Terkelsenbroe1827

USP22 positively regulated transcription factor FOXP3 activity in mouse regulatory T (Treg) cells.Loss of the gluconeogenic enzyme FBP1 promoted hepatocellular carcinoma development in mice.Metabolites produced in cancer cells interfered with resolution of DNA double-strand breaks.Mutagen-induced DNA lesions were not all resolved prior to mitosis, yielding mutational strand bias.A liquid biopsy-based method, dubbed EV-CLUE, discerned breast cancer invasiveness and metastasis.Modified PD-1 incorporating an unnatural amino acid covalently bound PD-L1 to shrink tumors in vivo.In mice, senescence-targeted CAR T cells extended survival in lung cancer and improved liver fibrosis.

Emergency tracheal intubation during major trauma resuscitation may be associated with unrecognised endobronchial intubation. The risk factors and outcomes associated with this issue have not previously been fully defined.

We retrospectively analysed adult patients admitted directly from the scene to the ED of a single level 1 trauma centre, who received either prehospital or ED tracheal intubation prior to initial whole-body CT from January 2008 to December 2019. Our objectives were to describe tube-to-carina distances (TCDs) via CT and to assess the risk factors and outcomes (mortality, length of intensive care unit stay and mechanical ventilation) of patients with endobronchial intubation (TCD <0 cm) using a multivariable model.

We included 616 patients and discovered 26 (4.2%) cases of endobronchial intubation identified on CT. Factors associated with an increased risk of endobronchial intubations were short body height (OR per 1 cm increase 0.89; 95% CI 0.84 to 0.94; p≤0.001), a high body mass index (OR 1.14; 95% CI 1.04 to 1.25; p=0.005) and ED intubation (OR 3.62; 95% CI 1.39 to 8.90; p=0.006). Eight of 26 cases underwent tube thoracostomy, four of whom had no evidence of underlying chest injury on CT. There was no statistically significant difference in mortality or length of stay although the absolute number of endobronchial intubations was small.

Short body height and high body mass index were associated with endobronchial intubation. Before considering tube thoracostomy in intubated major trauma patients suspected of pneumothorax, the possibility of unrecognised endobronchial intubation should be considered.

Short body height and high body mass index were associated with endobronchial intubation. Before considering tube thoracostomy in intubated major trauma patients suspected of pneumothorax, the possibility of unrecognised endobronchial intubation should be considered.T-cell exhaustion was a four-stage process; the transition to terminal exhaustion was irreversible.Berzosertib upped survival in those with platinum-resistant tumors and short platinum-free intervals.Whether metastases were seeded mono- or polyclonally depended on cancer site and treatment.Most oral cancers arise from oral potentially malignant lesions, which show varying grades of dysplasia. Risk of progression increases with increasing grade of dysplasia, however risk prediction among oral low-grade dysplasia (LGDs) i.e., mild and moderate dysplasia can be challenging as only 5-15% transform. Moreover, grading of dysplasia is subjective and varies with the area of the lesion being biopsied. To date, no biomarkers or tools are used clinically to triage oral LGDs. This study utilizes a combination of DNA ploidy and chromatin organization (CO) scores from cells obtained from lesion brushings to identify oral LGDs at high-risk of progression. A total of 130 lesion brushings from patients with oral LGDs were selected of which 16 (12.3%) lesions progressed to severe dysplasia or cancer. DNA ploidy and CO scores were analyzed from nuclear features measured by our in-house DNA image cytometry (DNA-ICM) system and used to classify brushings into low risk and high risk. A total of 57 samples were classified as high-risk of which 13 were progressors. High-risk DNA brushing was significant for progression (P = 0.001) and grade of dysplasia (P = 0.004). Multivariate analysis showed high-risk DNA brushing showed 5.1 to 8-fold increased risk of progression, a stronger predictor than dysplasia grading and lesion clinical features. DNA-ICM can serve as a non-invasive, high throughput tool to identify high-risk lesions several years prior to transformation. This will help clinicians focus on such lesions while low-risk lesions may be spared from unnecessary biopsies.The small-molecule tyrosine kinase inhibitor tucatinib outperformed placebo against brain metastases.Posterior fossa A (PFA) ependymomas required a hypoxic environment to maintain their epigenomes.IL18 engineered not to bind a decoy receptor, but not normal IL18, had antitumor efficacy in mice.Oxaliplatin caused ileal apoptosis and Tfh-cell enrichment and perturbed microbiota in colon cancer.Tumor antigen-loaded vesicles were transferred between dendritic cells for presentation to T cells.

Outcomes of surgery for Ménière's disease (MD) remain discordant. Recently, a new surgical procedure in which the endolymphatic duct is clipped was proposed. To date, only one prospective trial assessing this technique was published, yielding promising results. This protocol describes a prospective, double-blinded, randomised controlled trial that will be carried out to assess the effectiveness of this surgical intervention.

Eighty-four patients with intractable MD will be recruited from 13 hospitals in the Netherlands. Intraoperatively, randomisation will determine whether endolymphatic duct blockage (EDB) or endolymphatic sac decompression (ESD) will be performed. Randomisation will be 11 stratified for gender and duration of MD (recent-onset versus mature MD). All participants receive vestibular rehabilitation after surgery. Patients are followed up during 1 year after surgery. Follow-up visits will take place at 1 week, 3 months, 6 months and 12 months after surgery. The main study endpoint is proportion of patients who are free of vertigo spells at 12 months postoperatively. Secondary parameters include cumulative number of vertigo bouts, co-intervention, tinnitus, hearing, quality of life, cost effectiveness and a budget impact analysis. Total duration of the study is 4 years.

The primary analysis will follow the intention-to-treat principle. For the primary outcome, a χ

test will be performed. Secondary outcomes will be analysed using a linear mixed model (EDB versus decompression group) at the different time measurement point.

This study was reviewed and approved by a board of specialists before funding was obtained, as well as by the Medical Research Ethics Committee Leiden-The Hague-Delft and the boards of all participating centres. Results of this study will be published in international peer-reviewed scientific journals and will be presented on (inter)national scientific conferences and meetings.

NL9095 and ISRCTN12074571; Pre-Results.

NL9095 and ISRCTN12074571; Pre-Results.

While colon cancer (CC) risk is associated with several lifestyle-related factors, including physical inactivity, smoking and diet, the contribution of occupation to CC morbidity remains largely unclear. Growing evidence indicates that gastrointestinal infections like salmonellosis could contribute to CC development. We performed a nationwide registry study to assess potential associations between occupation (history) and CC, including also those occupations with known increased exposure to gastrointestinal pathogens like

METHODS Person-level occupational data for all residents in The Netherlands were linked to CC diagnosis data. Differences in the incidence of (overall, proximal and distal) CC among occupational sectors and risk groups were tested for significance by calculating standardised incidence ratios (SIRs) with 95% CIs using the general population as reference group. Effects of gender, age, exposure duration and latency were also assessed.

Significant differences in CC incidence were observedy suggest that occupation in itself provides a relatively small contribution to CC incidence. This is consistent with previous studies where a similar degree of variation in risk estimates was observed. The lack of an association with the high-risk occupations for salmonellosis might be due to higher levels of physical activity, a known protective factor for CC and other diseases, of people working in the agricultural sector, which might outweigh the potential Salmonella-associated risk of CC.

Integrated care aims to improve population health. Obesity and mental health are major health issues worldwide. learn more The complexity of the multifactorial drivers of these public health problems has led to the adoption of a whole system approach. This review aims to highlight factors that influence the planning, implementation and evaluation of whole system integrated care for these conditions.

Using the framework of Arksey and O' Malley, we will perform a comprehensive search in the following databases MEDLINE, CINAHL, PsychINFO, PubMed, British Nursing Database, Web of Science, Health Systems Evidence, Cochrane Library and University of York Centre for Reviews and Dissemination. Further hand-search of reference lists and the grey literature will be conducted. The search will be restricted to articles published from 2000 to 2020. The review is expected to be completed by August 2021. Full texts of the potential studies will be screened for the inclusion criteria. Quality of studies will be appraised. Narrative synthesis will be completed using data extracted from the included studies.

A favourable ethics opinion for this study was obtained from the Institute for Health Research Ethics Committee of the University of Bedfordshire (IHREC937). This review expects to identify information relating to factors that facilitate or hinder whole system integrated care for obesity and mental health. The finding from this review will be widely disseminated to stakeholders to inform implementation of whole system integrated care initiatives.

A favourable ethics opinion for this study was obtained from the Institute for Health Research Ethics Committee of the University of Bedfordshire (IHREC937). This review expects to identify information relating to factors that facilitate or hinder whole system integrated care for obesity and mental health. The finding from this review will be widely disseminated to stakeholders to inform implementation of whole system integrated care initiatives.

Evidence from previous pandemics, and the current COVID-19 pandemic, has found that risk of infection/severity of disease is disproportionately higher for ethnic minority groups, and those in lower socioeconomic positions. It is imperative that interventions to prevent the spread of COVID-19 are targeted towards high-risk populations. We will investigate the associations between social characteristics (such as ethnicity, occupation and socioeconomic position) and COVID-19 outcomes and the extent to which characteristics/risk factors might explain observed relationships in Scotland.The primary objective of this study is to describe the epidemiology of COVID-19 by social factors. Secondary objectives are to (1) examine receipt of treatment and prevention of COVID-19 by social factors; (2) quantify ethnic/social differences in adverse COVID-19 outcomes; (3) explore potential mediators of relationships between social factors and SARS-CoV-2 infection/COVID-19 prognosis; (4) examine whether occupational COVID-19 differences differ by other social factors and (5) assess quality of ethnicity coding within National Health Service datasets.