Direct In Vivo Cell Lineage Analysis in the Retrorsine and 2AAF Models of Liver Injury after Genetic Labeling in Adult and Newborn Rats

BACKGROUNDS AND AIMS:When hepatocyte proliferation is impaired, liver regeneration proceeds from the division of non parenchymal hepatocyte progenitors. Oval cells and Small Hepatocyte-like Progenitor Cells (SHPCs) represent the two most studied examples of such epithelial cells with putative stem cell capacity. In the present study we wished to compare the origin of SHPCs proliferating after retrorsine administration to the one of oval cells observed after 2-Acetyl-Amino fluorene (2-AAF) treatment. METHODOLOGY/PRINCIPAL FINDINGS:We used retroviral-mediated nlslacZ genetic labeling of dividing cells to study the fate of cells in the liver. Labeling was performed either in adult rats before treatment or in newborn animals. Labeled cells were identified and characterised by immunohistochemistry. In adult-labeled animals, labeling was restricted to mature hepatocytes. Retrorsine treatment did not modify the overall number of labeled cells in the liver whereas after 2-AAF administration unlabeled oval cells were recorded and the total number of labeled cells decreased significantly. When labeling was performed in newborn rats, results after retrorsine administration were identical to those obtained in adult-labeled rats. In contrast, in the 2-AAF regimen numerous labeled oval cells were present and were able to generate new labeled hepatocytes. Furthermore, we also observed labeled biliary tracts in 2-AAF treated rats. CONCLUSIONS:Our results strongly suggest that SHPCs are derived from hepatocytes and we confirm that SHPCs and oval cells do not share the same origin. We also show that hepatic progenitors are labeled in newborn rats suggesting future directions for in vivo lineage studies

The lived experiences of experienced Vipassana Mahasi meditators: an interpretative phenomenological analysis.

Research into the effects and mechanisms of mindfulness training draws predominantly on quantitative research. There is a lack of understanding about the subjective experiences of experienced mindfulness meditators, which may provide additional insights into the effects, processes and context of mindfulness training. This qualitative study explored the lived experiences of a novel group of experienced mindfulness meditators who practise Vipassana Mahasi (VM) meditation. The study aimed to understand how experienced VM practitioners make sense of the effects of practice and what processes they ascribe to it. Participants attended semistructured interviews, and their responses were analysed using interpretative phenomenological analysis. Results yielded overarching themes including (a) improvements in hedonic and eudaimonic well-being; (b) insights into self, others and perception of reality; (c) attaining equanimity; and (d) physical and interpersonal difficulties. Participants perceived VM as a ‘cleansing’ process whereby maladaptive responses were eliminated through mindfulness, other supportive mental qualities, decentering and nonattachment. The findings revealed a complex and dynamic set of interdependent outcomes and processes, which are reinforced by Buddhist teachings and ethical practices. This study highlights the need for additional interdisciplinary research into topics such as insight generation and supportive mental qualities cultivated during VM, novel states of well-being informed by Buddhist constructs and interpersonal difficulties related to long-term practice. Findings also suggest that incorporating Buddhist teachings and ethics into mindfulness-based interventions may enhance practitioner understanding and implementation of meditation techniques.N/

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

A comparison of blood pressure reductions following 12-weeks of isometric exercise training either in the laboratory or at home

Purpose: Isometric exercise training (IET) induced reductions in resting blood pressure (RBP) have been achieved in laboratory environments, but data in support of IET outside the lab is scarce. The aim of this study was to compare 12-weeks of home-based (HOM) IET with laboratory-based, face-to-face (LAB) IET in hypertensive adults. Methods: 22 hypertensive participants (24-60 years) were randomized to three conditions; HOM, LAB or control (CON). IET involved isometric handgrip training (4 x 2-minutes at 30% maximum voluntary contraction, 3 days per week). RBP was measured every 6-weeks (0, 6 and 12 weeks) during training and 6-weeks post-training (18 weeks). Results: Clinically meaningful, but not statistically significant reductions RBP were observed following 12 weeks of LAB IET (SBP -9.1±4.1; DBP-2.8±2.1 P>0.05), which was sustained for 6 weeks of detraining (SBP -8.2±2.9; DBP -4±2.9 P>0.05). RBP was reduced in the HOM group after 12 weeks of training (SBP -9.7±3.4; DBP - 2.2±2.0 P>0.05) which was sustained for an additional 6 weeks of detraining (SBP -5.5±3.4; DBP -4.6±1.8, P>0.05). Conclusions: Unsupervised home-based IET programs present an exciting opportunity for community-based strategies to combat hypertension but additional work is needed if IET is to be employed routinely outside the laboratory

On the role of computers in creativity-support systems

We report here on our experiences with designing computer-based creativity-support systems over several years. In particular, we present the design of three different systems incorporating different mechanisms of creativity. One of them uses an idea proposed by Rodari to stimulate imagination of the children in writing a picture-based story. The second one is aimed to model creativity in legal reasoning, and the third one uses low-level perceptual similarities to stimulate creation of novel conceptual associations in unrelated pictures.We discuss lessons learnt from these approaches, and address their implications for the question of how far creativity can be tamed by algorithmic approaches

A Postnatal Critical Period for Orientation Plasticity in the Cat Visual Cortex

Orientation selectivity of primary visual cortical neurons is an important requisite for shape perception. Although numerous studies have been previously devoted to a question of how orientation selectivity is established and elaborated in early life, how the susceptibility of orientation plasticity to visual experience changes in time remains unclear. In the present study, we showed a postnatal sensitive period profile for the modifiability of orientation selectivity in the visual cortex of kittens reared with head-mounted goggles for stable single-orientation exposure. When goggle rearing (GR) started at P16-P30, 2 weeks of GR induced a marked over-representation of the exposed orientation, and 2 more weeks of GR consolidated the altered orientation maps. GR that started later than P50, in turn, induced the under-representation of the exposed orientation. Orientation plasticity in the most sensitive period was markedly suppressed by cortical infusion of NMDAR antagonist. The present study reveals that the plasticity and consolidation of orientation selectivity in an early life are dynamically regulated in an experience-dependent manner

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

Measuring educational needs among patients with rheumatoid arthritis using the Dutch version of the Educational Needs Assessment Tool (DENAT)

The Educational Needs Assessment Tool (ENAT) was developed in the United Kingdom (UK) to systematically assess the educational needs of patients with arthritis. The aim of the present study was to describe the educational needs of Dutch patients with rheumatoid arthritis (RA) by using the Dutch version of the ENAT (DENAT). The original UK version of the ENAT, comprising 39 items grouped into seven domains, was translated into Dutch according to international guidelines for cross-cultural translation and adaptation. The DENAT was then sent to a random sample of 319 RA patients registered at the outpatient clinic of a university hospital. For each domain (score range 1–5, equalling low–high educational needs), a median score with the inter-quartile range was computed. The Kruskal–Wallis test was used to determine possible associations between educational needs and age, disease duration, gender and educational background. The response rate was 165 out of 319 (52%). The median educational needs scores were 2.5 for “managing pain”, 3.0 for “movement”, 2.0 for “feelings”, 4.0 for “arthritis process”, 4.0 for “treatments from health professionals”, 3.5 for “self-help measures” and 2.5 for “support systems”. Lower age and shorter disease duration were associated with more educational needs in the domain “support systems”. In addition, younger patients had more educational needs regarding managing pain and feelings than older patients. There were no associations between gender or educational background and educational needs. The DENAT has demonstrated its ability to identify individual educational needs of Dutch patients with RA. The lower age and shorter disease duration were associated with more educational needs. The practical applicability of the DENAT needs further research

Efficacy of essential oil mouthwash with and without alcohol: a 3-Day plaque accumulation model

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the antiplaque effect of a new alcohol free essential oil mouthwash with respect to a control of an essential oil with alcohol mouthwash, using an <it>in vivo </it>plaque regrowth model of 3-days.</p> <p>Methods</p> <p>The study was designed as a double-masked, randomized, crossover clinical trial, involving 30 volunteers to compare two different essential oil containing mouthwashes, during a 3-day plaque accumulation model. After receiving a thorough professional prophylaxis at the baseline, over the next 3-days each volunteer refrained from all oral hygiene measures and had two daily rinses with 20 ml of the test mouthwash (alcohol free essential oil) or the control mouthwash (essential oil with alcohol). At the end of the each experimental period, plaque was assessed and the panelists filled out a questionnaire. Each subject underwent a 14 days washout period and there was a second allocation.</p> <p>Results</p> <p>The essential oil mouthwash with ethanol shows a better inhibitory effect of plaque regrowth in 3-days than the mouthwash test with only essential oil in the whole mouth (plaque index = 2.18 against 2.46, respectively, p < 0.05); for the lower jaw (plaque index = 2.28 against 2.57, respectively, p < 0.05); for the upper jaw (plaque index = 2.08 against 2.35, respectively, p < 0.05); for the incisors (plaque index = 1.93 against 2.27, respectively, p < 0.05); and the canines (plaque index = 1.99 against 2.47, respectively, p < 0.05).</p> <p>Conclusion</p> <p>The essential oil containing mouthwash without alcohol seems to have a less inhibiting effect on the plaque regrowth than the traditional alcoholic solution.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01411618">NCT01411618</a></p

Regional block versus general anaesthesia for caesarean section and neonatal outcomes: a population-based study

<p>Abstract</p> <p>Background</p> <p>Anaesthesia guidelines recommend regional anaesthesia for most caesarean sections due to the risk of failed intubation and aspiration with general anaesthesia. However, general anaesthesia is considered to be safe for the foetus, based on limited evidence, and is still used for caesarean sections.</p> <p>Methods</p> <p>Cohorts of caesarean sections by indication (that is, planned repeat caesarean section, failure to progress, foetal distress) were selected from the period 1998 to 2004 (<it>N </it>= 50,806). Deliveries performed under general anaesthesia were compared with those performed under spinal or epidural, for the outcomes of neonatal intubation and 5-minute Apgar (Apgar5) <7.</p> <p>Results</p> <p>The risk of adverse outcomes was increased for caesarean sections under general anaesthesia for all three indications and across all levels of hospital. The relative risks were largest for low-risk planned repeat caesarean deliveries: resuscitation with intubation relative risk was 12.8 (95% confidence interval 7.6, 21.7), and Apgar5 <7 relative risk was 13.4 (95% confidence interval 9.2, 19.4). The largest absolute increase in risk was for unplanned caesareans due to foetal distress: there were five extra intubations per 100 deliveries and six extra Apgar5 <7 per 100 deliveries.</p> <p>Conclusion</p> <p>The infants most affected by general anaesthesia were those already compromised <it>in utero</it>, as evidenced by foetal distress. The increased rate of adverse neonatal outcomes should be weighed up when general anaesthesia is under consideration.</p