Portal Pressure Regulation following Kupffer Cell Activation: Control of Prostaglandin Production by Heme Oxygenases

Background: Portal pressure (PP) results from the interplay ofvasoconstrictors and vasodilators. Recently, we have shown that Kupffercell (KC) activation increases PP. Aims: The role of the vasodilatingcompounds nitric oxide (NO) and carbon monoxide (CO) was studied. Thehypothesis of the present study was that these vasodilators counteractthe PP increase following KC activation. Methods: Livers of ratsweighing 180-200 g were isolated and perfused. KCs were activated byzymosan A (cell wall particles from yeast; 150 mu g/ml). The effects ofNO and guanylate cyclase (GC) were evaluated by the NO synthaseinhibitor N-G-nitro-L-arginine methylester (L-NAME; 0.3 m M, and the GCinhibitor 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one(NS-2028, 1.0 mu M); the effects of the heme oxygenase (HO) derivedcompound CO were evaluated by direct administration of CO or inhibitionof HO by zinc protoporphyrin IX (ZnPP IX, 1.0 mu M). Results: Inisolated perfused rat livers, administration of L-NAME or NS-2028further raised PP increase following KC activation. This effect could bereduced by the cGMP analogue 8-Br-cGMP. Inhibition of HO caused markedamplification of PP increase in zymosan-treated organs. CO preventedthis PP increase cGMP independently. Interestingly, KC activation andsimultaneous inhibition of HO augmented the production of prostaglandinsD-2 and F-2 alpha and of thromboxane A(2). Accordingly, indomethacinblunted the increase of PP in zymosan/ZnPP-treated livers. Conclusions:NO restricts the initial PP increase after KC activation by GC-mediatedcGMP. CO from heme degradation limits the increase of PP after KCactivation eicosanoid dependently, but cGMP independently

Perceived physical fatigability predicts all-cause mortality in older adults

BACKGROUND: Perceived physical fatigability is highly prevalent in older adults and associated with mobility decline and other health consequences. We examined the prognostic value of perceived physical fatigability as an independent predictor of risk of death among older adults. METHODS: Participants (N = 2 906), mean age 73.5 [SD, 10.4] years, 54.2% women, 99.7% white enrolled in the Long Life Family Study, were assessed at Visit 2 (2014-2017) with 2.7 [SD, 1.0] years follow-up. The Pittsburgh Fatigability Scale (PFS), a 10-item, self-administered validated questionnaire (score range 0-50, higher = greater fatigability) measured perceived physical fatigability at Visit 2. Deaths post-Visit 2 through December 31, 2019 were identified by family members notifying field centers, reporting during another family member\u27s annual phone follow-up, an obituary, or Civil Registration System (Denmark). We censored all other participants at their last contact. Cox proportional hazard models predicted mortality by fatigability severity, adjusted for family relatedness and other covariates. RESULTS: Age-adjusted PFS Physical scores were higher for those who died (19.1 [SE, 0.8]) compared with alive (12.2, [SE, 0.4]) overall, as well as across age strata (p \u3c .001), except for those 60-69 years (p = .79). Participants with the most severe fatigability (PFS Physical scores ≥ 25) were over twice as likely to die (hazard ratio, 2.33 [95% CI, 1.65-3.28]) compared with those who had less severe fatigability (PFS Physical scores \u3c 25) after adjustment. CONCLUSIONS: Our work underscores the utility of the PFS as a novel patient-reported prognostic indicator of phenotypic aging that captures both overt and underlying disease burden that predicts death

Thermal Conversion of Guanylurea Dicyanamide into Graphitic Carbon Nitride via Prototype CNx Precursors

Guanylurea dicyanamide, [(H2N)C(-O)NHC(NH2)2][N(CN)2], has been synthesized by ion exchange reaction in aqueous solution and structurally characterized by single-crystal X-ray diffraction (C2/c, a = 2249.0(5) pm, b = 483.9(1) pm, c = 1382.4(3) pm, β = 99.49(3)°, V = 1483.8(5) × 106 pm3, T = 130 K). The thermal behavior of the molecular salt has been studied by thermal analysis, temperature-programmed X-ray powder diffraction, FTIR spectroscopy, and mass spectrometry between room temperature and 823 K. The results were interpreted on a molecular level in terms of a sequence of thermally induced addition, cyclization, and elimination reactions. As a consequence, melamine (2,4,6-triamino-1,3,5-triazine) is formed with concomitant loss of HNCO. Further condensation of melamine yields the prototypic CNx precursor melem (2,6,10-triamino-s-heptazine, C6N7(NH2)3), which alongside varying amounts of directly formed CNxHy material transforms into layered CNxHy phases without significant integration of oxygen into the core framework owing to the evaporation of HNCO. Thus, further evidence can be added to melamine and its condensation product melem acting as “key intermediates” in the synthetic pathway toward graphitic CNxHy materials, whose exact constitution is still a point at issue. Due to the characteristic formation process and hydrogen content a close relationship with the polymer melon is evident. In particular, the thermal transformation of guanylurea dicyanamide clearly demonstrates that the formation of volatile compounds such as HNCO during thermal decomposition may render a large variety of previously not considered molecular compounds suitable CNx precursors despite the presence of oxygen in the starting material

Thermal Diffusion and Quench Propagation in YBCO Pancake Coils Wound with ZnO-and Mylar Insulations

The thermal diffusion properties of several different kinds of YBCO insulations and the quench properties of pancake coils made using these insulations were studied. Insulations investigated include Nomex, Kapton, and Mylar, as well as insulations based on ZnO, Zn2GeO4, and ZnO-Cu. Initially, short stacks of YBCO conductors with interlayer insulation, epoxy, and a central heater strip were made and later measured for thermal conductivity in liquid nitrogen. Subsequently, three different pancake coils were made. The first two were smaller, each using one meter total of YBCO tape present as four turns around a G-10 former. One of these smaller coils used Mylar insulation co-wound with the YBCO tape, the other used YBCO tape onto which ZnO based insulation had been deposited. One larger coil was made which used 12 total meters of ZnO-insulated tape and had 45 turns. The results for all short sample and coil thermal conductivities were ~1-3 Wm-1K-1. Finally, quench propagation velocity measurements were performed on the coils (77 K, self field) by applying a DC current and then using a heater pulse to initiate a quench. Normal zone propagation velocity (NZP) values were obtained for the coils both in the radial direction and in the azimuthal direction. Radial NZP values (0.05-0.7 mm/s) were two orders of magnitude lower than axial values (~14-17 mm/s). Nevertheless, the quenches were generally seen to propagate radially within the coils, in the sense that any given layer in the coil is driven normal by the layer underneath it.Comment: 58 pages, 5 tables, 16 fig

Conventional methods fail to measure cp(omega) of glass-forming liquids

The specific heat is frequency dependent in highly viscous liquids. By solving the full one-dimensional thermo-viscoelastic problem analytically it is shown that, because of thermal expansion and the fact that mechanical stresses relax on the same time scale as the enthalpy relaxes, the plane thermal-wave method does not measure the isobaric frequency-dependent specific heat c_p(omega). This method rather measures a "longitudinal" frequency-dependent specific heat, a quantity defined and detailed here that is in-between c_p(omega) and c_v(omega). This result means that no wide-frequency measurements of c_p(omega) on liquids approaching the calorimetric glass transition exist. We briefly discuss consequences for experiment

Hearing treatment for reducing cognitive decline: Design and methods of the Aging and Cognitive Health Evaluation in Elders randomized controlled trial

IntroductionHearing impairment is highly prevalent and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders study is a multicenter randomized controlled trial to determine efficacy of hearing treatment in reducing cognitive decline in older adults. Clinicaltrials.gov Identifier: NCT03243422.MethodsEight hundred fifty participants without dementia aged 70 to 84 years with mild-to-moderate hearing impairment recruited from four United States field sites and randomized 1:1 to a best-practices hearing intervention or health education control. Primary study outcome is 3-year change in global cognitive function. Secondary outcomes include domain-specific cognitive decline, incident dementia, brain structural changes on magnetic resonance imaging, health-related quality of life, physical and social function, and physical activity.ResultsTrial enrollment began January 4, 2018 and is ongoing.DiscussionWhen completed in 2022, Aging and Cognitive Health Evaluation in Elders study should provide definitive evidence of the effect of hearing treatment versus education control on cognitive decline in community-dwelling older adults with mild-to-moderate hearing impairment

A New Crocodylian from the Late Maastrichtian of Spain: Implications for the Initial Radiation of Crocodyloids

The earliest crocodylians are known primarily from the Late Cretaceous of North America and Europe. The representatives of Gavialoidea and Alligatoroidea are known in the Late Cretaceous of both continents, yet the biogeographic origins of Crocodyloidea are poorly understood. Up to now, only one representative of this clade has been known from the Late Cretaceous, the basal crocodyloid Prodiplocynodon from the Maastrichtian of North America.The fossil studied is a skull collected from sandstones in the lower part of the Tremp Formation, in Chron C30n, dated at -67.6 to 65.5 Ma (late Maastrichtian), in Arén (Huesca, Spain). It is located in a continuous section that contains the K/P boundary, in which the dinosaur faunas closest to the K/P boundary in Europe have been described, including Arenysaurus ardevoli and Blasisaurus canudoi. Phylogenetic analysis places the new taxon, Arenysuchus gascabadiolorum, at the base of Crocodyloidea.The new taxon is the oldest crocodyloid representative in Eurasia. Crocodyloidea had previously only been known from the Palaeogene onwards in this part of Laurasia. Phylogenetically, Arenysuchus gascabadiolorum is situated at the base of the first radiation of crocodyloids that occurred in the late Maastrichtian, shedding light on this part of the cladogram. The presence of basal crocodyloids at the end of the Cretaceous both in North America and Europe provides new evidence of the faunal exchange via the Thulean Land Bridge during the Maastrichtian

Recruitment and baseline data of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study: A randomized trial of a hearing loss intervention for reducing cognitive decline

INTRODUCTIONHearing loss is highly prevalent among older adults and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a multicenter randomized control trial (partially nested within the infrastructure of an observational cohort study, the Atherosclerosis Risk in Communities [ARIC] study) to determine the efficacy of best-practice hearing treatment to reduce cognitive decline over 3 years. The goal of this paper is to describe the recruitment process and baseline results.METHODSMultiple strategies were used to recruit community-dwelling 70–84-year-old participants with adult-onset hearing loss who were free of substantial cognitive impairment from the parent ARIC study and de novo from the surrounding communities into the trial. Participants completed telephone screening, an in-person hearing, vision, and cognitive screening, and a comprehensive hearing assessment to determine eligibility.RESULTSOver a 24-month period, 3004 telephone screenings resulted in 2344 in-person hearing, vision, and cognition screenings and 1294 comprehensive hearing screenings. Among 1102 eligible, 977 were randomized into the trial (median age = 76.4 years; 53.5% female; 87.8% White; 53.3% held a Bachelor's degree or higher). Participants recruited through the ARIC study were recruited much earlier and were less likely to report hearing loss interfered with their quality of life relative to participants recruited de novo from the community. Minor differences in baseline hearing or health characteristics were found by recruitment route (i.e., ARIC study or de novo) and by study site.DISCUSSIONThe ACHIEVE study successfully completed enrollment over 2 years that met originally projected rates of recruitment. Substantial operational and scientific efficiencies during study startup were achieved through embedding this trial within the infrastructure of a longstanding and well-established observational study.HighlightsThe ACHIEVE study tests the effect of hearing intervention on cognitive decline.The study is partially nested within an existing cohort study.Over 2 years, 977 participants recruited and enrolled.Eligibility assessed by telephone and in-person for hearing, vision, and cognitive screening.The ACHIEVE study findings will have significant public health implications