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The Arctic is subjected to all-encompassing disruptions in marine ecosystems caused by anthropogenic warming. To provide reliable estimates of how future changes will affect the ecosystems, knowledge of Arctic marine ecosystem responses to past environmental variability beyond the instrumental era is essential. Here, we present a novel approach on how to evaluate the state of benthic marine biotic conditions during the deglacial and Holocene period on the Northeast Greenland shelf. Benthic foraminiferal species were assigned traits (e.g., oxygen tolerance, food preferences) aiming to identify past faunal changes as a response to external forcing mechanisms. This approach was applied on sediment cores from offshore Northeast Greenland. We performed numerical rate-of-change detection to determine significant changes in the benthic foraminiferal traits. That way, the significant abrupt trait changes can be assessed across sites, providing a better understanding of the impact of climate drivers on the traits. Our results demonstrate that during the last ~ 14,000 years, bottom water oxygen is the main factor affecting the variability in the benthic foraminiferal faunas in this area. Our results show that significant changes in the traits correspond to drastic climate perturbations. Specifically, the deglacial-Holocene transition and mid-Holocene warm period exhibited significant change, with several trait turnovers. [ABSTRACT FROM AUTHOR]

Background: Childhood trauma (CT) are frequently reported by patients with bipolar disorder (BD), but it is unclear whether and how CT contribute to patients' cognitive and psychosocial impairments. We aimed to examine the impact of CT on cognition and psychosocial functioning in a large sample of 345 patients with BD and 183 healthy control participants (HC) using the Childhood Trauma Questionnaire, neurocognitive tests and ratings of mood symptoms and functioning. Results: Patients showed broad cognitive impairments across memory, attention and executive function and functional disability despite being in partial or full remission and had higher levels of CT than HC. Higher levels of CT correlated with impairments across almost all cognitive domains and lower psychosocial functioning across BD patients and HC. Of these, the associations between CT and poorer working memory and lower psychosocial functioning, respectively, prevailed after adjusting for clinical and demographical variables. Diagnosis of BD and estimated verbal intelligence did not moderate these associations. Analysis of CT sub-categories showed that working memory impairments were related particularly to childhood physical and emotional abuse, while psychosocial difficulties were related to physical and emotional neglect. Conclusions: CT may have negative implications for working memory and psychosocial functioning across both BD and healthy populations. If the findings are replicated, this would suggest that early interventions that reduce the frequency of CT in vulnerable families may aid children's cognitive and psychosocial development. [ABSTRACT FROM AUTHOR]

Brain abscesses are often polymicrobial and of unclear primary origin. Here, we compare the use of next‐generation sequencing (NGS) technology with classical microbiological diagnostics for identification of clinically relevant microorganisms and describe the microbiome profiling with respect to the primary source of brain abscess. Thirty‐six samples from 36 patients, with primary brain abscesses, were subjected to both culture‐ and 16S/18S rRNA Sanger sequencing‐based diagnostics ("standard methods") and compared to a 16S/18S amplicon‐based NGS, which were also subjected to a microbiome diversity analyses. Forty‐seven species were identified with "standard methods" compared to 96 species with NGS, both confirming and adding to the number of species identified (p < 0.05). The variation of the brain abscess microbiome diversity was not continuous but could be stratified comparing the presumable origin of infection ("dental," "sinus," "disseminated," or "unknown"). Alpha diversity did not differ (p > 0.05) between groups while beta diversity differed significantly (p = 0.003) comparing disseminated vs the other presumable origin of infection. Interesting, clustering was also detected between "dental" and "sinusitis," although not significantly (p = 0.07). Microbiome‐based diagnostics can increase sensitivity without losing specificity. The bacterial beta diversity differed between the presumably origin of the brain abscess and might help to clarify the primary source of infection. [ABSTRACT FROM AUTHOR]

Aims: The once‐weekly administered glucagon‐like peptide 1 (GLP‐1) receptor agonist (GLP‐1RA) semaglutide, has, in clinical trials, demonstrated significant reductions in glycated haemoglobin A1c (HbA1c) and body weight in persons with type 2 diabetes. We evaluated the real‐world clinical effects of semaglutide once weekly in a hospital‐based diabetes out‐patient clinic. Methods: This retrospective observational cohort study included persons with type 2 diabetes (n = 119) on a broad range of antidiabetic medicine: GLP‐1RA naïve persons (n = 37) and GLP‐1RA‐experienced persons (n = 82). Person characteristics at inclusion: age [median (quartiles)]: 65 (57, 72) years; body weight 99 (86, 118) kg; body mass index (BMI) 33 (29, 38) kg/m²; HbA1c 61 (54, 69) mmol/mol/(7.7 (7.1, 8.5) %). Data were collected at baseline and after 3, 6 and 12 months of semaglutide treatment. Data were analysed using a general linear mixed model for repeated measurements. Results: After 12 months, the reductions in HbA1c were (mean [95% confidence interval]: GLP‐1RA naïve: −12.8 [−17.0, −8.5] mmol/mol/ −1.2 [−1.6, −0.8]% (p < 0.01) and GLP‐1RA experienced: −6.4 [−9.0, −3.8] mmol/mol/ −0.6 [−0.8, −0.4]% (p < 0.01), respectively. Body weight reductions in GLP‐1RA naïve: −5 [−6.9, −3.1] kg (p < 0.01) and GLP‐1RA experienced: −3.2 [−4.4, −2.0] kg (p < 0.01), respectively. Seventy‐five percent received 1 mg QW semaglutide. Conclusion: We observed effects of semaglutide once weekly on HbA1c and body weight comparable with the effects observed in clinical studies with fewer persons in our cohort receiving maximum dose of semaglutide. [ABSTRACT FROM AUTHOR]

Antagonistic interactions between the sexes are important drivers of evolutionary divergence. Interlocus sexual conflict is generally described as a conflict between alleles at two interacting loci whose identity and genomic location are arbitrary, but with opposite fitness effects in each sex. We build on previous theory by suggesting that when loci under interlocus sexual conflict are located on the sex chromosomes it can lead to cycles of antagonistic coevolution between them and therefore between the sexes. We tested this hypothesis by performing experimental crosses using Drosophila melanogaster where we reciprocally exchanged the sex chromosomes between five allopatric wild-type populations in a round-robin design. Disrupting putatively coevolved sex chromosome pairs resulted in increased male reproductive success in 16 of 20 experimental populations (10 of which were individually significant), but also resulted in lower offspring egg-to-adult viability that affected both male and female fitness. After 25 generations of experimental evolution these sexually antagonistic fitness effects appeared to be resolved. To formalize our hypothesis, we developed population genetic models of antagonistic coevolution using fitness expressions based on our empirical results. Our model predictions support the conclusion that antagonistic coevolution between the sex chromosomes is plausible under the fitness effects observed in our experiments. Together, our results lend both empirical and theoretical support to the idea that cycles of antagonistic coevolution can occur between sex chromosomes and illustrate how this process, in combination with autosomal coadaptation, may drive genetic and phenotypic divergence between populations. [ABSTRACT FROM AUTHOR]

A handful of studies have investigated sexually antagonistic constraints on achieving sex‐specific fitness optima, although exclusively through male‐genome‐limited evolution experiments. In this article, we established a female‐limited X chromosome evolution experiment, where we used an X chromosome balancer to enforce the inheritance of the X through the matriline, thus removing exposure to male selective constraints. This approach eliminates the effects of sexually antagonistic selection on the X chromosome, permitting evolution toward a single sex‐specific optimum. After multiple generations of selection, we found strong evidence that body size and development time had moved toward a female‐specific optimum, whereas reproductive fitness and locomotion activity remained unchanged. The changes in body size and development time are consistent with previous results, and suggest that the X chromosome is enriched for sexually antagonistic genetic variation controlling these particular traits. The lack of change in reproductive fitness and locomotion activity could be due to a number of mutually nonexclusive explanations, including a lack of sexually antagonistic variance on the X chromosome for those traits or confounding effects of the use of the balancer chromosome. This study is the first to employ female‐genome‐limited selection and adds to the understanding of the complexity of sexually antagonistic genetic variation. [ABSTRACT FROM AUTHOR]

Background: bla TEM-1 encodes a narrow-spectrum β-lactamase that is inhibited by β-lactamase inhibitors and commonly present in Escherichia coli. Hyperproduction of blaTEM-1 may cause resistance to penicillin/β-lactamase inhibitor (P/BLI) combinations.Objectives: To characterize EC78, an E. coli bloodstream isolate, resistant to P/BLI combinations, which contains extensive amplification of blaTEM-1 within the chromosome.Methods: EC78 was sequenced using Illumina and Oxford Nanopore Technology (ONT) methodology. Configuration of blaTEM-1 amplification was probed using PCR. Expression of blaTEM-1 mRNA was determined using quantitative PCR and β-lactamase activity was determined spectrophotometrically in a nitrocefin conversion assay. Growth rate was assessed to determine fitness and stability of the gene amplification was assessed by passage in the absence of antibiotics.Results: Illumina sequencing of EC78 identified blaTEM-1B as the only acquired β-lactamase preceded by the WT P3 promoter and present at a copy number of 182.6 with blaTEM-1B bracketed by IS26 elements. The chromosomal location of the IS26-blaTEM-1B amplification was confirmed by ONT sequencing. Hyperproduction of blaTEM-1 was confirmed by increased transcription of blaTEM-1 and β-lactamase activity and associated with a significant fitness cost; however, the array was maintained at a relatively high copy number for 150 generations. PCR screening for blaTEM amplification of isolates resistant to P/BLI combinations identified an additional strain containing an IS26-associated amplification of a blaTEM gene.Conclusions: IS26-associated amplification of blaTEM can cause resistance to P/BLI combinations. This adaptive mechanism of resistance may be overlooked if simple methods of genotypic prediction (e.g. gene presence/absence) are used to predict antimicrobial susceptibility from sequencing data. [ABSTRACT FROM AUTHOR]

Genomic conflict between the sexes is caused by differences in the optimal male and female reproductive strategies, and is a major contributor to genetic, phenotypic, and life history variation. While early experimental work appeared to strongly support the sexual conflict paradigm, recent work has produced more ambiguous results. Recent advances in experimental evolution studies combined with theoretical arguments can shed light on why measuring fitness under a conflict is so challenging, including the incidental alteration of mating dynamics, demographic effects, and inherent complexity in what quantity selection maximizes. We stress that non-intuitive results do not necessarily mean the absence of conflict, and follow-up experiments to determine why a priori predictions failed can ultimately teach us more than if they had been confirmed. [ABSTRACT FROM AUTHOR]

CMY-2 is the most common plasmid-mediated AmpC β-lactamase in Escherichia coli isolates of human and animal origin. The aim of this study was to elucidate the epidemiology of CMY-2-producing E. coli in Denmark. Strain and plasmid relatedness was studied in 93 CMY-2-producing clinical and commensal E. coli isolates collected from 2006 to 2012 from humans, retail poultry meat, broilers, and dogs. Multilocus sequence typing (MLST), antimicrobial susceptibility testing, and conjugation were performed in conjunction with plasmid replicon typing, plasmid multilocus sequence typing (pMLST), restriction fragment length polymorphism (RFLP), and sequencing of selected blaCMY-2-harboring plasmids. MLST revealed high strain diversity, with few E. coli lineages occurring in multiple host species and sample types. blaCMY-2 was detected on plasmids in 83 (89%) isolates. Most (75%) of the plasmids were conjugative and did not (96%) cotransfer resistance to antimicrobials other than cephalosporins. The main replicon types identified were IncI1-Iγ (55%) and IncK (39%). Isolates from different host species mainly carried distinct plasmid subtypes. Seven of the 18 human isolates harbored IncI1-IIγ/sequence type 2 (ST2), IncI1-Iγ/ST12, or IncK plasmids highly similar to those found among animal isolates, even though highly related human and animal plasmids differed by nonsynonymous single nucleotide polymorphisms (SNPs) or insertion sequence elements. This study clearly demonstrates that the epidemiology of CMY-2 can be understood only by thorough plasmid characterization. To date, the spread of this β-lactam resistance determinant in Denmark is mainly associated with IncK and IncI1-Iγ plasmids that are generally distributed according to host-specific patterns. These baseline data will be useful to assess the consequences of the increasing human exposure to CMY-2-producing E. coli via animal sources. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the population dynamics of CTX-M-producing Enterobacteriaceae in individual pigs on a farm positive for CTX-M-14-producing Escherichia coli. Fecal samples were collected once around the farrowing time from five sows and four times along the production cycle from two of their respective offspring. Multiple colonies per sample were isolated on cefotaxime-supplemented MacConkey agar with or without prior enrichment, resulting in 98 isolates identified by matrixassisted laser desorption ionization-time of flight mass spectrometry and tested for blaCTX-M. CTX-M-positive isolates (n = 86) were typed by pulsed-field gel electrophoresis (PFGE). Plasmids harboring blaCTX-M were characterized in 22 representative isolates by replicon typing and restriction fragment length polymorphism. Based on the PFGE results, all individuals shed unrelated CTX-M- 14-producing E. coli strains during the course of life. Concomitant shedding of CTX-M-2/97-producing Proteus mirabilis or Providencia rettgeri was observed in two sows and two offspring. At least two genetically unrelated CTX-M-producing E. coli strains were isolated from approximately one-fourth of the samples, with remarkable differences between isolates obtained by enrichment and direct plating. A clear decrease in strain diversity was observed after weaning. Dissemination of blaCTX-M-14 within the farm was attributed to horizontal transfer of an IncK plasmid that did not carry additional resistance genes and persisted in the absence of antimicrobial selective pressure. Assessment of strain diversity was shown to be influenced by the production stage from which samples were collected, as well as by the isolation method, providing useful information for the design and interpretation of future epidemiological studies of CTX-M-producing Enterobacteriaceae in pig farms. [ABSTRACT FROM AUTHOR]

Background On skin contact, nickel accumulates in the stratum corneum, where it is probably bound to proteins and amino acids. One probable contributor is filaggrin, which binds nickel avidly. Filaggrin gene ( FLG) null mutations lead to a complete lack of filaggrin production from the affected allele, and have been associated with an increased risk of nickel contact sensitization in German and Danish adults. Objectives To investigate whether the experimental nickel elicitation threshold level differed between heterozygous FLG mutation and non-mutation carriers. Method Thirteen nickel-sensitized female patients, seven heterozygous mutation carriers and six non-mutation carriers (genotyped for R501X, 2282del4, or R2447X), were patch tested and performed a repeated open application test ( ROAT) with a nickel sulfate dilution series. Logistic threshold dose-response analyses were used to test for differences between the two groups. Results No difference was found in the dose-response relationship between FLG mutation and non-mutation carriers. Conclusions On the basis of this small patient study, it appears that the elicitation threshold level for nickel is independent of FLG null mutation single-allele carrier status. [ABSTRACT FROM AUTHOR]

Objectives To determine the population structure and genetic relatedness of plasmids encoding CMY-2 β-lactamase in clinical Escherichia coli from humans and companion animals within a defined geographical area. Methods In total, 42 human and 73 companion animal isolates displaying an AmpC phenotype were isolated at a regional diagnostic reference laboratory in the upper Midwestern USA during 2009–11. Following PCR screening for transferable AmpC genes and plasmid transformation, blaCMY-2-positive plasmids were characterized by S1 nuclease PFGE, PCR-based replicon typing, antimicrobial susceptibility testing of transformants, conjugation experiments, plasmid multilocus sequence typing and restriction fragment length polymorphism. Results blaCMY-2 occurred in 6 (14%), 56 (86%) and 6 (75%) isolates from humans, dogs and cats, respectively. Usually plasmids carrying blaCMY-2 were conjugative (78%) and did not contain additional resistance genes (82%). The replicon types were IncI1 (52%), IncA/C (13%), IncFII (10%), IncI2 (5%), IncL/M (3%), IncB/O (2%) or non-typeable (15%). Related IncI1/ST12 plasmids were detected in one human and five canine isolates, while the remaining plasmids did not show similarity across host species. A novel epidemiological linkage of blaCMY-2 with IncL/M plasmids and a new CMY gene variant (blaCMY-108) were found in human isolates. Conclusions This study is one of the first One Health attempts to compare plasmids encoding CMY-2 β-lactamase among clinical isolates from humans and companion animals in the same region. The results indicate an unforeseen heterogeneity of plasmid backgrounds and suggest limited exchange between the two populations, in which blaCMY-2 occurred at very different frequencies and was harboured by distinct plasmid types. [ABSTRACT FROM PUBLISHER]

Background Loss-of-function mutations in the filaggrin gene ( FLG) are associated with xerosis, atopic dermatitis, and early onset of hand eczema. Irritant exposure is a risk factor for occupational hand eczema, and FLG mutations increase the risk of occupational irritant contact dermatitis on the hands in hospital cohorts. It is unknown whether FLG mutations affect the level of irritant exposure. Objectives To evaluate whether exposure to occupational irritants was dependent on FLG mutations, atopic dermatitis, and age at hand eczema onset. Methods Randomly chosen Danish adults completed a questionnaire on general health and occupational exposures. Genotyping for FLG mutations ( R501X, 2282del4, and R2447X) and patch testing were performed. Results Overall, 38.7% of subjects reported present or previous occupational exposure to irritants. Among individuals who reported hand eczema onset before entering their work life, 50.6% (45/89) of FLG non-mutation carriers became exposed to irritants, as compared with 28.6% (4/14) of heterozygous and 0% (0/6) of homozygous mutation carriers ( p = 0.006). Avoidance was conspicuous among mutation carriers reporting childhood hand eczema and atopic dermatitis (odds ratio 0.08, 95% confidence interval 0.01-0.65). Conclusions Carriers of FLG mutations who have had hand eczema onset in childhood avoid occupational exposure to irritants; the association is most marked with homozygous mutation status combined with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Current knowledge on extended-spectrum beta-lactamases (ESBLs) in animals is based largely on cross-sectional studies and qualitative data. The aim of this longitudinal study was to elucidate carriage proportions and fecal counts of ESBL-producing Escherichia coli in pigs during the production cycle. At each of three ESBL-positive single-sited farrow-to-finisher pig farms (farms A, B, and C) included in the study, individual fecal samples were taken from 17 to 20 sows I week before farrowing and from 2 piglets of each sow's litter four times from birth to slaughter (as piglets, weaners, and finishers). Cefotaxime (CTX)-resistant coliforms in feces were counted on MacConkey agar containing 2 γg/ml CTX and characterized for the presence of ESBL-encoding genes by PCR and sequencing. CTX-M-positive pigs were detected in all age groups at farms A (BLACTX-M-1 group, compatible with BLACTX-M-14/17) and B (bIa~XMl group, compatible with bla~XM!/Ôl), whereas only three weaners were positive at farm C (bla~XMl group, compatible with bla~XMl,6~). A significant decrease in carriage was detected during the production cycle, with on average 50% carriage immediately after birth, 58% just before weaning, 29% during weaning, and 12% during finishing. The observed reduction in numbers of CTX-M-positive pigs was accompanied by a significant reduction in mean fecal counts of CTX-resistant coliforms from ~107 CFU/g in piglets to - i03 CFU/g in finishers (P < 0.001). These findings provide novel information about the epidemiology of ESBLs at the farm level and have important implications for assessments of risks of meat contamination during slaughter. [ABSTRACT FROM AUTHOR]

The immune system targets virus-infected cells by different means. One of the essential antiviral mechanisms is apoptosis induced by ligation of tumor necrosis factor receptor 1 (TNFR1). This receptor can be activated by tumor necrosis factor alpha (TNF-α), which upon binding to TNFR1 induces the assembly of first an inflammatory and later a proapoptotic signaling complex. Here, we report that infection by human herpesvirus 6B (HHV-6B) inhibited poly(ADP-ribose) polymerase (PARP) cleav-age, caspase 3 and 8 activation, and IκBOα Ser-32 phosphorylation downstream of TNFR1, indicating inhibition of both the inflammatory and apoptotic signaling pathways. We identified a hitherto uncharacterized viral protein, U20, as sufficient for mediating this inhibition. U20 was shown to locate to the cell membrane, and overexpression inhibited PARP cleavage, caspase 3 and 8 activation, IκBOα Ser-32 phosphorylation, and NF-κB transcriptional activity. Moreover, small interfering RNA (siRNA) knockdown of U20 demonstrated that the protein is necessary for HHV-6B-mediated inhibition of TNFR signaling during infec-tion. These results suggest an important novel function of U20 as a viral immune evasion protein during HHV-6B infection. [ABSTRACT FROM AUTHOR]

Clear cell carcinomas (CCC) of themullerian systemare considered high grade tumors, but morphologically, the cells of CCC show both low and high grade features. The aims of the current study were to categorize CCC into low and high nuclear grade types, correlate their association with endometriosis, and then observe possible variations in pathogenesis based on their expression of p53 and Ki-67. We studied 41 pure mullerian CCCs and designated each as either a high (HNG) or low (LNG) nuclear grade tumor. Morphologically, 17 (41%) CCCs were LNG and 24 (59%) were HNG. Nine (38%) HNG and 2 (12%) LNG tumors showed positive immunostaining with p53. Endometriosis was associated with 8 (47%) LNG tumors and 8 (33%) HNG CCCs. Of the 11 cases with p53 alteration, 4 (1 LNG and 3 HNG) were associated with endometriosis. Conclusions: HNG CCCs, irrespective of their association with endometriosis, have alterations of p53. In general, LNG ovarian and endometrial CCCs, irrespective of their association with endometriosis/adenomyosis, are less likely to show p53 alteration. It appears that mullerian CCCs may have variable pathogenesis depending on their nuclear grade and association with endometriosis. A larger study is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Clear cell carcinomas (CCC) of themullerian systemare considered high grade tumors, but morphologically, the cells of CCC show both low and high grade features. The aims of the current study were to categorize CCC into low and high nuclear grade types, correlate their association with endometriosis, and then observe possible variations in pathogenesis based on their expression of p53 and Ki-67. We studied 41 pure mullerian CCCs and designated each as either a high (HNG) or low (LNG) nuclear grade tumor. Morphologically, 17 (41%) CCCs were LNG and 24 (59%) were HNG. Nine (38%) HNG and 2 (12%) LNG tumors showed positive immunostaining with p53. Endometriosis was associated with 8 (47%) LNG tumors and 8 (33%) HNG CCCs. Of the 11 cases with p53 alteration, 4 (1 LNG and 3 HNG) were associated with endometriosis. Conclusions: HNG CCCs, irrespective of their association with endometriosis, have alterations of p53. In general, LNG ovarian and endometrial CCCs, irrespective of their association with endometriosis/adenomyosis, are less likely to show p53 alteration. It appears that mullerian CCCs may have variable pathogenesis depending on their nuclear grade and association with endometriosis. A larger study is needed to validate these findings. [ABSTRACT FROM AUTHOR]

It was recently shown that filaggrin null mutation carrier status was associated with nickel allergy and self-reported intolerance to costume jewellery. Because of the biochemical characteristics of filaggrin, it may show nickel barrier properties in the stratum corneum. To investigate whether subjects with filaggrin null mutations report nickel dermatitis at an earlier age than wild-type individuals, and to analyse whether null mutation carriers have stronger patch test reactivity to nickel sulfate than do wild-type individuals. A total of 3471 Danes (18-69 years of age) answered a questionnaire about general health, and underwent patch testing and filaggrin genotyping. The mean number of years at risk of developing nickel dermatitis was significantly lower for the filaggrin null genotype than for the wild-type genotype when ear piercing status was considered. In positive patch test readings, the proportion of null mutants increased with increasing reaction strength. Filaggrin null mutations may lower the age of onset of nickel dermatitis. The hypothesis that ear piercings obscure the effect of filaggrin null mutations on the development of nickel allergy in statistical analyses was supported. An association between the null genotype and increased nickel sensitivity was indicated by patch test reading and questionnaire data. [ABSTRACT FROM AUTHOR]

Background: Contact allergy epidemics to chromate and nickel were addressed in Denmark in 1983 and 1990 by regulatory interventions. Objectives: To evaluate whether regulatory interventions on nickel and chromate exposure have reduced the proportion of strong patch test reactions. Methods: 22 506 patients with dermatitis aged 4–99 years were patch tested with nickel sulfate, potassium dichromate, or cobalt chloride between 1977 and 2009. Results: The proportion of 3+ reactions to nickel sulfate was reduced and almost disappeared after the mid- and late 1980s ( P-trend = 0.001). Today, 1+ and 2+ nickel reactions occur equally frequent. Cobalt chloride patch test reactivity reflected the nickel development to some degree. The proportion of 3+ reactions to potassium dichromate was reduced during the 1980s ( P-trend = 0.13), whereas the proportion of 2+ reactions to potassium dichromate have increased in recent years. Conclusions: The decrease in nickel sulfate and cobalt chloride 3+ patch test reactivity began long before the Danish nickel regulation came into effect. This could be because of research activity at the time as well as political attention in Northern Europe. The chromate content in cement regulation may have changed the epidemiology of patch test reactivity; however, in recent years, 2+ reactions to chromate have increased markedly, a development that should be carefully followed. [ABSTRACT FROM AUTHOR]

We report a rare case of primary lymphoma of fallopian tube in a 68-year-old woman who underwent total hysterectomy and bilateral salpingo-oophorectomy for endometrial carcinoma. The specimen showed a welldifferentiated endometrioid adenocarcinoma with superficial myometrial invasion. The left fallopian tube revealed a 1 cm nodule that histologically showed diffuse lymphoid follicles consisting of small cleaved lymphocytes and occasional larger cells. The cells were immunopositive for CD20, BCL-2, and BCL-6 but negative for CD3 and CD43. Polymerase chain reaction confirmed a monoclonal B-cell population. Fluorescence in-situ hybridization revealed at (14, 18) translocation. The patient had absent lymphadenopathy and negative CT scan of chest, abdomen, and pelvis. The findings were consistent with a primary low grade follicular lymphoma of fallopian tube. She did not receive chemotherapy and remained disease free for 13 months after surgery. Our case suggests that primary lymphoma of fallopian tube may be associated with a favorable prognosis. [ABSTRACT FROM AUTHOR]

Today, the decision to treat breast cancer patients with endocrine therapy relies solely on tumor expression of two predictive factors, the estrogen receptor and the progesterone receptor. Expression of these hormone receptors are, however, not a guarantee for a response to treatment and patients who experience response at first may become resistant after prolonged treatment. This paper describes the use of preclinical models to identify mechanisms and new markers for endocrine sensitivity and resistance and the translation of these data to clinical utility. [ABSTRACT FROM AUTHOR]

Abstract: The reproductive success of most fish depends partly on their ability to perform correct courtship behaviour. Alteration of this behaviour due to xenooestrogens can potentially affect the reproductive output and consequently population dynamics. In this lifetime study, zebrafish (Danio rerio) were exposed to environmentally realistic (0.05, 0.50 and 5.00ngL−1) nominal concentrations of 17α-ethinyloestradiol (EE2) in a flow-through system for 4 months, from egg until sexual maturity. At 0.05ngEE2L−1, the secondary sexual characteristics of the males were significantly feminised with development of urogenital papillae and change in body colour. At 0.50ngEE2L−1, the sex ratio was altered from 69% males in the control groups to 59% males. The courtship behaviour of the male zebrafish was not affected by these two lower EE2 concentrations. Only at the highest concentration of 5.00ngEE2L−1, where only 5% of the group developed into males, was a change in behaviour recorded, and these few males were unable to induce spawning. Accordingly, the courtship behaviour of zebrafish is more resistant to oestrogenic exposure than secondary sexual characteristics and gonad development. This study provides the first quantitative measure of zebrafish courtship behaviour. [Copyright &y& Elsevier]

Objectives . The aim of the survey was to determine current practices for antiplatelet- and heparin therapy in OPCAB surgery in the Nordic countries. Design . A postal survey questionnaire was sent to all 26 departments of Cardiothoracic Surgery in Norway, Sweden, Iceland, Finland, and Denmark. Results . The overall response rate was 100%. The respondents performed between 130 and 1000 CABG procedures per year. Between 0.3% and 42.0% of these procedures were performed as OPCAB. Preoperative antiplatelet therapy was administered by 48%, while 96% routinely administer postoperative antiplatelet therapy. In the postoperative antiplatelet therapy there was a trend toward a combination of aspirin and low molecular weight heparin. Perioperative anticoagulation practices with heparin varied among departments as well as reversal with protamine. Eighty percent of the respondents register postoperative complications. Conclusion . In the Nordic countries there is no uniform practice regarding antiplatelet therapy pre- and postoperatively as well as heparin therapy perioperatively. Dose regimens are highly variable and standard protocols have not yet been developed. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate whether prenatal exposure to the suspected estrogenic compound 4-tert-octylphenol (OP), influences oocyte number in newborn female mice. In addition, effects on the percentage distribution of prefollicular, follicular, and atretic oocytes were investigated. Pregnant mice were subcutaneously injected with OP (1 or 250 mg/kg) or vehicle alone on embryonic day 11.5–16.5 (plug=embryonic day 0.5). As a positive control for estrogenic effects, a group of animals was injected with the synthetic estrogen diethylstilbestrol (DES, 100 μg/kg). Ovaries from the offspring were collected on the day of birth and a stereologic method, the optical fractionator, was used to estimate the number of prefollicular, follicular, and atretic oocytes in the ovaries. The total number of oocytes was calculated as the sum of the three subpopulation estimates. Neither OP nor DES exposure could be observed to affect the total number of oocytes or the percentage distribution of atretic, prefollicular, and follicular oocytes. Thus, prenatal OP exposure does not appear to cause a serious threat to fetal female germ cell proliferation and survival, or early follicle formation. [Copyright &y& Elsevier]

Aim: To describe the use of composite endpoints (CEs) in cardiovascular outcome trials (CVOTs) of type 2 diabetes and to evaluate the significance of the individual outcomes included within these CEs from the perspectives of both patients and clinicians. Secondary objectives were to estimate the gradient of treatment effects and events across outcomes. Materials and Methods: Eligible studies were randomized controlled trials assessing CV outcomes for patients with diabetes from 2008 and onwards. Trials were identified by searching the reports from the CVOT Summit of the Diabetes & CV Disease EASD (European Association for the Study of Diabetes) Study Group. The individual outcomes comprising the CE were compared for differences in importance for patients and clinicians, proportion of events, and effect size. Results: We included 22 trials randomizing a mean of 8098 patients to an active intervention or a comparator group for an average of 33 months (standard deviation 16). All primary outcomes were CEs, and from a patient perspective there was no gradient of importance across outcomes in 22 of 22 (100%) CEs, while the gradient was small in 22 of 22 (100%) from a clinician perspective. The gradient of effect was moderate to large in 9 of 18 (50%) reporting studies, while assessment of events was available in 15 of 22 studies (68%), finding that three of 15 (20%) had a gradient of effect of more than 5% points between included outcomes. In 10 of 22 (45%) trial reports, the results were not clearly presented as based on a CE. Conclusions: To avoid misinterpretation, clinicians and regulatory authorities should be careful when interpreting the results of trials, of which the main outcomes are CEs. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented offering information related to the properties of skin protein filaggrin and epidermal nickel-binding.

The article present a case study of a 63-year-old woman with abdominal discomfort and was found to have a large pelvic mass on imaging. It mentions Hysterectomy with bilateral salpingo-oophorectomy revealed a 13×10×5 cm intact right solid adnexal mass with attached dilated fallopian tube; and also mentions Gross inspection revealed a yellowish-white solid firm multilobulated mass with shiny outer surface.

The article presents a case study of a 57-year-old female presented with 2 left vulvar masses. It discusses the histological examinations revealed the Verrucous carcinoma (VC) as a histologic subtype of squamous cell carcinoma characterized by highly differentiated squamous cells with a bulbous invasive pattern of the underlying stroma often associated and confused with giant condyloma of Buschke-Löwenstein.

Pollination by wild pollinators is a key ecosystem service threatened by anthropogenic-induced land-use change. The proximity to natural habitat has previously been shown to positively affect pollinator communities and improve crop yield and quality but empirical evidence is limited from most parts of the World. Here, across six farms in Southern Thailand, we investigated the significance of landscape-level effects of natural habitat (proportion of and distance to evergreen forest) on both visitation rate and richness of pollinators as well as fruit set of guava (Psidium guajava L.), a local economically-important crop in the tropics. Overall, the most abundant pollinator was the Asian honey bee Apis cerana (39% of all visits) and different species of stingless bees (37%). We found that pollinator richness was unrelated to the proportion and distance to evergreen forest, however, the proportion of forest within a 1, 5 and 10 km radius had a significant positive impact on visitation rate of wild pollinators. Still, neither the various forest parameters nor pollinator visitation rate showed a significant impact on fruit set of guava, perhaps because guava self-pollinates. This illustrates that landscape-level degradation of natural habitat may negatively impact pollinator communities without diminishing the crop yield of the farmers. [ABSTRACT FROM AUTHOR]

In-hospital dysglycemia is associated with adverse outcomes. Identifying patients at risk of in-hospital dysglycemia early on admission may improve patient outcomes. We analysed 117 inpatients admitted with pneumonia and type 2 diabetes monitored by continuous glucose monitoring. We assessed potential risk factors for in-hospital dysglycemia and adverse clinical outcomes. Time in range (3.9–10.0 mmol/l) decreased by 2.9 %-points [95 % CI 0.7–5.0] per 5 mmol/mol [2.6 %] increase in admission haemoglobin A1c, 16.2 %-points if admission diabetes therapy included insulin therapy [95 % CI 2.9–29.5], and 2.4 %-points [95 % CI 0.3–4.6] per increase in the Charlson Comorbidity Index (CCI) (integer, as a measure of severity and amount of comorbidities). Thirty-day readmission rate increased with an IRR of 1.24 [95 % CI 1.06–1.45] per increase in CCI. In-hospital mortality risk increased with an OR of 1.41 [95 % CI 1.07–1.87] per increase in Early Warning Score (EWS) (integer, as a measure of acute illness) at admission. Dysglycemia among hospitalised patients with pneumonia and type 2 diabetes was associated with high haemoglobin A1c, insulin treatment before admission, and the amount and severity of comorbidities (i.e., CCI). Thirty-day readmission rate increased with high CCI. The risk of in-hospital mortality increased with the degree of acute illness (i.e., high EWS) at admission. Clinical outcomes were independent of chronic glycemic status, i.e. HbA1c, and in-hospital glycemic status. [Display omitted] • Knowledge of risk factors for in-hospital dysglycemia detected early at admission is sparse. • High HbA1c, insulin treatment before admission, and many comorbidities are risk factors at admission for dysglycemia during hospitalisation. • Early identification of patients at risk of in-hospital dysglycemia could initiate interventions and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Aims: In hospitals, 15%–20% of patients have diabetes. Therefore, all healthcare professionals (HCPs) must have a basic knowledge of in‐hospital diabetes management. This survey assessed the knowledge of diabetes among HCPs in Denmark. Methods: A 27‐item questionnaire was developed and reviewed independently before the survey was distributed. The questionnaire contained seven baseline questions on the HCPs' current workplace, educational level, usual shift routines and years of experience, 18 multiple‐choice questions and 2 cases. Results: A total of 252 completed questionnaires were returned by 133 (52.8%) physicians, 101 (40.1%) nurses and 18 (7.1%) healthcare assistants. HCPs answered 50% of the questions correctly. Having experience from endocrinological departments increased the correct response score (0%‐100%) by 6.2% points (95% CI 0.3‐12.1) (p = 0.039) and 3.1% points (95% CI 1.5–4.7) for every increase in confidence level on a scale from 1 to 10 (p < 0.001). HCPs scored 8 out of 10 on a confidence level scale on average. In a fictive case, 50% of HCPs administered the correct bolus insulin dose. Hyperglycaemia (>10.0 mmol/L) and hypoglycaemia (<3.9 mmol/L) were correctly identified by around 40% of HCPs. Hypoglycaemia was rated more important than hyperglycaemia by most HCPs. Conclusion: Significant gaps in identifying hypo‐ and hyperglycaemia and correct administration of bolus insulin have been identified, which could be targeted in future education for HCPs. HCPs answered 50% of questions related to in‐hospital diabetes management correctly. Experience from endocrinological departments and self‐rated confidence levels are associated with HCPs' in‐hospital diabetes competencies. [ABSTRACT FROM AUTHOR]

Background and objective: Tuberculosis disease (TB) and tuberculosis infection (TBI) have been associated with increased risk of cardiovascular disease which may be connected to infection-related haemostatic changes. It is unknown if treatment of Mycobacterium tuberculosis influences haemostasis. Here, we assessed if TB or TBI treatment affects thrombelastography (TEG)-assessed haemostasis. Methods: Individuals with TB or TBI were included from a TB outpatient clinic in Copenhagen, Denmark. Patients treated with antithrombotic medication or systemic immunosuppressants were excluded. TEG analysis was performed before and after TB/TBI treatment using the TEG®6s analyser to provide data on the reaction time of clot initiation (R) (min), the speed of clot formation (K) (min) and clot build-up (Angle) (°), maximum clot strength (MA) (mm), and clot breakdown/fibrinolysis (LY30) (%). Differences in TEG were assessed using paired t tests. Results: We included eleven individuals with TB with median [interquartile range] [IQR] age 52 (Liu et al. in Medicine (United States) 95, 2016) years and mean (standard deviation) (SD) body mass index (BMI) 24.7 (6.3) kg/m2 as well as 15 individuals with TBI with median [IQR] age 49 (Wells et al. in Am J Respir Crit Care Med 204:583, 2021) years and BMI 26.0 (3.2) kg/m2. Treatment reduced MA for both TB (64.0 (6.3) vs. 57.9 (5.2) mm, p = 0.016) and TBI (61.3 (4.1) vs. 58.6 (5.0) mm, p = 0.023) whereas R, K, Angle and LY30 were unaffected. Conclusion: TEG analysis showed that treatments of TB and TBI were associated with reduced MA which may indicate the existence of cardiovascular benefits from therapy. Trial registration: Registered at ClinicalTrials.gov 05 April 2021 with registration number NCT04830462. [ABSTRACT FROM AUTHOR]

Background: Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. Methods: This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial. We recruit non-critically ill hospitalised general medical and orthopaedic patients with type 2 diabetes treated with basal, prandial, and correctional insulin (N = 166). In both arms, patients are monitored by POC glucose testing and diabetes management is done by ward nurses guided by in-hospital diabetes teams. In one of the arms, patients are monitored in addition to POC glucose testing by telemetric CGM viewed by the in-hospital diabetes teams only. The in-hospital diabetes teams have operational algorithms to titrate insulin in both arms. Outcomes are in-hospital glycaemic and clinical outcomes. Discussion: The DIATEC trial will show the glycaemic and clinical effects of in-hospital CGM handled by in-hospital diabetes teams with access to operational insulin titration algorithms in non-critically ill patients with type 2 diabetes. The DIATEC trial seeks to identify which hospitalised patients will benefit from CGM and in-hospital diabetes teams compared to POC glucose testing. This is essential information to optimise the use of healthcare resources before broadly implementing in-hospital CGM and diabetes teams. Trial registration: Prospectively registered at ClinicalTrials.gov with identification number NCT05803473 on March 27th 2023. [ABSTRACT FROM AUTHOR]

Indirect interactions are central to ecological and evolutionary dynamics in pollination communities, yet we have little understanding about the processes determining patterns of indirect interactions, such as those between pollinators through shared flowering plants. Instead, research has concentrated on the processes responsible for direct interactions and whole‐network structures. This is partly due to a lack of appropriate tools for characterising indirect interaction structures, because traditional network metrics discard much of this information.The recent development of tools for counting motifs (subnetworks depicting interactions between a small number of species) in bipartite networks enables detailed analysis of indirect interaction patterns. Here we generate plant–hummingbird pollination networks based on three major assembly processes—neutral effects (species interacting in proportion to abundance), morphological matching and phenological overlap—and evaluate the motifs associated with each one.We find that different processes produce networks with significantly different patterns of indirect interactions. Neutral effects tend to produce densely connected motifs, with short indirect interaction chains, and motifs where many specialists interact indirectly through a single generalist. Conversely, niche‐based processes (morphology and phenology) produced motifs with a core of interacting generalists, supported by peripheral specialists. These results have important implications for understanding the processes determining indirect interaction structures. A free Plain Language Summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the role of E. coli virulence-associated genes (VAGs) in predicting urinary tract infection (UTI) as the source of bacteremia in two distinct hospital populations, one with a large general catchment area and one dominated by referrals. Methods: E. coli bacteremias identified at Department of Clinical Microbiology (DCM), Hvidovre Hospital and DCM, Rigshospitalet in the Capital Region of Denmark from October to December 2018. Using whole genome sequencing (WGS), we identified 358 VAGs from 224 E. coli bacteremia. For predictive analysis, VAGs were paired with clinical source of UTI from local bacteremia databases. Results: VAGs strongly predicting of UTI as primary infection source of bacteremia were primarily found within the pap gene family. papX (PPV 96%, sensitivity 54%) and papGII (PPV 93%, sensitivity 56%) were found highly predictive, but showed low sensitivities. The strength of VAG predictions of UTI as source varied significantly between the two hospital populations. VAGs had weaker predictions in the tertiary referral center (Rigshospitalet), a disparity likely stemming from differences in patient population and department specialization. Conclusion: WGS data was used to predict the primary source of E. coli bacteremia and is an attempt on a new and different type of infection source identification. Genomic data showed potential to be utilized to predict the primary source of infection; however, discrepancy between the best performing profile of VAGs between acute care hospitals and tertiary hospitals makes it difficult to implement in clinical practice. [ABSTRACT FROM AUTHOR]

The diverse range of organizations contributing to the global research ecosystem is believed to enhance the overall quality and resilience of its output. Mid‐sized autonomous research institutes, distinct from universities, play a crucial role in this landscape. They often lead the way in new research fields and experimental methods, including those in social and organizational domains, which are vital for driving innovation. The EU‐LIFE alliance was established with the goal of fostering excellence by developing and disseminating best practices among European biomedical research institutes. As directors of the 15 EU‐LIFE institutes, we have spent a decade comparing and refining our processes. Now, we are eager to share the insights we've gained. To this end, we have crafted this Charter, outlining 10 principles we deem essential for research institutes to flourish and achieve ground‐breaking discoveries. These principles, detailed in the Charter, encompass excellence, independence, training, internationality and inclusivity, mission focus, technological advancement, administrative innovation, cooperation, societal impact, and public engagement. Our aim is to inspire the establishment of new institutes that adhere to these principles and to raise awareness about their significance. We are convinced that they should be viewed a crucial component of any national and international innovation strategies. [ABSTRACT FROM AUTHOR]

Objectives An Escherichia coli isolate, WGS1363, showed resistance to piperacillin/tazobactam but susceptibility to cephalosporins and contained a previously unrecognized β-lactamase, CTX-M-255, as the only acquired β-lactamase. CTX-M-255 was identical to CTX-M-27 except for a G239S substitution. Here, we characterize the hydrolytic spectrum of CTX-M-255 and a previously reported β-lactamase, CTX-M-178, also containing a G239S substitution and compare it to their respective parental enzymes, CTX-M-27 and CTX-M-15. Methods All β-lactamase genes were expressed in E. coli TOP10 and MICs to representative β-lactam-antibiotics were determined. Furthermore, bla CTX-M-15,   bla CTX-M-27, bla CTX-M-178 and bla CTX-M-255 with C-terminal His-tag fusions were affinity purified for enzyme kinetic assays determining Michaelis–Menten kinetic parameters against representative β-lactam-antibiotics and IC50s of clavulanate, sulbactam, tazobactam and avibactam. Results TOP10-transformants expressing bla CTX-M-178 and bla CTX-M-255 showed resistance to penicillin/β-lactamase combinations and susceptibility to cephalothin and cefotaxime in contrast to transformants expressing bla CTX-M-15 and bla CTX-M-27. Determination of enzyme kinetic parameters showed that CTX-M-178 and CTX-M-255 both lacked hydrolytic activity against cephalosporins and showed impaired hydrolytic efficiency against penicillin antibiotics compared to their parental enzymes. Both enzymes appeared more active against piperacillin compared to benzylpenicillin and ampicillin. Compared to their parental enzymes, IC50s of β-lactamase-inhibitors were increased more than 1000-fold for CTX-M-178 and CTX-M-255. Conclusions CTX-M-178 and CTX-M-255, both containing a G239S substitution, conferred resistance to piperacillin/tazobactam and may be characterized as inhibitor-resistant CTX-M β-lactamases. Inhibitor resistance was accompanied by loss of activity against cephalosporins and monobactams. These findings add to the necessary knowledge base for predicting antibiotic susceptibility from genotypic data. [ABSTRACT FROM AUTHOR]

Perceived physical exertion is increased when exercise is performed on metformin treatment, but the clinical relevance of this is unknown. In this post hoc analysis of a randomized, controlled trial, we investigated whether metformin treatment was associated with lower levels of free-living physical activity. Ninety individuals with overweight/obesity (BMI>25 m2/kg) and HbA1c-defined prediabetes (39-47 mmol/mol) were randomized to treatment with dapagliflozin (SGLT2-inhibitor; 10 mg once daily, n=30), metformin (850 mg twice daily, n=30) or no treatment (control, n=30) for 13 weeks in a parallel-group, open-label trial. Before (baseline), during (6 weeks) and immediately after (13 weeks) cessation of treatment, a 6-day assessment of physical activity and sedentary behaviour was performed using accelerometer-based physical activity monitors. Intention-to-treat analyses revealed no within-group changes or differences in change between the groups for any measures of physical activity or sedentary behaviour at neither 6 nor 13 weeks. Short-term metformin treatment does not reduce free-living physical activity level in individuals with overweight/obesity and HbA1c-defined prediabetes. [ABSTRACT FROM AUTHOR]

Aims: The aim of our meta‐analyses was to compare the effects of glucose‐lowering drugs on mortality, cardiovascular and renal endpoints for a range of type 2 diabetes (T2D) subgroups defined by their specific cardiovascular risk profile. Methods: Meta‐analyses comparing drugs within the classes of GLP‐1RAs and SGLT‐2 inhibitors were performed and compared to sulphonylureas and DPP‐4 inhibitors with available cardiovascular outcome trials. The comparison between the different classes of glucose‐lowering drugs included analyses of T2D populations with low risk and high risk for cardiovascular disease including populations with established cardiovascular disease and/or kidney disease. Outcomes included mortality, major cardiovascular adverse events (MACE), hospitalisation for heart failure (HHF) and a composite renal endpoint as applied in the underlying clinical trials. Results: SGLT‐2 inhibitors and GLP‐1RAs showed beneficial effects on mortality and MACE compared to the classes of DPP‐4 inhibitors and sulphonylureas. SGLT‐2 inhibitors were shown to be the most effective treatment in terms of HHF and kidney disease. Metformin was used as background therapy for the vast majority of participants in all included studies. Overall, the absolute effects of SGLT‐2 inhibitors and GLP‐1RAs on these important outcomes were evident for patients with established or at high risk for cardiovascular disease but limited for the low‐risk subgroup. Conclusions: The findings from our analyses substantiate the relevance of treatment with SGLT‐2 inhibitors or GLP‐1RAs as an add‐on to metformin in patients with T2D and a high risk for cardiovascular disease, and furthermore, support the recommendation for SGLT‐2 inhibitor treatment in patients with T2D and heart failure or established kidney disease. [ABSTRACT FROM AUTHOR]

Importance: It is unclear whether a lifestyle intervention can maintain glycemic control in patients with type 2 diabetes.Objective: To test whether an intensive lifestyle intervention results in equivalent glycemic control compared with standard care and, secondarily, leads to a reduction in glucose-lowering medication in participants with type 2 diabetes.Design, Setting, and Participants: Randomized, assessor-blinded, single-center study within Region Zealand and the Capital Region of Denmark (April 2015-August 2016). Ninety-eight adult participants with non-insulin-dependent type 2 diabetes who were diagnosed for less than 10 years were included. Participants were randomly assigned (2:1; stratified by sex) to the lifestyle group (n = 64) or the standard care group (n = 34).Interventions: All participants received standard care with individual counseling and standardized, blinded, target-driven medical therapy. Additionally, the lifestyle intervention included 5 to 6 weekly aerobic training sessions (duration 30-60 minutes), of which 2 to 3 sessions were combined with resistance training. The lifestyle participants received dietary plans aiming for a body mass index of 25 or less. Participants were followed up for 12 months.Main Outcomes and Measures: Primary outcome was change in hemoglobin A1c (HbA1c) from baseline to 12-month follow-up, and equivalence was prespecified by a CI margin of ±0.4% based on the intention-to-treat population. Superiority analysis was performed on the secondary outcome reductions in glucose-lowering medication.Results: Among 98 randomized participants (mean age, 54.6 years [SD, 8.9]; women, 47 [48%]; mean baseline HbA1c, 6.7%), 93 participants completed the trial. From baseline to 12-month follow-up, the mean HbA1c level changed from 6.65% to 6.34% in the lifestyle group and from 6.74% to 6.66% in the standard care group (mean between-group difference in change of -0.26% [95% CI, -0.52% to -0.01%]), not meeting the criteria for equivalence (P = .15). Reduction in glucose-lowering medications occurred in 47 participants (73.5%) in the lifestyle group and 9 participants (26.4%) in the standard care group (difference, 47.1 percentage points [95% CI, 28.6-65.3]). There were 32 adverse events (most commonly musculoskeletal pain or discomfort and mild hypoglycemia) in the lifestyle group and 5 in the standard care group.Conclusions and Relevance: Among adults with type 2 diabetes diagnosed for less than 10 years, a lifestyle intervention compared with standard care resulted in a change in glycemic control that did not reach the criterion for equivalence, but was in a direction consistent with benefit. Further research is needed to assess superiority, as well as generalizability and durability of findings.Trial Registration: clinicaltrials.gov Identifier: NCT02417012. [ABSTRACT FROM AUTHOR]

Understanding the end-Triassic mass extinction event (201.36 Ma) requires a clear insight into the stratigraphy of boundary sections, which allows for long-distance correlations and correct distinction of the sequence of events. However, even after the ratification of a Global Stratotype Section and Point, global correlations of TJB successions are hampered by the fact that many of the traditionally used fossil groups were severely affected by the crisis. Here, a new correlation of key TJB successions in Europe, U.S.A. and Peru, based on a combination of biotic (palynology and ammonites), geochemical (δ 13 C org ) and radiometric (U/Pb ages) constraints, is presented. This new correlation has an impact on the causality and temporal development during the end-Triassic event. It challenges the hitherto used standard correlation, which has formed the basis for a hypothesis that the extinction was caused by more or less instantaneous release of large quantities of light carbon (methane) to the atmosphere, with catastrophic global warming as a consequence. The new correlation instead advocates a more prolonged scenario with a series of feedback mechanisms, as it indicates that the bulk of the hitherto dated, high-titanium, quartz normalized volcanism of the Central Atlantic Magmatic Province (CAMP) preceded or was contemporaneous to the onset of the mass extinction. In addition, the maximum phase of the mass extinction, which affected both the terrestrial and marine ecosystems, was associated with a major regression and repeated, enhanced earthquake activity in Europe. A subsequent transgression resulted in the formation of hiati or condensed successions in many areas in Europe. Later phases of volcanic activity of the CAMP, producing low titanium, quartz normalized and high-iron, quartz normalized basaltic rocks, continued close to the first occurrence of Jurassic ammonites and the defined TJB. During this time the terrestrial ecosystem had begun to recover, but the marine ecosystem remained disturbed. [ABSTRACT FROM AUTHOR]

Research suggests that there are immediate benefits from knowledge breadth for creativity - even scientists just at the beginning of their academic journey should benefit from developing expertise in additional domains (Mannucci & Yong, [8]). In this commentary, Sonne-Hansen and colleagues argue that research leaders and organizations should encourage more "theory-guessing" by budding young scientists, rather than incentivizing safe mainstream research. In the late 1960s, Thomas Brock, a microbiologist from Cleveland, and his undergraduate student Hudson Freeze conducted research in Yellowstone National Park. From a sample of pink bacteria collected from Mushroom Spring, Brock and his student isolated a prokaryotic organism thriving at 70°C, which they named I Thermus aquaticus - i after the Greek word for "hot" and the Latin for "water.". [Extracted from the article]

Objectives The entity of ‘surface epithelial changes’ (SECs) was first described in 1995 [1]. Morphologically, SECs usually arise from malignant glands at the superficial aspect of well differentiated (WD) endometrioid carcinomas (ECs) and impart the appearance of a ‘maturational’ phenomenon at the surface of the cancer. Exhibiting a paradoxically bland histologic appearance, SECs typically show morphologic features that mimic benign entities, particularly endocervical microglandular hyperplasia (MGH). SECs have been associated with approximately half of WD endometrioid carcinomas many of which showed focal mucinous differentiation. Despite their morphologically benign histology, some have questioned whether the presence of SECs represents a ‘marker’ for an underlying malignancy, especially in postmenopausal women with endocervical or MGH-type SECs in their endometrial sampling. Since the biologic nature of SECs is unknown, we aimed to study the prevalence of KRAS gene mutations in SECs and the underlying WD endometrioid adenocarcinomas (EC) from which they directly arise. Methods 24 cases with biopsy proven SECs and ECs in their subsequent hysterectomy were retrieved. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue. PCR amplification for KRAS codons 12 and 13 was performed, followed by sequencing using capillary electrophoresis. Results KRAS codons 12 and 13 mutations were detected in 19 of 24 (79%) SECs, and 19 of 24 (79%) ECs. All SECs had the same KRAS mutation as the underlying EC. Conclusions Our results suggest that SECs are of neoplastic origin and that KRAS mutations play an important role in the tumorigenesis of ECs and SECs. [ABSTRACT FROM AUTHOR]

This secondary analysis aimed to investigate the effects of a 12 months intensive exercise-based lifestyle intervention on systemic markers of oxidative stress in persons with type 2 diabetes. We hypothesized lifestyle intervention to be superior to standard care in decreasing levels of oxidative stress. The study was based on the single-centre, assessor-blinded, randomised, controlled U-turn trial (ClinicalTrial.gov NCT02417012). Persons with type 2 diabetes ˂ 10 years, ˂ 3 glucose lowering medications, no use of insulin, BMI 25–40 kg/m2 and no severe diabetic complications were included. Participants were randomised (2:1) to either intensive exercise-based lifestyle intervention and standard (n = 64) or standard care alone (n = 34). Standard care included individual education in diabetes management, advice on a healthy lifestyle and regulation of medication by a blinded endocrinologist. The lifestyle intervention included five to six aerobic exercise sessions per week, combined with resistance training two to three times per week and an adjunct dietary intervention aiming at reduction of ∼500 kcal/day (month 0–4). The diet was isocaloric from months 5–12. The primary outcome of this secondary analysis was change in oxidative stress measured by 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and secondarily in 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), as markers of RNA and DNA oxidation, respectively, from baseline to 12-months follow-up. A total of 77 participants, 21 participants receiving standard care and 56 participants receiving the lifestyle intervention, were included in the analysis. Mean age at baseline was 54.1 years (SD 9.1), 41% were women and mean duration of type 2 diabetes was 5.0 years (SD 2.8). From baseline to follow-up the lifestyle group experienced a 7% decrease in 8-oxoGuo (−0.15 nmol/mmol creatinine [95% CI -0.27, −0.03]), whereas standard care conversely was associated with a 8.5% increase in 8-oxoGuo (0.19 nmol/mmol creatinine [95% CI 0.00, 0.40]). The between group difference in 8-oxoGuo was −0.35 nmol/mmol creatinine [95% CI -0.58, −0.12,], p = 0.003. No between group difference was observed in 8-oxodG. A 12 months intensive exercise-based lifestyle intervention was associated with a decrease in RNA, but not DNA, oxidation in persons with type 2 diabetes. [Display omitted] • Oxidative stress might be the common driver of complications in type 2 diabetes. • Advanced glycation endproducts may contribute considerably to the redox imbalance. • Exercise intervention decreases RNA oxidation. • Exercise intervention increase decoy receptors for advanced glycation endproducts. • Decrease in oxidative stress associated with increase in the decoy receptors. [ABSTRACT FROM AUTHOR]

The diagnosis of COVID-19 is based on detection of SARS-CoV-2 in oro-/nasopharyngel swabs, but due to discomfort and minor risk during the swab procedure, detection of SARS-CoV-2 has been investigated in other biological matrixes. In this proof-of-concept study, individuals with confirmed SARS-CoV-2 infection performed a daily air sample for five days. Air samples were obtained through a non-invasive electrostatic air sampler. Detection of SARS-CoV-2 RNA was determined with qRT-PCR. The association of positive samples with different exposures was evaluated through mixed-effect models. We obtained 665 air samples from 111 included participants with confirmed SARS-CoV-2 infection. Overall, 52 individuals (46.8%) had at least one positive air sample, and 129 (19.4%) air samples were positive for SARS-CoV-2. Participants with symptoms or a symptom duration ≤ four days had significantly higher odds of having a positive air sample. Cycle threshold values were significantly lower in samples obtained ≤ 4 days from symptom onset. Neither variant of SARS-CoV-2 nor method of air sampling were associated with a positive air sample. We demonstrate that SARS-CoV-2 is detectable in human breath by electrostatic air sampling with the highest detection rate closest to symptom onset. We suggest further evaluation of the air sampling technique to increase sensitivity. [ABSTRACT FROM AUTHOR]

Background. Although heterozygous filaggrin gene ( FLG) mutation carriers seem to have an increased risk of atopic, irritant and allergic nickel dermatitis, it remains unclear whether the risk of contact sensitization to allergens other than nickel is also elevated in FLG mutation carriers. Objectives. We hypothesized that heterozygous FLG mutation carriers who suffer from dermatitis will have strongly reduced or even absent filaggrin levels during episodes of inflammation, potentially increasing the penetration of contact allergens, and hence the risk of becoming sensitized. Materials and methods. During 2006-2008, 3335 randomly invited 18-69-year-old adult Danes participated in a general health examination, filled out a questionnaire, and were genotyped for the R501X and 2282del4 mutations in FLG. Results. A logistic regression analysis restricted to individuals who reported atopic dermatitis and frequent episodes of hand eczema showed a strong association between FLG mutations and contact sensitization to allergens other than nickel (odds ratio 5.71; 95% confidence interval 1.31-24.94). In participants without dermatitis, no association was found between contact sensitization and FLG mutations. Conclusion. FLG mutation carriers with self-reported dermatitis have an increased risk of contact sensitization to substances other than nickel, whereas FLG mutations alone may not, or may only slightly, increase the risk of sensitization. [ABSTRACT FROM AUTHOR]

Phytoestrogens (PEs) are naturally occurring plant components produced in a large range of plants. They can induce biologic responses in vertebrates by mimicking or modulating the action or production of endogenous hormones. This study examined mixtures of 12 food relevant PEs for effects on steroid hormone production, aromatase activity, estrogenic activity, and for interaction with the androgen receptor. The results show that a mixture of all tested PEs increased estradiol production and decreased testosterone production in H295R human adrenal corticocarcinoma cells, indicating an induced aromatase activity. Furthermore, exposure of the H295R cells to isoflavonoids caused a decrease in testosterone production, and various mixtures of PEs significantly stimulated MCF-7 human breast adenocarcinoma cell growth and induced aromatase activity in JEG-3 choriocarcinoma cells. The estrogenic effect in the MCF7 cells of the isoflavonoid mixture and coumestrol was supported by an observed increase in progesterone receptor protein expression as well as a decreased ERα expression. Overall, the results support that nutrition-relevant concentrations of PEs both alone and in mixtures possess various endocrine disrupting effects, all of which need to be considered when assessing the effects on human health. [ABSTRACT FROM AUTHOR]