Summary
Exercise training (‘exercise’) and hypocaloric diet (‘diet’) are frequently prescribed for weight loss in obesity. Whilst body weight changes are commonly used to evaluate lifestyle ...interventions, visceral adiposity (VAT) is a more relevant and stronger predictor for morbidity and mortality. A meta‐analysis was performed to assess the effects of exercise or diet on VAT (quantified by radiographic imaging). Relevant databases were searched through May 2014. One hundred seventeen studies (n = 4,815) were included. We found that both exercise and diet cause VAT loss (P < 0.0001). When comparing diet versus training, diet caused a larger weight loss (P = 0.04). In contrast, a trend was observed towards a larger VAT decrease in exercise (P = 0.08). Changes in weight and VAT showed a strong correlation after diet (R2 = 0.737, P < 0.001), and a modest correlation after exercise (R2 = 0.451, P < 0.001). In the absence of weight loss, exercise is related to 6.1% decrease in VAT, whilst diet showed virtually no change (1.1%). In conclusion, both exercise and diet reduce VAT. Despite a larger effect of diet on total body weight loss, exercise tends to have superior effects in reducing VAT. Finally, total body weight loss does not necessarily reflect changes in VAT and may represent a poor marker when evaluating benefits of lifestyle‐interventions.
In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related ...terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.
The efficient delivery of nanomaterials to specific targets for in vivo biomedical imaging is hindered by rapid sequestration by the reticuloendothelial system (RES) and consequent short circulation ...times. To overcome these two problems, we have prepared a new stealth PEG polymer conjugate containing a terminal 1,1-bisphosphonate (BP) group for strong and stable binding to the surface of ultrasmall-superparamagnetic oxide nanomaterials (USPIOs). This polymer, PEG(5)-BP, can be used to exchange the hydrophobic surfactants commonly used in the synthesis of USPIOs very efficiently and at room temperature using a simple method in 1 h. The resulting nanoparticles, PEG(5)-BP-USPIOs are stable in water or saline for at least 7 months and display a near-zero ζ-potential at neutral pH. The longitudinal (r 1) and transverse (r 2) relaxivities were measured at a clinically relevant magnetic field (3 T), revealing a high r 1 of 9.5 mM–1 s–1 and low r 2/r 1 ratio of 2.97, making these USPIOs attractive as T1-weighted MRI contrast agents at high magnetic fields. The strong T1-effect was demonstrated in vivo, revealing that PEG(5)-BP-USPIOs remain in the bloodstream and enhance its signal 6-fold, allowing the visualization of blood vessels and vascular organs with high spatial definition. Furthermore, the optimal relaxivity properties allow us to inject a dose 4 times lower than with other USPIOs. PEG(5)-BP-USPIOs can also be labeled using a radiolabeled-BP for visualization with single photon emission computed tomography (SPECT), and thus affording dual-modality contrast. The SPECT studies confirmed low RES uptake and long blood circulation times (t 1/2 = 2.97 h). These results demonstrate the potential of PEG(5)-BP-USPIOs for the development of targeted multimodal imaging agents for molecular imaging.
We present first results of the H2O Southern Galactic Plane Survey (HOPS), using the Mopra Radio Telescope with a broad-band backend and a beam size of about 2 arcmin. We have observed 100 deg2 of ...the southern Galactic plane at 12 mm (19.5-27.5 GHz), including spectral line emission from H2O masers, multiple metastable transitions of ammonia, cyanoacetylene, methanol and radio recombination lines. In this paper, we report on the characteristics of the survey and H2O maser emission. We find 540 H2O masers, of which 334 are new detections. The strongest maser is 3933 Jy and the weakest is 0.7 Jy, with 62 masers over 100 Jy. In 14 maser sites, the spread in the velocity of the H2O maser emission exceeds 100 km s−1. In one region, the H2O maser velocities are separated by 351.3 km s−1. The rms noise levels are typically between 1 and 2 Jy, with 95 per cent of the survey under 2 Jy. We estimate completeness limits of 98 per cent at around 8.4 Jy and 50 per cent at around 5.5 Jy. We estimate that there are between 800 and 1500 H2O masers in the Galaxy that are detectable in a survey with similar completeness limits to HOPS. We report possible masers in NH3 (11,9) and (8,6) emission towards G19.61−0.23 and in the NH3 (3,3) line towards G23.33−0.30.
Deposition of amyloid-β (Aβ) in the cerebral cortex is thought to be a pivotal event in Alzheimer's disease (AD) pathogenesis with a significant genetic contribution. Molecular imaging can provide an ...early noninvasive phenotype, but small samples have prohibited genome-wide association studies (GWAS) of cortical Aβ load until now. We employed florbetapir ((18)F) positron emission tomography (PET) imaging to assess brain Aβ levels in vivo for 555 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). More than six million common genetic variants were tested for association to quantitative global cortical Aβ load controlling for age, gender and diagnosis. Independent genome-wide significant associations were identified on chromosome 19 within APOE (apolipoprotein E) (rs429358, P=5.5 × 10(-14)) and on chromosome 3 upstream of BCHE (butyrylcholinesterase) (rs509208, P=2.7 × 10(-8)) in a region previously associated with serum BCHE activity. Together, these loci explained 15% of the variance in cortical Aβ levels in this sample (APOE 10.7%, BCHE 4.3%). Suggestive associations were identified within ITGA6, near EFNA5, EDIL3, ITGA1, PIK3R1, NFIB and ARID1B, and between NUAK1 and C12orf75. These results confirm the association of APOE with Aβ deposition and represent the largest known effect of BCHE on an AD-related phenotype. BCHE has been found in senile plaques and this new association of genetic variation at the BCHE locus with Aβ burden in humans may have implications for potential disease-modifying effects of BCHE-modulating agents in the AD spectrum.
We used fMRI in 85 healthy participants to investigate whether different parts of the left supramarginal gyrus (SMG) are involved in processing phonological inputs and outputs. The experiment ...involved 2 tasks (speech production (SP) and one-back (OB) matching) on 8 different types of stimuli that systematically varied the demands on sensory processing (visual vs. auditory), sublexical phonological input (words and pseudowords vs. nonverbal stimuli), and semantic content (words and objects vs. pseudowords and meaningless baseline stimuli). In ventral SMG, we found an anterior subregion associated with articulatory sequencing (for SP > OB matching) and a posterior subregion associated with auditory short-term memory (for all auditory > visual stimuli and written words and pseudowords > objects). In dorsal SMG, a posterior subregion was most highly activated by words, indicating a role in the integration of sublexical and lexical cues. In anterior dorsal SMG, activation was higher for both pseudoword reading and object naming compared with word reading, which is more consistent with executive demands than phonological processing. The dissociation of these four "functionally-distinct" regions, all within left SMG, has implications for differentiating between different types of phonological processing, understanding the functional anatomy of language and predicting the effect of brain damage.
Azathioprine, a purine antimetabolite immunosuppressant, photosensitizes the skin and causes the production of mutagenic reactive oxygen species. It is postulated to increase the risk of squamous ...cell carcinoma (SCC) and other skin cancers in organ transplant recipients (OTRs), but evidence from multiple, largely single‐center studies to date has been inconsistent. We aimed to resolve the issue of azathioprine's carcinogenicity by conducting a systematic review of the relevant literature and pooling published risk estimates to evaluate the risks of SCC, basal cell carcinoma (BCC), keratinocyte cancers (KCs) overall and other skin cancers in relation to azathioprine treatment. Twenty‐seven studies were included in total, with risk estimates from 13 of these studies able to be pooled for quantitative analysis. The overall summary estimate showed a significantly increased risk of SCC in relation to azathioprine exposure (1.56, 95% confidence interval CI 1.11–2.18). No significant associations between azathioprine treatment and BCC (0.96, 95% CI 0.66–1.40) or KC (0.84, 95% CI 0.59–1.21) risk were observed. There was significant heterogeneity between studies for azathioprine risk estimates and the outcomes of SCC, BCC and KC. The pooled findings of available evidence support the contention that treatment with azathioprine increases the risk of SCC in OTRs.
This meta‐analysis compares azathioprine with other immunosuppressants in organ transplant recipients and shows a significantly increased risk of squamous cell carcinoma in patients receiving azathioprine posttransplantation.
Data reported during the past 5 years indicate that rates of survival have increased among infants born at the borderline of viability, but less is known about how increased rates of survival among ...these infants relate to early childhood neurodevelopmental outcomes.
We compared survival and neurodevelopmental outcomes among infants born at 22 to 24 weeks of gestation, as assessed at 18 to 22 months of corrected age, across three consecutive birth-year epochs (2000-2003 epoch 1, 2004-2007 epoch 2, and 2008-2011 epoch 3). The infants were born at 11 centers that participated in the National Institute of Child Health and Human Development Neonatal Research Network. The primary outcome measure was a three-level outcome - survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, or death. After accounting for differences in infant characteristics, including birth center, we used multinomial generalized logit models to compare the relative risk of survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, and death.
Data on the primary outcome were available for 4274 of 4458 infants (96%) born at the 11 centers. The percentage of infants who survived increased from 30% (424 of 1391 infants) in epoch 1 to 36% (487 of 1348 infants) in epoch 3 (P<0.001). The percentage of infants who survived without neurodevelopmental impairment increased from 16% (217 of 1391) in epoch 1 to 20% (276 of 1348) in epoch 3 (P=0.001), whereas the percentage of infants who survived with neurodevelopmental impairment did not change significantly (15% 207 of 1391 in epoch 1 and 16% 211 of 1348 in epoch 3, P=0.29). After adjustment for changes in the baseline characteristics of the infants over time, both the rate of survival with neurodevelopmental impairment (as compared with death) and the rate of survival without neurodevelopmental impairment (as compared with death) increased over time (adjusted relative risks, 1.27 95% confidence interval {CI}, 1.01 to 1.59 and 1.59 95% CI, 1.28 to 1.99, respectively).
The rate of survival without neurodevelopmental impairment increased between 2000 and 2011 in this large cohort of periviable infants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT00063063 and NCT00009633 .).
The Gorkha earthquake (Magnitude 7.8) on 25 April 2015 and later aftershocks struck South Asia, killing approx.9,000 and damaging a large region. Supported by a large campaign of responsive satellite ...data acquisitions over the earthquake disaster zone, our team undertook a satellite image survey of the earthquakes induced geohazards in Nepal and China and an assessment of the geomorphic, tectonic, and lithologic controls on quake-induced landslides. Timely analysis and communication aided response and recovery and informed decision makers. We mapped 4,312 co-seismic and post-seismic landslides. We also surveyed 491 glacier lakes for earthquake damage, but found only 9 landslide-impacted lakes and no visible satellite evidence of outbursts. Landslide densities correlate with slope, peak ground acceleration, surface downdrop, and specific metamorphic lithologies and large plutonic intrusions.
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