Conditions determining the morphology and nanoscale magnetism of Co nanoparticles: Experimental and numerical studies

Co-based nanostructures ranging from core-shell to hollow nanoparticles were produced by varying the reaction time and the chemical environment during the thermal decomposition of Co2(CO)8. Both structural characterization and kinetic model simulation illustrate that the diffusivities of Co and oxygen determine the growth ratio and the final morphology of the nanoparticles. Exchange coupling between Co and Co-oxide in core/shell nanoparticles induced a shift of field-cooled hysteresis loops that is proportional to the shell thickness, as verified by numerical studies. The increased nanocomplexity when going from core/shell to hollow particles, also leads to the appearance of hysteresis above 300 K due to an enhancement of the surface anisotropy resulting from the additional spin-disordered surfaces.Comment: 29 pages including 11 figures embedded. Submitted to Phys. Rev.

Role of the oxygen partial pressure in the formation of composite Co-CoO nanoparticles by reactive aggregation

The magnetic properties of diluted films composed of nanocomposite Co-CoO nanoparticles (of ~8 nm diameter) dispersed in a Cu matrix have been investigated. The nanoparticles were formed in an aggregation chamber by sputtering at different Ar/O2 partial pressures (0-0.015). The exchange bias properties appear to be insensitive to the amount of O2 during their formation. However, the temperature dependence of the magnetization, M(T), exhibits two different contributions with relative intensities that correlate with the amount of O2. The magnetic results imply that two types of particles are formed, nanocomposite Co-CoO (determining the exchange bias) and pure CoO, as confirmed by transmission electron microscopy observations. Importantly, as the O2 partial pressure during the sputtering is raised the number of nanocomposite Co-CoO nanoparticles (exhibiting exchange bias properties) is reduced and, consequently, there is an increase in the relative amount of pure, antiferromagnetic CoO particles

Human hepatic HepaRG cells maintain an organotypic phenotype with high intrinsic CYP450 activity/metabolism and significantly outperform standard HepG2/C3A cells for pharmaceutical and therapeutic applications

Conventional in vitro human hepatic models for drug testing are based on the use of standard cell lines derived from hepatomas or primary human hepatocytes (PHHs). Limited availability, inter-donor functional variability and early phenotypic alterations of PHHs restrict their use; whilst standard cell lines such as HepG2 lack a substantial and variable set of liver-specific functions such as CYP450 activity. Alternatives include the HepG2-derivative C3A cells selected as a more differentiated and metabolically active hepatic phenotype. Human HepaRG cells are an alternative organotypic co-culture model of hepatocytes and cholangiocytes reported to maintain in vivo-like liver-specific functions, including intact Phase 1-3 drug metabolism. In this study, we compared C3A and human HepaRG cells using phenotypic profiling, CYP450 activity and drug metabolism parameters to assess their value as hepatic models for pre-clinical drug testing or therapeutics. Compared with C3As, HepaRG co-cultures, exhibit a more organotypic phenotype, including evidence of hepatic polarity with strong expression of CYP3A4, the major isoform involved in the metabolism of over 60% of marketed drugs. Significantly greater CYP450 activity and expression of CYP1A2, CYP2E1 and CYP3A4 genes in HepaRG cells (comparable with that of human liver tissue) was demonstrated. Moreover, HepaRG cells also preferentially expressed the hepatic integrin α5β1 – an important modulator of cell behaviour including growth and survival, differentiation and polarity. Drug metabolite profiling of phenacetin (CYP1A2) and testosterone (CYP3A4) using LC-MS/MS and HPLC, respectively, revealed HepaRGs had more intact (Phase 1-2) metabolism profile. Thus, HepaRG cells significantly outperform C3A cells for potential pharmaceutical and therapeutic applications

Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells

Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome

Long-term safety and outcome of a temporary self-expanding metallic stent for achalasia: a prospective study with a 13-year single-center experience

To prospectively evaluate the long-term clinical safety and efficacy of a newly designed self-expanding metallic stent (SEMS) in the treatment of patients with achalasia. Seventy-five patients with achalasia were treated with a temporary SEMS with a 30-mm diameter. The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4–5 days after stent placement. Follow-up data focused on dysphagia score, technique and clinical success, clinical remissions and failures, and complications and was performed at 6 months, 1 year, and within 3 to 5 years, 5 to 8 years, 8 to 10 years, and >10 years postoperatively. Stent placement was technically successful in all patients. Complications included stent migration (n = 4, 5.33%), chest pain (n = 28, 38.7%), reflux (n = 15, 20%), and bleeding (n = 9, 12%). No perforation or 30-day mortality occurred. Clinical success was achieved in all patients 1 month after stent removal. The overall remission rates at 6 months, 1, 1–3, 3–5, 5–8, 8–10, and >10 year follow-up periods were 100%, 96%, 93.9%, 90.9%, 100%, 100%, and 83.3%, respectively. Stent treatment failed in six patients, and the overall remission rate in our series was 92%. The median and mean primary patencies were 2.8 ± 0.28 years (95% CI: 2.25–3.35) and 4.28 ± 0.40 years (95% CI: 3.51–5.05), respectively. The use of temporary SEMSs with 30-mm diameter proved to be a safe and effective approach for managing achalasia with a long-term satisfactory clinical remission rate

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks