Vitiligo-like Depigmentation in a Patient Undergoing Treatment with Nivolumab for Advanced Renal-cell Carcinoma

Nivolumab is a fully human monoclonal antibody that targets the programmed cell death 1 (PD-1) immune checkpoint. It has been approved for its use in several types of advanced solid tumors, including melanoma, lung cancer, and renal cell carcinoma (RCC). The inhibition of PD-1 leads to an enhanced adaptive immune response against tumor cells through the activation of T-cells

Vitiligo-like Depigmentation in a Patient Undergoing Treatment with Nivolumab for Advanced Renal-cell Carcinoma

Nivolumab is a fully human monoclonal antibody that targets the programmed cell death 1 (PD-1) immune checkpoint. It has been approved for its use in several types of advanced solid tumors, including melanoma, lung cancer, and renal cell carcinoma (RCC). The inhibition of PD-1 leads to an enhanced adaptive immune response against tumor cells through the activation of T-cells

Dissecting the microglial response in transgenic models of amyloidogenesis and tauopathy

Amyloid-beta (Abeta) peptide deposits and hyperphosphorylated tau protein (phospho-tau) accumulate in Alzheimer’s disease (AD) brains. These abnormal protein aggregates leads to glial activation, synaptic dysfunction, neuronal loss and cognitive decline. While microglial response has mostly been analyzed in relation to Abeta accumulation, little is still known about inflammatory processes associated with tau pathology. Microglial reactivity and defective glial responses have been involved in these proteinopathies. Our aim is to clarify the effects of Abeta and tau separately, in order to improve the comprehension of their differential contribution to neuroinflammation and neurodegeneration. We compared the progression of these processes in an amyloidogenic AD model (APPSL/PS1M146L) and two different models of tauopathy (ThyTau22 and hP301S) from 2 to 18 months of age. Accumulation of aggregated proteins was assessed using specific anti- Abeta and phospho-tau antibodies. Inflammatory response was studied using a battery of microglial markers (Iba1, CD45, CD68, Trem2 and Gal-3). In the hippocampus of these models, Tau and Abeta pathologies initiated as early as 2 months of age and increased progressively with aging. Neuritic plaques induced a strong microglial activation associated to plaques in APP/PS1 mice. Interestingly, inflammatory markers and microglial reactivity were barely increased in the hippocampus of ThyTau mice in contrast to not only APP/PS1, but also to P301S mice, which displayed a prominent microglial response. Deciphering the specific effects of Abeta, tau and their different toxic species, would indeed enable the development of novel therapeutic strategies and drugs targeting neuroinflammatory pathways related to these proteinopathies.Universidad de Málaga. Campus de excelencia Andalucía-Tech. Supported by PI18/01557 (AG) and PI18/01556 (JV) grants from ISCiii of Spain co-financed by FEDER funds from European Union, and by grant PPIT.UMA.B1.2017/26 (RS-V)

Early outcomes from the Minimally Invasive Right Colectomy Anastomosis study (MIRCAST)

Anastomosis; ColectomyAnastomosi; ColectomiaAnastomosis; ColectomíaBackground The impact of method of anastomosis and minimally invasive surgical technique on surgical and clinical outcomes after right hemicolectomy is uncertain. The aim of the MIRCAST study was to compare intracorporeal and extracorporeal anastomosis (ICA and ECA respectively), each using either a laparoscopic approach or robot-assisted surgery during right hemicolectomies for benign or malignant tumours. Methods This was an international, multicentre, prospective, observational, monitored, non-randomized, parallel, four-cohort study (laparoscopic ECA; laparoscopic ICA; robot-assisted ECA; robot-assisted ICA). High-volume surgeons (at least 30 minimally invasive right colectomy procedures/year) from 59 hospitals across 12 European countries treated patients over a 3-year interval The primary composite endpoint was 30-day success, defined by two measures of efficacy—absence of surgical wound infection and of any major complication within the first 30 days after surgery. Secondary outcomes were: overall complications, conversion rate, duration of operation, and number of lymph nodes harvested. Propensity score analysis was used for comparison of ICA with ECA, and robot-assisted surgery with laparoscopy. Results Some 1320 patients were included in an intention-to-treat analysis (laparoscopic ECA, 555; laparoscopic ICA, 356; robot-assisted ECA, 88; robot-assisted ICA, 321). No differences in the co-primary endpoint at 30 days after surgery were observed between cohorts (7.2 and 7.6 per cent in ECA and ICA groups respectively; 7.8 and 6.6 per cent in laparoscopic and robot-assisted groups). Lower overall complication rates were observed after ICA, specifically less ileus, and nausea and vomiting after robot-assisted procedures. Conclusion No difference in the composite outcome of surgical wound infections and severe postoperative complications was found between intracorporeal versus extracorporeal anastomosis or laparoscopy versus robot-assisted surgery.The MIRCAST Study Group has received research intensification grants from the Regional Government of Cantabria, Spain, and a research grant from Intuitive Surgical (Sunnyvale, CA, USA). MIRCAST was designed and conducted independently at the Valdecilla Biomedical Research Institute (IDIVAL). The funding institutions had no influence in the design or conduct of the study

Paper-based chromatic toxicity bioassay by analysis of bacterial ferricyanide reduction

Water quality assessment requires a continuous and strict analysis of samples to guarantee compliance with established standards. Nowadays, the increasing number of pollutants and their synergistic effects lead to the development general toxicity bioassays capable to analyse water pollution as a whole. Current general toxicity methods, e.g. Microtox®, rely on long operation protocols, the use of complex and expensive instrumentation and sample pre-treatment, which should be transported to the laboratory for analysis. These requirements delay sample analysis and hence, the response to avoid an environmental catastrophe. In an attempt to solve it, a fast (15 min) and low-cost toxicity bioassay based on the chromatic changes associated to bacterial ferricyanide reduction is here presented. E. coli cells (used as model bacteria) were stably trapped on low-cost paper matrices (cellulose-based paper discs, PDs) and remained viable for long times (1 month at -20 °C). Apart from bacterial carrier, paper matrices also acted as a fluidic element, allowing fluid management without the need of external pumps. Bioassay evaluation was performed using copper as model toxic agent. Chromatic changes associated to bacterial ferricyanide reduction were determined by three different transduction methods, i.e. (i) optical reflectometry (as reference method), (ii) image analysis and (iii) visual inspection. In all cases, bioassay results (in terms of half maximal effective concentrations, EC50) were in agreement with already reported data, confirming the good performance of the bioassay. The validation of the bioassay was performed by analysis of real samples from natural sources, which were analysed and compared with a reference method (i.e. Microtox). Obtained results showed agreement for about 70% of toxic samples and 80% of non-toxic samples, which may validate the use of this simple and quick protocol in the determination of general toxicity. The minimum instrumentation requirements and the simplicity of the bioassay open the possibility of in-situ water toxicity assessment with a fast and low-cost protocolPostprint (author's final draft

Preventive behavior against SARS-CoV-2 infection in adults according to whether or not they live with children. A combined analysis of the nationwide COSMO-SPAIN and ENE-COVID surveys

Introduction: The protection of children is a major driver of behavior among those in charge of their care. We evaluated whether compliance with preventive measures against SARS-CoV-2 infection among adults living with children was different from that of those not living with them, in 2020. Methods: We used the COSMO-SPAIN (N = 867) and the nationally representative ENE-COVID (N = 29,926) surveys to estimate prevalence of compliance (95% confidence interval). Logistic model based standardization methods were applied to estimate standardized prevalence differences (SPrD) to the overall distribution of age, sex, education, history of COVID-19, and residence of other >60 yrs in the household. Results: We observed that adults living with children more frequently avoided bars (SPrDENE-COVID: 4.2%; 95% CI: 2.3-6.1), crowded places (SPrDCOSMO: 8.0%; 95% CI: 0.6-15.1) and did not use public transportation (SPrDENE-COVID: 4.9%; 95% CI: 3.0-6.7). They were also more worried about work and family conciliation (SPrDCOSMO: 12.2%; 95% CI: 4.8-19.5) and about closure of education centers (SPrDCOSMO: 26.5%; 95% CI: 19.4-33.6). Discussion: In general, adults living with children adopted slightly more frequently social distancing measures.IJ was hosted in the National Center of Epidemiology, thanks to a grant of Women for Africa 6th edition, with the contribution of ENDESA. COSMO-SPAIN was funded by Carlos III Health Institute and ENE-COVID was funded by Spanish Ministry of Health, Carlos III Health Institute, and Spanish National Health System.S