independent risks of infections and their recurrences in patients with diabetes, compared with control patients. Results. Upper respiratory infections were equally common among patients with diabetes and control patients. Patients with diabetes had a greater risk of lower respiratory tract infection (for patients with DM1: adjusted odds ratio AOR, 1.42 95% confidence interval {CI}, 0.96–2.08; for patients with DM2: AOR, 1.32 95% CI, 1.13–1.53), urinary tract infection (for patients with DM1: AOR, 1.96 95% CI, 1.49–2.58; for patients with DM2: AOR, 1.24 95% CI, 1.10–1.39), bacterial skin and mucous membrane infection (for patients with DM1: AOR, 1.59 95% CI, 1.12–2.24; for patients with DM2: AOR, 1.33 95% CI, 1.15–1.54), and mycotic skin and mucous membrane infection (for patients with DM1: AOR, 1.34 95% CI, 0.97–1.84; for patients with DM2: AOR, 1.44 95% CI, 1.27–1.63). Risks increased with recurrences of common infections. Conclusions. Patients with DM1 and DM2 are at increased risk for lower respiratory tract infection, urinary tract infection, and skin and mucous membrane infection. Studies are warranted into management of such infections in patients with diabetes.
Background and purpose: Apremilast is an orally administered phosphodiesterase‐4 inhibitor, currently in phase 2 clinical studies of psoriasis and other chronic inflammatory diseases. The inhibitory ...effects of apremilast on pro‐inflammatory responses of human primary peripheral blood mononuclear cells (PBMC), polymorphonuclear cells, natural killer (NK) cells and epidermal keratinocytes were explored in vitro, and in a preclinical model of psoriasis.
Experimental approach: Apremilast was tested in vitro against endotoxin‐ and superantigen‐stimulated PBMC, bacterial peptide and zymosan‐stimulated polymorphonuclear cells, immunonoglobulin and cytokine‐stimulated NK cells, and ultraviolet B light‐activated keratinocytes. Apremilast was orally administered to beige‐severe combined immunodeficient mice, xenotransplanted with normal human skin and triggered with human psoriatic NK cells. Epidermal skin thickness, proliferation index and inflammation markers were analysed.
Key results: Apremilast inhibited PBMC production of the chemokines CXCL9 and CXCL10, cytokines interferon‐γ and tumour necrosis factor (TNF)‐α, and interleukins (IL)‐2, IL‐12 and IL‐23. Production of TNF‐α by NK cells and keratinocytes was also inhibited. In vivo, apremilast significantly reduced epidermal thickness and proliferation, decreased the general histopathological appearance of psoriasiform features and reduced expression of TNF‐α, human leukocyte antigen‐DR and intercellular adhesion molecule‐1 in the lesioned skin.
Conclusions and implications: Apremilast displayed a broad pattern of anti‐inflammatory activity in a variety of cell types and decreased the incidence and severity of a psoriasiform response in vivo. Inhibition of TNF‐α, IL‐12 and IL‐23 production, as well as NK and keratinocyte responses by this phosphodiesterase‐4 inhibitor suggests a novel approach to the treatment of psoriasis.
High-throughput sequencing of ribosomal RNA gene (rDNA) amplicons has opened up the door to large-scale comparative studies of microbial community structures. The short reads currently produced by ...massively parallel sequencing technologies make the choice of sequencing region crucial for accurate phylogenetic assignments. While for 16S rDNA, relevant regions have been well described, no truly systematic design of 18S rDNA primers aimed at resolving eukaryotic diversity has yet been reported. Here we used 31,862 18S rDNA sequences to design a set of broad-taxonomic range degenerate PCR primers. We simulated the phylogenetic information that each candidate primer pair would retrieve using paired- or single-end reads of various lengths, representing different sequencing technologies. Primer pairs targeting the V4 region performed best, allowing discrimination with paired-end reads as short as 150 bp (with 75% accuracy at genus level). The conditions for PCR amplification were optimised for one of these primer pairs and this was used to amplify 18S rDNA sequences from isolates as well as from a range of environmental samples which were then Illumina sequenced and analysed, revealing good concordance between expected and observed results. In summary, the reported primer sets will allow minimally biased assessment of eukaryotic diversity in different microbial ecosystems.
Background
In recent years, the use of Indocyanine Green (ICG) fluorescence-guided surgery during open and laparoscopic procedures has exponentially expanded across various clinical settings. The ...European Association of Endoscopic Surgery (EAES) initiated a consensus development conference on this topic with the aim of creating evidence-based statements and recommendations for the surgical community.
Methods
An expert panel of surgeons has been selected and invited to participate to this project. Systematic reviews of the PubMed, Embase and Cochrane libraries were performed to identify evidence on potential benefits of ICG fluorescence-guided surgery on clinical practice and patient outcomes. Statements and recommendations were prepared and unanimously agreed by the panel; they were then submitted to all EAES members through a two-rounds online survey and results presented at the EAES annual congress, Barcelona, November 2021.
Results
A total of 18,273 abstracts were screened with 117 articles included. 22 statements and 16 recommendations were generated and approved. In some areas, such as the use of ICG fluorescence-guided surgery during laparoscopic cholecystectomy, the perfusion assessment in colorectal surgery and the search for the sentinel lymph nodes in gynaecological malignancies, the large number of evidences in literature has allowed us to strongly recommend the use of ICG for a better anatomical definition and a reduction in post-operative complications.
Conclusions
Overall, from the systematic literature review performed by the experts panel and the survey extended to all EAES members, ICG fluorescence-guided surgery could be considered a safe and effective technology. Future robust clinical research is required to specifically validate multiple organ-specific applications and the potential benefits of this technique on clinical outcomes.
Abstract Background This paper presents the latest international descriptive epidemiological data for invasive breast cancer amongst women, including incidence, survival and mortality, as well as ...information on mammographic screening programmes. Results Almost 1.4 million women were diagnosed with breast cancer worldwide in 2008 and approximately 459,000 deaths were recorded. Incidence rates were much higher in more developed countries compared to less developed countries (71.7/100,000 and 29.3/100,000 respectively, adjusted to the World 2000 Standard Population) whereas the corresponding mortality rates were 17.1/100,000 and 11.8/100,000. Five-year relative survival estimates range from 12% in parts of Africa to almost 90% in the United States, Australia and Canada, with the differential linked to a combination of early detection, access to treatment services and cultural barriers. Observed improvements in breast cancer survival in more developed parts of the world over recent decades have been attributed to the introduction of population-based screening using mammography and the systemic use of adjuvant therapies. Conclusion The future worldwide breast cancer burden will be strongly influenced by large predicted rises in incidence throughout parts of Asia due to an increasingly “westernised” lifestyle. Efforts are underway to reduce the global disparities in survival for women with breast cancer using cost-effective interventions.
NMR is able to probe water in different nano-scale environments of cement paste. It fully characterises morphology, density and composition of calcium silicate hydrate without destructive drying. ...Display omitted
► The density of C–S–H, the binding phase of cement is measured using NMR and XRD for the first time. ► The density is ρ=2.68g/cm3 for an underwater cured, never dried, paste. ► The measured Ca/(Si+Al) ratio and the molar water content are: 1.53 and 1.92 respectively. ► A pore size resolved desorption isotherm is presented for the first time.
1H nuclear magnetic resonance (NMR), supported by a measurement of the degree of hydration using X-ray diffraction, has been used to fully characterise the nano-scale porosity and composition of calcium–silicate–hydrate (C–S–H), the active component of cement. The resultant “solid” density and composition are ρ=2.68g/cm3; (Ca)1.53. (Si0.96,Al0.04)O3.51. (H2O)1.92 for an underwater cured, never-dried cement paste with an initial mix water-to-cement ratio of 0.4 after 28days of hydration. In addition, the first pore-type resolved desorption isotherm of cement that shows the location of water as a function of relative humidity has been measured. Critical to our results is verification of the assignment of the different NMR spin–spin relaxation time components. These have been corroborated with conventional analyses. The new methodology is key to enabling design of cement pastes with lower environmental impact.
The microscopic environment inside a metazoan organism is highly crowded. Whether individual cells can tailor their behavior to the limited space remains unclear. In this study, we found that cells ...measure the degree of spatial confinement by using their largest and stiffest organelle, the nucleus. Cell confinement below a resting nucleus size deforms the nucleus, which expands and stretches its envelope. This activates signaling to the actomyosin cortex via nuclear envelope stretch-sensitive proteins, up-regulating cell contractility. We established that the tailored contractile response constitutes a nuclear ruler-based signaling pathway involved in migratory cell behaviors. Cells rely on the nuclear ruler to modulate the motive force that enables their passage through restrictive pores in complex three-dimensional environments, a process relevant to cancer cell invasion, immune responses, and embryonic development.
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