Conformational change of the catalytic subunit of glucose-6-phosphatase in rat liver during the fetal-to-neonatal transition

The glucose-6-phosphatase system was investigated in fetal rat liver microsomal vesicles. Several observations indicate that the orientation of the catalytic subunit is different in the fetal liver in comparison with the adult form: (i) the phosphohydrolase activity was not latent using glucose- 6-phosphate as substrate, and in the case of other phosphoesters it was less latent; (ii) the intravesicular accumulation of glucose upon glucose-6- phosphate hydrolysis was lower; (iii) the size of the intravesicular glucose- 6-phosphate pool was independent of the glucose-6-phosphatase activities; (iv) antibody against the loop containing the proposed catalytic site of the enzyme inhibited the phosphohydrolase activity in fetal but not in adult rat liver microsomes. Glucose-6-phosphate, phosphate, and glucose uptake could be detected by both light scattering and/or rapid filtration method in fetal liver microsomes; however, the intravesicular glucose-6-phosphate and glucose accessible spaces were proportionally smaller than in adult rat liver microsomes. These data demonstrate that the components of the glucose-6- phosphatase system are already present, although to a lower extent, in fetal liver, but they are functionally uncoupled by the extravesicular orientation of the catalytic subunit

Coronary artery bypass grafting: Part 2—optimizing outcomes and future prospects

Since first introduced in the mid-1960s, coronary artery bypass grafting (CABG) has become the standard of care for patients with coronary artery disease. Surprisingly, the fundamental surgical technique itself did not change much over time. Nevertheless, outcomes after CABG have dramatically improved over the first 50 years. Randomized trials comparing percutaneous coronary intervention (PCI) to CABG have shown converging outcomes for select patient populations, providing more evidence for wider use of PCI. It is increasingly important to focus on the optimization of the short- and long-term outcomes of CABG and to reduce the level of invasiveness of this procedure. This review provides an overview on how new techniques and widespread consideration of evolving strategies have the potential to optimize outcomes after CABG. Such developments include off-pump CABG, clampless/anaortic CABG, minimally invasive CABG with or without extending to hybrid procedures, arterial revascularization, endoscopic vein harvesting, intraprocedural epiaortic scanning, graft flow assessment, and improved secondary prevention measures. In addition, this review represents a framework for future studies by summarizing the areas that need more rigorous clinical (randomized) evaluatio

Q134R: Small Chemical Compound with NFAT Inhibitory Properties Improves Behavioral Performance and Synapse Function in Mouse Models of Amyloid Pathology

Inhibition of the protein phosphatase calcineurin (CN) ameliorates pathophysiologic and cognitive changes in aging rodents and mice with aging-related Alzheimer\u27s disease (AD)-like pathology. However, concerns over adverse effects have slowed the transition of common CN-inhibiting drugs to the clinic for the treatment of AD and AD-related disorders. Targeting substrates of CN, like the nuclear factor of activated T cells (NFATs), has been suggested as an alternative, safer approach to CN inhibitors. However, small chemical inhibitors of NFATs have only rarely been described. Here, we investigate a newly developed neuroprotective hydroxyquinoline derivative (Q134R) that suppresses NFAT signaling, without inhibiting CN activity. Q134R partially inhibited NFAT activity in primary rat astrocytes, but did not prevent CN-mediated dephosphorylation of a non-NFAT target, either in vivo, or in vitro. Acute (≤1 week) oral delivery of Q134R to APP/PS1 (12 months old) or wild-type mice (3–4 months old) infused with oligomeric Aβ peptides led to improved Y maze performance. Chronic (≥3 months) oral delivery of Q134R appeared to be safe, and, in fact, promoted survival in wild-type (WT) mice when given for many months beyond middle age. Finally, chronic delivery of Q134R to APP/PS1 mice during the early stages of amyloid pathology (i.e., between 6 and 9 months) tended to reduce signs of glial reactivity, prevented the upregulation of astrocytic NFAT4, and ameliorated deficits in synaptic strength and plasticity, without noticeably altering parenchymal Aβ plaque pathology. The results suggest that Q134R is a promising drug for treating AD and aging-related disorders

The impact of avoiding cardiopulmonary by-pass during coronary artery bypass surgery in elderly patients: the Danish On-pump Off-pump Randomisation Study (DOORS)

<p>Abstract</p> <p>Background</p> <p>Coronary Artery Bypass Graft operation for ischemic heart disease provides improved quality of life and, in some patients, prolonged survival. Concern has, however, been raised about complications that may be related to the use of cardiopulmonary by-pass (CPB) and aortic cross-clamping. It has been hypothesized that when coronary artery by-pass grafting is performed without the use of CPB, the rate of serious complications is reduced.</p> <p>Methods/Design</p> <p>The trial is designed as an open, randomized, controlled, clinical trial with blinded assessment of end-points. Patients at or above 70 years of age, referred for surgical myocardial revascularisation, are included and randomised to receive coronary artery by-pass grafting either with or without the use of CPB and aortic cross-clamping. Follow-up is performed by clinical, biochemical, electrocardiographic, and angiographic data that are evaluated by independent committees that are blinded with respect to the result of the randomisation. End points include mortality, stroke, myocardial infarction, graft patency, quality of life, and cost-effectiveness. The trial is performed in four different Danish, cardiac surgery centres.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00123981</p

Bilateral versus single internal-thoracic-artery grafts at 10 years

BACKGROUND Multiple arterial grafts may result in longer survival than single arterial grafts after coronary-artery bypass grafting (CABG) surgery. We evaluated the use of bilateral internal-thoracic-artery grafts for CABG. METHODS We randomly assigned patients scheduled for CABG to undergo bilateral or single internal-thoracic-artery grafting. Additional arterial or vein grafts were used as indicated. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. RESULTS A total of 1548 patients were randomly assigned to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group) and 1554 to undergo single internal-thoracic-artery grafting (the single-graft group). In the bilateral-graft group, 13.9% of the patients received only a single internal-thoracic-artery graft, and in the single-graft group, 21.8% of the patients also received a radial-artery graft. Vital status was not known for 2.3% of the patients at 10 years. In the intention-to-treat analysis at 10 years, there were 315 deaths (20.3% of the patients) in the bilateral-graft group and 329 deaths (21.2%) in the single-graft group (hazard ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.12; P=0.62). Regarding the composite outcome of death, myocardial infarction, or stroke, there were 385 patients (24.9%) with an event in the bilateral-graft group and 425 patients (27.3%) with an event in the single-graft group (hazard ratio, 0.90; 95% CI, 0.79 to 1.03). CONCLUSIONS Among patients who were scheduled for CABG and had been randomly assigned to undergo bilateral or single internal-thoracic-artery grafting, there was no significant between-group difference in the rate of death from any cause at 10 years in the intention-to-treat analysis. Further studies are needed to determine whether multiple arterial grafts provide better outcomes than a single internal-thoracic-artery graft. (Funded by the British Heath Foundation and others; Current Controlled Trials number, ISRCTN46552265.

Advanced glass reinforced epoxy filled fly ash based geopolymer filler: preparation and characterization on piping materials

Abstract:The preparation and characterization of glass reinforced epoxy filled with different weight percentage of geopolymers filler attained from fly ashand epoxy resins are reported limited of study. Recent glass reinforced epoxy pipe are reported exhibits relatively low mechanical properties, which limit their usage in structural applications and in oil and gas industrial. Thus, this restriction could be overcome through the formation of the addition of geopolymer fillers to improve their strength and toughness. The glass fiber was impregnated with different weight percentage and different molarity of fly ash-based geopolymer and epoxy hardener resin. Composite samples were made manually by filament winding technique and cured under room temperature. The sections perpendicular to the fibers and surfaces of the composites were analyzed by means of scanning electron microscope to estimate the adhesion between geopolymer matrices and fiber reinforcement. Relatively, wide range of geopolymer weight percentage from 10 % to 30 % at which can obtain high compressive properties, maximal values of compressive strength is 94.64 MPa and compressive modulus 2373.58 MPa for the sample with 30 % weight percentage of filler loading. These new composites materials show expressively enhanced mechanical properties if matched to straight glass reinforced epoxy pipe without any geopolymer filler. The positive mixture of synthetic method with the use of industrial by-products has acceptable fabricating novel low cost aluminosilicate binders, thanks to their suitable bondin contradiction of materials frequently used in structural application, could be used within the field of oil and gas industr

Earliest Galaxies in the JADES Origins Field : Luminosity Function and Cosmic Star Formation Rate Density 300 Myr after the Big Bang

We characterize the earliest galaxy population in the JADES Origins Field, the deepest imaging field observed with JWST. We make use of ancillary Hubble Space Telescope optical images (five filters spanning 0.4-0.9 μm) and novel JWST images with 14 filters spanning 0.8−5 μm, including seven medium-band filters, and reaching total exposure times of up to 46 hr per filter. We combine all our data at &gt;2.3 μm to construct an ultradeep image, reaching as deep as ≈31.4 AB mag in the stack and 30.3-31.0 AB mag (5σ, r = 0.′′1 circular aperture) in individual filters. We measure photometric redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts z = 11.5−15. These objects show compact half-light radii of R 1/2 ∼ 50−200 pc, stellar masses of M ⋆ ∼ 107−108 M ☉, and star formation rates ∼ 0.1−1 M ☉ yr−1. Our search finds no candidates at 15 &lt; z &lt; 20, placing upper limits at these redshifts. We develop a forward-modeling approach to infer the properties of the evolving luminosity function without binning in redshift or luminosity that marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the impact of nondetections. We find a z = 12 luminosity function in good agreement with prior results, and that the luminosity function normalization and UV luminosity density decline by a factor of ∼2.5 from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical models for evolution of the dark matter halo mass function

QPRT: a potential marker for follicular thyroid carcinoma including minimal invasive variant; a gene expression, RNA and immunohistochemical study

Background The differential diagnosis between follicular thyroid adenoma and minimal invasive follicular thyroid carcinoma is often difficult for several reasons. One major aspect is the lack of typical cytological criteria in well differentiated specimens. New marker molecules, shown by poly- or monoclonal antibodies proved helpful. Methods We performed global gene expression analysis of 12 follicular thyroid tumours (4 follicular adenomas, 4 minimal invasive follicular carcinomas and 4 widely invasive follicular carcinomas), followed by immunohistochemical staining of 149 cases. The specificity of the antibody was validated by western blot analysis Results In gene expression analysis QPRT was detected as differently expressed between follicular thyroid adenoma and follicular thyroid carcinoma. QPRT protein could be detected by immunohistochemistry in 65% of follicular thyroid carcinomas including minimal invasive variant and only 22% of follicular adenomas. Conclusion Consequently, QPRT is a potential new marker for the immunohistochemical screening of follicular thyroid nodules