The term 'metabolically healthy obese (MHO)' is distinguished using body mass index (BMI), yet BMI is a poor index of adiposity. Some epidemiological data suggest that MHO carries a lower risk of ...cardiovascular disease (CVD) or mortality than being normal weight yet metabolically unhealthy.
We aimed to undertake a detailed phenotyping of individuals with MHO by using imaging techniques to examine ectopic fat (visceral and liver fat deposition) and myocardial function. We hypothesised that metabolically unhealthy individuals (irrespective of BMI) would have adverse levels of ectopic fat and myocardial dysfunction compared with MHO individuals.
Individuals were categorised as non-obese or obese (BMI ⩾30 kg m(-2)) and as metabolically healthy or unhealthy according to the presence or absence of metabolic syndrome.
Sixty-seven individuals (mean±s.d.: age 49±11 years) underwent measurement of (i) visceral, subcutaneous and liver fat using magnetic resonance imaging and proton magnetic resonance spectroscopy, (ii) components of metabolic syndrome, (iii) cardiorespiratory fitness and (iv) indices of systolic and diastolic function using tissue Doppler echocardiography.
Cardiorespiratory fitness was similar between all groups; abdominal and visceral fat was highest in the obese groups. Compared with age- and BMI-matched metabolically healthy counterparts, the unhealthy (lean or obese) individuals had higher liver fat and decreased early diastolic strain rate, early diastolic tissue velocity and systolic strain indicative of subclinical systolic and diastolic dysfunction. The magnitude of dysfunction correlated with the number of components of metabolic syndrome but not with BMI or with the degree of ectopic (visceral or liver) fat deposition.
Myocardial dysfunction appears to be related to poor metabolic health rather than simply BMI or fat mass. These data may partly explain the epidemiological evidence on CVD risk relating to the different obesity phenotypes.
Investigating the niche overlap of ecologically similar species can reveal the mechanisms that drive spatial partitioning in high-diversity systems. Understanding how food resources are used and ...whether the diets of neighboring species are different are particularly important when considering the coexistence and functional role of species. Territorial damselfish on coral reefs are considered to be herbivores that defend algal mats from other food competitors. However, this guild contains numerous small species whose functional role and dietary diversification is poorly understood. Here, the relationships between diet and spatial distribution of seven intermediate-sized territorial damselfishes at Kimbe Bay, Papua New Guinea (5°30′S, 150°05′E) were investigated. These species partition habitat across three reef zones with distinct patterns of fine-scale distribution. It was predicted that neighboring species partition food resources with minimal dietary overlap. Examination of isotope ratios of carbon and nitrogen delineated three distinct feeding strategies: pelagic, reef-based, and an intermediate group feeding on both prey types. None of the species appear to be strict herbivores. Adjacent species exhibited high–intermediate trophic niche partitioning when examining pelagic versus reef-based production sources, with two species previously described as benthic herbivores exhibiting pelagic feeding. The study demonstrates that diet reinforces the patterns of spatial partitioning and coexistence among ecologically similar damselfishes. These findings add to a growing view that interspecific differences among similar species are lost when categorizing species into broad functional classifications, and that previous studies suggesting that territorial damselfish are strictly reef-based feeders may not be applicable in all systems or for all species.
We describe a long-term observational study of a large cohort of patients with sporadic inclusion body myositis and propose a sporadic inclusion body myositis weakness composite index that is easy to ...perform during a clinic. Data collection from two groups of patients (Paris and Oxford) was completed either during a clinic visit (52%), or by extraction from previous medical records (48%). One hundred and thirty-six patients 57% males, 61 (interquartile range 55-69) years at onset were included. At the last visit all patients had muscle weakness (proximal British Medical Research Council scale <3/5 in 48%, distal British Medical Research Council scale <3/5 in 40%, swallowing problems in 46%). During their follow-up, 75% of patients had significant walking difficulties and 37% used a wheelchair (after a median duration from onset of 14 years). The sporadic inclusion body myositis weakness composite index, which correlated with grip strength (correlation coefficient: 0.47; P < 0.001) and Rivermead Mobility Index (correlation coefficient: 0.85; P < 0.001), decreased significantly with disease duration (correlation coefficient: −0.47; P < 0.001). The risk of death was only influenced by older age at onset of first symptoms. Seventy-one (52%) patients received immunosuppressive treatments prednisone in 91.5%, associated (in 64.8%) with other immunomodulatory drugs (intravenous immunoglobulins, methotrexate or azathioprine) for a median duration of 40.8 months. At the last assessment, patients who had been treated were more severely affected on disability scales (Walton P = 0.007, Rivermead Mobility Index P = 0.004) and on the sporadic inclusion body myositis weakness composite index (P = 0.04). The first stage of disease progression towards handicap for walking was more rapid among patients receiving immunosuppressive treatments (hazard ratio = 2.0, P = 0.002). This study confirms that sporadic inclusion body myositis is slowly progressive but not lethal and that immunosuppressive treatments do not ameliorate its natural course, thus confirming findings from smaller studies. Furthermore, our findings suggest that immunosuppressant drug therapy could have modestly exacerbated progression of disability. The sporadic inclusion body myositis weakness composite index might be a valuable outcome measure for future clinical trials, but requires further assessment and validation.
Summary Rationale Mounting data suggest that immune cell abnormalities participate in the pathogenesis of pulmonary arterial hypertension (PAH). Objective To determine whether the T lymphocyte subset ...composition in the systemic circulation and peripheral lung is altered in PAH. Methods Flow cytometric analyses were performed to determine the phenotypic profile of peripheral blood lymphocytes in idiopathic PAH (IPAH) patients ( n = 18) and healthy controls ( n = 17). Immunocytochemical analyses of lymphocytes and T cell subsets were used to examine lung tissue from PAH patients ( n = 11) and controls ( n = 11). Measurements and main results IPAH patients have abnormal CD8+ T lymphocyte subsets, with a significant increase in CD45RA+ CCR7− peripheral cytotoxic effector-memory cells ( p = 0.02) and reduction of CD45RA+ CCR7+ naive CD8+ cells versus controls ( p = 0.001). Further, IPAH patients have a higher proportion of circulating regulatory T cells (Treg ) and 4-fold increases in the number of CD3+ and CD8+ cells in the peripheral lung compared with controls ( p < 0.01). Conclusions Alterations in circulating T cell subsets, particularly CD8+ T lymphocytes and CD4+ Treg , in patients with PAH suggest that a dysfunctional immune system contributes to disease pathogenesis. A preponderance of CD3+ and CD8+ T lymphocytes in the peripheral lung of PAH patients supports this concept.
To enhance risk stratification for Wilms tumour (WT) in a pre-operative chemotherapy setting, we explored the prognostic significance and optimal age cutoffs in patients treated according to ...International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) protocols.
Patients(6 months-18 years) with unilateral WT were selected from prospective SIOP 93-01 and 2001 studies(1993-2016). Martingale residual analysis was used to explore optimal age cutoffs. Outcome according to age was analyzed by uni- and multivariable analysis, adjusted for sex, biopsy(yes/no), stage, histology and tumour volume at surgery.
5631 patients were included; median age was 3.4 years(IQR: 2-5.1). Estimated 5-year event-free survival (EFS) and overall survival (OS) were 85%(95%CI 83.5-85.5) and 93%(95%CI 92.0-93.4). Martingale residual plots detected no optimal age cutoffs. Multivariable analysis showed lower EFS with increasing age(linear trend P<0.001). Using previously described age categories, EFS was lower for patients aged 2-4(HR 1.34, P = 0.02), 4-10(HR 1.83, P<0.0001) and 10-18 years(HR 1.74, P = 0.01) as compared to patients aged 6 months-2 years. OS was lower for patients 4-10 years(HR 1.67, P = 0.01) and 10-18 years(HR 1.87, P = 0.04), but not for 2-4 years(HR 1.29, P = 0.23). Higher stage, histological risk group and tumour volume were independent adverse prognostic factors.
Although optimal age cutoffs could not be identified, we demonstrated the prognostic significance of age as well as previously described cutoffs for EFS (2 and 4 years) and OS (4 years) in children with WT treated with pre-operative chemotherapy. These findings encourage the consideration of age in the design of future SIOP-RTSG protocols.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Radial velocity observations from three instruments reveal the presence of a 4 MJup planet candidate orbiting the K giant HD 76920. HD 76920b has an orbital eccentricity of 0.856 0.009, making it the ...most eccentric planet known to orbit an evolved star. There is no indication that HD 76920 has an unseen binary companion, suggesting a scattering event rather than Kozai oscillations as a probable culprit for the observed eccentricity. The candidate planet currently approaches to about four stellar radii from its host star, and is predicted to be engulfed on a ∼100 Myr timescale due to the combined effects of stellar evolution and tidal interactions.
Over 520 different amino acid substitution variants have been previously identified in the systematic screening of 91 human DNA repair genes for sequence variation. Two algorithms were employed to ...predict the impact of these amino acid substitutions on protein activity. Sorting Intolerant from Tolerant (SIFT) classified 226 of 508 variants (44%) as "Intolerant." Polymorphism Phenotyping (PolyPhen) classed 165 of 489 amino acid substitutions (34%) as "Probably or possibly damaging." Another 9-15% of the variants were classed as "Potentially intolerant or damaging." The results from the two algorithms are highly associated, with concordance in predicted impact observed for approximately 62% of the variants. Twenty-one to thirty-one percent of the variant proteins are predicted to exhibit reduced activity by both algorithms. These variants occur at slightly lower individual allele frequency than do the variants classified as "Tolerant" or "Benign." Both algorithms correctly predicted the impact of 26 functionally characterized amino acid substitutions in the APE1 protein on biochemical activity, with one exception. It is concluded that a substantial fraction of the missense variants observed in the general human population are functionally relevant. These variants are expected to be the molecular genetic and biochemical basis for the associations of reduced DNA repair capacity phenotypes with elevated cancer risk.
To quantify, among patients with axial spondyloarthritis (axSpA), the benefit on work outcomes associated with commencing biologic therapy.
The British Society for Rheumatology Biologics Register in ...Axial Spondyloarthritis (BSRBRAS) recruited patients meeting Assessment of SpondyloArthritis International Society criteria for axSpA naïve to biological therapy across 83 centres in Great Britain. Work outcomes (measured using the Work Productivity and Activity Impairment Index) were compared between those starting biological therapy at the time of recruitment and those not. Differences between treatment groups were adjusted using propensity score matching. Results from BSRBR-AS were combined with other studies in a meta-analysis to calculate pooled estimates.
Of the 577 participants in this analysis who were in employment, 27.9% were starting biological therapy at the time of recruitment. After propensity score adjustment, patients undergoing biological therapy, at 12-month follow-up, experienced significantly greater improvements (relative to non-biological therapy) in presenteeism (-9.4%, 95% CI -15.3% to -3.5%), overall work impairment (-13.9%, 95% CI -21.1% to -6.7%) and overall activity impairment (-19.2%, 95% CI -26.3% to -12.2%). There was no difference in absenteeism (-1.5%, 95% CI -8.0 to 4.9). Despite these improvements, impact on work was still greater in the biological treated cohort at follow-up. In the meta-analysis including 1109 subjects across observational studies and trials, treatment with biological therapy was associated with significantly greater improvements in presenteeism, work impairment and activity impairment, but there was no difference in absenteeism.
There is consistent evidence that treatment with biological therapy significantly improves work productivity and activity impairment in people with axSpA. However, there remain substantial unmet needs in relation to work.
Context.
AT 2019abn was discovered in the nearby M51 galaxy by the Zwicky Transient Facility at more than two magnitudes and around three weeks prior to its optical peak.
Aims.
We aim to conduct a ...detailed photometric and spectroscopic follow-up campaign for AT 2019abn, with early discovery allowing for significant pre-maximum observations of an intermediate luminosity red transient (ILRT) for the first time.
Methods.
This work is based on the analysis of
u
′
B
V
r
′
i
′
z
′
H
photometry and low-resolution spectroscopy using the Liverpool Telescope, medium-resolution spectroscopy with the Gran Telescopio Canarias (GTC), and near-infrared imaging with the GTC and the Nordic Optical Telescope.
Results.
We present the most detailed optical light curve of an ILRT to date, with multi-band photometry starting around three weeks before peak brightness. The transient peaked at an observed absolute magnitude of
M
r
′
= −13.1, although it is subject to significant reddening from dust in M51, implying an intrinsic
M
r
′
∼ −15.2. The initial light curve showed a linear, achromatic rise in magnitude before becoming bluer at peak. After peak brightness, the transient gradually cooled. This is reflected in our spectra, which at later times show absorption from such species as Fe
I
, Ni
I
and Li
I
. A spectrum taken around peak brightness shows narrow, low-velocity absorption lines, which we interpret as likely to originate from pre-existing circumstellar material.
Conclusions.
We conclude that while there are some peculiarities, such as the radius evolution, AT 2019abn fits in well overall with the ILRT class of objects and is the most luminous member of the class seen to date.
Small piscivores are regarded as important regulators of the composition of coral reef fish communities, but few studies have investigated their predatory ecology or impact on assemblages of juvenile ...fishes. This study investigated the foraging ecology of a common coral reef predator, the dottyback
Pseudochromis fuscus
, using underwater focal animal observations. Observations were conducted at two times of year: the summer, when recruit fishes were an available food item and winter, when remaining juveniles had outgrown vulnerability to
P. fuscus
. During the summer,
P. fuscus
directed 76% of its strikes at invertebrates and 24% at recruiting juvenile fishes. When striking at fishes,
P. fuscus
exhibited two distinct feeding modes: an ambush (26% successful) and a pursuit mode (5% successful). Predator activity in the field peaked at midday, averaging 2.5 captures h
−1
of juvenile fishes. Monitoring of activity and foraging in the laboratory over 24-h periods found that
P. fuscus
was a diurnal predator and was active for 13 h d
−1
during the summer. The number of hours during which foraging was recorded differed greatly among individuals (
n
= 10), ranging from 4 to 13 h. The number of predatory strikes did not increase with standard length, but the success rate and consumption rate of juvenile fishes did increase with size. Estimated hourly mortality on juvenile fish ranged from 0.49 fish h
−1
in small
P. fuscus
individuals (30–39 mm standard length, SL; equating to 6.3 per 13 h day) to 2.4 fish h
−1
in large
P. fuscus
individuals (55–65 mm SL; 30.6 per 13 h day). During the winter,
P. fuscus
struck at invertebrates with a similar rate to the summer period. These observations of the predatory ecology of
P. fuscus
support the hypothesis that in coral reef systems, small piscivores, because of their high metabolism and activity, are probably important regulators of coral reef fish community composition.
PDF
