A school-based intervention program in promoting leisure-time physical activity: Trial protocol

Background: Regular participation in moderate-to-vigorous physical activity (MVPA) is important to manage obesity. Physical education (PE) is considered to play an important role in promoting lifelong participation in physical activity (PA) because it provides an existing network where cost-effective interventions can be implemented to produce sustainable change in health behavior. However, the association between compulsory school PA (e.g., PE lessons) and body composition levels has received mixed support in the literature. Therefore, the present study aimed to investigate whether a school-based intervention targeting salient PA benefits and barriers grounded on the theory of planned behavior would promote young people's participation in MVPA during leisure time and reduce body mass index (BMI) of overweight students. Methods/design: A total of 171 students from 3 secondary schools in Singapore underwent the control condition followed by the intervention condition. Both the conditions consisted of PE lessons twice per week over 4 weeks. In the control condition, PE teachers encouraged students to participate in PA during leisure time without providing persuasive message. While in the intervention condition, PE teachers delivered persuasive messages that targeted the salient benefits and barriers associated with PA to the students at the last 5 to 10 min of each PE lesson. PA levels over a week were measured objectively with wrist-mounted GENEActiv Original accelerometers and subjectively with self-reporting questionnaires three times (Baseline, Post 1, and Post 2) in each condition. Student's self-reported PA level was measured using the Leisure-Time Physical Activity Participation Questionnaire and the International Physical Activity Questionnaire, and their attitudes, intentions, subjective norms and perceived behavior control towards leisure-time PA were measured with a questionnaire based on the theory of planned behavior. Furthermore, students' intention, determination and willingness to engage in leisure-time PA were compared with the other activity (e.g., doing homework, shopping). Discussion: This study will provide the evidence on the effectiveness of a cost-effective school-based intervention on reducing BMI of overweight students through promoting sustained participation in leisure-time PA. It will also address methodological issues on the gaps between objective and subjective measures of PA. Trial registration: This trial is registered with the ISRCTN registry (ISRCTN73786157, 26/10/2017, retrospectively registered)

Case of relapsed AIDS-related plasmablastic lymphoma treated with autologous stem cell transplantation and highly active antiretroviral therapy

Plasmablastic lymphoma is a rare and aggressive malignancy strongly associated with HIV infection. The refractory/relapsed disease rate is high, and the survival rate is characteristically poor. There are no satisfactory salvage regimens for relapsed cases. We successfully performed autologous stem cell transplantation using a regimen consisting of MCNU (ranimustine), etoposide, cytarabine, and melphalan in a Japanese patient with relapsed AIDS-related plasmablastic lymphoma of the oral cavity. Highly active antiretroviral therapy continued during the therapy. Therapy-related toxicity was tolerable, and a total of 40 Gy of irradiation was administered after autologous stem cell transplantation. The patient has remained in complete remission for 16 months since transplantation

The cyclin-dependent kinase inhibitor 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole induces nongenotoxic, DNA replication-independent apoptosis of normal and leukemic cells, regardless of their p53 status

<p>Abstract</p> <p>Background</p> <p>Current chemotherapy of human cancers focuses on the DNA damage pathway to induce a p53-mediated cellular response leading to either G1 arrest or apoptosis. However, genotoxic treatments may induce mutations and translocations that result in secondary malignancies or recurrent disease. In addition, about 50% of human cancers are associated with mutations in the <it>p53 </it>gene. Nongenotoxic activation of apoptosis by targeting specific molecular pathways thus provides an attractive therapeutic approach.</p> <p>Methods</p> <p>Normal and leukemic cells were evaluated for their sensitivity to 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) through cell viability and caspase activation tests. The apoptotic pathway induced by DRB was analysed by immunfluorescence and immunoblot analysis. H2AX phosphorylation and cell cycle analysis were performed to study the dependance of apoptosis on DNA damage and DNA replication, respectively. To investigate the role of p53 in DRB-induced apoptosis, specific p53 inhibitors were used. Statistical analysis on cell survival was performed with the test of independence.</p> <p>Results</p> <p>Here we report that DRB, an inhibitor of the transcriptional cyclin-dependent kinases (CDKs) 7 and 9, triggers DNA replication-independent apoptosis in normal and leukemic human cells regardless of their p53 status and without inducing DNA damage. Our data indicate that (i) in p53-competent cells, apoptosis induced by DRB relies on a cytosolic accumulation of p53 and subsequent Bax activation, (ii) in the absence of p53, it may rely on p73, and (iii) it is independent of ATM and NBS1 proteins. Notably, even apoptosis-resistant leukemic cells such as Raji were sensitive to DRB.</p> <p>Conclusion</p> <p>Our results indicate that DRB represents a potentially useful cancer chemotherapeutic strategy that employs both the p53-dependent and -independent apoptotic pathways without inducing genotoxic stress, thereby decreasing the risk of secondary malignancies.</p

Total syntheses of shizukaols A and E

Shizukaols possess a common heptacyclic framework containing more than ten contiguousstereocenters and potential biological activities. Here we report that the total syntheses ofshizukaols A (1)and E(2), two lindenane-type dimers from the Chloranthaceae family, areachieved via a modified biomimetic Diels–Alder reaction. The common crucial biomimetic diene23and ethylene species (6,17) are obtained through either a highlyZ-selective olefination ofα-siloxy ketone with ynolate anions or an intramolecular Horner–Wadsworth–Emmons olefinationfrom commercially available Wieland–Miescher ketone (7). This synthetic approach here opensup practical avenues for the total syntheses of the intriguing Chloranthaceae family members, aswell as the understanding of their relevant biological action in natur

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

The broad-lined Type-Ic supernova SN 2022xxf and its extraordinary two-humped light curves: I. Signatures of H/He-free interaction in the first four months

We report on our study of supernova (SN) 2022xxf based on observations obtained during the first four months of its evolution. The light curves (LCs) display two humps of similar maximum brightness separated by 75 days, unprecedented for a broad-lined (BL) Type Ic supernova (SN IcBL). SN 2022xxf is the most nearby SN IcBL to date (in NGC 3705, z = 0.0037, at a distance of about 20 Mpc). Optical and near-infrared photometry and spectroscopy are used to identify the energy source powering the LC. Nearly 50 epochs of high signal-to-noise-ratio spectroscopy were obtained within 130 days, comprising an unparalleled dataset for a SN IcBL, and one of the best-sampled SN datasets to date. The global spectral appearance and evolution of SN 2022xxf points to typical SN Ic/IcBL, with broad features (up to ~1400 km s-1 and a gradual transition from the photospheric to the nebular phase. However, narrow emission lines (corresponding to ~1000-2500 km s-1 are present in the spectra from the time of the second rise, suggesting slower-moving circumstellar material (CSM). These lines are subtle, in comparison to the typical strong narrow lines of CSM-interacting SNe, for example, Type IIn, Ibn, and Icn, but some are readily noticeable at late times such as in Mg I \5170 and [O I] \l5577. Unusually, the near-infrared spectra show narrow line peaks in a number of features formed by ions of O and Mg. We infer the presence of CSM that is free of H and He. We propose that the radiative energy from the ejecta-CSM interaction is a plausible explanation for the second LC hump. This interaction scenario is supported by the color evolution, which progresses to the blue as the light curve evolves along the second hump, and the slow second rise and subsequent rapid LC drop. SN2022xxf may be related to an emerging number of CSM-interacting SNeIc, which show slow, peculiar LCs, bluecolors,and subtle CSM interaction lines.The progenitor stars of these SNe likely experienced an episode of mass loss consistingof H/He-free material shortly prio rto explosion

Contrasting views on the role of mesenchymal stromal/stem cells in tumour growth : a systematic review of experimental design

The effect of mesenchymal stromal/stem cells (MSCs) on tumour growth remains controversial. Experimental evidence supports both an inhibitory and a stimulatory effect. We have assessed factors responsible for the contrasting effects of MSCs on tumour growth by doing a meta-analysis of existing literature between 2000 and May 2017. We assessed 183 original research articles comprising 338 experiments. We considered (a) in vivo and in vitro experiments, (b) whether in vivo studies were syngeneic or xenogeneic, and (c) if animals were immune competent or deficient. Furthermore, the sources and types of cancer cells and MSCs were considered together with modes of cancer induction and MSC administration. 56% of all 338 experiments reported that MSCs promote tumour growth. 78% and 79% of all experiments sourced human MSCs and cancer cells, respectively. MSCs were used in their naïve and engineered form in 86% and 14% of experiments, respectively, the latter to produce factors that could alter either their activity or that of the tumour. 53% of all experiments were conducted in vitro with 60% exposing cancer cells to MSCs via coculture. Of all in vivo experiments, 79% were xenogeneic and 63% were conducted in immune-competent animals. Tumour growth was inhibited in 80% of experiments that used umbilical cord-derived MSCs, whereas tumour growth was promoted in 64% and 57% of experiments that used bone marrow- and adipose tissue-derived MSCs, respectively. This contrasting effect of MSCs on tumour growth observed under different experimental conditions may reflect differences in experimental design. This analysis calls for careful consideration of experimental design given the large number of MSC clinical trials currently underway.The South African Medical Research Council in terms of the SAMRC’s Flagship Award Project SAMRC-RFA-UFSP-01-2013/STEM CELLS, the SAMRC Extramural Stem Cell Research and Therapy Unit, the National Research Foundation of South Africa (grant no. 86942), the National Health Laboratory Services Research Trust (grant no. 94453), the University of Pretoria Research Development Programme (A0Z778), the University of Pretoria Vice Chancellor’s Postdoctoral Fellowship and the Institute for Cellular and Molecular Medicine of the University of Pretoria.http://www.springer.comseries/5584hj2019ImmunologyOral Pathology and Oral Biolog

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave transient was identified in data recorded by the Advanced LIGO detectors on 2015 September 14. The event candidate, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the gravitational wave data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network Circulars, giving an overview of the participating facilities, the gravitational wave sky localization coverage, the timeline and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the electromagnetic data and results of the electromagnetic follow-up campaign will be disseminated in the papers of the individual teams