Frequency and Circadian Timing of Eating May Influence Biomarkers of Inflammation and Insulin Resistance Associated with Breast Cancer Risk.

Emerging evidence suggests that there is interplay between the frequency and circadian timing of eating and metabolic health. We examined the associations of eating frequency and timing with metabolic and inflammatory biomarkers putatively associated with breast cancer risk in women participating in the National Health and Nutrition Examination 2009-2010 Survey. Eating frequency and timing variables were calculated from 24-hour food records and included (1) proportion of calories consumed in the evening (5 pm-midnight), (2) number of eating episodes per day, and (3) nighttime fasting duration. Linear regression models examined each eating frequency and timing exposure variable with C-reactive protein (CRP) concentrations and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Each 10 percent increase in the proportion of calories consumed in the evening was associated with a 3 percent increase in CRP. Conversely, eating one additional meal or snack per day was associated with an 8 percent reduction in CRP. There was a significant interaction between proportion of calories consumed in the evening and fasting duration with CRP (p = 0.02). A longer nighttime fasting duration was associated with an 8 percent lower CRP only among women who ate less than 30% of their total daily calories in the evening (p = 0.01). None of the eating frequency and timing variables were significantly associated with HOMA-IR. These findings suggest that eating more frequently, reducing evening energy intake, and fasting for longer nightly intervals may lower systemic inflammation and subsequently reduce breast cancer risk. Randomized trials are needed to validate these associations

Selective Fluorination Strategies

There is a great interest in the synthesis of fluorinated aromatic and heterocyclic compounds, which have a range of applications in the pharmaceutical industry. Many common routes to these compounds, however, are low yielding and or/expensive. This thesis is concerned with novel methods for the synthesis of fluoro-aromatics and fluoro-pyrazoles using conventional fluorinating agents, such as Selectfluor™, as well as using elemental fluorine and the flow reactor technology developed in Durham. Firstly, elemental fluorine was used to fluorinate a range of aromatics containing electron-donating substituents, using both batch and flow methods. These methods often afforded the desired compound but with little selectivity and low conversion from the starting materials. Following on from this, ipso fluoro-deboronation techniques using Selectfluor™, were employed to improve the selectivity and yields of the reaction and, in many cases, the desired mono-fluorinated arylfluoride could be accessed in good yield. A range of aryl boronic acid derivatives were explored as the substrate and the results showed that trifluoroborate salts were the most useful substrate. The ipso fluoro-deboronation of heterocyclic boronic acid derivatives was also investigated and showed some promising results. The synthesis of 4-fluoropyrazoles was investigated using three methods. Initially, a two-step process, where the 2-fluoro-1,3-diketone was synthesised and isolated and subsequently reacted with hydrazine, was employed. This allowed a range of 4-fluoropyrazoles to be obtained in high yield and purity. Secondly, a telescoped two-step continuous flow process was employed which did not require isolation of the intermediate 2-fluoro-1,3-diketone. This reaction gave good yields and required less solvent with significantly lower reaction times than the two-step process. Thirdly, C4 mono- and di-fluorination of 3,5-disubstituted pyrazoles was investigated using Selectfluor™ and elemental fluorine. This method gave low conversion from the starting material (50–60 %) but the desired 4-fluoropyrazoles and novel 4,4-difluoropyrazoles could be isolated

An integrated 4249 marker FISH/RH map of the canine genome

BACKGROUND: The 156 breeds of dog recognized by the American Kennel Club offer a unique opportunity to map genes important in genetic variation. Each breed features a defining constellation of morphological and behavioral traits, often generated by deliberate crossing of closely related individuals, leading to a high rate of genetic disease in many breeds. Understanding the genetic basis of both phenotypic variation and disease susceptibility in the dog provides new ways in which to dissect the genetics of human health and biology. RESULTS: To facilitate both genetic mapping and cloning efforts, we have constructed an integrated canine genome map that is both dense and accurate. The resulting resource encompasses 4249 markers, and was constructed using the RHDF5000-2 whole genome radiation hybrid panel. The radiation hybrid (RH) map features a density of one marker every 900 Kb and contains 1760 bacterial artificial chromosome clones (BACs) localized to 1423 unique positions, 851 of which have also been mapped by fluorescence in situ hybridization (FISH). The two data sets show excellent concordance. Excluding the Y chromosome, the map features an RH/FISH mapped BAC every 3.5 Mb and an RH mapped BAC-end, on average, every 2 Mb. For 2233 markers, the orthologous human genes have been established, allowing the identification of 79 conserved segments (CS) between the dog and human genomes, dramatically extending the length of most previously described CS. CONCLUSIONS: These results provide a necessary resource for the canine genome mapping community to undertake positional cloning experiments and provide new insights into the comparative canine-human genome maps

(What Can I Say) After I Say I\u27m Sorry?

With Ukulele arrangement. Contains advertisements and/or short musical examples of pieces being sold by publisher.https://digitalcommons.library.umaine.edu/mmb-vp/6986/thumbnail.jp

Altered Host Immunity, Human T Lymphotropic Virus Type I Replication, and Risk of Adult T-Cell Leukemia/Lymphoma: A Prospective Analysis from the ATL Cohort Consortium

Background: Adult T-cell leukemia/lymphoma (ATL) is a rare and often fatal outcome of infection with human T-lymphotropic virus type I (HTLV-I). Altered host immunity in HTLV-I carriers has been postulated as a risk factor for ATL, but is not well understood. Methods: We prospectively examined well-validated serologic markers of HTLV-I pathogenesis and host immunity in 53 incident ATL cases and 150 carefully matched asymptomatic HTLV-I carriers from eight population-based studies in Japan, Jamaica, the United States and Brazil. We used multivariable conditional logistic regression, conditioned on the matching factors (cohort/race, age, sex, and sample collection year), to evaluate the biomarkers’ associations with ATL in all subjects and by years (≤5, >5) from blood draw to ATL diagnosis. Results: In the pooled population, above-median soluble interleukin-2-receptor-alpha levels (sIL2R, v. ≤ median; odds ratio (OR), 95% confidence interval (CI)=4.08, 1.47-11.29) and anti-Tax seropositivity (anti-Tax; OR, 95% CI=2.97, 1.15-7.67), which indicate T cell activation and HTLV-I replication, respectively, were independently associated with an increased ATL risk. Above-median total immunoglobulin E levels (v. ≤ median; OR, 95% CI=0.45, 0.19-1.06), which indicate type 2 (B cell) activation, predicted a lower ATL risk. The sIL2R and anti-Tax associations with ATL were stronger in samples collected ≤5 years pre-diagnosis. Conclusions: The biomarker profile predictive of ATL risk suggests a role for heightened T cell activation and HTLV-I replication and diminished type 2 immunity in the etiology of ATL in HTLV-I carriers. Translation of these findings to clinical risk prediction or early ATL detection requires further investigation. Acknowledgements: This abstract is presented on behalf of the ATL Cohort Consortium

Eating disorder symptoms and their associations with anthropometric and psychiatric polygenic scores

BACKGROUND: Eating disorder (ED) symptoms are prevalent in the general population, but their shared genetic underpinnings with psychiatric, metabolic, and anthropometric traits are not known. Here, we examined if polygenic scores (PGSs) of traits associated with anorexia nervosa are also associated with adolescent ED symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC). METHODS: A total of 8654 participants with genotype data and at least one phenotypic measure were included from the ALSPAC study. We associated PGS from 25 traits (16 psychiatric, 4 metabolic, and 5 anthropometric) with eight ED symptoms, including behaviours such as fasting for weight loss and cognitions such as body dissatisfaction. RESULTS: Higher attention deficit hyperactivity disorder PGS and lower educational attainment PGS were associated with fasting for weight loss. Higher insomnia PGS was associated with increased body dissatisfaction. We found no evidence of an association between metabolic trait PGS and any ED symptom. Fat-free mass, fat mass, and body fat percentage PGSs, were positively associated with binge eating, excessive exercise, fasting for weight loss, body dissatisfaction, and weight and shape concern. CONCLUSIONS: ED symptoms are genetically associated with psychiatric and anthropometric, but not with metabolic traits. Our findings provide insights for future genetic research investigating on why some individuals with ED symptoms progress to develop threshold EDs while others do not

Quality and impact of pharmacology digital simulation education on pre-registration healthcare students a systematic literature review

ObjectiveThis review aimed to assess the quality and nature of the literature related to digital simulation-based pharmacology education. Specifically, we sought to understand the influence of simulations on the knowledge, satisfaction, and confidence of pre-registration nurses and other healthcare students participating in such educational programs.DesignSystematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. This study was registered in the Prospective Register of Systematic Reviews (PROSPERO, reg no: CRD42023437570).Data sourcesPubMed, MEDLINE, APA PsycInfo, ProQuest, Web of Science, ScienceDirect, and CINHAL databases were searched.Review methodsThe review focused on the quantitative findings from the studies published from 2016 to 2023. Only the studies that assessed the impact of digital simulation-based pharmacology education on pre-registration healthcare students' knowledge, satisfaction, and confidence were selected for review. Data were synthesized using a narrative approach. The Mixed Methods Appraisal Tool (MMAT) was used to assess the quality of the included articles. This was followed by a narrative synthesis to consolidate the themes.ResultOut of 1587 articles,16 met the inclusion criteria. A wide variety of digital technologies have been utilised, such as virtual simulation, computer simulation (2D/3D), mixed reality, and augmented reality, with the majority using virtual simulation. All studies implemented single-user simulations. The themes emerging from the narrative synthesis suggest that a digital simulation-based pharmacology course is an effective tool for enhancing students' knowledge, confidence, and satisfaction in learning pharmacological concepts. Furthermore, simulation-based teaching with a blended approach was found to be beneficial. However, the integration of the polypharmacy concept and the intra and interprofessional approach to teaching and learning was not evident in these studies.ConclusionThis systematic literature review provides evidence of the potential of digital simulation-based education in pharmacology teaching among healthcare pre-registration students. In future studies, the integration of polypharmacy content with an intra and interprofessional teaching-learning approach is recommende

Effect of a Perioperative, Cardiac Output-Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery A Randomized Clinical Trial and Systematic Review

Importance: small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm.Objective: to evaluate the clinical effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm.Design, setting, and participants: OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.Interventions: patients were randomly assigned to a cardiac output–guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).Main outcomes and measures: the primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care–free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.Results: baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk [RR], 0.84 [95% CI, 0.71-1.01]; absolute risk reduction, 6.8% [95% CI, ?0.3% to 13.9%]; P?=?.07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 [31.5%] vs control, 614/1476 [41.6%]; RR, 0.77 [95% CI, 0.71-0.83]) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths [4.9%] vs control, 206/3160 deaths [6.5%]; RR, 0.82 [95% CI, 0.67-1.01]) and mortality at longest follow-up (intervention, 267/3215 deaths [8.3%] vs control, 327/3160 deaths [10.3%]; RR, 0.86 [95% CI, 0.74-1.00]).Conclusions and relevance: in a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output–guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rate

Persistent thinness and anorexia nervosa differ on a genomic level

Thinness and anorexia nervosa are both characterised by persistent low weight. Individuals with anorexia nervosa concurrently report distorted perceptions of their body and engage in weight-loss behaviours, whereas individuals with thinness often wish to gain weight. Both conditions are heritable and share genomics with BMI, but are not genetically correlated with each other. Based on their pattern of genetic associations with other traits, we explored differences between thinness and anorexia nervosa on a genomic level. In Part 1, using publicly available data, we compared genetic correlations of persistent thinness/anorexia nervosa with eleven psychiatric disorders. In Part 2, we identified individuals with adolescent persistent thinness in the Avon Longitudinal Study of Parents and Children (ALSPAC) by latent class growth analysis of measured BMI from 10 to 24 years (n = 6594) and evaluated associations with psychiatric and anthropometric polygenic scores. In Part 1, in contrast to the positive genetic correlations of anorexia nervosa with various psychiatric disorders, persistent thinness showed negative genetic correlations with attention deficit hyperactivity disorder (r gAN = 0.08 vs. r gPT = −0.30), alcohol dependence (r gAN = 0.07 vs. r gPT = −0.44), major depressive disorder (rgAN = 0.27 vs. rgPT = −0.18) and post-traumatic stress disorder (rgAN = 0.26 vs. rgPT = −0.20). In Part 2, individuals with adolescent persistent thinness in the ALSPAC had lower borderline personality disorder polygenic scores (OR = 0.77; Q = 0.01). Overall, results suggest that genetic variants associated with thinness are negatively associated with psychiatric disorders and therefore thinness may be differentiable from anorexia nervosa on a genomic level

Marine substratum map of the Causeway Coast, Northern Ireland

A 1:30,000 substratum map for an area off the north coast of Ireland is presented. The study area is bounded in the south by the Causeway coastline and in the north by the following coordinates: top left corner (6°43′36″W, 55°17′N) and top right corner (6°27′W, 55°17′N). This mapping has been made possible through the availability of full seafloor coverage multibeam swath bathymetry and backscatter data (both gridded to 1 m), together with ground-truthing data collected over the past 40 years. Bathymetry data were used to generate terrain indices such as slope, rugosity, aspect, fine- and broad-scale Benthic Position Index, whilst the backscatter data were interpreted visually, subjected to an unsupervised classification process using QTC Multiview, and combined with the bathymetry-derived parameters into a clustermap in ArcGIS. The resulting maps allowed us to divide the seabed into 10 distinct acoustic classes, which, linked to sediment samples, diver surveys, underwater video-tows and remotely operated vehicle surveys, were converted into a substratum map. This is the most accurate seafloor substratum map to date for the north coast of Ireland and could form the basis for more in-depth geological, biological and hydrodynamic studies of this highly dynamic coastline