Phytohemagglutinin-Induced Mitotic Index in Blood Lymphocytes: A Potential Biomarker for Breast Cancer Risk

Background Cell proliferation is associated with the pathogenesis of cancer because it provides opportunities for accumulating genetic mutations. However, biomarkers of cell proliferation in response to environmental stimuli have not been adequately explored for breast cancer risk. Methods In a case-control study of 200 breast cancer patients and 360 healthy controls, we investigated the association between phytohemagglutinin (PHA)-induced mitotic index in blood lymphocyte and breast cancer risk. Results Having high mitotic index (>3.19%) was associated with an increased risk of breast cancer, with adjusted odds ratios (95% confidence interval) of 1.54 (1.03–2.30) and 2.03 (1.18–3.57) for all women and post-menopausal women, respectively. Mitotic index was correlated with some reproductive factors and body mass index in controls. Conclusions Our data suggest increased PHA-induced mitotic index in blood lymphocytes is associated with an increased breast cancer risk and that this association may be modulated by reproductive and other hormones

Fabrication of 58Co positron sources

A technique for producing 58Co positron sources for use in slow positron beams has been developed. The method has been successfully tested at the [mu]Ci and mCi level. Scaling up of the technique is under way to consistently produce 1-2 Ci sources from 60 g of irradiated nickel.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31106/1/0000002.pd

Accelerated brain aging towards transcriptional inversion in a zebrafish model of the K115fs mutation of human PSEN2

BACKGROUND:The molecular changes involved in Alzheimer's disease (AD) progression remain unclear since we cannot easily access antemortem human brains. Some non-mammalian vertebrates such as the zebrafish preserve AD-relevant transcript isoforms of the PRESENILIN genes lost from mice and rats. One example is PS2V, the alternative transcript isoform of the PSEN2 gene. PS2V is induced by hypoxia/oxidative stress and shows increased expression in late onset, sporadic AD brains. A unique, early onset familial AD mutation of PSEN2, K115fs, mimics the PS2V coding sequence suggesting that forced, early expression of PS2V-like isoforms may contribute to AD pathogenesis. Here we use zebrafish to model the K115fs mutation to investigate the effects of forced PS2V-like expression on the transcriptomes of young adult and aged adult brains. METHODS:We edited the zebrafish genome to model the K115fs mutation. To explore its effects at the molecular level, we analysed the brain transcriptome and proteome of young (6-month-old) and aged (24-month-old) wild type and heterozygous mutant female sibling zebrafish. Finally, we used gene co-expression network analysis (WGCNA) to compare molecular changes in the brains of these fish to human AD. RESULTS:Young heterozygous mutant fish show transcriptional changes suggesting accelerated brain aging and increased glucocorticoid signalling. These early changes precede a transcriptional 'inversion' that leads to glucocorticoid resistance and other likely pathological changes in aged heterozygous mutant fish. Notably, microglia-associated immune responses regulated by the ETS transcription factor family are altered in both our zebrafish mutant model and in human AD. The molecular changes we observe in aged heterozygous mutant fish occur without obvious histopathology and possibly in the absence of Aβ. CONCLUSIONS:Our results suggest that forced expression of a PS2V-like isoform contributes to immune and stress responses favouring AD pathogenesis. This highlights the value of our zebrafish genetic model for exploring molecular mechanisms involved in AD pathogenesis.Nhi Hin, Morgan Newman, Jan Kaslin, Alon M. Douek, Amanda Lumsden, Seyed Hani Moussavi Nik ... et al

The borders of booze Britain: alcohol controls and nationality

This paper seeks to understand how United Kingdom alcohol control policies, historically and currently, are both informed by and seek to inform how we conceptualise the nation and nationality. Using the latest minimum price per unit of alcohol policy as a point of departure and setting it the context of over three hundred years of alcohol controls, this paper exposes how the internal contradictions inherent in alcohol regulation are obscured by the deployment of nationalism as a rhetorical devic

Natural parenting : back to basics in infant care

Peer reviewe

Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment

The First Post-Kepler Brightness Dips of KIC 8462852

We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in October 2015, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1-2.5% dips, named "Elsie," "Celeste," "Skara Brae," and "Angkor", which persist on timescales from several days to weeks. Our main results so far are: (i) there are no apparent changes of the stellar spectrum or polarization during the dips; (ii) the multiband photometry of the dips shows differential reddening favoring non-grey extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale <<1um, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term "secular" dimming, which may be caused by independent processes, or probe different regimes of a single process

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior