How did smokers respond to standardised cigarette packaging with new, larger health warnings in the United Kingdom during the transition period? A cross-sectional online survey

Introduction: In the United Kingdom, standardised packaging for cigarettes was phased in between May 2016 and May 2017. We assessed whether there was an association between using standardised packs and warning salience, thoughts about the risks of smoking, thoughts about quitting, and awareness and use of stop-smoking websites. Methods: We conducted a cross-sectional online survey with current smokers aged 16 and over (N = 1865) recruited in two regions of England between February-April 2017, when both standardised and fully-branded packs were on the market. Participants were asked about use of standardised packs, warning salience (noticing, reading closely), and whether the packs they were using increased thoughts of the risks of smoking and quitting. They were also asked about awareness of stop-smoking websites, source of awareness (including warnings on packs), and whether they had visited a stop-smoking website. Results: Most participants reported currently using standardised packs (76.4%), 9.3% were not currently using them but had previously used them, and 14.3% had never used them. Compared with never users, current users were more likely to have noticed the warnings on packs often/very often (AOR (95%CI) = 2.76 (2.10, 3.63)), read them closely often/very often (AOR(95%CI) = 2.16 (1.51, 3.10)), thought somewhat/a lot about the health risks of smoking (AOR(95%CI) = 1.92 (1.38, 2.68)), and thought somewhat/a lot about quitting (AOR(95%CI) = 1.90 (1.30, 2.77)). They were also more likely to have noticed a stop-smoking website on packs. Conclusions: Consistent with the broad objectives of standardised packaging, we found that it was associated with increased warning salience and thoughts about risks and quittingOutput Status: Forthcoming/Available Onlin

Pulmonary hemodynamic responses to in utero ventilation in very immature fetal sheep

<p>Abstract</p> <p>Background</p> <p>The onset of ventilation at birth decreases pulmonary vascular resistance (PVR) resulting in a large increase in pulmonary blood flow (PBF). As the large cross sectional area of the pulmonary vascular bed develops late in gestation, we have investigated whether the ventilation-induced increase in PBF is reduced in immature lungs.</p> <p>Methods</p> <p>Surgery was performed in fetal sheep at 105 d GA (n = 7; term ~147 d) to insert an endotracheal tube, which was connected to a neonatal ventilation circuit, and a transonic flow probe was placed around the left pulmonary artery. At 110 d GA, fetuses (n = 7) were ventilated <it>in utero </it>(IUV) for 12 hrs while continuous measurements of PBF were made, fetuses were allowed to develop <it>in utero </it>for a further 7 days following ventilation.</p> <p>Results</p> <p>PBF changes were highly variable between animals, increasing from 12.2 ± 6.6 mL/min to a maximum of 78.1 ± 23.1 mL/min in four fetuses after 10 minutes of ventilation. In the remaining three fetuses, little change in PBF was measured in response to IUV. The increases in PBF measured in responding fetuses were not sustained throughout the ventilation period and by 2 hrs of IUV had returned to pre-IUV control values.</p> <p>Discussion and conclusion</p> <p>Ventilation of very immature fetal sheep <it>in utero </it>increased PBF in 57% of fetuses but this increase was not sustained for more than 2 hrs, despite continuing ventilation. Immature lungs can increase PBF during ventilation, however, the present studies show these changes are transient and highly variable.</p

Systemic Correlates of Angiographic Coronary Artery Disease

Coronary angiography allows a direct evaluation of coronary anatomy. The aim of the present investigation was to search for correlations between the magnitude of coronary artery disease, as assessed by angiography, and a number of systemic parameters. A group of 116 patients (80 male, 36 female) with coronary heart disease diagnosed by angiography, aged 62.0±10.5 years, was the subject of an observational study. Correlation and linear regression analysis using coronary artery disease burden (CADB - sum of the percentage of the luminal stenosis encountered in all the lesions of the coronary arterial trees) as dependent variable, and age, sex, plasma calcium, phosphorus, magnesium, glucose, HDL cholesterol, LDL cholesterol, triglycerides, uric acid, estimated glomerular filtration rate and body mass index as independent variables, were carried out. Significant correlation values versus CADB were seen with age (r 0.19, p 0.04), uric acid (r 0.18, p 0.048) and fasting plasma glucose (r 0.33, p<0.001). Linear regression analysis, yielding a global significance level of 0.002, showed a significant value for glucose (p 0.018) and for sex (0.008). In conclusion, among several systemic parameters studied, plasma glucose was found to be correlated to coronary artery atherosclerosis lesions

Efficient Gene Targeting by Homologous Recombination in Rat Embryonic Stem Cells

The rat is the preferred experimental animal in many biological studies. With the recent derivation of authentic rat embryonic stem (ES) cells it is now feasible to apply state-of-the art genetic engineering in this species using homologous recombination. To establish whether rat ES cells are amenable to in vivo recombination, we tested targeted disruption of the hypoxanthine phosphoribosyltransferase (hprt) locus in ES cells derived from both inbred and outbred strains of rats. Targeting vectors that replace exons 7 and 8 of the hprt gene with neomycinR/thymidine kinase selection cassettes were electroporated into male Fisher F344 and Sprague Dawley rat ES cells. Approximately 2% of the G418 resistant colonies also tolerated selection with 6-thioguanine, indicating inactivation of the hprt gene. PCR and Southern blot analysis confirmed correct site-specific targeting of the hprt locus in these clones. Embryoid body and monolayer differentiation of targeted cell lines established that they retained differentiation potential following targeting and selection. This report demonstrates that gene modification via homologous recombination in rat ES cells is efficient, and should facilitate implementation of targeted, genetic manipulation in the rat

Life experiences throughout the ifespan: What do people say (or not) about them?

Life experiences have been a topic of interest for researchers and clinicians for decades. Current knowledge is rooted in two distinct approaches, i.e., personality psychology and psychosomatics. Whereas the first is interested in ordinary life stories of nonclinical individuals, based on a more qualitative, in-depth, and person-driven approach, psychosomatics stresses negative events, mainly in clinical samples, and presents a more quantitative, general, and construct-driven approach. Consequently, available evidence is dispersed and unrelated and many basic questions remain unanswered. This study aimed to explore occurrence, developmental stage, valence, and impact of life experiences and to analyze critical answering patterns (i.e., “I don’t remember,” missingness). Through a cross-sectional retrospective design, 394 adults from the community answered the Lifetime Experiences Scale, which covers 75 life experiences organized in eight domains (i.e., school, job, health, leisure, living conditions, adverse experiences, achievements, and people and relationships). Occurrence of life experiences varied greatly, and the mean number of experiences reported was approximately 30. Regarding developmental stage, most experiences were reported in just one stage—mainly adulthood—however, some could be considered chronic. Globally, life experiences tended to be clearly rated as positive or as negative; additionally, assessed experiences were mainly appraised as positive. Moreover, participants presented their experiences as significant, rating them as high impact. Overall, critical answering patterns were not very expressive: “I don’t remember” and missing answers were below 2 and 5%, respectively, in the majority of experiences. These findings offer several important new insights, suggesting that life experiences are mainly an idiosyncratic topic.This manuscript is part of a doctoral dissertation, which had the support of the Portuguese Foundation for Science and Technology (FCT), through the PhD grant with the reference SFRH/ BD/76022/2011, funded by POPH-QREN-Typology 4.1-Advanced Training, reimbursed by the European Social Fund and national funds from State Budget. This study was conducted at Psychology Research Centre (UID/PSI/01662/2013), University of Minho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Education and Science through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653).info:eu-repo/semantics/publishedVersio

p73: A Multifunctional Protein in Neurobiology

p73, a transcription factor of the p53 family, plays a key role in many biological processes including neuronal development. Indeed, mice deficient for both TAp73 and ΔNp73 isoforms display neuronal pathologies, including hydrocephalus and hippocampal dysgenesis, with defects in the CA1-CA3 pyramidal cell layers and the dentate gyrus. TAp73 expression increases in parallel with neuronal differentiation and its ectopic expression induces neurite outgrowth and expression of neuronal markers in neuroblastoma cell lines and neural stem cells, suggesting that it has a pro-differentiation role. In contrast, ΔNp73 shows a survival function in mature cortical neurons as selective ΔNp73 null mice have reduced cortical thickness. Recent evidence has also suggested that p73 isoforms are deregulated in neurodegenerative pathologies such as Alzheimer’s disease, with abnormal tau phosphorylation. Thus, in addition to its increasingly accepted contribution to tumorigenesis, the p73 subfamily also plays a role in neuronal development and neurodegeneration

Kelvin-Helmholtz instability in the presence of variable viscosity for mudflow resuspension in estuaries

The temporal stability of a parallel shear flow of miscible fluid layers of dif- ferent density and viscosity is investigated through a linear stability analysis and direct numerical simulations. The geometry and rheology of this Newto- nian fluid mixing can be viewed as a simplified model of the behavior of mud- flow at the bottom of estuaries for suspension studies. In this study, focus is on the stability and transition to turbulence of an initially laminar configuration. A parametric analysis is performed by varying the values of three control pa- rameters, namely the viscosity ratio, the Richardson and Reynolds numbers, in the case of initially identical thickness of the velocity, density and viscosity profiles. The range of parameters has been chosen so as to mimic a wide variety of real configurations. This study shows that the Kelvin-Helmholtz instability is controlled by the local Reynolds and Richardson numbers of the inflection point. In addition, at moderate Reynolds number, viscosity strat- ification has a strong influence on the onset of instability, the latter being enhanced at high viscosity ratio, while at high Reynolds number, the influ- ence is less pronounced. In all cases, we show that the thickness of the mixing layer (and thus resuspension) is increased by high viscosity stratification, in particular during the non-linear development of the instability and especially pairing processes. This study suggests that mud viscosity has to be taken into account for resuspension parameterizations because of its impact on the inflec- tion point Reynolds number and the viscosity ratio, which are key parameters for shear instabilities

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease