Iodo-Nonoxynol-9-Derivatives and Methods for Their Use

Mono- and di-iodinated nonoxynol-9-derivatives and methods for their use are disclosed

Nucleosynthesis of Heavy Elements by Neutron Capture

Nucleosynthesis of elements heavier than the iron group by neutron capture on both slow and fast time scales is evaluated. The s-process calculations of Clayton, Fowler, Hull, and Zimmerman (1961) have been revised to include more recent experimental results on abundances and neutron capture cross- sections. The solar-system s-process abundances indicate a history of neutron exposure distributions characterized by decreasing probability of high integrated flux; an exponential exposure distribution is extracted. Estimates are made of the s-process contribution to each isotopic abundance; a table gives the amounts of elements produced by each process in the solar-system material. The r-process calculations are carried out using a semi-empirical atomic-mass law to determine neutron-binding energies and betadecay probabilities. The solar-system r-process material has probably been synthesized in two distinct types of environments, e.g., one of about 4 sec duration with temperature 2.4 X 10 K and neutron density 5 X tO , and the other of the same or longer duration with temperature 1.0 X 10 K and neutron density 3 X 1O both of these environments could be found in an object with mass 10 Mo

Intestinal activation of Notch signaling induces rapid onset hepatic steatosis and insulin resistance.

Here we investigate the effects of expressing an activated mutant of Notch (ICD-E) in an inducible transgenic mouse model. Hepatic expression of ICD-E in adult animals has no detectable phenotype, but simultaneous induction of ICD-E in both the liver and small intestine results in hepatic steatosis, lipogranuloma formation and mild insulin resistance within 96 hours. This supports work that suggests that fatty liver disease may result from disruption of the gut-liver axis. In the intestine, ICD-E expression is known to produce a transient change in the proportion of goblet cells followed by shedding of the recombinant epithelium. We report additional intestinal transcriptional changes following ICD-E expression, finding significant transcriptional down-regulation of rpL29 (ribosomal protein L29), which is implicated in the regulation of intestinal flora. These results provide further evidence of a gut-liver axis in the development of fatty liver disease and insulin resistance and validate a new model for future studies of hepatic steatosis

Productivity in relation to organization of a surgical department : a retrospective observational study

Background Responsible and efficient resource utilization are important factors in healthcare. The aim of this study was to investigate how total case time differs between two differently organized surgical departments. Methods This is a retrospective observational study of a cohort of patients undergoing elective surgery for breast cancer or malignant melanoma in a university hospital setting in Sweden. All patients were operated on by the same set of surgeons but in two different surgical departments: a general surgery (GS) and a cardiothoracic (CT) surgery department. Patients were selected to the two departments from a waiting list in the order of referral for surgery. The effect of being operated on at the CT department compared to the GS department was estimated by linear regression. Results The final study cohort comprised 349 patients in the GS department and 177 patients in the CT department. Both groups were similar regarding surgical procedures, American Society of Anesthesiologists' score, body mass index, age, sex, and the skill level of the operating surgeon. These covariates were included in the linear regression model. The total case time, defined by the Procedural Time Glossary as room set-up start to room clean-up finish, was significantly shorter for the patients who underwent a surgical procedure at the CT department compared to the GS department, even after adjusting for the background characteristics of the patients and surgeon. After adjusting for the selected covariates, the average difference in total case time between the two departments was - 30.67 min (p = 0.001). Conclusions A significantly shorter total case time was measured for operations in the CT department. Plausible explanations may be more beneficial organizational factors, such as staffing ratio, skill mix in the operating room team, and working behavioral aspects regarding resource utilization.Peer reviewe

The Novel CYP2A6 Inhibitor, DLCI-1, Decreases Nicotine Self-Administration in Mice.

During tobacco and e-cigarette use, nicotine is mainly metabolized in the human liver by cytochrome P450 2A6 (CYP2A6). Given that a slower CYP2A6 metabolism has been associated with less vulnerability to develop nicotine dependence, the current studies sought to validate a novel CYP2A6 inhibitor, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), for its effects on intravenous nicotine self-administration. Male and female mice were trained to self-administer nicotine across daily sessions. Once stable responding was achieved, DLCI-1 or vehicle control was administered prior to nicotine sessions. We found that the lower 25 mg/kg and moderate 50 mg/kg doses of DLCI-1 induced a significant decrease in nicotine intake for both males and females. DLCI-1 was further shown to be more effective than a moderate 1 mg/kg dose of bupropion on reducing nicotine intake and did not exert the adverse behavioral effects found with a high 75 mg/kg dose of bupropion. Although mice treated with DLCI-1 self-administered significantly less nicotine, similar nicotine-mediated behavioral effects on locomotion were observed. Together, along with the analysis of nicotine metabolites during self-administration, these findings support the contention that blocking hepatic nicotine metabolism would allow for similar activation of nicotinic acetylcholine receptors at lower nicotine doses. Moreover, these effects of DLCI-1 were specific to nicotine self-administration, as DLCI-1 did not result in any behavioral changes during food self-administration. Taken together, these studies validate DLCI-1 as a novel compound to decrease nicotine consumption, which may thereby promote tobacco and nicotine product cessation. SIGNIFICANCE STATEMENT: Current pharmacological approaches for nicotine and tobacco cessation have only been able to achieve limited efficaciousness in promoting long-term abstinence. In this work, we characterize the effects of a novel compound, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), which inhibits the main enzyme that metabolizes nicotine, and we report a significant decrease in intravenous nicotine self-administration in male and female mice, supporting the potential of DLCI-1 as a novel tobacco cessation pharmacotherapeutic

Low Pressure Greenhouse Concepts for Mars

A project was initiated to begin testing some environmental limits for managing plant growth systems. These limits will help determine some of the concepts for building plant enclosures for use on Mars. In particular, this study focuses on the effects of reduced atmospheric pressures. Structural design is considered as it relates to the biological processes that would occur within that structure. The design must be closely tied to the functionality of the biological system and has a few primary concerns that need to be tested to resolve the question as to the path of the design. Early tests indicate that plants can survive and grow at low (greater than 76 mb) pressure

Human keratinocytes have two interconvertible modes of proliferation.

Single stem cells, including those in human epidermis, have a remarkable ability to reconstitute tissues in vitro, but the cellular mechanisms that enable this are ill-defined. Here we used live imaging to track the outcome of thousands of divisions in clonal cultures of primary human epidermal keratinocytes. Two modes of proliferation were seen. In 'balanced' mode, similar proportions of proliferating and differentiating cells were generated, achieving the 'population asymmetry' that sustains epidermal homeostasis in vivo. In 'expanding' mode, an excess of cycling cells was produced, generating large expanding colonies. Cells in expanding mode switched their behaviour to balanced mode once local confluence was attained. However, when a confluent area was wounded in a scratch assay, cells near the scratch switched back to expanding mode until the defect was closed. We conclude that the ability of a single epidermal stem cell to reconstitute an epithelium is explained by two interconvertible modes of proliferation regulated by confluence.The initial association of holoclone and paraclone type behaviour in clonal cultures of NFSK with stem and balanced progenitor dynamics was due to BDS working in collaboration with PHJ, VN-N, David Doupé and Allon Klein, based on the quantitative analysis of published and unpublished colony size distributions6 . We thank Gözde Akdeniz & David Doupé for experimental work that led up to the project that was analysed by Allon Klein and Genneth Zhang, Patrick Lombard at the Wellcome TrustMedical Research Council Cambridge Stem Cell Institute for Bioinformatics analysis and Esther Choolun for technical assistance. We acknowledge the support of the Wellcome Trust, Cambridge Cancer Centre, Medical Research Council, the NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research) and Cancer Research UK (Programme grant C609/A17257).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncb328

The KRESCENT Program (2005-2015) : an evaluation of the state of Kidney Research Training in Canada

Background: The Kidney Research Scientist Core Education and National Training (KRESCENT) Program was launched in 2005 to enhance kidney research capacity in Canada and foster knowledge translation across the 4 themes of health research. Objective: To evaluate the impact of KRESCENT on its major objectives and on the careers of trainees after its first 10 years. Methods: An online survey of trainees (n = 53) who had completed or were enrolled in KRESCENT was conducted in 2015. Information was also obtained from curriculum vitae (CVs). A bibliometric analysis assessed scientific productivity, collaboration, and impact in comparison with unsuccessful applicants to KRESCENT over the same period. The analysis included a comparison of Canadian with international kidney research metrics from 2000 to 2014. Results: Thirty-nine KRESCENT trainees completed the survey (74%), and 44 trainees (83%) submitted CVs. KRESCENT trainees had a high success rate at obtaining grant funding from the Canadian Institutes of Health Research (CIHR; 79%), and 76% of Post-Doctoral Fellows received academic appointments at the Assistant Professor level within 8 months of completing training. The majority of trainees reported that KRESCENT had contributed significantly to their success in securing CIHR funding (90%), and to the creation of knowledge (93%) and development of new methodologies (50%). Bibliometric analysis revealed a small but steady decline in total international kidney research output from 2000 to 2014, as a percentage of all health research, although overall impact of kidney research in Canada increased from 2000-2005 to 2009- 2014 compared with other countries. KRESCENT trainees demonstrated increased productivity, multiauthored papers, impact, and international collaborations after their training, compared with nonfunded applicants. Conclusions: The KRESCENT Program has fostered kidney research career development and contributed to increased capacity, productivity, and collaboration. To further enhance knowledge creation and translation in kidney research in Canada, programs such as KRESCENT should be sustained via long-term funding partnerships.Mise en contexte: Le programme KRESCENT (Kidney Research Scientist Core Education and National Training) a été lancé en 2005 pour augmenter la capacité de la recherche sur les maladies du rein à travers le Canada, et pour encourager la transmission des connaissances au sein des quatre axes de recherche en santé. Objectifs de l’étude: Cette étude avait pour but d’évaluer les répercussions du programme KRESCENT sur ses principaux objectifs ainsi que des retombées sur la carrière des stagiaires participants, dix ans après sa création. Méthodologie: Un sondage en ligne a été mené en 2015 auprès des stagiaires (n = 53) ayant été admis ou ayant complété le programme KRESCENT. Des renseignements ont également été obtenus par la consultation de curriculum vitae (CV). Une analyse bibliométrique a évalué la productivité scientifique et la collaboration des participants ainsi que les répercussions de leur participation à KRESCENT sur leur carrière. Les données de cette analyse ont été comparées à celles des candidats n’ayant pas été retenus au cours de la même période. L’analyse comprenait également une comparaison des données canadiennes avec celles obtenues en recherche sur les maladies du rein ailleurs dans le monde

Opportunities for authentic simulated patients

Background and aim/objectives: Traditionally, simulated patients are played by actors and / or fellow peers taking part in the simulation-based training. Literature indicates that there are many benefits to employing real people in simulation scenarios especially when the training addresses empathy and communication (Oh et al. 2015). The question therefore is why do we not involve actual service users as ‘authentic simulated patients’ or ‘authentic standardised patients’ (abbreviated to ‘authentic SPs’) in the scenarios? Yet, literature also points to the need for consistency (Wilbur et al. 2018, Lewis et al. 2017) in simulation-based learning concerning exam situations such as Objective Standardised Clinical Examination (OSCE)s, which may be more difficult to achieve when a person contributes with their lived experience rather than their acting skills. Additionally, the training of simulated patients / standardised patients is variable and inconsistent, which calls for a renewed approach that acknowledges and adapts to the requirements and abilities of authentic SPs. The aim of this talk is to present a framework and checklist for the involvement of SPs with the lived experience to explore what the opportunities for the employment of ‘authentic simulated patients’ is. The anticipated benefits they bring to the learning experience will be discussed, whilst considering the risks for the services user, learners, and educators alike. Method or activity: A framework using a checklist for the involvement of ‘authentic SPs’ has been developed, which is based on a systematic search of literature reviews as well as on discussions with simulation practitioners and educators. It draws on examples from practice of those involving persons with learning disabilities in the structuring of the simulation learning activities in an undergraduate nursing course. Results/Findings discussion: The talk will present the overall ‘authentic SP’ framework and how the checklist could be applied. For this, examples from practice will be given such as involving persons with learning disabilities as SP in simulation-based learning. Conclusion: The framework and checklist will provide simulationists with an approach and tool to consider the involvement of ‘authentic SPs’ to enrich the learning experience in a mutually beneficial way. References: Lewis KL, Bohnert CA, Gammon WL, Hölzer H, Lyman L, Smith C, Thompson TM, Wallace A, Gliva-McConvey G. The association of standardized patient educators (ASPE) standards of best practice (SOBP). Advances in Simulation. 2017 Dec;2(1):1-8. Oh PJ, Jeon KD, Koh MS. The effects of simulation-based learning using standardized patients in nursing students: A meta-analysis. Nurse education today. 2015 May 1;35(5):e6-15. Wilbur K, Elmubark A, Shabana S. Systematic review of standardized patient use in continuing medical education. Journal of Continuing Education in the Health Professions. 2018 Jan 1;38(1):3-10