Leukocyte-reduced platelet-rich plasma (LR-PRP) is a therapy for tendinopathy of the Achilles tendon (TAT); however, there is scarce information regarding LR-PRP effects in rabbit models of TAT. We ...compared, at 4 and 12 weeks (w), the LR-PRP and placebo (PBS) effects on ultrasonography, histology and relative gene expression of collagen types I (COL1A1) and III (COL3A1) and vascular endothelial growth factor (VEGF) in 24 rabbits with TAT induced by collagenase. The rabbits (treated with both treatments) were euthanatised after either 4 or 12 w. A healthy group (HG (n = 6)) was included. At 4 and 12 w, the LR-PRP group had a no statistically different histology score to the HG. At w 4, the COL1A1 expression was significantly higher in the LR-PRP group when compared to HG, and the expression of COL3A1 from both LR-PRP and PBS-treated tendons was significantly higher when compared to the HG. At w 12, the expression of COL3A1 remained significantly higher in the PBS group in comparison to the LR-PRP group and the HG. At w 4, the LR-PRP group presented a significantly higher expression of VEGF when compared to the PBS group and the HG. In conclusion, LR-PRP treatment showed regenerative properties in rabbits with TAT.
HADES RV programme with HARPS-N at TNG Maldonado, J.; Petralia, A.; Damasso, M. ...
Astronomy and astrophysics (Berlin),
07/2021, Volume:
651
Journal Article
Peer reviewed
Open access
Context.
It is now well-established that small, rocky planets are common around low-mass stars. However, the detection of such planets is challenged by the short-term activity of host stars.
Aims.
...The HARPS-N red Dwarf Exoplanet Survey programme is a long-term project at the Telescopio Nazionale
Galileo
aimed at monitoring nearby, early-type, M dwarfs, using the HARPS-N spectrograph to search for small, rocky planets.
Methods.
A total of 174 HARPS-N spectroscopic observations of the M0.5V-type star GJ 9689 taken over the past seven years have been analysed. We combined these data with photometric measurements to disentangle signals related to the stellar activity of the star from possible Keplerian signals in the radial velocity data. We ran an MCMC analysis, applying Gaussian process regression techniques to model the signals present in the data.
Results.
We identify two periodic signals in the radial velocity time series, with periods of 18.27 and 39.31 d. The analysis of the activity indexes, photometric data, and wavelength dependency of the signals reveals that the 39.31 d signal corresponds to the stellar rotation period. On the other hand, the 18.27 d signal shows no relation to any activity proxy or the first harmonic of the rotation period. We, therefore, identify it as a genuine Keplerian signal. The best-fit model describing the newly found planet, GJ 9689 b, corresponds to an orbital period of
P
b
= 18.27 ± 0.01 d and a minimum mass of
M
P
sin
i
= 9.65 ± 1.41
M
⊕
.
Obesity, a risk factor for coronary artery disease (CAD), is associated with inflammation and reactive oxygen species (ROS) production, while advanced glycation end-products, through their receptor ...(AGER or RAGE), play an important role on these processes. The aim of this study was to analyze the expression levels of RAGE, NADPH oxidase subunits, and catalase in adipose tissue in relation with CAD.
Patients undergoing heart surgery were included in two groups: with and without CAD. Epicardial adipose tissue (EAT) and subcutaneous adipose tissue (SAT) biopsies were analyzed for gene expression by RT-quantitative PCR, immunohistochemistry, or western blot.
RAGE mRNA and protein expression in SAT from patients with CAD was lower than in patients without CAD. However, there was no change in EAT from patients with or without CAD. P22-PHOX and RAGE gene expression were higher in EAT than in SAT, whereas catalase mRNA levels were lower. NADPH oxidase subunits and catalase mRNA expression were not influenced by CAD. Whereas NADPH oxidase-dependent oxidative response of SAT and EAT to lipid circulating levels could be different; glycemic levels were not related with the analyzed genes expression.
This study demonstrates that RAGE expression in SAT, but not in EAT, is down-regulated in patients with CAD with respect to those without CAD. Although changes were not observed for NADPH oxidase subunits or catalase expression between CAD and non-CAD patients, a possible relationship between ROS production and RAGE expression in adipose tissues cannot be ruled out.
The worldwide dissemination of carbapenemase-producing Escherichia coli lineages belonging to high-risk clones poses a challenging public health menace. The aim of this work was to investigate ...genomic features of a colonizing multidrug-resistant strain of Klebsiella pneumoniae carbapenemase (KPC)-producing E. coli from our institution.
Whole-genome sequencing was done by Illumina MiSeq-I, and de novo assembly was achieved using SPAdes. Resistome, mobilome, plasmids, virulome, and integrons were analysed using ResFinder, AMRFinder, ISFinder, PlasmidFinder, MOB-suite, VirulenceFinder, and IntegronFinder. Sequence types (STs) were identified with pubMLST and BIGSdb databases. Conjugation assays were also performed.
Escherichia coli HA25pEc was isolated from a rectal swab sample taken within the framework of the hospital epidemiological surveillance protocol for detection of carbapenemase-producing Enterobacterales. Escherichia coli HA25pEc corresponded to the first report of ST648 co-harbouring blaKPC-2 and blaCTX-M-15 in Latin America from a colonized patient. It had 19 antibiotic resistance genes (ARGs), including blaKPC-2, located on a Tn4401a isoform. Conjugation assays revealed that blaKPC-2 was not transferred by conjugation to E. coli J53 under our experimental conditions.
Escherichia coli ST648 has been detected previously in companion and farm animals as well as in hospital- and community-acquired infections worldwide. Although scarcely reported as KPC-producers, our finding in a culture surveillance with several acquired ARGs, including blaCTX-M-15, alerts the potential of this clone for worldwide unnoticed spreading of extreme drug resistance to β-lactams. These data reinforce the importance of carrying out molecular surveillance to identify reservoirs and warn about the dissemination of new international clones in carbapenemase-bearing patients.
Purpose: To compare efficacy in terms of pathologic response in LARC patients treated with preoperative chemoradiation, with or without a short-intense course of induction oxaliplatin.
Patients and ...Methods: From 05/98 to 10/02, 114 patients were treated with preoperative chemoradiation (4500–5040cGy + oral Tegafur 1200mg/day) for cT3-4N+/xM0 rectal cancer. Starting 05/01, 52 consecutive patients additionally received induction FOLFOX-4, oxaliplatin (85mg/m2 iv d1), 5-FU (400mg/m2 iv bolus d1) and 600mg/m2 iv continuous infusion in 22h with leucovorin (200mg iv) d1 and d2, every 15 days (2 cycles), followed by the previously described Tegafur chemoradiation regime. Surgery was performed in 5–6 weeks. Pathological assessment investigated post-treatment T and N status in the rectal wall and peri-rectal tissues.
Results: Patients, tumor and treatment characteristics were comparable between groups. Incidence of pT0 specimens was significantly increased by induction FOLFOX-4 (P = 0.006). Total T and N downstaging were 58% versus 75% and 42% versus 40%, respectively (P = ns). T downstaging of ≥2 categories was significantly superior in FOLFOX-4 group (P = 0.029).
Conclusions: Short-intense induction FOLFOX-4 significantly improves pathologic complete response in LARC patients treated with tegafur-sensitized preoperative chemoradiation. The 44% rate of pT0-1 specimens observed in the oxaliplatin group should impulse innovative surgical approaches to promote ano-rectal sphincter conserving protocols.
Isolation of colistin- and carbapenem-resistant Klebsiella pneumoniae (CCR-Kp) is increasing in hospital settings worldwide, which is related to increased morbidity, mortality and healthcare costs. ...The aim of this work was to perform whole-genome sequencing (WGS), genomic and phylogenetic analysis, and conjugation assays of an extensively drug-resistant (XDR) CCR-Kp isolate from Argentina.
WGS of strain KpS26 isolated from a bloodstream infection was performed using Illumina MiSeq-I, and de novo assembly was achieved using SPAdes v.3.11. A maximum likelihood tree was created using MEGA7 based on core genome single nucleotide polymorphisms from whole-genome alignment of K. pneumoniae isolates identified in silico as sequence type 15 (ST15). The resistome, plasmids and integrons were analysed using ResFinder, AMRFinderPlus, ISfinder, plasmidSPAdes, PlasmidFinder and IntegronFinder. Standard conjugation was performed.
KpS26 belonged to ST15, which is less common than ST258, ST25 and ST11 that are globally reported as responsible for CCR-Kp outbreaks. Fourteen transferable antimicrobial resistance genes (ARGs), including blaKPC-2 in a novel genetic platform transferable by conjugation, were detected contributing to the XDR phenotype. The amino acid substitution T157P in the protein encoded by the pmrB gene of KpS26, previously reported as being responsible for resistance to colistin in K. pneumoniae lineages globally disseminated, was also identified in this strain.
The XDR CCR-Kp isolate analysed here shows that ST15 is also disseminating blaKPC-2 in Argentina alongside other ARGs, evidencing that KPC epidemiology continues to be shaped by intricate and assorted ways of lateral gene transfer.
The accurate detection of nucleic acids from certain biological pathogens is critical for the diagnosis of human diseases. However, amplified detection of RNA molecules from a complex sample by ...direct detection of RNA/DNA hybrids remains a challenge. Here, we show that type IIS endonuclease FokI is able to digest DNA duplexes and DNA/RNA hybrids when assisted by a dumbbell-like fluorescent sensing oligonucleotide. As proof of concept, we designed a battery of sensing oligonucleotides against specific regions of the SARS-CoV-2 genome and interrogated the role of FokI relaxation as a potential nicking enzyme for fluorescence signal amplification. FokI-assisted digestion of SARS-CoV-2 probes increases the detection signal of ssDNA and RNA molecules and decreases the limit of detection more than 3.5-fold as compared to conventional molecular beacon approaches. This cleavage reaction is highly specific to its target molecules, and no detection of other highly related B-coronaviruses was observed in the presence of complex RNA mixtures. In addition, the FokI-assisted reaction has a high multiplexing potential, as the combined detection of different viral RNAs, including different SARS-CoV-2 variants, was achieved in the presence of multiple combinations of fluorophores and sensing oligonucleotides. When combined with isothermal rolling circle amplification technologies, FokI-assisted digestion reduced the detection time of SARS-CoV-2 in COVID-19-positive human samples with adequate sensitivity and specificity compared to conventional reverse transcription polymerase chain reaction approaches, highlighting the potential of FokI-assisted signal amplification as a valuable sensing mechanism for the detection of human pathogens.
We present 20 yr of radial velocity (RV) measurements of the M1 dwarf Gl15A, combining five years of intensive RV monitoring with the HARPS-N spectrograph with 15 yr of archival HIRES/Keck RV data. ...We have carried out an MCMC-based analysis of the RV time series, inclusive of Gaussian Process (GP) approach to the description of stellar activity induced RV variations. Our analysis confirms the Keplerian nature and refines the orbital solution for the 11.44-day period super Earth, Gl15A b, reducing its amplitude to 1.68−0.18+0.17$1.68^{+0.17}_{-0.18}$1.68−0.18+0.17 m s−1 (M sin i = 3.03−0.44+0.46 M⊕$M \textrm{sin} i = 3.03^{+0.46}_{-0.44} M_{\oplus}$ Msini=3.03−0.44+0.46M⊕), and successfully models a long-term trend in the combined RV dataset in terms of a Keplerian orbit with a period around 7600 days and an amplitude of 2.5−1.0+1.3$2.5^{+1.3}_{-1.0}$2.5−1.0+1.3 m s−1, corresponding to a super-Neptune mass (M sin i = 36−18+25 M⊕$M \textrm{sin} i = 36^{+25}_{-18} M_{\oplus}$Msini=36−18+25M⊕) planetary companion. We also discuss the present orbital configuration of Gl15A planetary system in terms of the possible outcomes of Lidov–Kozai interactions with the wide-separation companion Gl15B in a suite of detailed numerical simulations. In order to improve the results of the dynamical analysis, we have derived a new orbital solution for the binary system, combining our RV measurements with astrometric data from the WDS catalogue. The eccentric Lidov–Kozai analysis shows the strong influence of Gl15B on the Gl15A planetary system, which can produce orbits compatible with the observed configuration for initial inclinations of the planetary system between 75° and 90°, and can also enhance the eccentricity of the outer planet well above the observed value, even resulting in orbital instability, for inclinations around 0° and 15°−30°. The Gl15A system is the multi-planet system closest to Earth, at 3.56 pc, and hosts the longest period RV sub-Jovian mass planet discovered so far. Its orbital architecture constitutes a very important laboratory for the investigation of formation and orbital evolution scenarios for planetary systems in binary stellar systems.
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