Background Healthcare professionals (HCPs) on the front lines against COVID-19 may face increased workload and stress. Understanding HCPs' risk for burnout is critical to supporting HCPs and maintaining the quality of healthcare during the pandemic. Methods To assess exposure, perceptions, workload, and possible burnout of HCPs during the COVID-19 pandemic we conducted a cross-sectional survey. The main outcomes and measures were HCPs' self-assessment of burnout, indicated by a single item measure of emotional exhaustion, and other experiences and attitudes associated with working during the COVID-19 pandemic. Findings A total of 2,707 HCPs from 60 countries participated in this study. Fifty-one percent of HCPs reported burnout. Burnout was associated with work impacting household activities (RR = 1�57, 95% CI = 1�39-1�78, P<0�001), feeling pushed beyond training (RR = 1�32, 95% CI = 1�20-1�47, P<0�001), exposure to COVID-19 patients (RR = 1�18, 95% CI = 1�05-1�32, P = 0�005), and making life prioritizing decisions (RR = 1�16, 95% CI = 1�02-1�31, P = 0�03). Adequate personal protective equipment (PPE) was protective against burnout (RR = 0�88, 95% CI = 0�79-0�97, P = 0�01). Burnout was higher in high-income countries (HICs) compared to low-and middle-income countries (LMICs) (RR = 1�18; 95% CI = 1�02-1�36, P = 0�018).

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The market for decaffeinated coffees has been increasingly expanding over the years. Caffeine extraction may result in losses of other compounds such as chlorogenic acids (CGA) and, consequently, their 1,5-gamma-quinolactones (CGL) in roasted coffee. These phenolic compounds are important for flavor formation as well as the health effects of coffee; therefore, losses due to decaffeination need to be investigated. The present study evaluates the impact of decaffeination processing on CGA and CGL levels of green and roasted arabica coffees. Decaffeination produced a 16% average increase in the levels of total CGA in green coffee (dry matter), along with a 237% increase in CGL direct precursors. Different degrees of roasting showed average increments of 5.5-18% in CGL levels of decaffeinated coffee, compared to regular, a change more consistent with observed levels of total CGA than with those of CGL direct precursors in green samples. On the other hand, CGA levels in roasted coffee were 3-9% lower in decaffeinated coffee compared to regular coffee. Although differences in CGA and CGL contents of regular and decaffeinated roasted coffees appear to be relatively small, they may be enough to affect flavor characteristics as well as the biopharmacological properties of the final beverage, suggesting the need for further study.

Although it has been shown that mast cell-deficient mice have diminished innate immune responses against bacteria, the most important immunoprotective factors secreted from activated mast cells have not been identified. Mouse mast cell protease 6 is a tetramer-forming tryptase. This serine protease is abundant in the secretory granules and is exocytosed upon bacterial challenge. Here we have described the generation of a mast cell protease-6-null mouse. Our discovery that mice lacking this neutral protease cannot efficiently clear Klebsiella pneumoniae from their peritoneal cavities reveals an essential role for this serine protease, and presumably its human ortholog, in innate immunity.Approximately 50% of the weight of a mature tissue mast cell (MC) 2 consists of protease-serglycin proteoglycan complexes stored in the secretory granules. In humans, ␤ tryptases are the most abundant MC-restricted neutral proteases (1-3). The corresponding tryptases in mice are mouse MC protease (mMCP)-6 (4, 5) and mMCP-7 (6), with mMCP-6 being the most similar in amino acid sequence and substrate specificity to human tryptase (hTryptase) ␤1 (7-9). MCs are the only cells that express mMCP-6, and this serine protease is particularly abundant in those MCs that reside in the peritoneal cavity, skin, and lung (4,5,10).Numerous biochemical studies have been carried out to understand the biosynthesis and substrate preference of mMCP-6. This tryptase is initially translated as a zymogen with a 245-mer mature domain. When the signal and propeptides are proteolytically removed, the mature protease spontaneously forms tetramers with the active site of each monomer facing the central core of the tetramer unit, as first described for its human ortholog (11). A positively charged face forms on the surface of each monomer, thereby allowing mature mMCP-6 to interact with negatively charged serglycin proteoglycans in the Golgi complex. The resulting tryptase-serglycin macromolecular complexes are then targeted and packaged in the cell secretory granules. When exocytosed, these complexes are retained in connective tissues for hours because of their large sizes (12). Protease inhibitors are abundant in blood. Nevertheless, no circulating protease inhibitor has been identified that rapidly inactivates mMCP-6 or hTryptase ␤1. Substrate specificity studies carried out using varied peptide combinatorial libraries revealed that recombinant mMCP-6 (7) and hTryptase ␤1 (8, 9) prefer to cleave peptides having a Pro at residues P2 to P5 and a Lys or Arg at residue P1. However, due to the unique structural constraints of the tetramer unit, the abilities of mMCP-6 and hTryptase ␤1 to cleave large-sized proteins are very limited. Thus, the importance of these evolutionally conserved enzymes in MC-dependent reactions remains to be determined.MC development in vivo is highly dependent on the cytokine kit ligand/stem cell factor on the surface of mesenchymal cells and its tyrosine kinase receptor c-Kit/CD117 on the surface of MC-committed progenitors. Signaling...

Epithelial tumor cells transit to a mesenchymal state in response to extracellular cues, in a process known as epithelial-to-mesenchymal transition (EMT). The precise nature of these cues has not been fully defined, an important issue given that EMT is an early event in tumor metastasis. Here, we have found that a population of metastasis-prone mouse lung adenocarcinoma cells expresses Notch and Notch ligands and that the Notch ligand Jagged2 promotes metastasis. Mechanistically, Jagged2 was found to promote metastasis by increasing the expression of GATA-binding ( IntroductionLung cancer is the foremost cause of cancer-related death in Western countries, and metastasis is the leading cause of death in patients with lung cancer. Improving clinical outcomes will require a better understanding of the biological processes that initiate metastasis. Toward that goal, mouse models have been generated that develop lung adenocarcinomas with high or low propensities for invasion and metastasis. Mice that express K-ras G12D alleles inducibly, conditionally, or somatically develop lung adenocarcinomas with low invasive and metastatic potential (1-5), whereas mice that express K-ras G12D and p53 R172H alleles develop lung adenocarcinomas that metastasize widely (6-9). Thus, K-ras-driven mouse models of lung cancer acquire metastatic potential with the addition of a second mutation commonly found in lung cancer.Investigators have used mouse models of cancer to study the biological basis of metastasis. In one working hypothesis, epithelial tumor cells acquire the ability to invade and disseminate by undergoing epithelial-to-mesenchymal transition (EMT), which is characterized by a loss of cell-cell attachments and apical-basal polarization and gain of mesenchymal and invasive properties (10-19). The process of EMT is regulated by several transcriptional suppressor families, including the zinc-finger proteins Snail1 and Snail2, the 2-handed zinc-finger δEF1 family factors

Desempenho de uma população brasileira no teste de alfabetização funcional para adultos na área de saúde ABSTRACT OBJECTIVE:To analyze the scoring obtained by an instrument, which evaluates the ability to read and understand items in the health care setting, according to education and age. METHODS:The short version of the Test of Functional Health Literacy in Adults was administered to 312 healthy participants of different ages and years of schooling. The study was conducted between 2006 and 2007, in the city of São Paulo, Southeastern Brazil. The test includes actual materials such as pill bottles and appointment slips and measures reading comprehension, assessing the ability to read and correctly pronounce a list of words and understand both prose passages and numerical information. Pearson partial correlations and a multiple regression model were used to verify the association between its scores and education and age. RESULTS:The mean age of the sample was 47.3 years (SD=16.8) and the mean education was 9.7 years (SD=5; range: 1 -17). A total of 32.4% of the sample showed literacy/numeracy defi cits, scoring in the inadequate and marginal functional health literacy ranges. Among the elderly (65 years or older) this rate increased to 51.6%. There was a positive correlation between schooling and scores (r=0.74; p<0.01) and a negative correlation between age and the scores (r=-0.259; p<0.01). The correlation between the scores and age was not signifi cant when the effects of education were held constant (rp=-0.031, p=0.584). A signifi cant association (B=3.877, Beta=0.733; p<0.001) was found between schooling and scores. Age was not a signifi cant predictor in this model p=0.584). CONCLUSIONS:The short version of the Test of Functional Health Literacy in Adults was a suitable tool to assess health literacy in the study population. The high number of individuals classifi ed as functional illiterates in this test highlights the importance of special assistance to help them properly understand directions for healthcare.

Context An association between tobacco smoking and prostate cancer (PCa) incidence and mortality was suggested in an earlier meta-analysis of 24 prospective studies in which dose–response associations and risks per unit of tobacco use were not examined. Objective We investigated the association between several measures of tobacco use and PCa mortality (primary outcome) and incidence (secondary outcome) including dose–response association. Evidence acquisition Relevant articles from prospective studies were identified by searching the PubMed and Web of Science databases (through January 21, 2014) and reference lists of relevant articles. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects methods. We also calculated population attributable risk (PAR) for smoking and PCa mortality. Evidence synthesis We included 51 articles in this meta-analysis (11 823 PCa deaths, 50 349 incident cases, and 4 082 606 cohort participants). Current cigarette smoking was associated with an increased risk of PCa death (RR: 1.24; 95% CI, 1.18–1.31), with little evidence for heterogeneity and publication bias. The number of cigarettes smoked per day had a dose–response association with PCa mortality ( p = 0.02; RR for 20 cigarettes per day: 1.20). The PAR for cigarette smoking and PCa deaths in the United States and Europe were 6.7% and 9.5%, respectively, corresponding to >10 000 deaths/ year in these two regions. Current cigarette smoking was inversely associated with incident PCa (RR: 0.90; 95% CI, 0.85–0.96), with high heterogeneity in the results. However, in studies completed in 1995 or earlier (considered as completed before the prostate-specific antigen screening era), ever smoking showed a positive association with incident PCa (RR: 1.06; 95% CI, 1.00–1.12) with little heterogeneity. Conclusions Combined evidence from observational studies shows a modest but statistically significant association between cigarette smoking and fatal PCa. Smoking appears to be a modifiable risk factor for PCa death. Patient summary Smoking increases the chance of prostate cancer death. Not smoking prevents this harm and many other tobacco-related diseases.

Background Healthcare professionals (HCPs) on the front lines against COVID-19 may face increased workload and stress. Understanding HCPs' risk for burnout is critical to supporting HCPs and maintaining the quality of healthcare during the pandemic. Methods To assess exposure, perceptions, workload, and possible burnout of HCPs during the COVID-19 pandemic we conducted a cross-sectional survey. The main outcomes and measures were HCPs' self-assessment of burnout, indicated by a single item measure of emotional exhaustion, and other experiences and attitudes associated with working during the COVID-19 pandemic. Findings A total of 2,707 HCPs from 60 countries participated in this study. Fifty-one percent of HCPs reported burnout. Burnout was associated with work impacting household activities (RR = 1�57, 95% CI = 1�39-1�78, P<0�001), feeling pushed beyond training (RR = 1�32, 95% CI = 1�20-1�47, P<0�001), exposure to COVID-19 patients (RR = 1�18, 95% CI = 1�05-1�32, P = 0�005), and making life prioritizing decisions (RR = 1�16, 95% CI = 1�02-1�31, P = 0�03). Adequate personal protective equipment (PPE) was protective against burnout (RR = 0�88, 95% CI = 0�79-0�97, P = 0�01). Burnout was higher in high-income countries (HICs) compared to low-and middle-income countries (LMICs) (RR = 1�18; 95% CI = 1�02-1�36, P = 0�018).