Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose ...antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations.
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•Early life is a critical window of host-microbe metabolic interaction•Low-dose penicillin treatment amplifies diet-induced obesity•A transient early microbiota perturbation leads to long-term increased adiposity•The penicillin-altered microbiota has a causal role in inducing metabolic changes
Early-life transient perturbations of the intestinal microbiota drive changes in metabolism and body composition that persist in adult life.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Social distancing and lockdown measures taken to contain the spread of COVID-19 may have distributional economic costs beyond the contraction of GDP. Here we evaluate the capacity of individuals to ...work under a lockdown based on a Lockdown Working Ability index which considers their teleworking capacity and whether their occupation is essential or closed. Our analysis reveals substantial and uneven potential wage losses across the distribution all around Europe and we consistently find that both poverty and wage inequality rise in all European countries. Under four different scenarios (2 months of lockdown and 2 months of lockdown plus 6 months of partial functioning of closed occupations at 80%, 70% and 60% of full capacity) we estimate for 29 European countries an average increase in the headcount poverty index that goes from 4.9 to 9.4 percentage points and a mean loss rate for poor workers between 10% and 16.2%. The average increase in the Gini coefficient ranges between 3.5% to 7.3% depending on the scenario considered. Decomposing overall wage inequality in Europe, we find that lockdown and social distance measures produce a double process of divergence: both inequality within and between countries increase.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
While the association of lean mass (LM) with bone mass is well understood, the association of fat mass (FM) with bone mass is controversial. Our results support that adolescents with higher ...levels of adiposity have greater bone mass, but this association is fully explained by their higher levels of LM.
Introduction
We aimed (1) to study the independent association of FM and LM with bone mass and (2) to study the differences in bone mass by weight status in adolescents, after controlling for relevant confounders, such as physical activity (PA), calcium intake, and LM.
Methods
Participants were 330 adolescents (167 boys, 12.5–17.5 years) from the HELENA study. The relationships of FM (DXA,
n
= 330; BodPod,
n
= 282) and LM (DXA,
n
= 330) with different bone variables (whole body, total hip, lumbar spine, and femoral neck) were analyzed by linear regression, and differences between weight status were analyzed by ANCOVA.
Results
Fat mass (DXA) was positively associated with bone variables in both sexes, after adjustment for height, calcium intake, and sexual maturation. Additional adjustment by PA slightly increases the associations. However, adjustment for LM inverted these associations. Similar results were obtained using BodPod instead of DXA for assessing FM. Overweight/obese adolescents had higher BMC than their non-overweight peers in most of regions studied. Additional adjustment for PA slightly increased the differences between weight status groups, while adjusting for LM inverted the associations. LM was strong and positively associated with all bone variables in both sexes. Additional adjustment for PA or FM did not change the results.
Conclusions
Adolescents with higher levels of adiposity have greater bone mass, but this association is explained by their higher levels of LM.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Canary Islands are recognized as an area of particular interest to exploit and to promote the use of renewable energies as a way to reduce its energy dependence on fossil fuels and ultimately ...reach energy self-sufficiency and sustainability. A common major problem in mid-latitude small and remote islands is the low annual precipitation rate and the associated freshwater scarcity, leading to the installation of desalination plants powered by oil. In this context, the assessment of wave energy potential along with socioeconomic and environmental factors in a selected area at the north side of Gran Canaria Island shows that wave power availability is adequate for its exploitation and there are no sources of potential conflicts that prevent the installation of wave energy converters. In particular, the harvesting of wave energy to power existing seawater desalination plants, fully based in the use of oil, is considered as a viable, appealing and advantageous alternative over the direct injection to the electric network.
•Wave power availability in the north flank of Gran Canaria Island is assessed.•Environmental and socioeconomic points are rated to detect potential problems avoiding the installation of WEC’s.•Exploitation of wave energy to power oil-based seawater desalination plants results to be a viable and advantageous option.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this work, we assessed the efficacy and safety of brentuximab vedotin (BV) plus ESHAP (BRESHAP) as second-line therapy for Relapsed/Refractory Hodgkin lymphoma (RRHL) to improve the results before ...autologous stem-cell transplantation (ASCT).
This was a multicenter, open-label, phase I–II trial of patients with RRHL after first-line chemotherapy. Treatment had three 21-day cycles of etoposide, solumedrol, high-dose AraC, and cisplatin. BV was administered at three dose levels (0.9, 1.2, and 1.8 mg/kg) intravenous on day ‒1 to 3 + 3 cohorts of patients. Final BV dose was 1.8 mg/kg. Responding patients proceeded to ASCT, followed by three BV courses (1.8 mg/kg, every 21 days). Main end points for evaluation were maximum tolerable dose and overall and complete response (CR) before ASCT.
A total of 66 patients were recruited (median age 36 years; range 18–66): 40 were primary refractory, 16 early relapse and 10 late relapse. There were 39 severe adverse events were reported in 22 patients, most frequently fever (n = 25, 35% neutropenic), including 3 deaths. Grade 3–4 hematological toxicity presented in 28 cases: neutropenia (n = 21), thrombocytopenia (n = 14), and anemia (n = 7). Grade ≥3–4 extrahematological adverse events (≥5%) were non-neutropenic fever (n = 13) and hypomagnesaemia (n = 3). Sixty-four patients underwent stem-cell mobilization; all collected >2×10e6/kg CD34+ cells (median 5.75; range 2.12–33.4). Overall response before transplant was 91% (CI 84% to 98%), including 70% (CRs 95% CI 59% to 81%). 60 patients were transplanted with no failure engraftments. Post-transplant response was CR in 49 patients (82% CI 73% to 91%) and partial responses in six (10% CI 5% to 15%). After a mean follow-up of 27 months, the 30-month time to treatment to failure was 74% (95% CI 68% to 80%), progression-free survival 71% (95% CI 65% to 77%), and overall survival 91% (CI 84% to 98%).
BRESHAP looks a safe and effective pre-transplant induction regimen, does not jeopardize transplant and allows long-term remissions and survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
Background
The molecular basis and effects of proton pump inhibitor (PPI) therapy on PPI‐responsive oesophageal eosinophilia (PPI‐REE) and eosinophilic oesophagitis (EoE) remain unknown.
Aim
...To compare symptom‐histological and cytokine gene expression in PPI‐REE and EoE patients, at baseline and after specific treatment.
Methods
In consecutive adult patients with an EoE phenotype (dysphagia/food impaction, typical endoscopic findings and > 15 eos/HPF), gene expression of eotaxin‐3, IL‐13, and IL‐5 were determined in distal and proximal oesophagus, at baseline and after omeprazole 40 mg b.d. for 8 weeks. PPI‐REE was defined by clinicohistological response. PPI nonresponders (EoE) were offered treatment with topical steroids.
Results
Fifty three patients were re‐evaluated on PPI therapy. 23 patients (43%) had PPI‐REE and 30 patients (57%) had EoE. At baseline, eotaxin‐3/IL‐13/IL‐5 gene expression was indistinguishable between EoE and PPI‐REE, excepting increased IL‐5 expression in proximal oesophagus (12.54 vs. 57, P = 0.029). PPI therapy significantly decreased eotaxin‐3/IL‐13 in PPI‐REE, at both oesophageal sites (P ≤ 0.008), and IL‐5 in distal (P = 0.016), but not in proximal oesophagus. Patients with steroid‐responsive EoE also showed a significant decrease in eotaxin‐3/IL‐5 expression at both oesophageal sites. In EoE patients, initial PPI trial significantly decreased distal oesophageal eosinophilia (63.78 to 41.79 eos/HPF, P = 0.025) and led to symptom remission in 16%, but did not influence Th2 markers.
Conclusions
Baseline cytokine gene expression in PPI‐REE was nearly indistinguishable from EoE. PPI therapy significantly downregulated oesophageal eotaxin‐3/Th2‐cytokine gene expression in PPI‐REE, similarly to that seen in steroid‐responsive EoE. A subset of EoE patients showed clinicohistological improvement on PPI therapy.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
We report on the discovery of a new member of the magnetar class, SGR J1935+2154, and on its timing and spectral properties measured by an extensive observational campaign carried out between 2014 ...July and 2015 March with Chandra and XMM–Newton (11 pointings). We discovered the spin period of SGR J1935+2154 through the detection of coherent pulsations at a period of about 3.24 s. The magnetar is slowing down at a rate of
$\dot{P} = 1.43(1)\times 10^{-11}$
s s−1 and with a decreasing trend due to a negative
$\ddot{P}$
of −3.5(7) × 10−19 s s−2. This implies a surface dipolar magnetic field strength of ∼2.2 × 1014 G, a characteristic age of about 3.6 kyr and a spin-down luminosity Lsd ∼1.7 × 1034 erg s−1. The source spectrum is well modelled by a blackbody with temperature of about 500 eV plus a power-law component with photon index of about 2. The source showed a moderate long-term variability, with a flux decay of about 25 per cent during the first four months since its discovery, and a re-brightening of the same amount during the second four months. The X-ray data were also used to study the source environment. In particular, we discovered a diffuse emission extending on spatial scales from about 1 arcsec up to at least 1 arcmin around SGR J1935+2154 both in Chandra and XMM–Newton data. This component is constant in flux (at least within uncertainties) and its spectrum is well modelled by a power-law spectrum steeper than that of the pulsar. Though a scattering halo origin seems to be more probable we cannot exclude that part, or all, of the diffuse emission is due to a pulsar wind nebula.
Summary
Iron is an essential but potentially harmful nutrient, poorly soluble in aerobic conditions, and not freely available in the human host. To acquire iron, bacteria have evolved high affinity ...iron acquisition systems that are expressed under iron limitation often in conjunction with virulence determinants. Because excess iron can be dangerous, intracellular iron must be tightly controlled. In mycobacteria, IdeR functions as a global iron dependent transcriptional regulator, but because inactivation of ideR is lethal for Mycobacterium tuberculosis, it has not been possible to use genetics to fully characterize this protein's function or examine the requirement of iron regulation during tuberculosis infection. In this work, a conditional M. tuberculosis ideR mutant was generated and used to study the basis of IdeR's essentiality. This investigation uncovered positive regulation of iron storage as a critical aspect of IdeR's function in regular culture and a prominent factor for survival under stresses associated with life in macrophages. Moreover, this study demonstrates that IdeR is indispensable in the mouse model of tuberculosis, thereby linking iron homeostasis to virulence in M. tuberculosis.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Scalar field effects on the orbit of S2 star Amorim, A; Bauböck, M; Benisty, M ...
Monthly notices of the Royal Astronomical Society,
11/2019, Volume:
489, Issue:
4
Journal Article
Peer reviewed
Open access
ABSTRACT
Precise measurements of the S-stars orbiting SgrA* have set strong constraints on the nature of the compact object at the centre of the Milky Way. The presence of a black hole in that region ...is well established, but its neighbouring environment is still an open debate. In that respect, the existence of dark matter in that central region may be detectable due to its strong signatures on the orbits of stars: the main effect is a Newtonian precession which will affect the overall pericentre shift of S2, the latter being a target measurement of the GRAVITY instrument. The exact nature of this dark matter (e.g. stellar dark remnants or diffuse dark matter) is unknown. This article assumes it to be a scalar field of toroidal distribution, associated with ultralight dark matter particles, surrounding the Kerr black hole. Such a field is a form of ‘hair’ expected in the context of superradiance, a mechanism that extracts rotational energy from the black hole. Orbital signatures for the S2 star are computed and shown to be detectable by GRAVITY. The scalar field can be constrained because the variation of orbital elements depends both on the relative mass of the scalar field to the black hole and on the field mass coupling parameter.
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