A diverse and balanced human gut microbiota is crucial for maintaining normal human physiological functions. However, the impact of indoor microbiome and metabolites on gut microbiota is not well understood.
A self-administered questionnaire was used to collect information on more than 40 personal and environmental characteristics and dietary habits from 56 children in Shanghai, China. Shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS) were used to characterize the indoor microbiome and metabolomic/chemical exposure in children\'s living rooms. PacBio full-length 16 S rRNA sequencing was used to characterize children\'s gut microbiota. Associations between environmental characteristics and gut microbiota diversity/composition were assessed using PERMANOVA and regression.
In total, 6247 and 318 indoor and gut microbial species and 1442 indoor metabolites were characterized. Age of children (R2 = 0.033, p = 0.008), age start kindergarten (R2 = 0.029, p = 0.03), living adjacent to heavy traffic (R2 = 0.031, p = 0.01) and drinking soft drinks (R2 = 0.028, p = 0.04) significantly impacted overall gut microbial composition, consistent with previous studies. Having pets/plants and frequent vegetable intake were positively associated with gut microbiota diversity and the Gut Microbiome Health Index (GMHI), while frequent juice and fries intake decreased gut microbiota diversity (p < 0.05). The abundance of indoor Clostridia and Bacilli was positively associated with gut microbial diversity and GMHI (p < 0.01). Total indoor indole derivatives and 6 indole metabolites (L-tryptophan, indole, 3-methylindole, indole-3-acetate, 5-hydroxy-L-tryptophan and indolelactic acid, p < 0.05) were positively associated with the abundance of total protective gut bacteria, suggesting a potential role in promoting gut health. Neural network analysis revealed that these indole derivatives were derived from indoor microorganisms.
The study is the first to report associations between indoor microbiome/metabolites and gut microbiota, highlighting the potential role of indoor microbiome in shaping human gut microbiota.

UNASSIGNED: In metastatic colorectal cancer (mCRC), the efficacy of immune checkpoint blockade (ICB) has so far been limited to patients with microsatellite instability high tumors (MSI-H). Unfortunately, most mCRC patients suffer from non-immunogenic microsatellite stable (MSS) tumors. Therefore, new combinatorial strategies are urgently needed to enhance the immunogenicity of MSS tumors to finally increase the number of patients benefiting from ICB.
UNASSIGNED: The AVETUX trial aimed to combine the PD-L1 antibody avelumab with the standard of care chemotherapy combination FOLFOX and the anti-EGFR antibody cetuximab. Furthermore, we performed a central radiological review of the pre- and on-treatment computed tomography scans to better define the individual response to treatment.
UNASSIGNED: In total, 43 patients were treated of which 39 patients were confirmed as RAS/BRAF wildtype in central tissue review and finally response evaluated. A final progression-free survival (PFS) of 11.1 (range: 0.8 to 22.3 months) and a herein updated final overall survival (OS) of 32.9 months (range: 0.8 to 47.1 months) was reached. We observed a strong median depth of response of 67.5% tumor shrinkage and deepness of response correlated significantly with survival. On the other hand, early tumor shrinkage was not an indicator of better outcome at a cut-off of 20% (median values). In a next step, we correlated the individual best radiological response with potential ICB response biomarkers and found that the clonality and diversity, but not frequency of tumor infiltrating lymphocytes (TiLs) and peripheral blood mononuclear cells (PBMCs), strongly correlated with response. In summary, we report the final overall survival of the AVETUX trial and propose T cell clonality and diversity as a potential marker to predict response to chemo-immunotherapy combinations in MSS mCRC by performing a central radiological review.
UNASSIGNED: ClinicalTrials.gov, identifier (NCT03174405).

Climate policies could improve air quality, thereby generating health benefits and thus increasing labour input for economic growth. Nevertheless, health benefits are usually overlooked in evaluation frameworks of climate policies. In this paper, a dynamic recursive computable general equilibrium (CGE) model is adopted to define how climate policies are related to air pollution, namely [Formula: see text] concentrations. Health benefits of climate policies are divided into reduction of [Formula: see text]-related morbidity and mortality. The CGE model results show that both carbon tax and emission trading scheme (ETS) decrease morbidity and mortality; therefore, under climate policies, [Formula: see text]-related labour loss decreases, and thus increasing labour input triggers an economic boom. Carbon tax generates more health benefits in short term, while health benefits of ETS policy will gradually increase in long term. Hence, we conclude that regarding health benefits, a long-term ETS policy is preferable to a long-term carbon tax. This finding implies that the recently established nationwide ETS market in China is meaningful, as it will generate more health benefits in future. Nevertheless, the quantified health benefits in this paper still cannot compensate GDP loss induced by climate policy implementations, implying that it is a challenging task to unbiasedly model health benefits of climate policies. Hence, we have recommended that the scopes and contents of health benefits should be expanded in evaluations of climate policies.

Salivary gland (SG) development, maturation, and homeostasis require coordinated roles of transcription factors (TFs) that dictate specific cell identities and fate. The ETS family of proteins are important transcriptional drivers of diverse cell lineages, tissue development, and differentiation programs and hence are also likely to play an important role in the SG. Here we have leveraged genomic and epigenomic data of the SG to examine the expression profile of ETS genes and identified 2 closely related paralogs, Elf5 and Ehf, that are highly expressed in distinct epithelial subpopulations. By using a well-defined mouse knockout model of Elf5, we show that Elf5, despite its enriched expression in the acinar cells, is functionally dispensable for maintaining the homeostatic state of the adult SG epithelium. The lack of a discernible phenotype of the Elf5-null SG might be due to possible functional redundancy with Ehf or other ETS factors. To probe this possibility and to examine the specific consequences of Ehf loss in the SG, we used CRISPR-Cas9 to generate mice in which the DNA-binding ETS domain of Ehf is disrupted due to an insertion mutation. We demonstrate that the Ehf mutant (EhfMut) mice exhibit a distinct cellular phenotype with decreased granular convoluted tubules that are accompanied by an increased accumulation of the intercalated Sox9-positive ductal cell population. Interestingly, the ductal phenotype of the EhfMut animals is highly pronounced in males, reaffirming the established sexual dimorphism of the SG that exists in rodents. Our results show that unlike Elf5, Ehf plays a nonredundant role in directing ductal cell differentiation of the SG and highlights the phenotypic subtlety in mutant mice of closely related TFs and the importance of careful consideration of cell type-specific studies.

OBJECTIVE: The aim of the study was to investigate the empathy level and caring behaviors perceptions of nursing students.
METHODS: This cross-sectional and correlational study was conducted with 276 nursing students.
RESULTS: The mean Empathic Tendency Scale score was 62.71 ± 5.10 (min. 20 to max. 100), indicating a low level of empathy. The mean of the Caring Assessment Questionnaire was 5.42 ± 0.80 (min. 1 to max. 7), showing a good perception of caring behaviors. There was a positive, low, and significant relationship between empathy and caring behaviors (r = 0.286, p < 0.001).
CONCLUSIONS: This study revealed that nursing students have low-level empathy and high-level caring behaviors.
CONCLUSIONS: Throughout the educational process, the students\' caring competencies, which include empathy and caring behaviors, developed. It is suggested that humanistic and value-oriented pedagogical approaches be incorporated into nursing curricula.

To determine secondhand smoke (SHS) concentrations in prisons during the week of implementation of a new, national prisons smoke-free policy.
Repeated measurement of SHS concentrations immediately before and after implementation of smoke-free policies across all 15 prisons in Scotland, and comparison with previously gathered baseline data from 2016.
Fine particulate matter (PM2.5) measurements at a fixed location over a continuous 6-day period were undertaken at the same site in each prison as previously carried out in 2016. Outdoor air quality data from the nearest local authority measurement station were acquired to determine the contribution of outdoor air pollution to indoor prison measurement of PM2.5.
Air quality improved in all prisons comparing 2016 data with the first full working day postimplementation (overall median reduction -81%, IQR -76% to -91%). Postimplementation indoor PM2.5 concentrations were broadly comparable with outdoor concentrations suggesting minimal smoking activity during the period of measurement.
This is the first evaluation of changes in SHS concentrations across all prisons within a country that has introduced nationwide prohibition of smoking in prisons. All prisons demonstrated immediate substantial reductions in PM2.5 following policy implementation. A smoke-free prisons policy reduces the exposure of prison staff and prisoners to SHS.

Environmental tobacco smoke (ETS) exposure is considered an important public health issue in pediatric population. In this study, we aimed to investigate parents\' knowledge on side effects of passive smoking and counseling for parental smoking among pediatricians and family practitioners. Participants were biological parents of pediatric patients up to the age of 18 years old who attended Pediatric Hospital of Medical University of Warsaw. The questionnaire included 28 questions and queries on environmental tobacco smoke in children\'s environment. Medical students identified potential subjects and handed out previously created questionnaires. In total, 506 parents of children aged 0⁻18 years old were interviewed; 41% (207/506) of parents were smokers, 23% (114/506) were asked about ETS exposure by their pediatricians and 41% (205/506) by family physicians during routine visits. Only a minority of the respondents confirmed having \"no smoking\" policy in their car 31% (157/506) or in their households 24% (121/506). All parents believed that passive smoking could cause at least one harmful effect: most common were more frequent respiratory infections (43%), asthma (40%), and low birth weight (37%). Among smoking parents, 38% (78/207) has tried to quit smoking for their child\'s health sake; 63% (131/207) of smokers have never been asked to quit smoking by their doctor. Parents\' understanding of passive smoking among children differs from current medical knowledge. Rates of screening and counseling for parental smoking in pediatric and family practices are still unsatisfactory.

BACKGROUND: Disease assessment for recurrent glioblastoma (GBM) represents a challenge, especially with the use of antiangiogenic agents. Moreover, validated neuroradiological predictors of outcome are lacking. Recently, the concept of early tumor shrinkage (ETS) has been developed to better assess the ability of treatments in determining a rapid and remarkable tumor response. The aim of the study was to evaluate the role of ETS in predicting survival of GBM patients treated with BEV.
METHODS: We examined the radiological data of patients with recurrent GBM treated with bevacizumab (BEV) or fotemustine (FTM) in the randomized phase II AVAREG trial (EudraCT: 2011-001363-46). Radiologic assessments at first disease assessment (day 46) were used to calculate the relative change in the sum of the products of perpendicular diameters of all measurable lesions determined by either T1 contrast and T2/FLAIR.
RESULTS: In patients treated with BEV, the best ETS cut-off was reduction of 15% with T1 contrast and of 40% with T2/FLAIR. Adopting this cut-off for T1 contrast radiological changes, ETS was a significant predictor of OS for patients treated with BEV (HR = 0.511, 95%CI:0.269-0.971, p = 0.040). The cut-off obtained for T2/FLAIR was not significantly correlated with OS (p = 0.102), but we found a trend for correlation with survival when considering the variable as continuous (p = 0.058).
CONCLUSIONS: ETS evaluating T1 contrast reduction is a helpful predictor of survival in patients with recurrent GBM treated with BEV, and if validated in a larger prospective trial could be a helpful surrogate endpoint.

BACKGROUND: The thioredoxin system maintains redox balance through the action of thioredoxin and thioredoxin reductase. Thioredoxin regulates the activity of various substrates, including those that function to counteract cellular oxidative stress. These include the peroxiredoxins, methionine sulfoxide reductase A and specific transcription factors. Of particular relevance is Redox Factor-1, which in turn activates other redox-regulated transcription factors.
METHODS: Experimentally defined transcription factor binding sites in the human thioredoxin and thioredoxin reductase gene promoters together with promoters of the major thioredoxin system substrates involved in regulating cellular redox status are discussed. An in silico approach was used to identify potential putative binding sites for these transcription factors in all of these promoters.
CONCLUSIONS: Our analysis reveals that many redox gene promoters contain the same transcription factor binding sites. Several of these transcription factors are in turn redox regulated. The ARE is present in several of these promoters and is bound by Nrf2 during various oxidative stress stimuli to upregulate gene expression. Other transcription factors also bind to these promoters during the same oxidative stress stimuli, with this redundancy supporting the importance of the antioxidant response. Putative transcription factor sites were identified in silico, which in combination with specific regulatory knowledge for that gene promoter may inform future experiments.
CONCLUSIONS: Redox proteins are involved in many cellular signalling pathways and aberrant expression can lead to disease or other pathological conditions. Therefore understanding how their expression is regulated is relevant for developing therapeutic agents that target these pathways.

BACKGROUND: Spatially-resolved air pollution models can be developed in large areas. The resulting increased exposure contrasts and population size offer opportunities to better characterize the effect of atmospheric pollutants on respiratory health. However the heterogeneity of these areas may also enhance the potential for confounding. We aimed to discuss some analytical approaches to handle this trade-off.
METHODS: We modeled NO2 and PM10 concentrations at the home addresses of 1082 pregnant mothers from EDEN cohort living in and around urban areas, using ADMS dispersion model. Simulations were performed to identify the best strategy to limit confounding by unmeasured factors varying with area type. We examined the relation between modeled concentrations and respiratory health in infants using regression models with and without adjustment or interaction terms with area type.
RESULTS: Simulations indicated that adjustment for area limited the bias due to unmeasured confounders varying with area at the costs of a slight decrease in statistical power. In our cohort, rural and urban areas differed for air pollution levels and for many factors associated with respiratory health and exposure. Area tended to modify effect measures of air pollution on respiratory health.
CONCLUSIONS: Increasing the size of the study area also increases the potential for residual confounding. Our simulations suggest that adjusting for type of area is a good option to limit residual confounding due to area-associated factors without restricting the area size. Other statistical approaches developed in the field of spatial epidemiology are an alternative to control for poorly-measured spatially-varying confounders.