An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge Geodia barretti. This includes three new metabolites, namely geobarrettin A?C (1?3) and four known compounds, barettin (4), 8,9-dihydrobarettin (5), 6-bromoconicamin (6), and l-6-bromohypaphorine (7). The chemical structures of compounds 1?7 were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A (1) was assigned by ECD analysis and Marfey's method employing the new reagent l-Na-(1-fluoro-2,4-dinitrophenyl)tryptophanamide (l-FDTA). The isolated compounds were screened for anti-inflammatory activity using human dendritic cells (DCs). Both 2 and 3 reduced DC secretion of IL-12p40, but 3 concomitantly increased IL-10 production. Maturing DCs treated with 2 or 3 before co-culturing with allogeneic CD4? T cells decreased T cell secretion of IFN-?, indicating a reduction in Th1 differentiation. Although barettin (4) reduced DC secretion of IL-12p40 and IL-10 (IC50 values 11.8 and 21.0 µM for IL-10 and IL-12p40, respectively), maturing DCs in the presence of 4 did not affect the ability of T cells to secrete IFN-? or IL-17, but reduced their secretion of IL-10. These results indicate that 2 and 3 may be useful for the treatment of inflammation, mainly of the Th1 type.
An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge Geodia barretti. This includes three new metabolites, namely geobarrettin A?C (1?3) and four known compounds, barettin (4), 8,9-dihydrobarettin (5), 6-bromoconicamin (6), and l-6-bromohypaphorine (7). The chemical structures of compounds 1?7 were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A (1) was assigned by ECD analysis and Marfey's method employing the new reagent l-Na-(1-fluoro-2,4-dinitrophenyl)tryptophanamide (l-FDTA). The isolated compounds were screened for anti-inflammatory activity using human dendritic cells (DCs). Both 2 and 3 reduced DC secretion of IL-12p40, but 3 concomitantly increased IL-10 production. Maturing DCs treated with 2 or 3 before co-culturing with allogeneic CD4? T cells decreased T cell secretion of IFN-?, indicating a reduction in Th1 differentiation. Although barettin (4) reduced DC secretion of IL-12p40 and IL-10 (IC50 values 11.8 and 21.0 µM for IL-10 and IL-12p40, respectively), maturing DCs in the presence of 4 did not affect the ability of T cells to secrete IFN-? or IL-17, but reduced their secretion of IL-10. These results indicate that 2 and 3 may be useful for the treatment of inflammation, mainly of the Th1 type.
A total of 1075 Russians from the Russian part of Karelia were genotyped at high-resolution for the human leukocyte antigen loci HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 using next generation sequencing methods. The haplotypic and allelic profiles as well as Hardy-Weinberg proportions of this population sample were evaluated. As the most frequent 6-locus haplotype, A*03:01?g?~?B*07:02?g?~?C*07:02?g?~?DRB1*15:01?g?~?DQB1*06:02?g?~?DPB1*04:01?g was identified with an estimated frequency of 3.5%. No deviation from Hardy-Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database under the population name "Russia Karelia" and the identifier AFN3430.
The abrupt 8.2 ka cold event has been widely described from Greenland and North Atlantic records. However, its expression in shelf seas is poorly documented, and the temporal resolution of most marine records is inadequate to precisely determine the chronology of major events. A robust hydrographical reconstruction can provide an insight on climatic reaction times to perturbations to the Atlantic Meridional Overturning Circulation. Here we present an annually-resolved temperature and water column stratification reconstruction based on stable isotope geochemistry of Arctica islandica shells from the Fladen Ground (northern North Sea) temporally coherent with Greenland ice core records. Our age model is based on a growth increment chronology obtained from four radiometrically-dated shells covering the 8290-8100?cal BP interval. Our results indicate that a sudden sea level rise (SSLR) event-driven column stratification occurred between ages 8320-8220?cal BP. Thirty years later, cold conditions inhibited water column stratification but an eventual incursion of sub-Arctic waters into the North Sea re-established density-driven stratification. The water temperatures reached their minimum of ~3.7?°C 55 years after the SSLR. Intermittently-mixed conditions were later established when the sub-Arctic waters receded.
International reports have suggested that food allergies and food-induced anaphylaxis have increased in children. We investigated the incidence of emergency food reactions over a 10-year period.
This study retrospectively reviewed the medical records of children presenting to Umeå University hospital, Sweden, with an emergency food reaction from January 1, 2006 to December 31, 2015. Cases were identified using discharge codes for allergies and anaphylaxis. Anaphylaxis cases were included if they fulfilled the international criteria.
We found emergency food allergy reactions in 519 children (58% boys) from 2006-2015 at a median age of 1.3 years. One-third were hospitalised (32%) including 71/99 cases of anaphylaxis. Milk and eggs were the most commonly identified triggers. Emergency reactions to eggs increased during the study period with a Spearman rank correlation coefficient of 0.770 (p
Studies from several countries suggest that erecting fences on bridges more commonly used for suicide by jumping may be an effective way of reducing the risk of suicide by jumping from these bridges. Distribution of suicides by jumping off bridges has not yet been studied on a national level in any country. This study included all suicides by jumping from high places registered in the Norwegian Cause of Death Registry (COD) in the period 1999-2010 (n = 319). Combining data from the COD registry and information from police records, 71 cases of suicide by jumping off a bridge were identified involving 36 bridges. This form of suicide constituted approximately 1% of all suicides in Norway in the period 1999-2010. Almost half of these suicides were registered at only 6 bridges. Three Norwegian bridges were secured during the observation period of this study. Two bridges had barriers installed on the full length of the bridge with 11 suicides registered before barriers were installed, and none after. On the 1 bridge that was only partially secured, no change in numbers of suicides was observed after barriers were installed. One-third of jumps from bridges occurred over land. We found that although suicide by jumping off bridges was a relatively rare event, there is a potential for saving lives by installing physical barriers on bridges that are more commonly used for suicide by jumping.
Norwegian adolescents currently drink and smoke less on average than previous cohorts. Based on cross-sectional survey data, the individual and familial characteristics of 15-year-old non-users and users of alcohol and tobacco were compared to identify correlates to abstinence.
The survey was approved by the Norwegian Social Science Service. The sample consisted of 3107 adolescents from a 2011 school-based survey, of which 848 (27.3%) did not drink alcohol nor use tobacco. Associations with leisure time activities, risk perceptions, parenting style and social factors were analysed by logistic regression.
Most of the non-drinkers were also non-users of tobacco. Abstainers (neither alcohol nor tobacco use) tended to have less unorganized and more hobby-related leisure time activities, higher risk perceptions for smoking, and monitoring or emotionally supportive parents. They more rarely reported close relationships with their best friend and were more likely to report lower occurrences of drinking and smoking among friends or siblings.
Differences in perceived parenting styles and a lower degree of unorganized leisure in the abstainer group points to monitoring and closer emotional ties between parents and children as important factors in adolescent abstinence. An implication of these results is that promoting hobby-based activities might be a useful strategy for preventing alcohol and tobacco use in young people.
In most parts of the world, curatively intended treatment for esophageal cancer includes neoadjuvant therapy, either with chemoradiotherapy or chemotherapy alone, followed by esophagectomy. Currently 18F-FDG positron emission tomography/computed tomography (PET/CT) is used for preoperative disease staging, but is not well established in the evaluation of neoadjuvant treatment.
To evaluate changes in PET parameters in relation to the histological primary tumor response in the surgical specimen in patients randomized to neoadjuvant chemoradiotherapy or chemotherapy.
Patients were randomized between either neoadjuvant chemotherapy or chemoradiotherapy followed by esophagectomy.18F-FDG PET/CT exams were conducted at baseline and following neoadjuvant treatment. Standardized uptake ratio (SUR) values were measured in the primary tumor and compared as regards histological responders and non-responders as well as different treatment arms.
Seventy-nine patients were enrolled and 51 were available for analysis. A significant rate of SUR reduction was observed ( P?=?0.02) in the primary tumor in histological responders compared to non-responders. Changes in SUR were significantly greater in responders following chemoradiotherapy ( P?=?0.02), but not following chemotherapy alone ( P?=?0.49). There was no statistically significant difference in SUR in patients with a complete histological response compared to those with a subtotal response.
Our results are similar to those of previous studies and show that changes in the rate of SUR can be used reliably to differentiate histological responders from non-responders after neoadjuvant treatment with either chemoradiotherapy or chemotherapy. Limitations of current PET technology are likely to restrict the possibility of accurately ruling out limited residual disease.
