Moderate exercise induces trained immunity in macrophages.

Despite its importance in protecting the host from infections and injury, excessive inflammation may lead to serious human diseases including autoimmune disorders, cardiovascular diseases, diabetes, and cancer. Exercise is a known immunomodulator; however, whether exercise causes long-term changes in inflammatory responses and how these changes occur are lacking. Here, we show that chronic moderate-intensity training of mice leads to persistent metabolic rewiring and changes to chromatin accessibility in bone marrow-derived macrophages (BMDMs), which, in turn, tempers their inflammatory responses. We show that BMDMs from exercised mice exhibited a decrease in lipopolysaccharide (LPS)-induced NF-κB activation and proinflammatory gene expression along with an increase in M2-like-associated genes when compared with BMDMs from sedentary mice. This was associated with improved mitochondrial quality and increased reliance on oxidative phosphorylation accompanied with reduced mitochondrial reactive oxygen species (ROS) production. Mechanistically, assay for transposase-accessible chromatin (ATAC)-seq analysis showed changes in chromatin accessibility of genes associated with inflammatory and metabolic pathways. Overall, our data suggest that chronic moderate exercise can influence the inflammatory responses of macrophages by reprogramming their metabolic and epigenetic landscape.NEW & NOTEWORTHY In this study, we explain how long-term moderate exercise training can reduce inflammation in mouse macrophages by reprogramming the way they sense and respond to the presence of pathogens. We completed a thorough analysis and showed that these changes persist in macrophages because exercise improves the ability of cells to utilize oxygen without producing damaging compounds, and changes the way they access their DNA.

Oxyhemoglobin changes in the prefrontal cortex in response to cognitive tasks: a systematic review.

PURPOSE OF THE STUDY: the aim of this study was to synthesize PFC fNIRS outcomes on the effects of cognitive tasks compared to resting/baseline tasks in healthy adults from studies utilizing a pre/post design. MATERIAL AND METHODS: original research studies were searched from seven databases (MEDLINE, EMBASE, CENTRAL, CINAHL, SCOPUS, PEDro and PubMed). Subsequently, two independent reviewers screened the titles and abstracts followed by full-text reviews to assess the studies' eligibility. RESULTS: eleven studies met the inclusion criteria and had data abstracted and quality assessed. Methodology varied considerably and yet cognitive tasks resulted in the ΔO2Hb increasing in 8 of the 11 and ΔHHb decreasing in 8 of 8 studies that reported this outcome. The cognitive tasks from 10 of the 11 studies were classified as "Working Memory" and "Verbal Fluency Tasks". CONCLUSIONS: although, the data comparison was challenging provided the heterogeneity in methodology, the results across studies were similar.

Exploring the impact of the COVID-19 pandemic on pediatric surgical services.

Inevitably, along with other healthcare specializations, pediatric surgery was affected by the Coronavirus disease-19 (COVID-19) pandemic. Children were reported to manifest mild to moderate symptoms and mortality was primarily observed in patients aged <1 year and having underlying comorbidities. Most of the cases were asymptomatic in children, hence, posing a challenge for pediatric surgery centers to take drastic measures to reduce the virus transmission. Telemedicine was introduced and out-patient consultations were conducted online as out-patient clinics were closed. Elective surgeries were postponed with delayed appointments while the healthcare sector was diverted towards tackling COVID-19. Case urgency was classified and triaged, leading to limited surgeries being performed only in COVID-19 negative patients following an extensive screening process. The screening process consisted of online history taking and RT-PCR tests. Newer practices such as mouth rinse, video laryngoscopy, and anesthesia were introduced to restrict patients from crying, coughing, and sneezing, as an attempt to avoid aerosolization of viral particles and safely conduct pediatric surgeries during the pandemic. Surgical trainees were also affected as the smaller number of surgeries conducted reduced the clinical experience available to medical enthusiasts. There is still room for advanced practices to be introduced in pediatric surgery and restore all kinds of surgeries to improve the quality of life of the patient.

Cardiac Mesenchymal Cells Cultured at Physiologic Oxygen Tension Have Superior Therapeutic Efficacy in Heart Failure Caused by Myocardial Infarction.

Stem/progenitor cells are usually cultured at atmospheric O2 tension (21%); however, since physiologic O2 tension in the heart is ∼5%, using 21% O2 may cause oxidative stress and toxicity. Cardiac mesenchymal cells (CMCs), a newly discovered and promising type of progenitor cells, are effective in improving left ventricle (LV) function after myocardial infarction (MI). We have previously shown that, compared with 21% O2, culture at 5% O2 increases CMC proliferation, telomerase activity, telomere length, and resistance to severe hypoxia in vitro. However, it is unknown whether these beneficial effects of 5% O2 in vitro translate into greater therapeutic efficacy in vivo in the treatment of heart failure. Thus, murine CMCs were cultured at 21% or 5% O2. Mice with heart failure caused by a 60-min coronary occlusion followed by 30 days of reperfusion received vehicle, 21% or 5% O2 CMCs via echocardiography-guided intraventricular injection. After 35 days, the improvement in LV ejection fraction effected by 5% O2 CMCs was > 3 times greater than that afforded by 21% O2 CMCs (5.2 vs. 1.5 units, P < 0.01). Hemodynamic studies (Millar catheter) yielded similar results both for load-dependent (LV dP/dt) and load-independent (end-systolic elastance) indices. Thus, two independent approaches (echo and hemodynamics) demonstrated the therapeutic superiority of 5% O2 CMCs. Further, 5% O2 CMCs, but not 21% O2 CMCs, significantly decreased scar size, increased viable myocardium, reduced LV hypertrophy and dilatation, and limited myocardial fibrosis both in the risk and non-infarcted regions. Taken together, these results show, for the first time, that culturing CMCs at physiologic (5%) O2 tension provides superior therapeutic efficacy in promoting cardiac repair in vivo. This concept may enhance the therapeutic potential of CMCs. Further, culture at 5% O2 enables greater numbers of cells to be produced in a shorter time, thereby reducing costs and effort and limiting cell senescence. Thus, the present study has potentially vast implications for the field of cell therapy.

Treating symptomatic coronary artery disease in patients with Von Willebrand disease.

There is limited data on the occurrence of coronary artery disease (CAD) in patients with Von Willebrand disease and the literature is even scarce on their management. We at our institute reviewed the medical records of 198 patients with Von Willebrand disease over a period of 15years, of which 6 were found to have symptomatic CAD. Acute coronary syndrome was noted in 3 patients while the remaining 3 had stable angina. Cardiac catheterization showed that left main coronary artery was the culprit vessel in all of these patients. In terms of management, stents were placed in 3 patients, two of them underwent coronary artery bypass grafting, and the remaining one patient was medically managed. Aspirin, and in some patients clopidogrel, was well tolerated with minimal side effects.

Composition-controlled synthesis of bimetallic gold-silver nanoparticles.

This paper reports findings of an investigation of the synthesis of monolayer-capped binary gold-silver (AuAg) bimetallic nanoparticles that is aimed at understanding the control factors governing the formation of the bimetallic compositions. The synthesis of alkanethiolate-capped AuAg nanoparticles was carried out using two related synthetic protocols using aqueous sodium borohydride as a reducing agent. One involves a two-phase reduction of AuCl(4)(-), which is dissolved in organic solution, and Ag(+), which is dissolved in aqueous solution. The other protocol involves a two-phase reduction of AuCl(4)(-) and AgBr(2)(-), both of which are dissolved in the same organic solution. AuAg nanoparticles of 2-3 nm core sizes with different compositions in the range of 0-100% Au have been synthesized. The two synthetic routes were compared in terms of bimetallic composition and size properties. Our new findings have allowed us to establish the correlation between synthetic feeding of metals and metal compositions in the bimetallic nanoparticles, which have important implications to the exploration of gold-based bimetallic nanoparticles for constructing sensing and catalytic nanomaterials.