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Background: Thoracic epidural analgesia (TEA) and intravenous patient‐controlled analgesia (IV‐PCA) are widely used to mitigate immediate postoperative pain; however, their effects on long‐term disability‐free survival are poorly documented. This study aimed to compare the effects of postoperative TEA and IV‐PCA on disability‐free survival in patients who underwent thoracic or abdominal surgery. Methods: This post hoc analysis of a prospective observational study included 845 inpatients aged ≥55 years that underwent elective thoracic and abdominal surgery between 1 April 2016 and 28 December 2018 in a tertiary care hospital. Inverse probability of treatment weighted (IPTW) using stabilized inverse propensity scores was adopted to minimize bias. The primary outcome in this study was disability‐free survival, defined as survival with a 12‐item World Health Organization Disability Assessment Schedule 2.0 score of <16%, assessed at 3 months and 1 year after surgery. Results: The final analysis included 601 patients who received TEA and 244 who received IV‐PCA. After IPTW, the weighted incidence of disability‐free survival at 3 months and 1 year was 60.5% and 61.4% in the TEA group and 78.3% and 66.2% in the IV‐PCA group, respectively. The adjusted OR for disability‐free survival at 3 months and 1 year was 0.84 (95% confidence interval [CI]: 0.50–1.39) and 1.21 (95% CI: 0.72–2.05), respectively, for the TEA group. Conclusion: No significant differences were observed in the disability‐free survival at 3 months and 1 year after elective thoracic and abdominal surgery in patients aged ≥55 years who received TEA or IV‐PCA. Significance statement: This study is the first in our setting to document the long‐term effects of patient‐controlled analgesia. In a post hoc analysis of our prospective cohort study, we show that although differences in chronic postsurgical pain exist at 3 months post‐surgery, disability‐free survival rates at 1 year do not differ irrespective of the choice of patient‐controlled analgesia. The findings of this study highlight the need for shared decision‐making between clinicians and patients. [ABSTRACT FROM AUTHOR]

Interferon‐beta has been suggested as a trigger of psoriasis, yet a systematic investigation is lacking. This study aimed to assess the risk of developing psoriasis following interferon‐beta treatment, utilizing a pharmaco‐epidemiological approach to investigate the role of interferon‐beta in psoriasis pathogenesis. We included all treatment‐naïve patients with multiple sclerosis (MS) in Denmark who initiated interferon‐beta treatment for MS from January 1996 to June 2023. These patients were compared to a control cohort of patients with MS treated with other disease‐modifying drugs. We compared the incidence rates of psoriasis before and during the treatment. Data for this study were extracted from the Danish MS Registry and integrated with information from other national Danish health registries. Among 7174 patients treated with interferon‐beta, the incidence rate of psoriasis post‐treatment initiation was slightly higher (2.01 per 1000 person‐years) compared to the rate prior to treatment (1.67 per 1000 person‐years). This increase did not achieve statistical significance (P = 0.53), with an incidence rate ratio (IRR) of 1.20 (95% confidence interval [CI] 0.68–2.13). The control cohort showed an increase in psoriasis incidence post‐treatment initiation (3.12 per 1000 person‐years) compared to prior (1.11 per 1000 person‐years), with an IRR of 2.80 (95% CI 1.36–4.77, P = 0.0038). This registry‐based self‐controlled study does not support the theory that interferon‐beta acts as a trigger for psoriasis development. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Discussion and conclusion A link between androgen use and the risk of cancers, especially prostate and breast cancer, has been suggested. The knowledge about a possible association is limited.The study aimed to investigate cancer incidence rates, particularly those related to prostate and breast cancer, in male androgen users and compare them to a control group.We included male androgen users identified through a nationwide anti‐doping testing program in Danish fitness centers from 2006 to 2018. We paired each case with 50 male controls of the same age, selected randomly. The cohort was followed from baseline and until 2023. The outcome was the incidence of prostate cancer, breast cancer, or any cancer excluding non‐melanoma skin cancer.The study included 1,189 androgen users and 59,450 controls, with a mean age of 27 years at enrolment. During the follow‐up period with a mean length of 11 years, 13 androgen users, and 612 controls were diagnosed with cancer. This resulted in an incidence rate ratio of 1.05 (95% CI: 0.55–1.81). None of the androgen users were diagnosed with prostate or breast cancer.Male androgen users did not face an increased short‐term risk of cancer, neither overall nor related to prostate or breast cancer. Our study indicates that the absolute risk of malignancies in androgen users is comparable to that in the background population. However, we cannot exclude androgens as a cancer risk factor due to the limited sample size, relatively short follow‐up period, and subject age. [ABSTRACT FROM AUTHOR]

The transition zone between the upper forest boundary and the treeless alpine vegetation (i.e., the treeline ecotone) is expected to shift upward in elevation with global warming. Multiple factors in addition to climate are influencing tree establishment, but it is uncertain to what degree. In this study, we took advantage of a unique dataset with field measurements of mountain birch trees acquired from 32 boreal–alpine treeline ecotone sites situated along a 1100‐km latitudinal gradient in Norway to investigate the role of climate, herbivory, topography, and vegetation on the establishment success of trees. To represent tree establishment, we recorded occurrence, survival, and height growth of short juvenile birch trees (stem height ≤1 m) as response variables at each site in 2008, 2012, and 2018. We used already available climate and herbivory data, and airborne laser scanning (ALS) and unmanned aerial vehicle (UAV) surveyed imagery together with field measurements to compute topography and vegetation explanatory variables per site on microsite scale (approx. 1 m2). We observed a clear decrease in short juvenile birch tree establishment due to livestock herbivory, evidenced by lower occurrence, reduced survival rate, and diminished height growth in treeline ecotones with higher livestock densities. Winter precipitation and the two land cover classes, tree‐covered area and lee side vegetation, were also important for tree establishment. However, the direction and magnitude of the relationships depended on the stage of establishment. While winter precipitation can lead to higher tree occurrence, long‐term survival is not necessarily ensured, reflecting diverse requirements for optimal conditions of tree establishment. Thus, our results show that occurrence, survival, and height growth of short juvenile birch trees differ in their requirements to climate, topography, and vegetation, but tree establishment is consistently low with livestock herbivory. Overall, our results suggest that treeline ecotones will shift toward higher elevations in areas with little or no livestock herbivory and close to already established trees and in lee sides. Regarding management and conservation issues, our results suggest that free‐roaming livestock can reduce tree establishment and hinder treeline ecotone shifts into threatened alpine ecosystems, at least for birch‐dominated treelines. [ABSTRACT FROM AUTHOR]

SUMMARY: Arabidopsis thaliana diverged from A. arenosa and A. lyrata at least 6 million years ago. The three species differ by genome‐wide polymorphisms and morphological traits. The species are to a high degree reproductively isolated, but hybridization barriers are incomplete. A special type of hybridization barrier is based on the triploid endosperm of the seed, where embryo lethality is caused by endosperm failure to support the developing embryo. The MADS‐box type I family of transcription factors is specifically expressed in the endosperm and has been proposed to play a role in endosperm‐based hybridization barriers. The gene family is well known for its high evolutionary duplication rate, as well as being regulated by genomic imprinting. Here we address MADS‐box type I gene family evolution and the role of type I genes in the context of hybridization. Using two de‐novo assembled and annotated chromosome‐level genomes of A. arenosa and A. lyrata ssp. petraea we analyzed the MADS‐box type I gene family in Arabidopsis to predict orthologs, copy number, and structural genomic variation related to the type I loci. Our findings were compared to gene expression profiles sampled before and after the transition to endosperm cellularization in order to investigate the involvement of MADS‐box type I loci in endosperm‐based hybridization barriers. We observed substantial differences in type‐I expression in the endosperm of A. arenosa and A. lyrata ssp. petraea, suggesting a genetic cause for the endosperm‐based hybridization barrier between A. arenosa and A. lyrata ssp. petraea. Significance Statement: We address MADS‐box type I gene family evolution using de‐novo assembled genomes of A. arenosa and A. lyrata ssp. petraea and predict orthologs, copy number and structural genomic variation related to the type I loci. We observe substantial differences in MADS‐box type‐I expression in the endosperm suggesting a genetic cause for an endosperm‐based hybridization barrier. [ABSTRACT FROM AUTHOR]

Honey bees are efficient pollinators of flowering plants, aiding in the plant reproductive cycle and acting as vehicles for evolutionary processes. Their role as agents of selection and drivers of gene flow is instrumental to the structure of plant populations, but historically, our understanding of their influence has been limited to predominantly insect‐dispersed flowering species. Recent metagenetic work has provided evidence that honey bees also forage on pollen from anemophilous species, suggesting that their role as vectors for transmission of plant genetic material is not confined to groups designated as entomophilous, and leading us to ask: could honey bees act as dispersal agents for non‐flowering plant taxa? Using an extensive pollen metabarcoding dataset from Canada, we discovered that honey bees may serve as dispersal agents for an array of sporophytes (Anchistea, Claytosmunda, Dryopteris, Osmunda, Osmundastrum, Equisetum) and bryophytes (Funaria, Orthotrichum, Sphagnum, Ulota). Our findings also suggest that honey bees may occasionally act as vectors for the dispersal of aquatic phototrophs, specifically Coccomyxa and Protosiphon, species of green algae. Our work has shed light on the broad resource‐access patterns that guide plant‐pollinator interactions and suggests that bees could act as vectors of gene flow, and potentially even agents of selection, across Plantae. [ABSTRACT FROM AUTHOR]

Severe skin pain when exposed to long wave ultraviolet radiation or visible light is the main symptom of erythropoietic protoporphyria (EPP). Treatment options for EPP are inadequate and new treatments are needed but hampered by the lack of valid efficacy outcomes. Phototesting with well‐defined illumination of the skin can be performed reliably. We aimed to provide an overview of phototest procedures used to evaluate EPP treatments. Systematic searches of Embase, MEDLINE and the Cochrane Library were performed. Searches identified 11 studies using photosensitivity as efficacy outcome. The studies used eight different phototest protocols. Illuminations were performed with a filtered high‐pressure mercury arc, or a xenon arc lamp equipped with monochromator or filters. Some used broadband, others narrowband illumination. In all protocols phototests were performed on the hands or the back. Endpoints were minimal dose required to induce either first symptom of discomfort, erythema, urticaria or intolerable pain. Other endpoints were change in erythema intensity or diameter of any type of flare after exposure compared to before. In conclusion, protocols displayed extensive variability in illumination set‐up and evaluation of phototest reactions. Implementation of a standardized phototest method will allow more consistent and reliable outcome evaluation in future therapeutic research of protoporphyric photosensitivity. [ABSTRACT FROM AUTHOR]

Individuals differ in the nature of the immune responses they produce, affecting disease susceptibility and ultimately health and fitness. These differences have been hypothesized to have an origin in events experienced early in life that then affect trajectories of immune development and responsiveness. Here, we investigate how early‐life immune expression profiles influence life history outcomes in a natural population of field voles, Microtus agrestis, in which we are able to monitor variation between and within individuals through time by repeat sampling of individually marked animals. We analysed the co‐expression of 20 immune genes in early life to create a correlation network consisting of three main clusters, one of which (containing Gata3, Il10 and Il17) was associated with later‐life reproductive success and susceptibility to chronic bacterial (Bartonella) infection. More detailed analyses supported associations between early‐life expression of Il17 and reproductive success later in life, and of Il10 expression early in life and later infection with Bartonella. We also found significant association between an Il17 genotype and the early‐life expression of Il10. Our results demonstrate that immune expression profiles can be manifested during early life with effects that persist through adulthood and that shape the variability among individuals in susceptibility to infection and fitness widely seen in natural populations. [ABSTRACT FROM AUTHOR]

Aim: Liraglutide treatment is associated with gallbladder‐related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon‐like peptide 2 (GLP‐2), are known to regulate gallbladder motility and may be implicated in gallbladder‐related disorders associated with liraglutide treatment. Materials and Methods: In a double‐blind, 12‐week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4 kg/m2 (mean ± standard deviation)] with obesity were randomized 1:1 to once‐daily subcutaneous liraglutide (escalated from 0.6 mg to 3.0 mg once‐daily) or placebo. During liquid meal tests performed at baseline, after the first dose and following 12 weeks of treatment, we evaluated postprandial gallbladder dynamics and plasma responses of CCK, FGF19 and GLP‐2. Results: Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)0‐240 min 24.8 vs. 48.0 min × ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC0‐240 min 33.7 vs. 48.5 ng/ml × min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP‐2 responses (AUC0‐240 min 3650 vs. 4894 min × pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC0‐240 min 3760 vs. 4882 min × pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC0‐240 min 762 vs. 670 min × pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC0‐240 min 873 vs. 628 min × pmol/L; TR 1.39 (1.12; 1.73)]. Conclusion: Compared with placebo, treatment with liraglutide decreased postprandial FGF19 and GLP‐2 concentrations and increased postprandial CCK concentrations, which may explain the delayed postprandial gallbladder refilling observed in individuals with obesity treated with liraglutide. [ABSTRACT FROM AUTHOR]

Objective: Self‐control is a meaningful predictor of crucial life outcomes. Knowingly, genes contribute substantially to differences in self‐control, but behavioral genetic findings are often misinterpreted regarding environmental influences. Therefore, we reinvestigate the heritability of self‐control as well as potential environmental influences, namely parenting and a chaotic home environment. Method: We used cross‐sectional and longitudinal data from the German twin family study TwinLife (N = 3354 individuals), structured in a multicohort design in which 13‐, 19‐, and 25‐year‐old twins rated their self‐control, parents' behavior, and home environment. Results: Results showed increasing mean levels and 1‐year stabilities for self‐control accompanied by substantial genetic influences, increasing particularly from ages 19 to 25 (53% to 76%). While chaotic home environments and negative parenting were phenotypically associated with lower self‐control, twin difference models revealed that differences in these individually perceived "environments" directly predicted self‐control differences (β = −0.16 to −0.28) within families when controlling for genetic and environmental similarities. Conclusions: In addition to the genetic anchoring of self‐control, results indicate that environmental factors such as negative family environments are meaningful and depend on individual perceptions within families. Interventions for enhancing self‐control should, therefore, rely on individual perspectives rather than objective characteristics of home environments. [ABSTRACT FROM AUTHOR]

Apicomplexans are a protozoan phylum of obligate parasites which may be highly virulent during acute infections, but may also persist as chronic infections which appear to have little fitness cost. Babesia microti is an apicomplexan haemoparasite that, in immunocompromised individuals, can cause severe, potentially fatal disease. However, in its natural host, wild field voles (Microtus agrestis), it exhibits chronic infections that have no detectable impact on survival or female fecundity. How is damage minimized, and what is the impact on the host's immune state and health? We examine the differences in immune state (here represented by expression of immune‐related genes in multiple tissues) associated with several common chronic infections in a population of wild field voles. While some infections show little impact on immune state, we find strong associations between immune state and B. microti. These include indications of clearance of infected erythrocytes (increased macrophage activity in the spleen) and activity likely associated with minimizing damage from the infection (anti‐inflammatory and antioxidant activity in the blood). By analysing gene expression from the same individuals at multiple time points, we show that the observed changes are a response to infection, rather than a risk factor. Our results point towards continual investment to minimize the damage caused by the infection. Thus, we shed light on how wild animals can tolerate some chronic infections, but emphasize that this tolerance does not come without a cost. [ABSTRACT FROM AUTHOR]

Background: Cutaneous malignant melanoma (MM) is potentially aggressive, and numerous clinically suspicious pigmented skin lesions are excised, causing unnecessary mutilation for patients at high healthcare costs, but without histopathological evidence of MM. The high number of excisions may be lowered by using more accurate diagnostics. Tape stripping (TS) of clinically suspicious lesions is a non‐invasive diagnostic test of MM that can potentially lower the number needed to biopsy/excise. Materials and methods: The aim is to determine the diagnostic accuracy of TS in detecting MM in clinically suspicious pigmented skin lesions. This systematic review following PRISMA guidelines searched PubMed, Web of Science, and Embase (September 2022) using melanoma combined with tape stripping, adhesive patch(es), pigmented lesion assay, or epidermal genetic information retrieval. Results: Ten studies were included. Sensitivity ranged from 68.8% (95% confidence interval [CI] 51.5, 82.1) to 100% (95% CI 91.0, 100). Specificity ranged from 69.1% (95% CI 63.8, 74.0) to 100% (95% CI 78.5, 100). A pooled analysis of five studies testing the RNA markers LINC00518 and PRAME found a sensitivity of 86.9% (95% CI 81.7, 90.8) and a specificity of 82.4% (95% CI 80.8, 83.9). Conclusion: Overall quality of studies was low, and the reliability of sensitivity and specificity is questionable. However, TS may supplement well‐established diagnostic methods as pooled analysis of five studies indicates a moderate sensitivity. Future studies are needed to obtain more reliable data as independent studies with no conflict of interest. [ABSTRACT FROM AUTHOR]

With growing urbanization, it is becoming increasingly important to design cities in a manner that sustains and enhances biodiversity and ecosystem services. Native bees are critical pollinators that have experienced substantive declines over the past several decades. These declines have captured the attention of the public, particularly urbanites, prompting a large interest in protecting pollinators and their habitats in cities across North America and Europe. Unfortunately, we currently lack research about specific features of urban environments that can enhance the fitness of pollinators. We carried out an intensive study of Bombus impatiens, the Common Eastern Bumblebee, in the city of Toronto (Canada's largest city), to better understand landscape parameters that provide high‐quality habitat for this species and likely other generalist bees. We divided the city into 270 grid cells and sampled a large number of worker bees, which were then genotyped at twelve hypervariable microsatellite loci. The genetic data allowed us to quantify the effective number of colonies and foraging distance for bumblebees in our study area. We then asked how the city's landscape and human population demography and income are associated with the availability of high‐quality habitat for B. impatiens. Several aspects of Toronto's landscape influenced colony density and foraging range. Urbanization had a clear effect on both colony density and foraging distance of workers. On the other hand, functional (i.e., not cosmetic) green space was often associated with higher quality habitats for bumblebees. Our study suggests several planning strategies to enhance habitat quality for bumblebees and other pollinators in cities. [ABSTRACT FROM AUTHOR]

Objective: Hypertension contributes to increased risk of cardiovascular disease in patients with Turner syndrome (TS). Our objective was to evaluate blood pressure (BP) in girls with TS followed longitudinally through childhood and adolescence compared to a newly established BP reference material. Design: Cohort study with data collected from 1991 to 2019 consisting of a population‐based reference cohort and a group of girls with TS followed at a single tertiary centre. Patients/Participants: Reference population of 1888 healthy girls with 4890 BP recordings and 60 girls with TS with 365 BP recordings. Measurements: Difference in diastolic BP (DBP) and systolic BP (SBP), expressed in standard deviation scores (SDS), between girls with TS and the reference population, unadjusted and adjusted for BMI. Difference in BP (SDS) between TS subgroups (karyotype, oestrogen treatment, cardiac diagnosis). Results: The girls with TS had significantly higher DBP (mean ± SD, 0.72 SDS ± 0.95; p <.001) and SBP (0.53 SDS ± 1.11; p =.001) than the reference population. Adjusted for BMI, girls with TS had significantly higher DBP (mean ± SE, 0.71 SDS ± 0.12; p <.001) but not SBP (0.17 SDS ± 0.16; p =.29). There was no significant difference in DBP (median, IQR: 0.97 SDS, 0.30–1.58 vs. 0.76 SDS, 0.10–1.20; p =.31) or SBP (0.51 SDS, 0.15–1.30 vs. 0.57 SDS, −0.30 to 1.05; p =.67) between individuals with or without a cardiac diagnosis. In the TS population, 55% (31/56) had at least one BP recording above the hypertension threshold. Conclusions: Our findings indicate that standardised longitudinal routine monitoring of BP in girls with TS already in childhood is of utmost importance. [ABSTRACT FROM AUTHOR]

Nephroblastoma is an embryonal tumour that has rarely been reported in laboratory rats. In this case report, a large nephroblastoma with peritoneal seeding was found during necropsy in an 11‐month‐old, female, Sprague Dawley rat. The rat had a history of indirect exposure to nano‐TiO2 (titanium dioxide nanoparticles) during maternal gestation. A firm mass in the upper right abdominal quadrant was palpated. Four weeks later, the animal quickly declined. Nephroblastoma was confirmed by histopathology. Only one rat developed nephroblastoma among the ten littermates. Nephroblastomas in Sprague Dawley rats are typically spontaneous tumours with non‐malignant mesenchymal elements. The capability to induce a nephroblastoma with nano‐TiO2 is less likely in this case. [ABSTRACT FROM AUTHOR]

Aim: Hypertension has been reported in up to 4.0% of American children, but no national data exist in Europe. We studied the frequency of registered hypertension in Danish children and evaluated the data.Methods: This 2014-2015 study focused on patients under the age of 16 registered with hypertension in the Danish National Patient Register and 10 paediatric departments in central and eastern Denmark. The diagnoses were coded according to the International Classification of Diseases, 10th revision. All the subjects' medical records were reviewed, including any confirmed diagnoses.Results: There were 55 784 children under 16 in the study regions at 30 April 2014. By May 2015, 222 of those had been registered with hypertension: 200 in the Danish National Patient Register and 191 in the 10 paediatric departments. Their medical records confirmed hypertension in 187 and 185 cases, respectively. The prevalence of registered and confirmed hypertension was 222/553 784 (0.04%). The positive predictive values of hypertension were 187/200 (94%) and 185/191 (97%), and the completeness of diagnosed hypertension was 187/222 (84%) and 185/222 (83%).Conclusion: The registers had high-quality positive predictive values and completeness, but only 0.04% of the Danish children were registered with a verified diagnosis of hypertension. [ABSTRACT FROM AUTHOR]

Aim: In this study, we explored spatial patterns of phylogenetic diversity (PD) and endemism in the flora of Norway and tested hypothesized post‐glacial environmental drivers of PD, including temperature, precipitation, edaphic factors and time since glacial retreat. Location: Norway. Taxon: Vascular plants (Trachaeophyta). Methods: We produced a multi‐locus maximum‐likelihood (ML) phylogeny using a combination of newly produced DNA sequences from herbarium specimens and sequences available from public repositories. We combined the phylogeny with species occurrence data to estimate PD and phylogenetic endemism across Norway, using a spatial randomization to judge statistical significance. We used multiple‐model inference to identify environmental variables that contributed the most to the patterns of PD. Finally, we estimated phylogenetic turnover and used this to identify Norwegian plant assemblages in terms of composition and evolutionary history. Results: Our ML phylogeny contained 87% of all currently described native Norwegian vascular plants. Assemblages were phylogenetically overdispersed in warmer and wetter regions of Norway, as well as in regions with a longer post‐glacial history. In cold and dry regions, plant assemblages were phylogenetically clustered, and characterized by neo‐endemism, while the mild and wet regions were characterized by both paleo‐ and neo‐endemism. PD was positively correlated with summer temperature and habitat heterogeneity, and peaked in the southeast of Norway. Main conclusions: Both contemporary ecological factors (climate and habitat heterogeneity), and post‐glacial history seem to have shaped the phylogenetic structure of the flora of Norway. The flora in the far north of Norway appear to be a result of recent diversification while the coastal regions are assemblages of deeper lineages. Our results suggest that there is an evolutionary signal in the distribution of the Norwegian vascular flora. [ABSTRACT FROM AUTHOR]

Summary: Genomic imprinting regulates parent‐specific transcript dosage during seed development and is mainly confined to the endosperm. Elucidation of the function of many imprinted genes has been hampered by the lack of corresponding mutant phenotypes, and the role of imprinting is mainly associated with genome dosage regulation or allocation of resources. Disruption of imprinted genes has also been suggested to mediate endosperm‐based post‐zygotic hybrid barriers depending on genetic variation and gene dosage. Here, we have analyzed the conservation of a clade from the MADS‐box type I class transcription factors in the closely related species Arabidopsis arenosa, A. lyrata, and A. thaliana, and show that AGL36‐like genes are imprinted and maternally expressed in seeds of Arabidopsis species and in hybrid seeds between outbreeding species. In hybridizations between outbreeding and inbreeding species the paternally silenced allele of the AGL36‐like gene is reactivated in the hybrid, demonstrating that also maternally expressed imprinted genes are perturbed during hybridization and that such effects on imprinted genes are specific to the species combination. Furthermore, we also demonstrate a quantitative effect of genetic diversity and temperature on the strength of the post‐zygotic hybridization barrier. Markedly, a small decrease in temperature during seed development increases the survival of hybrid F1 seeds, suggesting that abiotic and genetic parameters play important roles in post‐zygotic species barriers, pointing at evolutionary scenarios favoring such effects. Open Research Badges: This article has earned an Open Data Badge for making publicly available the digitally‐shareable data necessary to reproduce the reported results. The data is available at https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA562212. All sequences generated in this study have been deposited in the National Center for Biotechnology Information Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra/) with project number PRJNA562212. Significance Statement: We have investigated the hypothesis that imprinted genes mediate reproductive barriers between species in the context of genetic and environmental variance, and demonstrate that perturbation of imprinted genes, genetic diversity as well as environmental factors act in concert to define the strength of endosperm‐based Arabidopsis hybridization barriers. [ABSTRACT FROM AUTHOR]

Immunity is a central component of fitness in wild animals, but its determinants are poorly understood. In particular, the importance of locomotory activity as a constraint on immunity is unresolved. Using a piscine model (Gasterosteus aculeatus), we combined a 25‐month observational time series for a wild lotic habitat with an open flume experiment to determine the influence of locomotor activity (countercurrent swimming) on natural variation in immune function. To maximize the detectability of effects in our flume experiment, we set flow velocity and duration (10 cm/s for 48 hr) just below the point at which exhaustion would ensue. Following this treatment, we measured expression in a set of immune‐associated genes and infectious disease resistance through a standard challenge with an ecologically relevant monogenean infection (Gyrodactylus gasterostei). In the wild, there was a strong association of water flow with the expression of immune‐associated genes, but this association became modest and more complex when adjusted for thermal effects. Our flume experiment, although statistically well‐powered and based on a scenario near the limits of swimming performance in stickleback, detected no countercurrent swimming effect on immune‐associated gene expression or infection resistance. The field association between flow rate and immune expression could thus be due to an indirect effect, and we tentatively advance hypotheses to explain this. This study clarifies the drivers of immune investment in wild vertebrates; although locomotor activity, within the normal natural range, may not directly influence immunocompetence, it may still correlate with other variables that do. [ABSTRACT FROM AUTHOR]

We present a blue mussel exposure system where the fate of microplastics (polystyrene beads) is tracked during exposure and depuration phases. This enabled the establishment of a complete mass balance. Quantification of beads in mussels was done with a novel enzymatic digestion protocol. We found a similar relative distribution of beads for 2 environmentally realistic concentrations (5 and 100 beads L−1) and no substantial egestion of particles within 2 h of depuration. Environ Toxicol Chem 2019;38:99–105. © 2018 SETAC A complete mass balance of microplastic beads in a blue mussel exposure system was established by quantifying beads in 4 compartments: the exposure water, the mussel after exposure, the depuration water, and the mussel after depuration. MP = microplastic. [ABSTRACT FROM AUTHOR]

Background: Preservatives such as formaldehyde and formaldehyde‐releasers are common causes of contact allergy. Objectives: To examine trends in contact allergy to formaldehyde and formaldehyde‐releasers in patch tested patients in Denmark over a 10‐year period (2007‐2016), and to investigate relevant sources of formaldehyde among the patients. Methods: A cross‐sectional registry study on patch test data from patients tested with formaldehyde and formaldehyde‐releasers (N = 8463) was performed. The presence of released formaldehyde in products from formaldehyde‐allergic patients was identified with chemical analyses (chromotropic acid or acetylacetone test). Results: The prevalence of contact allergy to formaldehyde 1% was 1.5%, and ranged between 0.97% and 2.3%, with a decreasing trend in this 10‐year period. Contact allergy to formaldehyde 2% was found in 2.4%, and no significant trend was observed. Quaternium‐15 was the formaldehyde‐releaser most often positive (0.86%). Patients allergic to formaldehyde often had simultaneous positive patch test reactions to formaldehyde‐releasers (36%). Almost 63% of the patients with formaldehyde allergy used products that released formaldehyde; cosmetics were the most common sources. Conclusions: Although contact allergy to formaldehyde 1% decreased in this 10‐year time period, contact allergies to formaldehyde and formaldehyde‐releasers overall remain frequent in patients. In most cases, formaldehyde‐allergic patients are exposed to ≥1 products containing formaldehyde. Improved regulation on permitted amounts of free formaldehyde in cosmetics is still warranted, including direct labelling of formaldehyde when it is present in small but relevant amounts. [ABSTRACT FROM AUTHOR]

Summary: Background: To be effective, sunscreens must be applied in a sufficient quantity and reapplication is recommended. No previous study has investigated whether time spent on sunscreen application is important for the achieved photoprotection. Aim: To determine whether time spent on sunscreen application is related to the amount of sunscreen used during a first and second application. Methods: Thirty‐one volunteers wearing swimwear applied sunscreen twice in a laboratory environment. Time spent and the amount of sunscreen used during each application was measured. Subjects' body surface area accessible for sunscreen application (BSA) was estimated from their height, weight and swimwear worn. The average applied quantity of sunscreen after each application was calculated. Results: Subjects spent on average 4 minutes and 15 seconds on the first application and approximately 85% of that time on the second application. There was a linear relationship between time spent on application and amount of sunscreen used during both the first and the second application (P < .0001). Participants applied 2.21 grams of sunscreen per minute during both applications. After the first application, subjects had applied a mean quantity of sunscreen of 0.71 mg/cm2 on the BSA, and after the second application, a mean total quantity of 1.27 mg/cm2 had been applied. Conclusion: We found that participants applied a constant amount of sunscreen per minute during both a first and a second application. Measurement of time spent on application of sunscreen on different body sites may be useful in investigating the distribution of sunscreen in real‐life settings. [ABSTRACT FROM AUTHOR]

Abstract: The animal immune response has hitherto been viewed primarily in the context of resistance only. However, individuals can also employ a tolerance strategy to maintain good health in the face of ongoing infection. To shed light on the genetic and physiological basis of tolerance, we use a natural population of field voles, Microtus agrestis, to search for an association between the expression of the transcription factor Gata3, previously identified as a marker of tolerance in this system, and polymorphism in 84 immune and nonimmune genes. Our results show clear evidence for an association between Gata3 expression and polymorphism in the Fcer1a gene, with the explanatory power of this polymorphism being comparable to that of other nongenetic variables previously identified as important predictors of Gata3 expression. We also uncover the possible mechanism behind this association using an existing protein–protein interaction network for the mouse model rodent, Mus musculus, which we validate using our own expression network for M. agrestis. Our results suggest that the polymorphism in question may be working at the transcriptional level, leading to changes in the expression of the Th2‐related genes, Tyrosine‐protein kinase BTK and Tyrosine‐protein kinase TXK, and hence potentially altering the strength of the Th2 response, of which Gata3 is a mediator. We believe our work has implications for both treatment and control of infectious disease. [ABSTRACT FROM AUTHOR]

Immune defense is temperature dependent in cold-blooded vertebrates ( CBVs) and thus directly impacted by global warming. We examined whether immunity and within-host infectious disease progression are altered in CBVs under realistic climate warming in a seasonal mid-latitude setting. Going further, we also examined how large thermal effects are in relation to the effects of other environmental variation in such a setting (critical to our ability to project infectious disease dynamics from thermal relationships alone). We employed the three-spined stickleback and three ecologically relevant parasite infections as a 'wild' model. To generate a realistic climatic warming scenario we used naturalistic outdoors mesocosms with precise temperature control. We also conducted laboratory experiments to estimate thermal effects on immunity and within-host infectious disease progression under controlled conditions. As experimental readouts we measured disease progression for the parasites and expression in 14 immune-associated genes (providing insight into immunophenotypic responses). Our mesocosm experiment demonstrated significant perturbation due to modest warming (+2°C), altering the magnitude and phenology of disease. Our laboratory experiments demonstrated substantial thermal effects. Prevailing thermal effects were more important than lagged thermal effects and disease progression increased or decreased in severity with increasing temperature in an infection-specific way. Combining laboratory-determined thermal effects with our mesocosm data, we used inverse modeling to partition seasonal variation in Saprolegnia disease progression into a thermal effect and a latent immunocompetence effect (driven by nonthermal environmental variation and correlating with immune gene expression). The immunocompetence effect was large, accounting for at least as much variation in Saprolegnia disease as the thermal effect. This suggests that managers of CBV populations in variable environments may not be able to reliably project infectious disease risk from thermal data alone. Nevertheless, such projections would be improved by primarily considering prevailing thermal effects in the case of within-host disease and by incorporating validated measures of immunocompetence. [ABSTRACT FROM AUTHOR]

Widespread ocean acidification ( OA) is modifying the chemistry of the global ocean, and the Arctic is recognized as the region where the changes will progress at the fastest rate. Moreover, Arctic species show lower capacity for cellular homeostasis and acid-base regulation rendering them particularly vulnerable to OA. In the present study, we found physiological differences in OA response across geographically separated populations of the keystone Arctic copepod Calanus glacialis. In copepodites stage CIV, measured reaction norms of ingestion rate and metabolic rate showed severe reductions in ingestion and increased metabolic expenses in two populations from Svalbard (Kongsfjord and Billefjord) whereas no effects were observed in a population from the Disko Bay, West Greenland. At pHT 7.87, which has been predicted for the Svalbard west coast by year 2100, these changes resulted in reductions in scope for growth of 19% in the Kongsfjord and a staggering 50% in the Billefjord. Interestingly, these effects were not observed in stage CV copepodites from any of the three locations. It seems that CVs may be more tolerant to OA perhaps due to a general physiological reorganization to meet low intracellular pH during hibernation. Needless to say, the observed changes in the CIV stage will have serious implications for the C. glacialis population health status and growth around Svalbard. However, OA tolerant populations such as the one in the Disko Bay could help to alleviate severe effects in C. glacialis as a species. [ABSTRACT FROM AUTHOR]

Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and red tattoos may be associated with increased risk of skin cancer due to potential carcinogens in tattoo inks. This combination has not been studied previously. Immunocompetent C3.Cg/TifBomTac hairless mice (n=99) were tattooed on their back with a popular red tattoo ink. This often used ink is banned for use on humans because of high content of the potential carcinogen 2-anisidine. Half of the mice were irradiated with three standard erythema doses UVR thrice weekly. Time to induction of first, second and third squamous cell carcinoma (SCC) was measured. All UV-irradiated mice developed SCCs. The time to the onset of the first and second tumor was identical in the red-tattooed group compared with the control group (182 vs 186 days and 196 vs 203 days, P=ns). Statistically, the third tumor appeared slightly faster in the red-tattooed group than in the controls (214 vs 224 days, P=.043). For the second and third tumor, the growth rate was faster in the red-tattooed group compared with the control (31 vs 49 days, P=.009 and 30 vs 38 days, P=.036). In conclusion, no spontaneous cancers were observed in skin tattooed with a red ink containing 2-anisidine. However, red tattoos exposed to UVR showed faster tumor onset regarding the third tumor, and faster growth rate of the second and third tumor indicating red ink acts as a cocarcinogen with UVR. The cocarcinogenic effect was weak and may not be clinically relevant. [ABSTRACT FROM AUTHOR]

Coalescent-based analyses have been recommended for species delimitation and tree reconstruction. Yet, despite recent advances in molecular methods, acquiring sufficient genetic data often precludes coalescent-based analyses in nonmodel organisms. We show that these methods are accessible to questions in nonmodel systems. Specifically, we use coalescent-based analyses to investigate evolutionary independence and relationships among chromosomally distinct members (sibling species) of a black fly (Diptera: Simuliidae) species complex. Our dataset consists of nuclear DNA (nuDNA) and mitochondrial DNA (mtDNA) markers - the former developed using the black fly transcriptome and available genomes from model relatives. We show that individual gene trees exhibit considerable discordance among one another and reveal little about potential species limits. Consistent species tree topologies are obtained from analyses of nuDNA, both with and without the inclusion of mtDNA data. Nodes on the tree receive robust support with the addition of mtDNA. Coalescent-based species validation approaches recognize all sibling species. However, unlike species tree analyses, the addition of mtDNA data does not improve or alter the results. Thus, analyses of nuDNA alone can validate sibling species. Contrary to these results, population genetic patterns of neutral diversity, within-locus recombination, and linkage disequilibrium suggest that sibling species represent a single species with high levels of nucleotide polymorphism, large effective population sizes, and extensive gene flow. Demographic patterns inferred from neutrality tests integrate seemingly disparate results by showing signatures of gene flow among structured populations that are expanding in size. Thus, admixture associated with geographic range expansions may be assimilating sibling species into a single genetic lineage. [ABSTRACT FROM AUTHOR]

Background Previous studies showed that 5 μg of ramosetron, a serotonin (5-hydroxytryptamine: 5- HT)-3 receptor antagonist, is only effective in male patients with irritable bowel syndrome ( IBS) with diarrhea ( IBS-D). We hypothesized that either dose 1.25, 2.5, or 5 μg of ramosetron would be effective in female patients with IBS-D. Methods This randomized, double-blind, placebo-controlled, phase II dose-finding exploratory trial included 409 female outpatients with IBS-D treated in Japan. They were administered oral placebo ( n=102), or 1.25 μg ( n=104), 2.5 μg ( n=104), or 5 μg ( n=99) of ramosetron once daily for 12 weeks after a 1-week baseline period. The primary endpoint was monthly responder rates of global improvement of IBS symptoms in the first month. Secondary endpoints included global improvement in the other months, abdominal pain/discomfort, weekly mean changes in the Bristol Stool Form Scale ( BSFS), and IBS- QOL. Key Results Middle dose (2.5 μg) of ramosetron significantly improved abdominal pain/discomfort at second month (62.5%, P=.002), third month (60.6%, P=.005), and the last evaluation point (63.5%, P=.002) and weekly BSFS ( P<.05) except at Week 8, 11, and 12 than placebo. IBS- QOL did not change. Ramosetron induced more constipation than placebo. Conclusions & Inferences The trial suggested that 2.5 μg of ramosetron is the most effective and least harmful option for treating female patients with IBS-D (Clinicaltrials.gov ID: NCT01274000). [ABSTRACT FROM AUTHOR]

Objectives The incidence of actinic keratosis ( AK) is increasing, and several treatment options are available. The aim of this study was to describe clinical characteristics and treatment patterns in patients with AK treated by Danish dermatologists. Methods A multicenter, non-interventional, cross-sectional study was conducted. Three dermatology hospital departments and seven private dermatology clinics enrolled eligible AK patients consecutively during one week. Results A total of 312 patients were included. Non-melanoma skin cancer ( NMSC) was previously reported in 51.0% of patients and currently suspected in 9.4% of AK-affected anatomical regions. Lesions of AK were located primarily on the face (38.6%), scalp (12.8%), and hands (11.2%). Actinic keratosis commonly presented with multiple AK lesions (38.6%) and field cancerization (38.5%). The treatments used most frequently were cryotherapy (57.7%) and photodynamic therapy ( PDT) with methyl aminolevulinate (17.1%) and imiquimod (11.2%). The likelihood of receiving cryotherapy was higher for men (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.10-2.47) and increased with age (2.2% per year, 0.4-4.0%). PDT represented the most frequently applied treatment for severe actinic damage and was more likely to be prescribed to women ( OR 4.08, 95% CI 2.22-7.47) and young patients ( OR 0.97 per year, 95% CI 0.95-0.99). The prevalence of severe actinic damage (17.3% versus 9.6%) and intake of immunosuppressive medication (29.0 versus 2.0) were higher among hospital patients compared with those treated in private practices ( P < 0.0001). Conclusions The majority of AK patients in Danish dermatology clinics have a history of skin cancer, and NMSC is suspected in almost 10% of AK-affected regions. Cryotherapy is the most frequently used treatment overall, except in instances of severe actinic damage, in which PDT is the first-choice treatment. [ABSTRACT FROM AUTHOR]

Abstract: Ionic self‐assembly (ISA) is a proven method that exploits non‐covalent interactions to generate supramolecular materials. Here, we have expanded the scope of this approach fabricating thin films with nanoscopic order maintained over centimeters. Cationic layers of benzalkonium surfactants form a lamellar template. The template is able to host layers of negatively charged polyaromatic functional units, here demonstrated with β‐naphthol‐derived azo‐dyes. We show that a variety of these functional building blocks can be incorporated in the lamellar template through ISA. Sixteen different materials were produced, characterized, and processed into thin films, with lamellar order perpendicular to the substrate. Thus, a design concept is demonstrated in which diverse functional motifs can be isolated and ordered in a 2D lattice between layers of alkyl chains in bulk and in thin films, in which the molecular order is maintained and aligned to the substrate. [ABSTRACT FROM AUTHOR]

Diffusivities of methyl acetate, methanol and water in poly(vinyl acetate) and fully and partially hydrolyzed poly(vinyl alcohol) have been measured by capillary column inverse gas chromatography and/or gravimetric sorption. Data from the literature have been used when available for comparison. Overall the diffusivities show good consistency in terms of their temperature and concentration dependences. The free-volume model has been applied to all the data with excellent results. In most cases the dramatic changes in diffusivities with temperature and concentration can be captured using only a few experimental data points and two regression parameters. This demonstrates that the free-volume theory is a valuable tool for the design of equipment for processing and devolatilization of polymer − solvent systems. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Sluiceways at hydroelectric dams are designed to enable floating ice and debris to pass through the dams and may be used as an effective, nonturbine, surface route for out-migrating fishes to pass through dams. Each year, the sluiceway at The Dalles Dam on the Columbia River, USA, is normally operated between 1 April and 30 November and the spillway between 10 April and 31 August to enable downstream-migrating juvenile Pacific salmonids to pass. The only route available for fishes to pass the dam between 1 December and 31 March is through the turbines. This study evaluated downstream passage of adult steelheadOncorhynchus mykissat The Dalles Dam during various periods between 1 November and 10 April for years 2008 through 2010. The purpose of the study was to determine the efficacy of operating the sluiceway between 1 December and 31 March to provide a relatively safe, nonturbine, surface outlet for downstream passage of adult steelhead that overwinter in the lower Columbia River (i.e., fallbacks) or for adult steelhead attempting to emigrate back to the marine environment after spawning (i.e., kelts). We applied a fixed-location hydroacoustic technique to estimate downstream passage rates at the sluiceway and turbines. The sluiceway was used by 91–99% of the adult steelhead during all sampling periods; the remaining 1–9% passed through the turbines. This implies that adult steelhead preferred the sluiceway for downstream passage at the dam. Our results indicate that keeping the sluiceway open between 1 December and 31 March may provide an optimal, nonturbine surface route for downstream passage of overwintering or postspawned adult steelhead at The Dalles Dam. Similar operations are relevant at hydroelectric dams with surface-flow outlets, such as sluiceways, for safe downstream passage of fish species of management concern. Received July 19, 2012; accepted March 27, 2013 [ABSTRACT FROM PUBLISHER]

Hypercapnia and hyperoxia give rise to vasodilation and vasoconstriction, respectively. This study investigates the influence of hypercapnia and hyperoxia on venous vessel size in the human brain. Venous vessel radii were measured in response to hypercapnia and hyperoxia. The venous vessel radii were determined by calculation of the changes in R2* and R2 that are induced by breathing 6% CO2 or pure oxygen. The experimental paradigm consisted of two 3-min intervals of inhaling 6% CO2 or 100% O2 interleaved with three 2-min intervals of breathing air. Hypercapnic and hyperoxic experiments were performed on eight subjects on a 3T scanner. Parametric maps of mean venous vessel radius were calculated from the changes in R2* and R2, which were measured by simultaneous acquisition of gradient-echo and spin-echo signals. The mean venous vessel radii in hypercapnia were 7.3 ± 0.3 μm in gray matter and 6.6 ± 0.5 μm in white matter. The corresponding vessel radii in hyperoxia were 5.6 ± 0.2 μm in gray matter and 5.4 ± 0.2 μm in white matter. These results show that the venous vessel radius was larger in hypercapnia than that in hyperoxia in both gray matter and white matter ( P < 0.005), which agrees with the hypothesis that hypercapnia causes vasodilation and hyperoxia induces vasoconstriction. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Several neurotransmitters, including acetylcholine, regulate neuronal tone by suppressing a non-inactivating low-threshold voltage-gated potassium current generated by the M-channel. Agonist dependent control of the M-channel is mediated by calmodulin, activation of anchored protein kinase C (PKC), and depletion of the phospholipid messenger phosphatidylinositol 4,5-bisphosphate (PIP2). In this report, we show how this trio of second messenger responsive events acts synergistically and in a stepwise manner to suppress activity of the M-current. PKC phosphorylation of the KCNQ2 channel subunit induces dissociation of calmodulin from the M-channel complex. The calmodulin-deficient channel has a reduced affinity towards PIP2. This pathway enhances the effect of concomitant reduction of PIP2, which leads to disruption of the M-channel function. These findings clarify how a common lipid cofactor, such as PIP2, can selectively regulate ion channels. [ABSTRACT FROM AUTHOR]

We investigated species limits and phylogenetic relationships among chromosomally distinct North American members of the Simulium malyschevi species-group. Maximum parsimony and Bayesian analyses were conducted based on 12S, COII, cyt b and ITS-1 gene sequences. In terms of species limits, monophyly was highly supported for each chromosomally and morphologically distinct taxon analysed ( S. decimatum, S. defoliarti, S. malyschevi, and S. murmanum). In contrast, support for monophyly of morphologically homogeneous S. arcticum complex members was significant only in one case ( S. saxosum) and not the other ( S. negativum). Considering the overall topology, three principal conclusions were drawn: (i) the status of S. subvariegatum as a member of the S. malyschevi species-group remains uncertain. This species either was excluded from the malyschevi-group or formed a sister group with S. malyschevi at the base of the tree; (ii) although S. murmanum and S. decimatum branch after S. malyschevi, the position of the two species relative to each other remains unresolved; and (iii) the structurally homogeneous S. arcticum species complex was not monophyletic due to the inclusion of S. defoliarti. Further investigation may warrant changes to current malyschevi-group classification. Molecular datasets alone may be insufficient for resolving relationships among particular lineages of black flies. [ABSTRACT FROM AUTHOR]

A revolutionary advance in ecological immunology is that postgenomic technologies now allow molecular mediators defined in laboratory models to be measured at the mRNA level in field studies of many naturally occurring species. Here, we demonstrate the application of such an approach to generate meaningful immunological profiles for wild mammals. We sampled a natural field vole population across the year ( n = 307) and developed a battery of cellular assays in which functionally different pro- and anti-inflammatory signalling responses (transcription factors and cytokines) were activated and quantified by Q-PCR. Temporal trends were the strongest feature in the expression data, although some life history stages (mating vs. nonmating males and pregnant females) were also associated with significant variation. There was a striking set of significant negative associations between inflammatory mediators and condition indices reflecting packed erythrocyte volume and relative liver size, spleen size and splenocyte count. Grouped (principal component) measures of inflammatory and anti-inflammatory expression were high in winter, with minima in the breeding season that occurred earlier for grouped anti-inflammatory responses than for grouped inflammatory responses. Some individual immunological mediators also showed patterns unrelated to the breeding season or annual periodic cues. For example, interferon regulatory factor 5 (IRF5) expression declined throughout the study period, indicating a systematic trend in antimicrobial defences. Pinpointing the causes and consequences of such variation may help identify underlying environmental drivers of individual fitness and demographic fluctuation. [ABSTRACT FROM AUTHOR]

The article determines whether the instructor successfully used technology to create an effective online teaching and learning environment. It discusses trends in online education and examines the lecture as a method of teaching and promoting learning. It also talks about the role of the teacher and the concept of teaching presence.

The purinergic P2X7 receptors are expressed in different cell types where they have varied functions, including regulation of cell survival. The P2X7 receptors are also expressed in exocrine glands, but their integrated role in secretion is unclear. The aim of our study was to determine whether the P2X7 receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X7−/− (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca2+ activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X7−/− mice, and in contrast, tear secretion was increased in P2X7−/− mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more dependent on the P2X7 receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X7 receptor expression. ATP and carbachol increased intracellular Ca2+ activity, but responses depended on the gland type, presence of the P2X7 receptor and the sex of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X7 receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion. Our data also indicate that there is an interaction between purinergic and cholinergic receptor signalling and that function of the P2X7 receptor is suppressed in females. We conclude that the P2X7 receptors are important in short-term physiological regulation of exocrine gland secretion. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the effect of carbon dioxide on the solubility and diffusivity of dichloromethane in polyetherimide using high pressure inverse gas chromatography. It notes that helium served as the inert carrier gas in this study. Results of the study showed that the presence of carbon dioxide led to a decrease in dichloromethane solubility. The study also found that carbon dioxide resulted to a significant increase in the diffusion coefficient.

Accurate prevalence data for acquired cryptorchidism are currently sparse and systematic prospective studies have not yet been reported. Our aim was to determine the prevalence of testicular ascent in childhood. In a prospective longitudinal population-based child cohort from Copenhagen, Denmark (1997–2007), testicular position was examined according to a standardised protocol in a total of 1072 boys, at birth ( n = 1051), at 3 months ( n = 983), 18 months ( n = 888), 36 months ( n = 790) and again once between 4½ and 10 years of age ( n = 509). Ascensus testis was defined as ascent of the testis into a cryptorchid position after normal scrotal position at birth. A congenital cryptorchid testis with spontaneous postnatal descent followed by recurrence of cryptorchidism was named recurrent cryptorchidism. Ascensus testis occurred in 0.2%, 0.6% and 0.6% of boys at 3, 18 and 36 months of age respectively. When including recurrent cryptorchidism the prevalence was 0.2%, 1.2% and 0.8% respectively. Ascensus testis accounts for 58% of all cases of cryptorchidism (congenital and acquired) at 18 months, 71% at 36 months and thereafter 69%. Ascensus testis accounts for more than half of cryptorchid testes seen in childhood and occurs in both previously scrotal and cryptorchid testes. We therefore recommend that all boys should have testis position checked regularly during childhood, at least up to 3 years of age. [ABSTRACT FROM AUTHOR]

Although the molecules and cells involved in triggering immune responses against parasitic worms (helminths) remain enigmatic, research has continued to implicate expansions of T-helper type 2 (Th2) cells and regulatory T-helper (Treg) cells as a characteristic response to these organisms. An intimate association has also emerged between Th2 responses and wound-healing functions. As helminth infections in humans are associated with a strong Th2/Treg immunoregulatory footprint (often termed a ‘modified Th2’ response), plausible links have been made to increased susceptibility to microbial pathogens in helminth-infected populations in the tropics and to the breakdowns in immunological control (allergy and autoimmunity) that are increasing in frequency in helminth-free developed countries. Removal of helminths and their anti-inflammatory influence may also have hazards for populations exposed to infectious agents, such as malaria and influenza, whose worst effects are mediated by excessive inflammatory reactions. The patterns seen in the control of helminth immunity are discussed from an evolutionary perspective. Whilst an inability to correctly regulate the immune system in the absence of helminth infection might seem highly counter-adaptive, the very ancient and pervasive relationship between vertebrates and helminths supports a view that immunological control networks have been selected to function within the context of a modified Th2 environment. The absence of immunoregulatory stimuli from helminths may therefore uncover maladaptations that were not previously exposed to selection. [ABSTRACT FROM AUTHOR]

BACKGROUND: Viral safety is of paramount importance for human plasma–derived therapeutic proteins. Recent reports of blood-associated transmission and continuous regional outbreaks of dengue fever have prompted a validation of clearance of dengue virus in the manufacture processes of the plasma-derived products. STUDY DESIGN AND METHODS: A high titer of cultured dengue virus serotype 2 was spiked into process samples before individual steps of albumin and immunoglobulin manufacture processes, including cold ethanol precipitation, cation-exchange chromatography, pasteurization, solvent/detergent treatment, and virus filtration. Clearance of dengue virus was quantified with TCID50 assays in the culture of Vero E6 cells and, when appropriate, real-time polymerase chain reaction (RT-PCR) assays. RESULTS: The individual process steps were all effective in the inactivation and/or removal of dengue virus, and the data obtained clearly demonstrate that the risk of dengue virus transmission was reduced cumulatively by at least 10.12 and at least 14.24 log in the albumin and immunoglobulin manufacture processes, respectively. CONCLUSION: The dedicated viral inactivation and/or removal approaches currently implemented in the manufacture of plasma-derived products provide a good safety margin with regard to the transmission of dengue virus. [ABSTRACT FROM AUTHOR]

This article discusses a study which examined the solubility and diffusivity of cosolvents and carbon dioxide in a photoresist polymer. The study used the inverse gas chromatography and static capsule methods in measuring the solubility and diffusivity of the materials. It revealed an increase in the solubility and diffusivity of the cosolvents due to the presence of low pressures of carbon dioxide.

Liquid–liquid and vapor–liquid phase equilibria for the binary, ternary, and quaternary systems of vinyl acetate, surfactant, water, and poly(vinyl acetate) (PVAc) were obtained using liquid–liquid equilibria, inverse gas chromatography, and the headspace methods. The Flory–Huggins interaction parameters for the different species in the emulsion polymerization of PVAc latices are reported. These parameters could not be used to predict the phase equilibria because of their strong dependence on concentration. The UNIFAC‐vdW‐FV model was applied to predict the vapor–liquid equilibria in the binary and ternary systems containing vinyl acetate, 4‐nonylphenol polyethoxilate surfactant, and PVAc. The predicted results compare favorably with the experimental data for all systems. Diffusion coefficients were also measured for the solvents in the PVAc. Analysis confirmed that the diffusion in the latex particles was so fast compared to the reaction that the assumption of uniform monomer composition through the particles was valid. On the other hand, the results indicate that the complex thermodynamic interactions will lead to changes with time in the monomer concentration in the reacting polymer phase. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007 [ABSTRACT FROM AUTHOR]

Background Non-human primates are an invaluable part of biomedical research. Strict regulations insure animals have a maximum likelihood of well-being and optimum health during the course of experimental procedures. Objective assessment of well-being is a critical component of these assurances. Methods Here we describe an objective and quantitative system we used to identify two well-being concerns in laboratory rhesus monkeys (Macaca mulatta). We provide a series of indicators for use by laboratory personnel to promote laboratory primate well-being. The indicators measure (1) potentially life threatening clinical concerns, (2) developing clinical issues, (3) atypical behaviors, and (4) laboratory performance. We include specific criteria to facilitate veterinary intervention. Results The assessment, applied to two case studies reported here, enabled swift veterinary intervention returning the animals to a healthy state. Conclusions The measures described here provide a battery of observable and objective measures across multiple dimensions that can further ensure both excellent science and veterinary care. [ABSTRACT FROM AUTHOR]

Excitatory amino acid transporters (EAATs) maintain the balance between pathological and physiological conditions by limiting the extracellular concentration of glutamate within the CNS and thus preventing excitotoxic injury. The loss of EAAT2 has been associated with the development of neurological diseases such as amyotrophic lateral sclerosis. It has therefore been suggested that the over-expression of specific EAATs may provide some degree of neuroprotection. However, the inability to isolate and study the function of the different EAAT isoforms in a cell type-specific manner has made it difficult to determine the exact contribution of individual EAATs toward neuroprotection or neurodegeneration in the context of excitotoxic injury. To address this question, we transduced hippocampal slice cultures from 1-week-old C57B/6 mice with recombinant adeno-associated virus carrying an EAAT2 gene expression cassette. EAAT2 gene expression was driven in neurons with the neuron-specific enolase promoter. Using this model system, we were able to induce a significant increase in the expression of functional EAAT2. Consequently, a significant increase in CA1 neuronal damage was observed in slices over-expressing EAAT2 in neurons following an acute exposure to exogenous glutamate. These data suggest that the increased expression of EAAT2 within neurons may contribute to neurodegeneration. [ABSTRACT FROM AUTHOR]