peptide into these targeted bioinspired nanovesicle , where the active PSA enzyme presents in these cells converts the drug to its active form. Our dually targeted PSA/PSMA hybrid vesicles has successfully improved site-specific prodrug delivery to tackle advanced prostate cancer, offering a novel and effective prostate cancer treatment.
  Vitamin D displays a broad spectrum of cardioprotective effects, preventing oxidative stress, inflammation and thrombosis and improving endothelial function. Previous studies have associated vitamin D deficiency with more extended and severe coronary artery disease (CAD) and worse outcome, and especially among patients with ST-segment elevation myocardial infarction (STEMI). However, few data have been reported on the association of vitamin D levels with the angiographic findings and epicardial reperfusion in STEMI patients undergoing primary percutaneous coronary intervention (pPCI), that was therefore the aim of the present study.
 
  A consecutive cohort of patients admitted for STEMI and treated with pPCI were included. The levels of 25(OH)D were assessed at admission by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). Hypovitaminosis D was defined for 25(OH)D<10ng/ml. We included in our study 450 patients, divided according to tertiles values of 25(OH)D. Lower vitamin D was ad reperfusion, Future dedicated studies will shed light on the prognostic implications of hypovitaminosis D in these patients and the potential therapeutic perspectives.The discovery of insulin 100 years ago and its application to the treatment of human disease in the years since have marked a major turning point in the history of medicine. The availability of purified insulin allowed for the establishment of its physiological role in the regulation of blood glucose and ketones, the determination of its amino acid sequence, and the solving of its structure. Over the last 50 years, the function of insulin has been applied into the discovery of the insulin receptor and its signaling cascade to reveal the role of impaired insulin signaling-or resistance-in the progression of type 2 diabetes. It has also become clear that insulin signaling can impact not only classical insulin-sensitive tissues, but all tissues of the body, and that in many of these tissues the insulin signaling cascade regulates unexpected physiological functions. Despite these remarkable advances, much remains to be learned about both insulin signaling and how to use this molecular knowledge to advance the treatment of type 2 diabetes and other insulin-resistant states.Down syndrome (DS) is a genetic neurodevelopmental disorder. In individuals with DS, a multidisciplinary approach to care is required to prevent multiple medical complications. The aim of this study was to describe the rehabilitation, medical care, and educational and social support provided to school-aged French DS patients with varying neuropsychological profiles. A mixed study was conducted. Quantitative data were obtained from a French multicentre study that included patients aged 4-20 years with diverse genetic syndromes. Qualitative data were collected by semi-structured face-to-face interviews and focus groups. Ninety-five DS subjects with a mean age of 10.9 years were included. Sixty-six per cent had a moderate intellectual disability (ID) and 18.9% had a severe ID.  https://www.selleckchem.com/  Medical supervision was generally multidisciplinary but access to medical specialists was often difficult. In terms of education, 94% of children under the age of six were in typical classes. After the age of 15, 75% were in medico-social institutions. Analysis of multidisciplinary rehabilitation conducted in the public and private sectors revealed failure to access physiotherapy, psychomotor therapy and occupational therapy, but not speech therapy. The main barrier encountered by patients was the difficulty accessing appropriate facilities due to a lack of space and long waiting lists. In conclusion, children and adolescents with DS generally received appropriate care. Though the management of children with DS has been improved considerably, access to health facilities remains inadequate.
  We aimed to develop and validate a prediction model, based on clinical history and examination findings on initial diagnosis of coronavirus disease 2019 (COVID-19), to identify patients at risk of critical outcomes.
 
  We used data from the SEMI-COVID-19 Registry, a cohort of consecutive patients hospitalized for COVID-19 from 132 centres in Spain (23rd March to 21st May 2020). For the development cohort, tertiary referral hospitals were selected, while the validation cohort included smaller hospitals. The primary outcome was a composite of in-hospital death, mechanical ventilation, or admission to intensive care unit. Clinical signs and symptoms, demographics, and medical history ascertained at presentation were screened using least absolute shrinkage and selection operator, and logistic regression was used to construct the predictive model.
 
  There were 10433 patients, 7850 in the development cohort (primary outcome 25.1%, 1967/7850) and 2583 in the validation cohort (outcome 27.0%, 698/2583). The PRIORITY model included age, cardiovascular disease, chronic kidney disease, dyspnoea, tachypnoea, confusion, systolic blood pressure, and SpO
  ≤93% or oxygen requirement. The model showed high discrimination for critical illness in both the development (C-statistic 0.823; 95% confidence interval (CI) 0.813, 0.834) and validation (C-statistic 0.794; 95%CI 0.775, 0.813) cohorts. A freely available web-based calculator was developed based on this model (https//www.evidencio.com/models/show/2344).
 
  The PRIORITY model, based on easily obtained clinical information, had good discrimination and generalizability for identifying COVID-19 patients at risk of critical outcomes.
 The PRIORITY model, based on easily obtained clinical information, had good discrimination and generalizability for identifying COVID-19 patients at risk of critical outcomes.Genome editing provides novel strategies for improving plant traits but mostly relies on conventional plant genetic transformation and regeneration procedures, which can be inefficient. In this study, we have engineered a Barley stripe mosaic virus-based sgRNA delivery vector (BSMV-sg) that is effective in performing heritable genome editing in Cas9-transgenic wheat plants. Mutated progenies were present in the next generation at frequencies ranging from 12.9% to 100% in three different wheat varieties, and 53.8%-100% of mutants were virus free. We also achieved multiplex mutagenesis in progeny using a pool of BSMV-sg vectors harboring different sgRNAs. Furthermore, we devised a virus-induced transgene-free editing procedure to generate Cas9-free wheat mutants by crossing BSMV-infected Cas9-transgenic wheat pollen with wild-type wheat. Our study provides a robust, convenient, and tissue culture-free approach for genome editing in wheat through virus infection.