Patients with HFPEF (n = 20; age: 68 ± 2 years; left ventricular ejection fraction 64 ± 2%) underwent right heart catheterization and radial arterial cannulation for measurement of hemodynamics at ...rest and during peak symptom-limited exercise, as described previously (3). Pretreatment exercise hemodynamic responses (presented as delta values for pre-placebo vs. pre-milrinone) were generally not significantly different: heart rate (28 ± 5 vs. 30 ± 3 beats/min), mean arterial pressure (21 ± 4 vs. 22 ± 3 mm Hg), mean pulmonary artery pressure (17 ± 2 vs. 23 ± 2 mm Hg), cardiac index (1.8 ± 0.2 vs. 2.3 ± 0.2 l/min/m2), and stroke volume index (6 ± 1 vs. 4 ± 1 ml/m2).
The role of chromatin structure in lineage commitment of multipotent hematopoietic progenitors (HPCs) is presently unclear. We show here that CD34+ HPCs possess a post-replicative chromatin globally ...devoid of the repressive histone mark H3K27me3. This H3K27-unmodified chromatin is required for recruitment of lineage-determining transcription factors (TFs) C/EBPα, PU.1, and GATA-1 to DNA just after DNA replication upon cytokine-induced myeloid or erythroid commitment. Blocking DNA replication or increasing H3K27me3 levels prevents recruitment of these TFs to DNA and suppresses cytokine-induced erythroid or myeloid differentiation. However, H3K27me3 is rapidly associated with nascent DNA in more primitive human and murine HPCs. Treatment of these cells with instructive cytokines leads to a significant delay in accumulation of H3K27me3 in nascent chromatin due to activity of the H3K27me3 demethylase UTX. Thus, HPCs utilize special mechanisms of chromatin modification for recruitment of specific TFs to DNA during early stages of lineage specification.
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•Accumulation of H3K27me3 on nascent DNA occurs rapidly in undifferentiated HPCs•Accumulation of H3K27me3 on nascent DNA is delayed 12 hr following induction•This delay is caused by induction of the H3K27me3 KDM UTX•“Open” nascent chromatin facilitates recruitment of lineage-specifying TFs to DNA
Petruk et al. find that hematopoietic progenitor cells possess a state of post-replicative chromatin globally devoid of the repressive histone mark H3K27me3. This de-condensed chromatin is required for recruitment of lineage-determining transcription factors to DNA just after replication in early stages of cytokine-induced myeloid or erythroid lineage specification.
Recent advances in nanotechnology applied to medicine and regenerative medicine have an enormous and unexploited potential for future space and terrestrial medical applications. The Nanoparticles and ...Osteoporosis (NATO) project aimed to develop innovative countermeasures for secondary osteoporosis affecting astronauts after prolonged periods in space microgravity. Calcium- and Strontium-containing hydroxyapatite nanoparticles (nCa-HAP and nSr-HAP, respectively) were previously developed and chemically characterized. This study constitutes the first investigation of the effect of the exogenous addition of nCa-HAP and nSr-HAP on bone remodeling in gravity (1 g), Random Positioning Machine (RPM) and onboard International Space Station (ISS) using human bone marrow mesenchymal stem cells (hBMMSCs). In 1 g conditions, nSr-HAP accelerated and improved the commitment of cells to differentiate towards osteoblasts, as shown by the augmented alkaline phosphatase (ALP) activity and the up-regulation of the expression of bone marker genes, supporting the increased extracellular bone matrix deposition and mineralization. The nSr-HAP treatment exerted a protective effect on the microgravity-induced reduction of ALP activity in RPM samples, and a promoting effect on the deposition of hydroxyapatite crystals in either ISS or 1 g samples. The results indicate the exogenous addition of nSr-HAP could be potentially used to deliver Sr to bone tissue and promote its regeneration, as component of bone substitute synthetic materials and additive for pharmaceutical preparation or food supplementary for systemic distribution.
In this study, our aim was to explore how coronary artery bypass grafting affects quality of life, and how this varies with age, particularly with patients at risk of deterioration.
In a ...retrospective, multicentre cohort study, patients with isolated coronary artery bypass grafting and electively operated between January 2011 and January 2015 with pre- and postoperative quality-of-life data were included. Patients were classified into 3 age groups: <65, 65-79 and ≥80 years. Quality of life was measured up to 1-year follow-up using the Short Form-12 or the Short Form-36 health survey. A multivariable, linear regression analysis, with an adjustment for confounders, was used to evaluate the association between age and quality of life.
A total of 2606 patients were included in this study. Upon one-year of follow-up, the mean physical health of patients increased from 54 at baseline to 68, and mental health increased from 60 to 67. We observed decreased mental health in 20% of patients aged <65 years, 20% of patients aged 65-79 years and 29% of patients aged ≥80 years (P = 0.039). In this study, age was not associated with a lower physical or mental component score (P = 0.054 and P = 0.13, respectively). Independent risk factors for a decrease in quality of life consist of a better physical and mental score at baseline (P < 0.001) and a reduced left ventricular function (P < 0.001).
Most patients experience a relevant increase in physical and mental quality of life, but a proportion of patients aged ≥80 years undergo significant deterioration in mental health.
The thermal behavior of metoprolol tartrate (2
R
,3
R
)-2,3-dihydroxybutanedioic acid; 1-4-(2-methoxyethyl)phenoxy-3-(propan-2-ylamino)propan-2-ol, a
β
-adrenergic blocker used in the treatment of ...hypertension and other cardiac problems, was investigated using thermogravimetry (TG), differential thermal analysis (DTA), differential scanning calorimetry (DSC), evolved gas analysis by thermogravimetry coupled with infrared spectroscopy (TG-FTIR), hot-stage microscopy and high-performance liquid chromatography coupled with mass spectrometry (HPLC–MS). TG/DTA and TG-FTIR showed that metoprolol melts at 123.3 °C and 124.2 (N
2
and air, respectively) and started decomposing at 155.4 °C (in N
2
) and 152.6 °C (in air) in two steps of mass loss with the release of carbon monoxide, carbon dioxide and water from the decomposition of tartaric acid in the first step and carbon dioxide, ammonia, dimethyl ether, 1-ethoxy-4-methylbenzene and isopropyl isocyanate in the second step. DSC curves demonstrated that the sample melts at 121.7 °C, quite similar to that observed in DTA, with no recrystallization on cooling. Hot-stage microscopy allowed seeing the melting process of metoprolol, which appeared in a temperature similar to that observed in the other thermal analytical techniques. HPLC–MS analysis permitted characterizing some solid intermediates of drug degradation, indicating that probably there is an intermolecular interaction between the molecules during the decomposition, creating larger molecules. Based on these results, a tentative mechanism for metoprolol tartrate thermal decomposition was proposed.
Contained rupture of the ascending aorta is a rare condition, but the severity of this complication enforces strict guidelines for its prevention and a prompt diagnosis, once already occurred.
A ...66-year-old man with a history of type 2 diabetes, longstanding aortic valve stenosis and aortic root aneurysm of 47 mm was hospital admitted for elective surgery. A Bentall-De Bono procedure was performed in order to replace the stenotic bicuspid aortic valve and exclude the dilated portion of the aortic wall. Intraoperatively, a discontinuity of the aortic wall, just above the aortic annulus, at the non-coronary sinus of Valsalva was incidentally observed. The aortic wall discontinuity was none other than a contained aortic rupture. The preoperative CT-scan images were afterwards analyzed by the radiologist, in order to identify the contained aortic rupture. Indeed a false aneurysm of the non-coronary sinus of Valsalva of a maximum diameter of 15 mm was detected, thanks to a 3D reconstruction.
The diagnosis of contained aortic rupture is certainly demanding, particularly in absence of signs or symptoms of rupture in a chamber of the heart or in the pericardium. Although this case represents a consensus of experts' opinion, the recognition of these specific cases in which the risk of dissection, rupture or death is at its highest, would allow to operate at the appropriate time, improving the outcomes.
Abstract Background Complete cytoreductive surgery (CCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is on the verge of becoming the gold standard treatment for selected patients ...presenting peritoneal metastases (PM) of colorectal origin. PM is scored with the peritoneal cancer index (PCI), which is the main prognostic factor. However, small bowel (SB) involvement could exert an independent prognostic impact. Aim To define an adequate cut-off for the PCI and to appraise whether SB involvement exerts an impact on this cut-off. Patients and methods Patients ( n = 139) treated with CCRS plus HIPEC were prospectively verified and retrospectively analyzed. One hundred presented with SB involvement of different extents and at different locations. Results All the patients with a PCI ≥15 exhibited SB involvement. Five-year overall survival was 48% when the PCI was <15 vs 12% when it was ≥15 ( p < 0.0001. The multivariate analysis retained two prognostic factors: PCI ≥15 ( p = 0.02, HR = 1.8), and the involvement of area 12 (lower ileum) ( p = 0.001, HR = 3.1). When area 12 was invaded, it significantly worsened the prognosis: 5-year overall survival of patients with a PCI <15 and area 12 involved was 15%, close to that of patients with a PCI ≥15 (12%) and far lower than that of patients with a PCI <15 and no area 12 involvement (70%). Conclusion A PCI greater than 15 appears to be a relative contraindication for treatment of colorectal PM with CCRS + HIPEC. Involvement of the lower ileum is also a negative prognostic factor to be taken into consideration.
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