Intestinal commensal microbiota and cytokines regulate Fut2+ Paneth cells for gut defense.

Paneth cells are intestinal epithelial cells that release antimicrobial peptides, such as α-defensin as part of host defense. Together with mesenchymal cells, Paneth cells provide niche factors for epithelial stem cell homeostasis. Here, we report two subtypes of murine Paneth cells, differentiated by their production and utilization of fucosyltransferase 2 (Fut2), which regulates α(1,2)fucosylation to create cohabitation niches for commensal bacteria and prevent invasion of the intestine by pathogenic bacteria. The majority of Fut2- Paneth cells were localized in the duodenum, whereas the majority of Fut2+ Paneth cells were in the ileum. Fut2+ Paneth cells showed higher granularity and structural complexity than did Fut2- Paneth cells, suggesting that Fut2+ Paneth cells are involved in host defense. Signaling by the commensal bacteria, together with interleukin 22 (IL-22), induced the development of Fut2+ Paneth cells. IL-22 was found to affect the α-defensin secretion system via modulation of Fut2 expression, and IL-17a was found to increase the production of α-defensin in the intestinal tract. Thus, these intestinal cytokines regulate the development and function of Fut2+ Paneth cells as part of gut defense.

Intestinal homeostasis and inflammation: Gut microbiota at the crossroads of pancreas-intestinal barrier axis.

The pancreas contains exocrine glands, which release enzymes (e.g., amylase, trypsin, and lipase) that are important for digestion and islets, which produce hormones. Digestive enzymes and hormones are secreted from the pancreas into the duodenum and bloodstream, respectively. Growing evidence suggests that the roles of the pancreas extend to not only the secretion of digestive enzymes and hormones but also to the regulation of intestinal homeostasis and inflammation (e.g., mucosal defense to pathogens and pathobionts). Organ crosstalk between the pancreas and intestine is linked to a range of physiological, immunological, and pathological activities, such as the regulation of the gut microbiota by the pancreatic proteins and lipids, the retroaction of the gut microbiota on the pancreas, the relationship between inflammatory bowel disease, and pancreatic diseases. We herein discuss the current understanding of the pancreas-intestinal barrier axis and the control of commensal bacteria in intestinal inflammation.

Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT. METHODS: The human intestinal bacteriomes and viromes from 9 patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophage-based and CRISPR spacer-based host bacteria-phage associations in samples from recipients before and after FMT and in donor samples were examined. The gene functions of intestinal microorganisms affected by FMT were evaluated. RESULTS: Metagenomic sequencing of both the viromes and bacteriomes revealed that FMT does change the characteristics of intestinal bacteriomes and viromes in recipients after FMT compared with those before FMT. In particular, many Proteobacteria, the fecal abundance of which was high before FMT, were eliminated, and the proportion of Microviridae increased in recipients. Most temperate phages also behaved in parallel with the host bacteria that were altered by FMT. Furthermore, the identification of bacterial and viral gene functions before and after FMT revealed that some distinctive pathways, including fluorobenzoate degradation and secondary bile acid biosynthesis, were significantly represented. CONCLUSIONS: The coordinated action of phages and their host bacteria restored the recipients' intestinal flora. These findings show that the restoration of intestinal microflora functions reflects the success of FMT.

Disparities in exposure to television advertising of sugar-sweetened and non-nutritive sweetened beverages among U.S. adults and teens, 2007-2013.

The objective of this study was to estimate disparities in exposure to television advertising of sugar-sweetened and non-nutritive sweetened beverages among U.S. adults and teens. Data (2007-2013) came from the National Consumer Survey and included 115,510 adult respondents (age 18+) and 8635 teen respondents (age 12-17). The data was originally accessed in 2018 and analyzed in 2019-2020. The main outcomes were individual-level estimated exposure to advertisements for regular soda, diet soda, and energy/sport drinks. The main exposures were by race/ethnicity, household income, and educational attainment. Non-white adults (teens) were exposed to an estimated (per year) 101.5 (190.1) regular soda ads, 49.5 (61.2) diet soda ads, and 157.1 (279.6) energy/sport ads per year while white respondents were exposed to 97.5 (127.7) regular soda ads, 45.8 (44.2) diet soda ads, and 123.9 (192.0) energy/sport ads per year. Adult (teen) respondents who were non-white with low incomes and with low educational attainment were exposed to 4.7% (53.7%) more regular soda ads, 6.6% (43.8%) more diet ads, and 23.2% (56.2%) more energy/sport ads than respondents who were white with high incomes and high educational attainment. Demographic and socio-economic groups with a higher prevalence of obesity were exposed to significantly more advertisements for sugar-sweetened beverages. When evaluating potential policies to regulate marketing of sugar-sweetened and non-nutritive sweetened beverages, policymakers should consider the disparate exposure of at-risk populations to advertising of sugar-sweetened and non-nutritive sweetened beverages.

Elevated A20 promotes TNF-induced and RIPK1-dependent intestinal epithelial cell death.

Intestinal epithelial cell (IEC) death is a common feature of inflammatory bowel disease (IBD) that triggers inflammation by compromising barrier integrity. In many patients with IBD, epithelial damage and inflammation are TNF-dependent. Elevated TNF production in IBD is accompanied by increased expression of the TNFAIP3 gene, which encodes A20, a negative feedback regulator of NF-κB. A20 in intestinal epithelium from patients with IBD coincided with the presence of cleaved caspase-3, and A20 transgenic (Tg) mice, in which A20 is expressed from an IEC-specific promoter, were highly susceptible to TNF-induced IEC death, intestinal damage, and shock. A20-expressing intestinal organoids were also susceptible to TNF-induced death, demonstrating that enhanced TNF-induced apoptosis was a cell-autonomous property of A20. This effect was dependent on Receptor Interacting Protein Kinase 1 (RIPK1) activity, and A20 was found to associate with the Ripoptosome complex, potentiating its ability to activate caspase-8. A20-potentiated RIPK1-dependent apoptosis did not require the A20 deubiquitinase (DUB) domain and zinc finger 4 (ZnF4), which mediate NF-κB inhibition in fibroblasts, but was strictly dependent on ZnF7 and A20 dimerization. We suggest that A20 dimers bind linear ubiquitin to stabilize the Ripoptosome and potentiate its apoptosis-inducing activity.

Antigen-Specific Mucosal Immunity Regulates Development of Intestinal Bacteria-Mediated Diseases.

BACKGROUND & AIMS: Dysregulation of the microbiome has been associated with development of complex diseases, such as obesity and diabetes. However, no method has been developed to control disease-associated commensal microbes. We investigated whether immunization with microbial antigens, using CpG oligodeoxynucleotides and/or curdlan as adjuvants, induces systemic antigen-specific IgA and IgG production and affects development of diseases in mice. METHODS: C57BL/6 mice were given intramuscular injections of antigens (ovalbumin, cholera toxin B-subunit, or pneumococcal surface protein A) combined with CpG oligodeoxynucleotides and/or curdlan. Blood and fecal samples were collected weekly and antigen-specific IgG and IgA titers were measured. Lymph nodes and spleens were collected and analyzed by enzyme-linked immunosorbent assay for antigen-specific splenic T-helper 1 cells, T-helper 17 cells, and memory B cells. Six weeks after primary immunization, mice were given a oral, nasal, or vaginal boost of ovalbumin; intestinal lamina propria, bronchial lavage, and vaginal swab samples were collected and antibodies and cytokines were measured. Some mice were also given oral cholera toxin or intranasal Streptococcus pneumoniae and the severity of diarrhea or pneumonia was analyzed. Gnotobiotic mice were gavaged with fecal material from obese individuals, which had a high abundance of Clostridium ramosum (a commensal microbe associated with obesity and diabetes), and were placed on a high-fat diet 2 weeks after immunization with C ramosum. Intestinal tissues were collected and analyzed by quantitative real-time polymerase chain reaction. RESULTS: Serum and fecal samples from mice given injections of antigens in combination with CpG oligodeoxynucleotides and curdlan for 3 weeks contained antigen-specific IgA and IgG, and splenocytes produced interferon-gamma and interleukin 17A. Lamina propria, bronchial, and vaginal samples contained antigen-specific IgA after the ovalbumin boost. This immunization regimen prevented development of diarrhea after injection of cholera toxin, and inhibited lung colonization by S pneumoniae. In gnotobiotic mice colonized with C ramosum and placed on a high-fat diet, the mice that had been immunized with C ramosum became less obese than the nonimmunized mice. CONCLUSIONS: Injection of mice with microbial antigens and adjuvant induces antigen-specific mucosal and systemic immune responses. Immunization with S pneumoniae antigen prevented lung infection by this bacteria, and immunization with C ramosum reduced obesity in mice colonized with this microbe and placed on a high-fat diet. This immunization approach might be used to protect against microbe-associated disorders of intestine.

The long-lasting impact of unemployment on life satisfaction: results of a longitudinal study over 20 years in East Germany.

BACKGROUND: Economic disruption in East Germany at the time of reunification (1990) resulted in a noticeable increase in unemployment. The present study provides data from a German cohort for over 20 years. The aim was to examine how the frequency of experiencing unemployment affects life satisfaction and whether their relationship changes over time. METHODS: In the Saxon Longitudinal Study, an age-homogeneous sample was surveyed annually from 1987 to 2016. Since 1996, 355 people (54% female) have been examined for issues related to unemployment. Life satisfaction was measured with both the Global Satisfaction with Life Scale and the Questions on Life SatisfactionModules questionnaire. RESULTS: In 1996, the participants were 23 years old and 50% of the sample was affected by unemployment. At all 16 different measuring points, participants who were never unemployed indicated higher life satisfaction than those who were once unemployed. The repeatedly unemployed consistently reported the lowest values of life satisfaction. In each year, there were significant differences with small to medium effect sizes. CONCLUSION: Our results support the notion that the adverse effects of unemployment on life satisfaction increase with the time spent unemployed. In 2016, only 2% of the cohort were currently unemployed, but differences between people with and without unemployment experience still exist. This indicates that the negative effect of the unemployment experience will last for a very long time. To the best of our knowledge, this is the first study that demonstrates the effect so persistently at so many measurement points for over 20 years.

Should We Divide Crohn's Disease Into Ileum-Dominant and Isolated Colonic Diseases?

Crohn's disease (CD) is an inflammatory bowel disease that can involve any region of the gastrointestinal tract. First described in 1932 as terminal ileitis or regional enteritis, it predominately involves the ileum with or without colonic involvement. Isolated colonic CD was first described in 1960 and since then the phenotypic classification of CD has evolved to stratify patients into isolated ileal, ileocolonic, or isolated colonic involvement. In the current review we evaluate the published literature regarding differences in epidemiology, natural history, pathogenesis, response to therapy, and disease monitoring, when stratified by disease location. Based on the available evidence consideration could be given to a new classification for CD, which splits it into ileum dominant (isolated ileal and ileocolonic) and isolated colonic disease. This may allow for a more optimized approach to clinical care and scientific research for CD.

Social relations and presence of others predict bystander intervention: Evidence from violent incidents captured on CCTV.

Are individuals willing to intervene in public violence? Half a century of research on the "bystander effect" suggests that the more bystanders present at an emergency, the less likely each of them is to provide help. However, recent meta-analytical evidence questions whether this effect generalizes to violent emergencies. Besides the number of bystanders present, an alternative line of research suggests that pre-existing social relations between bystanders and conflict participants are important for explaining whether bystanders provide help. The current paper offers a rare comparison of both factors-social relations and the number of bystanders present-as predictors of bystander intervention in real-life violent emergencies. We systematically observed the behavior of 764 bystanders across 81 violent incidents recorded by surveillance cameras in Copenhagen, Denmark. Bystanders were sampled with a case-control design, their behavior was observed and coded, and the probability of intervention was estimated with multilevel regression analyses. The results confirm our predicted association between social relations and intervention. However, rather than the expected reversed bystander effect, we found a classical bystander effect, as bystanders were less likely to intervene with increasing bystander presence. The effect of social relations on intervention was larger in magnitude than the effect of the number of bystanders. We assess these findings in light of recent discussions about the influence of group size and social relations in human helping. Further, we discuss the utility of video data for the assessment of real-life bystander behavior.

A comprehensive understanding of the gut mucosal immune system in allergic inflammation.

Despite its direct exposure to huge amounts of microorganisms and foreign and dietary antigens, the gut mucosa maintains intestinal homeostasis by utilizing the mucosal immune system. The gut mucosal immune system protects the host from the invasion of infectious pathogens and eliminates harmful non-self antigens, but it allows the cohabitation of commensal bacteria in the gut and the entry of dietary non-self antigens into the body via the mucosal surface. These physiological and immunological activities are regulated by the ingenious gut mucosal immune network, comprising such features as gut-associated lymphoid tissue, mucosal immune cells, cytokines, chemokines, antimicrobial peptides, secretory IgA, and commensal bacteria. The gut mucosal immune network keeps a fine tuned balance between active immunity (against pathogens and harmful non-self antigens) and immune tolerance (to commensal microbiota and dietary antigens), thus maintaining intestinal healthy homeostasis. Disruption of gut homeostasis results in persistent or severe gastrointestinal infection, inflammatory bowel disease, or allergic inflammation. In this review, we comprehensively introduce current knowledge of the gut mucosal immune system, focusing on its interaction with allergic inflammation.

Regulation of Rac1 and Reactive Oxygen Species Production in Response to Infection of Gastrointestinal Epithelia.

Generation of reactive oxygen species (ROS) during infection is an immediate host defense leading to microbial killing. APE1 is a multifunctional protein induced by ROS and after induction, protects against ROS-mediated DNA damage. Rac1 and NAPDH oxidase (Nox1) are important contributors of ROS generation following infection and associated with gastrointestinal epithelial injury. The purpose of this study was to determine if APE1 regulates the function of Rac1 and Nox1 during oxidative stress. Gastric or colonic epithelial cells (wild-type or with suppressed APE1) were infected with Helicobacter pylori or Salmonella enterica and assessed for Rac1 and NADPH oxidase-dependent superoxide production. Rac1 and APE1 interactions were measured by co-immunoprecipitation, confocal microscopy and proximity ligation assay (PLA) in cell lines or in biopsy specimens. Significantly greater levels of ROS were produced by APE1-deficient human gastric and colonic cell lines and primary gastric epithelial cells compared to control cells after infection with either gastric or enteric pathogens. H. pylori activated Rac1 and Nox1 in all cell types, but activation was higher in APE1 suppressed cells. APE1 overexpression decreased H. pylori-induced ROS generation, Rac1 activation, and Nox1 expression. We determined that the effects of APE1 were mediated through its N-terminal lysine residues interacting with Rac1, leading to inhibition of Nox1 expression and ROS generation. APE1 is a negative regulator of oxidative stress in the gastrointestinal epithelium during bacterial infection by modulating Rac1 and Nox1. Our results implicate APE1 in novel molecular interactions that regulate early stress responses elicited by microbial infections.

ELMO1 Regulates Autophagy Induction and Bacterial Clearance During Enteric Infection.

Macrophages are specialized phagocytic cells involved in clearing invading pathogens. Previously we reported that engulfment and cell motility protein 1 (ELMO1) in macrophages mediates bacterial internalization and intestinal inflammation. Here we studied the role of ELMO1 in the fate of internalized targets. ELMO1 is present in the intracellular vesicles and enhances accumulation of the protein LC3B following engulfment of Salmonella or treatment with autophagy-inducing rapamycin. The protein ATG5 and the kinase ULK1 are involved in classical autophagy, while LC3-associated phagocytosis is ULK1 independent. ATG5 but not ULK1 cooperated with ELMO1 in LC3 accumulation after infection, suggesting the ELMO1 preferentially regulated LC3-associated phagocytosis. Because LC3-associated phagocytosis delivers cargo for degradation, the contribution of ELMO1 to the lysosome degradation pathways was evaluated by studying pH and cathepsin B activity. ELMO1-depleted macrophages showed a time-dependent increase in pH and a decrease in cathepsin B activity associated with bacterial survival. Together, ELMO1 regulates LC3B accumulation and antimicrobial responses involved in the clearance of enteric pathogens. This paper investigated how innate immune pathways involving ELMO1 work in a coordinated fashion to eliminate bacterial threats. ELMO1 is present in the phagosome and enhances bacterial clearance by differential regulation of lysosomal acidification and enzymatic activity.

Splenic irradiation before hematopoietic stem cell transplantation for chronic myeloid leukemia: long-term follow-up of a prospective randomized study.

In the context of discussions on the reproducibility of clinical studies, we reanalyzed a prospective randomized study on the role of splenic irradiation as adjunct to the conditioning for hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML). Between 1986 and 1989, a total of 229 patients with CML were randomized; of these, 225 (98 %; 112 with, 113 without splenic irradiation) could be identified in the database and their survival updated. Results confirmed the early findings with no significant differences in all measured endpoints (overall survival at 25 years: 42.7 %, 32.0-52.4 % vs 52.9 %, 43.2-62.6 %; p = 0.355, log rank test). Additional splenic irradiation failed to reduce relapse incidence. It did not increase non-relapse mortality nor the risk of late secondary malignancies. Comforting are the long-term results from this predefined consecutive cohort of patients: more than 60 % were alive at plus 25 years when they were transplanted with a low European Society for Blood and Marrow Transplantation (EBMT) risk sore. This needs to be considered today when treatment options are discussed for patients who failed initial tyrosine kinase inhibitor therapy and have an available low risk HLA-identical donor.

Warming before and after epidural block before general anaesthesia for major abdominal surgery prevents perioperative hypothermia: A randomised controlled trial.

BACKGROUND: Epidural analgesia (EDA) is known to be an independent risk factor for perioperative hypothermia and its many known adverse effects. Combined general and epidural anaesthesia decreases intraoperative core temperature more rapidly than general anaesthesia alone. Hence, adequate warming procedures are needed for these patients. OBJECTIVE: We evaluated the effects of active skin-surface warming before and/or after initiation of EDA during general anaesthesia as a procedure to prevent perioperative hypothermia. DESIGN: A randomised controlled trial. SETTING: Department of Anaesthesiology in a general hospital in Germany from January 2013 until August 2014. PATIENTS: After obtaining written informed consent, we included 99 adult patients undergoing elective major abdominal surgery under combined general anaesthesia and EDA with an expected duration of surgery of at least 120 min. Patients were excluded if they were under 18 years of age, classified as American Society of Anesthesiologists' physical status 4 or higher or if patients refused EDA. INTERVENTIONS: Patients were randomly assigned to one of three groups and received either only passive insulation, 15 min of active air-forced warming after EDA and before induction of general anaesthesia, or two periods, each of 15 min, of active air-forced warming before and after EDA. Core and skin temperatures were measured at several time points throughout the study. MAIN OUTCOME MEASURES: The primary outcome measure was the incidence of hypothermia on arrival in the ICU. The secondary outcome measure was the incidence of postoperative shivering. In addition, the perioperative change in body core temperature was recorded. RESULTS: Without prewarming (n = 32), 72% of patients became hypothermic (<36°C) at the end of anaesthesia. Fifteen minutes of warming after insertion of the epidural catheter and before initiation of general anaesthesia reduced the incidence of postoperative hypothermia to 6% (n = 33). After two periods of 15 min of warming before and after insertion of the epidural catheter, no patient became hypothermic (n = 34). Prewarming in either 'warming' group prevents the initial temperature drop which was observed in the control group. CONCLUSION: Warming for 15 min before and after initiation of EDA in patients receiving combined anaesthesia is effective in preventing postoperative hypothermia. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov (identifier: NCT01795482).

Brain angiogenesis inhibitor 1 is expressed by gastric phagocytes during infection with Helicobacter pylori and mediates the recognition and engulfment of human apoptotic gastric epithelial cells.

After Helicobacter pylori infection in humans, gastric epithelial cells (GECs) undergo apoptosis due to stimulation by the bacteria or inflammatory cytokines. In this study, we assessed the expression and function of brain angiogenesis inhibitor 1 (BAI1) in the engulfment of apoptotic GECs using human tissue and cells. After induction of apoptosis by H. pylori or camptothecin, there was a 5-fold increase in the binding of apoptotic GECs to THP-1 cells or peripheral blood monocyte-derived macrophages as assayed by confocal microscopy or conventional and imaging flow cytometry. Binding was impaired 95% by pretreating apoptotic cells with annexin V, underscoring the requirement for phosphatidylserine recognition. The phosphatidylserine receptor BAI1 was expressed in human gastric biopsy specimens and gastric phagocytes. To confirm the role of BAI1 in apoptotic cell clearance, the functional domain of BAI1 was used as a competitive inhibitor or BAI1 expression was inhibited by small interfering RNA. Both approaches decreased binding and engulfment >40%. Exposing THP-1 cells to apoptotic cells inhibited IL-6 production from 1340 to <364 pg/ml; however, this decrease was independent of phagocytosis. We conclude that recognition of apoptotic cells by BAI1 contributes to their clearance in the human gastric mucosa and this is associated with anti-inflammatory effects.

Helicobacter pylori infection inhibits phagocyte clearance of apoptotic gastric epithelial cells.

Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR(+) mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori-induced macrophage TNF-α, which was expressed at higher levels in H. pylori-infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori-infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.

Intraoperative temperature monitoring with zero heat flux technology (3M SpotOn sensor) in comparison with sublingual and nasopharyngeal temperature: An observational study.

BACKGROUND: Perioperative hypothermia is common in patients undergoing general anaesthesia and is associated with important adverse events. The 'gold standard' for monitoring body core temperature - the pulmonary artery catheter - is invasive and unsuitable for most patients. For routine clinical practice, other sites and methods of temperature monitoring are commonly used. OBJECTIVE: The aim of this study was to evaluate a new temperature sensor (3M SpotOn) using the 'zero heat flux' method attached to the forehead, and compare it to sublingual and nasopharyngeal sensors in terms of correlation, accuracy and precision. DESIGN: An observational study. SETTING: University Medical Center Schleswig Holstein, Campus Kiel, Germany from October 2013 to January 2014. PATIENTS: One hundred and twenty patients scheduled for elective gynaecological or trauma surgery undergoing general anaesthesia were enrolled into this study. Data of 83 patients were finally analysed. Patients with unexpected blood loss, haemodynamic instability determined by the need for continuous norepinephrine infusion and/or need for postoperative ventilation were excluded from this study. INTERVENTION: Temperature monitoring was established after induction of anaesthesia with sublingual and nasopharyngeal probes, and the SpotOn sensor. MAIN OUTCOME MEASURES: Body temperature was measured 15, 45 and 75 min after induction of anaesthesia from sublingual and nasopharyngeal probes and the 3M SpotOn sensor at precisely the same moment. RESULTS: Analysis of 83 data sets revealed that 3M SpotOn temperatures were almost identical with nasopharyngeal temperatures (mean difference 0.07 °C; P = 0.1424) and slightly lower than sublingual temperatures by 0.35 °C (P < 0.0001). Coefficients of determination (r) for both methods were between 0.87 (SpotOn vs. nasopharyngeal measurement) and 0.77 (SpotOn vs. sublingual measurement). Bland-Altman analysis revealed a bias (SD) between 0.07 °C (0.21) (SpotOn vs. nasopharyngeal) and -0.35 °C (0.29) (SpotOn vs. sublingual measurement). CONCLUSION: With respect to correlation, accuracy and precision, the 3M SpotOn sensor provides a good measurement of body temperature in comparison to the nasopharyngeal probe and an acceptable measurement in comparison with sublingual thermometry. It is adequate for clinical use. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02031159.

Extracellular adenosine regulates colitis through effects on lymphoid and nonlymphoid cells.

Adenosine is a purine metabolite that can mediate anti-inflammatory responses in the digestive tract through the A(2A) adenosine receptor (A(2A)AR). We examined the role of this receptor in the control of inflammation in the adoptive transfer model of colitis. Infection of A(2A)AR(-/-) mice with Helicobacter hepaticus increased colonic inflammation scores compared with uninfected A(2A)AR controls. Comparison of T cell subsets in wild-type and A(2A)AR(-/-) mice revealed differences in markers associated with activated helper T (Th) cells and regulatory T (Treg) cells. Previous studies showed that expression of A(2A)AR on CD45RB(HI) and CD45RB(LO) Th cells is essential for the proper regulation of colonic inflammation. Adoptive transfer of CD45RB(HI) with CD45RB(LO) from wild-type mice into RAG1(-/-)/A(2A)AR(-/-) mice induced severe disease within 3 wk, although transfer of the same subsets into RAG1(-/-) mice does not induce colitis. This suggests that the presence of A(2A)AR on recipient cells is also important for controlling colitis. To investigate the role of A(2A)AR in myeloid cells, chimeric recipients were generated by injection of bone marrow from RAG1(-/-) or RAG1(-/-)/A(2A)AR(-/-) mice into irradiated RAG1(-/-) mice. After adoptive transfer, these recipients did not develop colitis, regardless of A(2A)AR expression by the donor. Together, our results suggest that the control of inflammation in vivo is dependent on A(2A)AR signaling through multiple cell types that collaborate in the regulation of colitis by responding to extracellular adenosine.