A Multimethod Approach for Investigating Algal Toxicity of Platinum Nanoparticles

The ecotoxicity of platinum nanoparticles (PtNPs) widely used in for example automotive catalytic converters, is largely unknown. This study employs various characterization techniques and toxicity end points to investigate PtNP toxicity toward the green microalgae Pseudokirchneriella subcapitata and Chlamydomonas reinhardtii. Growth rate inhibition occurred in standard ISO tests (EC50 values of 15–200 mg Pt/L), but also in a double-vial setup, separating cells from PtNPs, thus demonstrating shading as an important artifact for PtNP toxicity. Negligible membrane damage, but substantial oxidative stress was detected at 0.1–80 mg Pt/L in both algal species using flow cytometry. PtNPs caused growth rate inhibition and oxidative stress in P. subcapitata, beyond what was accounted for by dissolved Pt, indicating NP-specific toxicity of PtNPs. Overall, P. subcapitata was found to be more sensitive toward PtNPs and higher body burdens were measured in this species, possibly due to a favored binding of Pt to the polysaccharide-rich cell wall of this algal species. This study highlights the importance of using multimethod approaches in nanoecotoxicological studies to elucidate toxicity mechanisms, influence of NP-interactions with media/organisms, and ultimately to identify artifacts and appropriate end points for NP-ecotoxicity testing

Anastomosis término-terminal yeyunal revestida con colgajo mesentérico en equinos

Postoperative complications after intestinal anastomosis remain the main concern in abdominal surgery in horses. The aim of this study was to describe an end-to-end jejunal anastomosis with a mesenteric flap covering technique and its macroscopic and postoperative histological characteristics. This technique is based on a reinforcement to the conventional surgery performed with a simple interrupted suture pattern to prevent postoperative complications. Five previously premedicated horses with xylazine 0.5 mg/kg, acepromazine 0.03 mg/kg and tramadol 2 mg/kg were induced to general anesthesia with diazepam 0.25 mg/kg and ketamine 2.2 mg/kg. General anesthesia was maintained with a minimum alveolar concentration of 1.4 ± 0.2% of isoflurane. A midline abdominal wall approach was made. A 10 cm jejunal segment was selected for resection and end-to-end anastomosis. A mesenteric flap large enough and proportional to the perimeter of the suture line was cut to cover the anastomotic area, fixing it to the intestinal serosa with a simple non-perforating discontinuous suture. Two animals underwent relaparotomy on the 7th and 30th postoperative days to describe the macroscopic and histopathological characteristics of the anastomotic area. In the macroscopic evaluation, no adhesions were observed and the mesenteric lined was well adhered to the anastomotic line, without contraction or displacement. Histopathological findings evidenced a healing process and adaptation of the mesenteric flap to loose connective tissue, which included fibrocytes, collagen, and slight edema. This technique turned out to be effective and could be useful in cases where equine intestinal resection anastomosis is necessary.Las complicaciones posoperatorias tras la anastomosis intestinal siguen siendo la principal preocupación en la cirugía abdominal en equinos. El objetivo del presente estudio fue describir una anastomosis término-terminal yeyunal con técnica de recubrimiento de colgajo mesentérico y sus características macroscópicas e histológicas posoperatorias. Esta técnica se fundamenta en un refuerzo a la cirugía convencional realizada con patrón de sutura simple interrumpida para prevenir complicaciones posoperatorias. Cinco equinos previamente premedicados con xilacina 0.5 mg/kg, acepromacina 0.03 mg/kg y tramadol 2 mg/kg fueron inducidos a anestesia general con diazepam 0.25 mg/kg y ketamina 2.2 mg/kg. La anestesia general se mantuvo con una concentración alveolar mínima de 1.4 ± 0.2% de isofluorano. Se hizo un abordaje de la pared abdominal por línea media. Se seleccionó un segmento yeyunal de 10 cm para resección y anastomosis término-terminal. Se cortó un colgajo mesentérico lo suficientemente grande y proporcional al perímetro de la línea de sutura para recubrir el área anastomótica, fijándose a la serosa intestinal con sutura discontinua no perforante simple. Dos animales fueron sometidos a relaparotomía en los días 7 y 30 posoperatorios para describir las características macroscópicas e histopatológicas del área anastomótica. En la evaluación macroscópica no se observaron adherencias y el recubrimiento mesentérico estaba bien adherido a la línea anastomótica, sin contracción ni desplazamiento. Los hallazgos histopatológicos evidenciaron un proceso de curación y adaptación del colgajo mesentérico a un tejido conectivo laxo, que incluía fibrocitos, colágeno y un ligero edema. Esta técnica resultó ser eficaz y podría ser útil en los casos en que sea necesaria la anastomosis de resección intestinal equina

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health