Context. The JAXA Hayabusa2 mission will perform the first ever sample return from a primitive asteroid. The target near-Earth asteroid (162173) Ryugu will be reached in mid-2018 and its samples will ...be returned to the Earth by the end of 2020. Aims. We want to improve the current knowledge of the compositional and rotational properties of Ryugu, which are still presenting some uncertainties that might affect the mission operations and scientific return. Methods. We acquired high-quality photometric time-series data with the FORS2 instrument at the Very Large Telescope of the European Southern Observatory (ESO-VLT, Chile). We also acquired four FORS2 visible spectra and three X-shooter spectra in the 0.35−2.15 μm range, at different rotational phases. Results. We obtained the currently highest-quality visual light-curve of Ryugu. A best solution of ~7.63 h is found for the rotational period, while a short-period solution (i.e., P ≈ 3.8 h) is ruled out by the clearly non-symmetric light-curve. The obtained spectra are generally similar and featureless, but present a drop-off of the reflectance at <0.45 μm, suggesting the presence of aqueously altered minerals on Ryugu. The best meteorite analogs for Ryugu are represented by thermally altered CM carbonaceous chondrites. Conclusions. Our new photometric data help to refine the target reference model used by the Hayabusa2 team for the mission preparation and implementation, improving our knowledge of Ryugu’s spin properties. Our new spectra constrain the compositional and geological context of the Ryugu’s surface in order to prepare the planning of mission observations and support the working group for the selection of possible landing and sampling sites.
Age has historically been used to predict negative post-surgical outcomes. The concept of frailty was introduced to explain the discrepancies that exist between patients’ chronological and ...physiological age. The efficacy of the modified frailty index (mFI) to predict surgical risk is not clear.
We sought to synthesize the current literature to quantify the impact of frailty as a prognostic indicator across all surgical specialties.
Pubmed and Cochrane databases were screened from inception to 1 January 2018.
Studies utilizing the modified Frailty Index (mFI) as a post-operative indicator of any type of surgery. The mFI was selected based on a preliminary search showing it to be the most commonly applied index in surgical cohorts.
Articles were selected via a two-stage process undertaken by two reviewers (AP and DS). Statistical analysis was performed in Revman (Review manager V5.3). The random-effects model was used to calculate the Risk Ratios (RR).
The primary outcomes: post-operative complications, re-admission, re-operation, discharge to a skilled care facility, and mortality.
This meta-analysis of 16 studies randomizes 683,487 patients, 444,885 frail, from gastrointestinal, vascular, orthopedic, urogenital, head and neck, emergency, neurological, oncological, cardiothoracic, as well as general surgery cohorts. Frail patients were more likely to experience complications (RR 1.48, 95%CI 1.35–1.61; p < 0.001), major complications (RR 2.03, 95%CI 1.26–3.29; p = 0.004), and wound complications (RR 1.52, 95%CI 1.47–1.57; p < 0.001). Furthermore, frail patients had higher risk of readmission (RR 1.61, 95%CI 1.44–1.80; p < 0.001) and discharge to skilled care (RR 2.15, 95%CI 1.92–2.40; p < 0.001). Notably, the risk of mortality was 4.19 times more likely in frail patients (95% CI 2.96–5.92; p < 0.001).
and Relevance: This study is the first to synthesize the evidence across multiple surgical specialties and demonstrates that the mFI is an underappreciated prognostic indicator that strongly correlates with the risk of post-surgical morbidity and mortality. This supports that formal incorporation of pre-operative frailty assessment improves surgical decision-making.
•The mFI correlates with higher rates of post-operative complications, readmission, reoperation, and mortality.•Formal incorporation of preoperative frailty assessment using the mFI can improve surgical risk stratification.
During aging, deterioration in cardiac structure and function leads to increased susceptibility to heart failure. The need for interventions to combat this age-related cardiac decline is becoming ...increasingly urgent as the elderly population continues to grow. Our understanding of cardiac aging, and aging in general, is limited. However, recent studies of age-related decline and its prevention through interventions like exercise have revealed novel pathological and cardioprotective pathways. In this review, we summarize recent findings concerning the molecular mechanisms of age-related heart failure and highlight exercise as a valuable experimental platform for the discovery of much-needed novel therapeutic targets in this chronic disease.
Macrophages populate the healthy myocardium and, depending on their phenotype, may contribute to tissue homeostasis or disease. Their origin and role in diastolic dysfunction, a hallmark of cardiac ...aging and heart failure with preserved ejection fraction, remain unclear. Here we show that cardiac macrophages expand in humans and mice with diastolic dysfunction, which in mice was induced by either hypertension or advanced age. A higher murine myocardial macrophage density results from monocyte recruitment and increased hematopoiesis in bone marrow and spleen. In humans, we observed a parallel constellation of hematopoietic activation: circulating myeloid cells are more frequent, and splenic
F-FDG PET/CT imaging signal correlates with echocardiographic indices of diastolic dysfunction. While diastolic dysfunction develops, cardiac macrophages produce IL-10, activate fibroblasts, and stimulate collagen deposition, leading to impaired myocardial relaxation and increased myocardial stiffness. Deletion of IL-10 in macrophages improves diastolic function. These data imply expansion and phenotypic changes of cardiac macrophages as therapeutic targets for cardiac fibrosis leading to diastolic dysfunction.
Activin type II receptor (ActRII) ligands have been implicated in muscle wasting in aging and disease. However, the role of these ligands and ActRII signaling in the heart remains unclear. Here, we ...investigated this catabolic pathway in human aging and heart failure (HF) using circulating follistatin-like 3 (FSTL3) as a potential indicator of systemic ActRII activity. FSTL3 is a downstream regulator of ActRII signaling, whose expression is up-regulated by the major ActRII ligands, activin A, circulating growth differentiation factor-8 (GDF8), and GDF11. In humans, we found that circulating FSTL3 increased with aging, frailty, and HF severity, correlating with an increase in circulating activins. In mice, increasing circulating activin A increased cardiac ActRII signaling and FSTL3 expression, as well as impaired cardiac function. Conversely, ActRII blockade with either clinical-stage inhibitors or genetic ablation reduced cardiac ActRII signaling while restoring or preserving cardiac function in multiple models of HF induced by aging, sarcomere mutation, or pressure overload. Using unbiased RNA sequencing, we show that activin A, GDF8, and GDF11 all induce a similar pathologic profile associated with up-regulation of the proteasome pathway in mammalian cardiomyocytes. The E3 ubiquitin ligase, Smurf1, was identified as a key downstream effector of activin-mediated ActRII signaling, which increased proteasome-dependent degradation of sarcoplasmic reticulum Ca
ATPase (SERCA2a), a critical determinant of cardiomyocyte function. Together, our findings suggest that increased activin/ActRII signaling links aging and HF pathobiology and that targeted inhibition of this catabolic pathway holds promise as a therapeutic strategy for multiple forms of HF.
Aim
To evaluate the anti‐inflammatory effects of glutamine and the underlying signal pathway mechanisms in lipopolysaccharide (LPS)‐stimulated human dental pulp cells (HDPCs).
Methods
Human dental ...pulp cells were exposed to 10 μg mL−1 LPS and various concentrations of glutamine for 24 h. The production of PGE2 and nitric oxide was determined by enzyme‐linked immunosorbent assay (ELISA) and Griess reagent kit, respectively. Cytokines were examined by ELISA, reverse transcriptase‐polymerase chain reaction (RT‐PCR) and real‐time PCR. iNOS and COX protein expression as well as signal pathways were accessed by Western blot. The data were analysed by anova with Bonferroni's test (α = 0.05).
Results
Glutamine reduced LPS‐induced iNOS and COX‐2 protein expression as well as production of NO and PGE2 in a dose‐dependent fashion. Additionally, glutamine suppressed the production and mRNA expression of inflammatory cytokines including interleukin‐1β (IL‐1β), TNF‐α, and IL‐8. Furthermore, glutamine attenuated phosphorylation of extracellular signal‐regulated kinase (ERK), p38, c‐Jun N‐terminal kinase (JNK) and IκB‐α, and nuclear translocation of NF‐kB p65, but enhanced mitogen‐activated protein kinase phosphatase‐1 (MKP‐1) expression in LPS‐treated HDPCs.
Conclusion
Glutamine exerted an anti‐inflammatory effect via activation of MKP‐1 and inhibition of the NF‐kB and MAPK pathways in LPS‐treated HDPCs.
Aims.
The satellite Linus orbiting the main-belt asteroid (22) Kalliope exhibited mutual occultation and transit events in late 2021. A photometric campaign was organised and observations were ...undertaken by the TRAPPIST-South, SPECULOOS-Artemis, OWL-Net, and BOAO telescopes, with the goal to further constrain dynamical and photometric models of this sizeable asteroid-satellite system.
Methods.
Our dynamical model is sufficiently complex, featuring multipoles (up to the order of
ℓ
= 2), internal tides, and external tides. The model was constrained by astrometry (spanning 2001–2021), occultations, adaptive-optics imaging, and calibrated photometry, as well as relative photometry. Our photometric model was substantially improved. A new precise (<0.1 mmag) light curve algorithm was implemented, based on polygon intersections, which are computed exactly by including partial eclipses and partial visibility of polygons. Moreover, we implemented a ‘cliptracing’ algorithm, again based on polygon intersections, in which partial contributions to individual pixels are computed exactly. Both synthetic light curves and synthetic images then become very smooth.
Results.
Based on our combined solution, we confirmed the size of Linus, namely, (28 ± 1)km. However, this solution exhibits some tension among the light curves and the PISCO speckle-interferometry dataset, acquired simultaneously with the 2021 events. This indicates that improvements of the shape are still possible. In most solutions, Linus is darker than Kalliope, with the single-scattering albedos
A
w
= 0.40 vs. 0.44. This is confirmed on deconvolved images. A detailed revision of astrometric data has allowed us to revise also the
J
2
≡ −
C
20
value of Kalliope. Most importantly, a homogeneous body is excluded. For a differentiated body, two solutions exist: low-oblateness (
C
20
≃ −0.12), with a spherical iron core, and, alternatively, high-oblateness (
C
20
≃ −0.22) with an elongated iron core. These values correspond, respectively, to the low- and high-energy collisions we studied via SPH simulations in our previous work.
Despite optimal pharmacotherapy and cognitive-behavioral treatments, a proportion of patients with obsessive-compulsive disorder (OCD) remain refractory to treatment. Neurosurgical ablative or ...nondestructive stimulation procedures to treat these refractory patients have been investigated. However, despite the potential benefits of these surgical procedures, patients show significant surgery-related complications. This preliminary study investigated the use of bilateral thermal capsulotomy for patients with treatment-refractory OCD using magnetic resonance-guided focused ultrasound (MRgFUS) as a novel, minimally invasive, non-cranium-opening surgical technique. Between February and May 2013, four patients with medically refractory OCD were treated with MRgFUS to ablate the anterior limb of the internal capsule. Patients underwent comprehensive neuropsychological evaluations and imaging at baseline, 1 week, 1 month and 6 months following treatment. Outcomes were measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety (HAM-A), and treatment-related adverse events were evaluated. The results showed gradual improvements in Y-BOCS scores (a mean improvement of 33%) over the 6-month follow-up period, and all patients showed almost immediate and sustained improvements in depression (a mean reduction of 61.1%) and anxiety (a mean reduction of 69.4%). No patients demonstrated any side effects (physical or neuropsychological) in relation to the procedure. In addition, there were no significant differences found in the comprehensive neuropsychological test scores between the baseline and 6-month time points. This study demonstrates that bilateral thermal capsulotomy with MRgFUS can be used without inducing side effects to treat patients with medically refractory OCD. If larger trials validate the safety, effectiveness and long-term durability of this new approach, this procedure could considerably change the clinical management of treatment-refractory OCD.
Context.
The close approach of the near-Earth asteroid (99942) Apophis to Earth in 2029 will provide a unique opportunity to examine how the physical properties of the asteroid could be changed due ...to the Earth’s gravitational perturbation. As a result, the Republic of Korea is planning a rendezvous mission to Apophis.
Aims.
Our aim was to use photometric data from the apparitions in 2020−2021 to refine the shape model and spin state of Apophis.
Methods.
Using thirty-six 1- to 2-meter-class ground-based telescopes and the Transiting Exoplanet Survey Satellite, we carried out a photometric observation campaign throughout the 2020−2021 apparition. The convex shape model and spin state were refined using the light-curve inversion method.
Results.
According to our best-fit model, Apophis is rotating in a short-axis mode with rotation and precession periods of 264.178 h and 27.38547 h, respectively. The angular momentum vector orientation of Apophis was found to be (275°, −85°) in the ecliptic coordinate system. The ratio of the dynamic moments of inertia of this asteroid was fitted to
I
a
:
I
b
:
I
c
= 0.64 : 0.97 : 1, which corresponds to an elongated prolate ellipsoid. These findings regarding the spin state and shape model can be used to both design the space mission scenario and investigate the impact of the Earth’s tidal force during close encounters.
Biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs) are the earliest tissue-engineered vascular grafts (TEVGs) to be used clinically. These TEVGs transform into living blood ...vessels in vivo, with an endothelial cell (EC) lining invested by smooth muscle cells (SMCs); however, the process by which this occurs is unclear. To test if the seeded BMCs differentiate into the mature vascular cells of the neovessel, we implanted an immunodeficient mouse recipient with human BMC (hBMC)-seeded scaffolds. As in humans, TEVGs implanted in a mouse host as venous interposition grafts gradually transformed into living blood vessels over a 6-month time course. Seeded hBMCs, however, were no longer detectable within a few days of implantation. Instead, scaffolds were initially repopulated by mouse monocytes and subsequently repopulated by mouse SMCs and ECs. Seeded BMCs secreted significant amounts of monocyte chemoattractant protein-1 and increased early monocyte recruitment. These findings suggest TEVGs transform into functional neovessels via an inflammatory process of vascular remodeling.
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