Search

Background Anemia and blood loss occur often in patients with ST‐segment–elevation myocardial infarction (STEMI). In‐hospital hemoglobin drop is associated with 1‐year mortality in patients with acute coronary syndrome. However, data on the effect of hemoglobin reduction on myocardial salvage and long‐term outcomes are scarce. We investigated the impact of in‐hospital hemoglobin drop on myocardial salvage and 5‐year mortality in patients with STEMI treated with primary percutaneous coronary intervention. Methods and Results In‐hospital hemoglobin drop was defined as a decrease in hemoglobin levels from admission and nadir hemoglobin values. Patients were categorized as having the following: no drop, minimal drop (

ObjectiveTo determine the relationship between sleep quality and CSF markers of Alzheimer disease (AD) pathology in late midlife.MethodsWe investigated the relationship between sleep quality and CSF AD biomarkers in a cohort enriched for parental history of sporadic AD, the Wisconsin Registry for Alzheimer's Prevention. A total of 101 participants (mean age 62.9 ± 6.2 years, 65.3% female) completed sleep assessments and CSF collection and were cognitively normal. Sleep quality was measured with the Medical Outcomes Study Sleep Scale. CSF was assayed for biomarkers of amyloid metabolism and plaques (β-amyloid 42 [Aβ42]), tau pathology (phosphorylated tau [p-tau] 181), neuronal/axonal degeneration (total tau [t-tau], neurofilament light [NFL]), neuroinflammation/astroglial activation (monocyte chemoattractant protein-1 [MCP-1], chitinase-3-like protein 1 [YKL-40]), and synaptic dysfunction/degeneration (neurogranin). To adjust for individual differences in total amyloid production, Aβ42 was expressed relative to Aβ40. To assess cumulative pathology, CSF biomarkers were expressed in ratio to Aβ42. Relationships among sleep scores and CSF biomarkers were assessed with multiple regression, controlling for age, sex, time between sleep and CSF measurements, and CSF assay batch.ResultsWorse subjective sleep quality, more sleep problems, and daytime somnolence were associated with greater AD pathology, indicated by lower CSF Aβ42/Aβ40 and higher t-tau/Aβ42, p-tau/Aβ42, MCP-1/Aβ42, and YKL-40/Aβ42. There were no significant associations between sleep and NFL or neurogranin.ConclusionsSelf-report of poor sleep was associated with greater AD-related pathology in cognitively healthy adults at risk for AD. Effective strategies exist for improving sleep; therefore sleep health may be a tractable target for early intervention to attenuate AD pathogenesis.

ObjectivesTo determine the ability of 11 sildenafil analogues to discriminate between cyclic nucleotide phosphodiesterases (cnPDEs) and to characterise their inhibitory potencies (Ki values) of PDE5A1-dependent guanosine cyclic monophosphate (cGMP) hydrolysis.MethodsSildenafil analogues were identified by virtual ligand screening (VLS) and screened for their ability to inhibit adenosine cyclic monophosphate (cAMP) hydrolysis by PDE1A1, PDE1B1, PDE2A1, PDE3A, PDE10A1 and PDE10A2, and cGMP hydrolysis by PDE5A, PDE6C, PDE9A2 for a low (1 nm) and high concentration (10 μm). Complete IC50 plots for all analogues were performed for PDE5A-dependent cGMP hydrolysis. Docking studies and scoring were made using the ICM molecular modelling software.Key findingsThe analogues in a low concentration showed no or low inhibition of PDE1A1, PDE1B1, PDE2A1, PDE3A, PDE10A1 and PDE10A2. In contrast, PDE5A and PDE6C were markedly inhibited to a similar extent by the analogues in a low concentration, whereas PDE9A2 was much less inhibited. The analogues showed a relative narrow range of Ki values for PDE5A inhibition (1.2-14 nm). The sildenafil molecule was docked in the structure of PDE5A1 co-crystallised with sildenafil. All the analogues had similar binding poses as sildenafil.ConclusionsSildenafil analogues that inhibit cellular cGMP efflux are potent inhibitors of PDE5A and PDE6C.

Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11bDTR mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.

The giant, single-celled organism Stentor coeruleus has a long history as a model system for studying pattern formation and regeneration in single cells. Stentor [1, 2] is a heterotrichous ciliate distantly related to familiar ciliate models, such as Tetrahymena or Paramecium. The primary distinguishing feature of Stentor is its incredible size: a single cell is 1 mm long. Early developmental biologists, including T.H. Morgan [3], were attracted to the system because of its regenerative abilities-if large portions of a cell are surgically removed, the remnant reorganizes into a normal-looking but smaller cell with correct proportionality [2, 3]. These biologists were also drawn to Stentor because it exhibits a rich repertoire of behaviors, including light avoidance, mechanosensitive contraction, food selection, and even the ability to habituate to touch, a simple form of learning usually seen in higher organisms [4]. While early microsurgical approaches demonstrated a startling array of regenerative and morphogenetic processes in this single-celled organism, Stentor was never developed as a molecular model system. We report the sequencing of the Stentor coeruleus macronuclear genome and reveal key features of the genome. First, we find that Stentor uses the standard genetic code, suggesting that ciliate-specific genetic codes arose after Stentor branched from other ciliates. We also discover that ploidy correlates with Stentor's cell size. Finally, in the Stentor genome, we discover the smallest spliceosomal introns reported for any species. The sequenced genome opens the door to molecular analysis of single-cell regeneration in Stentor.

In patients treated with macitentan (Opsumit®, Actelion Pharmaceuticals Ltd., Basel, Switzerland) for pulmonary arterial hypertension (PAH), prevention and/or effective management of treatment-related adverse events may improve adherence. However, management of these adverse events can be challenging and the base of evidence and clinical experience for macitentan is limited. In the absence of evidence, consensus recommendations from physicians experienced in using macitentan to treat PAH may benefit patients and physicians who are using macitentan. Consensus recommendations were developed by a panel of physicians experienced with macitentan and PAH using a modified Delphi process. Over three iterations, panelists developed and refined a series of statements on the use of macitentan in PAH and rated their agreement with each statement on a Likert scale. The panel of 18 physicians participated and developed a total of 118 statements on special populations, add-on therapy, drug-drug interactions, warnings and precautions, hospitalization and functional class, and adverse event management. The resulting consensus recommendations are intended to provide practical guidance on real-world issues in using macitentan to treat patients with PAH.

Introduction: Rewarming from accidental hypothermia is often complicated by hypothermia-induced cardiovascular dysfunction, which could lead to shock. Current guidelines do not recommend any pharmacological treatment at core temperatures below 30°C, due to lack of knowledge. However, previous in vivo studies have shown promising results when using phosphodiesterase 3 (PDE3) inhibitors, which possess the combined effects of supporting cardiac function and alleviating the peripheral vascular resistance through changes in cyclic nucleotide levels. This study therefore aims to investigate whether PDE3 inhibitors milrinone, amrinone, and levosimendan are able to modulate cyclic nucleotide regulation in hypothermic settings.Materials and methods: The effect of PDE3 inhibitors were studied by using recombinant phosphodiesterase enzymes and inverted erythrocyte membranes at six different temperatures—37°C, 34°C, 32°C, 28°C, 24°C, and 20°C- in order to evaluate the degree of enzymatic degradation, as well as measuring cellular efflux of both cAMP and cGMP. The resulting dose-response curves at every temperature were used to calculate IC50 and Ki values.Results: Milrinone IC50 and Ki values for cGMP efflux were significantly lower at 24°C (IC50: 8.62 ± 2.69 µM) and 20°C (IC50: 7.35 ± 3.51 µM), compared to 37°C (IC50: 22.84 ± 1.52 µM). There were no significant changes in IC50 and Ki values for enzymatic breakdown of cAMP and cGMP.Conclusion: Milrinone, amrinone and levosimendan, were all able to suppress enzymatic degradation and inhibit extrusion of cGMP and cAMP below 30°C. Our results show that these drugs have preserved effect on their target molecules during hypothermia, indicating that they could provide an important treatment option for hypothermia-induced cardiac dysfunction.

En los primeros años del siglo XXI, una serie de gobiernos latinoamericanos se alejaron de la adhesión a determinadas visiones sobre el sistema internacional y las relaciones internacionales que habían primado durante la última década del siglo pasado. Esto llevó, en algunos casos, a proyectar discursos de confrontación con Estados Unidos y a la diversificación de sus relaciones con otros Estados no occidentales. Siguiendo las proposiciones del realismo periférico, aquellos que siguieron este accionar deberían haber sido castigados por no alinearse con las prescripciones del principal formador de reglas del sistema internacional. Sin embargo, esto no ocurrió en todos los casos. En el presente artículo se hace un breve análisis de las relaciones bilaterales entre Brasil y Estados Unidos entre 2003 y 2016, contemplando la dimensión discursiva y el accionar del primero frente a la respuesta de Washington en las dimensiones política, económica y militar. Esto permite formular una primera hipótesis en torno a las diferencias entre distintos países periféricos no contempladas por la teoría en su formato original. Se propone incorporar el rol del valor estratégico que algunos de estos representan para las grandes potencias, variable que condiciona las relaciones entre ambos actores.

Bose-Einstein condensation of excitons, in which excitons condense into a single coherent quantum state, known as an exciton condensate, enables frictionless energy transfer, but typically occurs under extreme conditions in highly ordered materials, such as graphene double layers. In contrast, photosynthetic light-harvesting complexes demonstrate extremely efficient transfer of energy in disordered systems under ambient conditions. Here, we establish a link between the two phenomena by investigating the potential for exciton-condensate-like amplification of energy transport in room-temperature light harvesting. Using a model of the Fenna-Matthews-Olson complex and accounting for intrachromophore electron correlation explicitly through the addition of multiple sites to the individual chromophores, we observe amplification of the exciton population in the particle-hole reduced density matrix through an exciton-condensate-like mechanism. The exciton-condensate-like amplification evolves with the dynamics of exciton transfer, and the nature of amplification is influenced by intra- and interchromophore entanglement, as well as the initial excitation model and number of sites per chromophore. Tuning intrachromophore coupling also increases the rate of exciton transfer with a maximum enhancement of nearly 100%. The research provides fundamental connections between exciton condensation and exciton transport in light-harvesting complexes with potential applications for harnessing the exciton-condensate-like mechanism to enhance energy transfer in synthetic systems and create new materials capable of highly efficient energy transfer.

INTRODUCTION: We examined whether the aging suppressor KLOTHO gene's functionally advantageous KL‐VS variant (KL‐VS heterozygosity [KL‐VSHET]) confers resilience against deleterious effects of aging indexed by cerebrospinal fluid (CSF) biomarkers of neuroinflammation (interleukin‐6 [IL‐6], S100 calcium‐binding protein B [S100B], triggering receptor expressed on myeloid cells [sTREM2], chitinase‐3‐like protein 1 [YKL‐40], glial fibrillary acidic protein [GFAP]), neurodegeneration (total α‐synuclein [α‐Syn], neurofilament light chain protein), and synaptic dysfunction (neurogranin [Ng]). METHODS: This Alzheimer disease risk‐enriched cohort consisted of 454 cognitively unimpaired adults (Mage = 61.5 ± 7.75). Covariate‐adjusted multivariate regression examined relationships between age (mean‐split[age ≥ 62]) and CSF biomarkers (Roche/NeuroToolKit), and whether they differed between KL‐VSHET (N = 122) and non‐carriers (KL‐VSNC; N = 332). RESULTS: Older age was associated with a poorer biomarker profile across all analytes (Ps ≤ 0.03). In age‐stratified analyses, KL‐VSNC exhibited this same pattern (Ps ≤ 0.05) which was not significant for IL‐6, S100B, Ng, and α‐Syn (Ps ≥ 0.13) in KL‐VSHET. Although age‐related differences in GFAP, sTREM2, and YKL‐40 were evident for both groups (Ps ≤ 0.01), the effect magnitude was markedly stronger for KL‐VSNC. DISCUSSION: Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults were attenuated in KL‐VSHET. Highlights: Older age was associated with poorer profiles across all cerebrospinal fluid biomarkers of neuroinflammation, neurodegeneration, and synaptic dysfunction.KLOTHO KL‐VS non‐carriers exhibit this same pattern, which is does not significantly differ between younger and older KL‐VS heterozygotes for interleukin‐6, S100 calcium‐binding protein B, neurogranin, and total α‐synuclein.Although age‐related differences in glial fibrillary acidic protein, triggering receptor expressed on myeloid cells, and chitinase‐3‐like protein 1 are evident for both KL‐VS groups, the magnitude of the effect is markedly stronger for KL‐VS non‐carriers.Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults are attenuated in KL‐VS heterozygotes. [ABSTRACT FROM AUTHOR]

Objective: Saugeye (Sauger Sander canadensis × Walleye S. vitreus) have been introduced in reservoirs for several purposes, including as a top‐down control to combat stunting in crappie Pomoxis spp. populations. However, no comprehensive diet evaluation has been completed in southern reservoirs. Our objectives were to assess variability in saugeye diet compositions, explore factors influencing crappie presence in saugeye diets, and investigate trends in prey size to inform management strategies regarding predatory control of crappie populations. Methods: We collected 2638 saugeye diets from six Oklahoma reservoirs. We used permutational multivariate analysis of variance to test differences in diet compositions among saugeye lengths, study reservoirs, and seasons, and we used logistic regression models to correlate the presence of crappie in diets with saugeye size, season, crappie abundance, productivity, and turbidity. Finally, we used bivariate plots of diet indices and quantile regression to explore trends in prey importance and prey size relative to saugeye size. Result: Saugeye diet compositions were best explained by saugeye size, followed by study reservoir and season. Saugeye exhibited an ontogenetic shift from Inland Silverside Menidia beryllina to shad Dorosoma spp., and crappie were eaten infrequently in comparison. The presence of crappie prey in diets was most correlated with saugeye size (primarily large saugeye), followed by higher crappie abundance, lower reservoir productivity, and season (highest in fall). Saugeye consumed larger prey than most piscivores relative to predator size. Conclusion: Our results indicated that dominant prey of saugeye transitioned from smaller‐bodied fishes to larger shad as they grew when both prey types were available, which may have implications for growth and recruitment. Ultimately, the low and variable use of crappie prey may lead to inconsistent predatory effects on crappie populations, and large saugeye may exert greater top‐down pressure on crappie in lakes with lower productivity or higher crappie abundance. Impact statementDominant prey type of saugeye in Oklahoma reservoirs transitioned from Inland Silverside to Gizzard Shad as they grew, and crappie were eaten infrequently in comparison. Large saugeye may exert greater top‐down pressure on crappie populations in lakes with lower productivity or higher crappie abundance. [ABSTRACT FROM AUTHOR]

Measurement(s) muscle electrophysiology trait Technology Type(s) electromyography • multi-electrode array system • strain gauges Factor Type(s) isometric hand gesture • electromyography Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13625828

La agroindustria genera una gran variedad de alimentos de alto valor nutricional para la ganadería; estos son cada más utilizados por varios beneficios, por ejemplo, no genera competencia con el consumidor humano, genera menores costos y reducción del impacto ambiental de los residuos. El fluten feed (GF) es uno de estos subproductos derivado de la molienda húmeda de maíz con propiedades nutricionales que cumplen con varios de los requerimientos básicos de alimentación bovina, aunque sus características organolépticas pueden limitar su consumo. El objetivo de este trabajo fue proveer mayor comprensión de las interacciones de diferentes inclusiones de GF con los microorganismos ruminales a través de mediciones in situ de gases de fermentación, y cómo este proceso puede ser modulado a través de parámetros químicos de la dieta. Las comparaciones realizadas entre la interacción de inclusión de GF y la concentración de gases entéricos fueron altamente significativa (p

Objective: To evaluate the impact of severe tricuspid valve insufficiency (TVI) at the time of left ventricular assist device (LVAD) implantation on the hemodynamic and LVAD parameters in an acute ovine model. Methods: Stable heart failure (HF) was induced in 10 ovines through the application of 3 ± 1 coronary ligations. Once stable HF was obtained (after 15 ± 5 days), the animals were supported with an LVAD. Hemodynamic data and pump parameters were obtained and compared in 2 settings; first with LVAD in place after weaning from the cardiopulmonary bypass machine (no TVI condition) and second following the induction of severe TVI through resection of the tricuspid valve (TVI condition). Results: There were no statistically significant differences in the hemodynamic and pump parameters between TVI condition and no TVI conditions except for lower cardiac output in the TVI condition (2 [1.38-2.8] L/min vs 3.2 [1.55-3.7] L/min, P = .027) and the expected greater central venous pressure in the TVI condition (26 [24-31] mm Hg vs 15 [13-25] mm Hg, P = .020). A median pump flow of 2.8 (2.45-3.75) L/min versus 2.9 (2.75-3.8) L/min in the TVI condition and no TVI condition was documented (P = .160). Conclusions: Results from this acute animal study suggest that severe TVI in HF with preserved right ventricular function does not have significant impact on the LVAD pump parameters. The observed reduction in cardiac output may warrant further investigations, especially under loading conditions.

Microgrids are a rapidly evolving and increasingly common form of local power generation used to serve the needs of both rural and urban communities. In this paper, we present a methodology to evaluate the evolution of the sustainability of stand-alone microgrids projects. The proposed methodology considers a composite sustainability index (CSI) that includes both positive and negative impacts of the operation of the microgrid in a given community. The CSI is constructed along environmental, social, economic and technical dimensions of the microgrid. The sub-indexes of each dimension are aggregated into the CSI via a set of adaptive weighting factors, which indicate the relative importance of the corresponding dimension in the sustainability goals. The proposed methodology aims to be a support instrument for policy makers especially when defining sound corrective measures to guarantee the sustainability of small, isolated microgrid projects. To validate the performance of the proposed methodology, a microgrid installed in the northern part of Chile (Huatacondo) has been used as a benchmarking project..

This paper presents results from using an asynchronous Web-based discussion forum coupled with an integrated student peer rating system as one component of an introductory Information Systems (IS) course with high enrollment (e.g. a class with over 100 students). There are two major issues with the typical introductory IS course: it covers too many topics, and it is difficult to engage students in active learning in a classroom environment due to large class sizes. To address these issues, an open source discussion forum was modified and used for topical discussion outside of the classroom. Students were allowed to participate in a discussion about topics of their choice and were encouraged to rate their peers' contribution in forum. Overall, students evaluated the online forum discussion positively and provided suggestions for improvement.

This work documents and evaluates the tropospheric gas-phase chemical mechanism MOGUNTIA in the three-dimensional chemistry transport model TM5-MP. Compared to the modified CB05 (mCB05) chemical mechanism previously used in the model, MOGUNTIA includes a detailed representation of the light hydrocarbons (C1–C4) and isoprene, along with a simplified chemistry representation of terpenes and aromatics. Another feature implemented in TM5-MP for this work is the use of the Rosenbrock solver in the chemistry code, which can replace the classical Euler backward integration method of the model. Global budgets of ozone (O3), carbon monoxide (CO), hydroxyl radicals (OH), nitrogen oxides (NOx), and volatile organic compounds (VOCs) are analyzed, and their mixing ratios are compared with a series of surface, aircraft, and satellite observations for the year 2006. Both mechanisms appear to be able to satisfactorily represent observed mixing ratios of important trace gases, with the MOGUNTIA chemistry configuration yielding lower biases than mCB05 compared to measurements in most of the cases. However, the two chemical mechanisms fail to reproduce the observed mixing ratios of light VOCs, indicating insufficient primary emission source strengths, oxidation that is too fast, and/or a low bias in the secondary contribution to C2–C3 organics via VOC atmospheric oxidation. Relative computational memory and time requirements of the different model configurations are also compared and discussed. Overall, the MOGUNTIA scheme simulates a large suite of oxygenated VOCs that are observed in the atmosphere at significant levels. This significantly expands the possible applications of TM5-MP.

A new global high-resolution coupled climate model, EC-Earth3P-HR has been developed by the EC-Earth consortium, with a resolution of approximately 40 km for the atmosphere and 0.25∘ for the ocean, alongside with a standard-resolution version of the model, EC-Earth3P (80 km atmosphere, 1.0∘ ocean). The model forcing and simulations follow the High Resolution Model Intercomparison Project (HighResMIP) protocol. According to this protocol, all simulations are made with both high and standard resolutions. The model has been optimized with respect to scalability, performance, data storage and post-processing. In accordance with the HighResMIP protocol, no specific tuning for the high-resolution version has been applied. Increasing horizontal resolution does not result in a general reduction of biases and overall improvement of the variability, and deteriorating impacts can be detected for specific regions and phenomena such as some Euro-Atlantic weather regimes, whereas others such as the El Niño–Southern Oscillation show a clear improvement in their spatial structure. The omission of specific tuning might be responsible for this. The shortness of the spin-up, as prescribed by the HighResMIP protocol, prevented the model from reaching equilibrium. The trend in the control and historical simulations, however, appeared to be similar, resulting in a warming trend, obtained by subtracting the control from the historical simulation, close to the observational one.

We introduce the open-source tool noisi for the forward and inverse modeling of ambient seismic cross-correlations with spatially varying source spectra. It utilizes pre-computed databases of Green's functions to represent seismic wave propagation between ambient seismic sources and seismic receivers, which can be obtained from existing repositories or imported from the output of wave propagation solvers. The tool was built with the aim of studying ambient seismic sources while accounting for realistic wave propagation effects. Furthermore, it may be used to guide the interpretation of ambient seismic auto- and cross-correlations, which have become preeminent seismological observables, in light of nonuniform ambient seismic sources. Written in the Python language, it is accessible for both usage and further development and efficient enough to conduct ambient seismic source inversions for realistic scenarios. Here, we introduce the concept and implementation of the tool, compare its model output to cross-correlations computed with SPECFEM3D_globe, and demonstrate its capabilities on selected use cases: a comparison of observed cross-correlations of the Earth's hum to a forward model based on hum sources from oceanographic models and a synthetic noise source inversion using full waveforms and signal energy asymmetry.

It is important to understand how future environmental policies will impact both climate change and air pollution. Although targeting near-term climate forcers (NTCFs), defined here as aerosols, tropospheric ozone, and precursor gases, should improve air quality, NTCF reductions will also impact climate. Prior assessments of the impact of NTCF mitigation on air quality and climate have been limited. This is related to the idealized nature of some prior studies, simplified treatment of aerosols and chemically reactive gases, as well as a lack of a sufficiently large number of models to quantify model diversity and robust responses. Here, we quantify the 2015–2055 climate and air quality effects of non-methane NTCFs using nine state-of-the-art chemistry–climate model simulations conducted for the Aerosol and Chemistry Model Intercomparison Project (AerChemMIP). Simulations are driven by two future scenarios featuring similar increases in greenhouse gases (GHGs) but with “weak” (SSP3-7.0) versus “strong” (SSP3-7.0-lowNTCF) levels of air quality control measures. As SSP3-7.0 lacks climate policy and has the highest levels of NTCFs, our results (e.g., surface warming) represent an upper bound. Unsurprisingly, we find significant improvements in air quality under NTCF mitigation (strong versus weak air quality controls). Surface fine particulate matter (PM2.5) and ozone (O3) decrease by -2.2±0.32 µg m−3 and -4.6±0.88 ppb, respectively (changes quoted here are for the entire 2015–2055 time period; uncertainty represents the 95 % confidence interval), over global land surfaces, with larger reductions in some regions including south and southeast Asia. Non-methane NTCF mitigation, however, leads to additional climate change due to the removal of aerosol which causes a net warming effect, including global mean surface temperature and precipitation increases of 0.25±0.12 K and 0.03±0.012 mm d−1, respectively. Similarly, increases in extreme weather indices, including the hottest and wettest days, also occur. Regionally, the largest warming and wetting occurs over Asia, including central and north Asia (0.66±0.20 K and 0.03±0.02 mm d−1), south Asia (0.47±0.16 K and 0.17±0.09 mm d−1), and east Asia (0.46±0.20 K and 0.15±0.06 mm d−1). Relatively large warming and wetting of the Arctic also occur at 0.59±0.36 K and 0.04±0.02 mm d−1, respectively. Similar surface warming occurs in model simulations with aerosol-only mitigation, implying weak cooling due to ozone reductions. Our findings suggest that future policies that aggressively target non-methane NTCF reductions will improve air quality but will lead to additional surface warming, particularly in Asia and the Arctic. Policies that address other NTCFs including methane, as well as carbon dioxide emissions, must also be adopted to meet climate mitigation goals.

Auxin promotes lateral root emergence from pericycle cells in the root vasculature. Here the authors show that induction of the plasmodesmal regulator PDLP5 during lateral root emergence restricts the spatial scope of auxin signaling to the cells overlying the primordia.

Background: Radiodermatitis is a frequent side effect of breast cancer radiotherapy (RT). Treating radiation oncologist should know the prevention and treatment of every grade of radiodermatitis. Aims: The aim of this study was to compare the topical corticosteroid and moisturizer usage in breast cancer RT. Materials and Methods: Fifty patients with early-stage breast cancer undergoing breast-conserving surgery referred to our department for adjuvant RT between October 2009 and October 2016 were compared with regard to topical steroid or moisturizer usage. Patients were followed up weekly after the start of treatment. Results: Mean age was 46 years. Twenty-four patients had stage 1 breast cancer and 26 patients had stage 2 disease. KPS (Karnofsky performance score) was 100 for all patients. Five patients (20.8%) had grade 2 and seven (29.1%) patients had grade 1 acute radiodermatitis in the first group. Eleven (42.3%) patients had grade 2 and 12 (46.1%) patients had grade 1 acute radiodermatitis in the second group. Thirteen (54.1%) patients in the first group had no acute radiodermatitis and three (11.5%) patients in the second group had no acute radiodermatitis. No patient in either group experienced grade 3 radiodermatitis. Conclusions: Daily use of topical betamethasone for breast cancer RT improves dermal sparing, reduces acute radiodermatitis, and may be recommended for patients receiving RT to the breast.

Atherosclerosis is the leading cause of death worldwide and leukocyte recruitment is a key element of this phenomenon, thus allowing immune cells to enter the arterial wall. There, in concert with accumulating lipids, the invading leukocytes trigger a plethora of inflammatory responses which promote the influx of additional leukocytes and lead to the continued growth of atherosclerotic plaques. The recruitment process follows a precise scheme of tethering, rolling, firm arrest, crawling and transmigration and involves multiple cellular and subcellular players. This review aims to provide a comprehensive up-to-date insight into the process of leukocyte recruitment relevant to atherosclerosis, each from the perspective of endothelial cells, monocytes and macrophages, neutrophils, T lymphocytes and platelets. In addition, therapeutic options targeting leukocyte recruitment into atherosclerotic lesions—or potentially arising from the growing body of insights into its precise mechanisms—are highlighted.

Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion imaging technique, which can detect more distinct microstructural features compared to conventional Diffusion Tensor Imaging (DTI). NODDI allows the signal to be divided into multiple water compartments and derive measures for orientation dispersion index (ODI), neurite density index (NDI) and volume fraction of isotropic diffusion compartment (FISO). This study aimed to investigate which diffusion metric—fractional anisotropy (FA), mean diffusivity (MD), NDI, ODI, or FISO—is most influenced by aging and reflects cognitive function in a population of healthy older adults at risk for Alzheimer’s disease (AD). Age was significantly associated with all but one diffusion parameters and regions of interest. NDI and MD in the cingulate region adjacent to the cingulate cortex showed a significant association with a composite measure of Executive Function and was proven to partially mediate the relationship between aging and Executive Function decline. These results suggest that both DTI and NODDI parameters are sensitive to age-related differences in white matter regions vulnerable to aging, particularly among older adults at risk for AD.

This article aims to understand what makes member states complement federal healthcare policy beyond the instruments planned by federal policy. We employ a Multiple Streams approach to study how Swiss member states use their discretion in order to complement federal healthcare regulation with the aim of decreasing outpatient healthcare expenditures at the cantonal level. Based on a written survey in the Swiss cantons, we perform a Fuzzy Set Qualitative Comparative Analysis (fsQCA), which places a keen emphasis on complex patterns. The method identifies what combinations of determinants make it particularly likely that a canton opts for complementary policy activity. Several configurations prove to foster such activity. While this is important, it is also important to pay attention to the constellations that precisely do not foster complementary policy activity. Our analysis of the cantonal choices on governing outpatient healthcare reveals that party politics in the executive and/or the public administration play a major role in this task, whereas neither organized interests within the medical profession nor individual policy entrepreneurs are crucial. Federalist systems offer opportunities for policy innovations the federal level ultimately may benefit from.

BACKGROUND: For patients with difficult venous access after long-term intravenous drug use, rapid point-of-care hepatitis C virus (HCV) RNA quantification in capillary whole blood with the Xpert® HCV Viral Load Fingerstick (VL FS) test (60 minutes) is a convenient and reliable method for diagnosing chronic HCV infection, monitoring treatment and detecting reinfection. However, an expensive GeneXpert® system must be available on site. In decentralised settings with a low case-load, dried blood spot (DBS) testing might be an alternative. METHODS: Between December 2019 and January 2021, patients with an indication for HCV RNA quantification and informed consent provided 100 µl capillary whole blood each for on-site Xpert® HCV VL FS testing (reference) and DBS testing in the laboratory. For the latter, 100 µl blood, collected with an EDTA Minivette®, were transferred to a Whatman® 903 filter card. After drying for at least 1 hour, the DBS sample was packed into a sealable plastic bag with desiccant and sent to the central laboratory of our hospital, where it was stored at –20°C. For HCV RNA extraction, the whole DBS was cut out with an 18-mm puncher and transferred into 1.3 ml guanidinium thiocyanate-containing buffer (provided by Cepheid®). After mixing and incubating at room temperature for 2–3 hours, 1 ml supernatant was analysed with the Xpert® HCV VL test (105 minutes) (filter paper absorbs 0.3 ml). RESULTS: Of 109 paired samples from 67 patients, 38 (34.9%) were positive with the Xpert® HCV VL FS test. Sensitivity and specificity of DBS testing were 89.5% (34/38; 95% confidence interval [CI] 75.9–95.8%) and 97.2% (69/71; 95% CI 90.3–99.2%), respectively. The six (5.5%) discordant results (four false negative, two false positive) all were observed in samples with HCV RNA detectable below the limit of quantification after 2–8 weeks of pan-genotypic direct-acting antiviral treatment or 5 weeks after acute hepatitis C in a patient clearing HCV spontaneously. Quantifiable results (n = 30; 16 genotype 1, 7 genotype 3, 4 genotype 4, 1 genotype 1a and 3a, 2 unknown; HCV RNA range: 2.74–6.66 log IU/ml) correlated well (R2 = 0.981). On average, uncorrected DBS test results were 1.30 ± 0.14 log IU/ml lower than Xpert® HCV VL FS test results (~42 μl instead of the expected 1000 μl plasma used). Storage of DBS samples at room temperature for 7 days before freezing reduced HCV RNA by 0.29 ± 0.12 log IU/ml. CONCLUSION: HCV RNA can reliably be quantified with the Xpert® HCV VL test in capillary dried blood spot samples. Thus, access to capillary HCV RNA quantification for diagnosing chronic HCV infection, monitoring treatment and detecting reinfection can be extended to decentralised settings with a low case load.

Disease lesion mimic mutants (DLMMs) are characterized by the spontaneous development of necrotic spots with various phenotypes designated as necrotic (nec) mutants in barley. The nec mutants were traditionally considered to have aberrant regulation of programmed cell death (PCD) pathways, which have roles in plant immunity and development. Most barley nec3 mutants express cream to orange necrotic lesions contrasting them from typical spontaneous DLMMs that develop dark pigmented lesions indicative of serotonin/phenolics deposition. Barley nec3 mutants grown under sterile conditions did not exhibit necrotic phenotypes until inoculated with adapted pathogens, suggesting that they are not typical DLMMs. The F2 progeny of a cross between nec3-γ1 and variety Quest segregated as a single recessive susceptibility gene post-inoculation with Bipolaris sorokiniana, the causal agent of the disease spot blotch. Nec3 was genetically delimited to 0.14 cM representing 16.5 megabases of physical sequence containing 149 annotated high confidence genes. RNAseq and comparative analysis of the wild type and five independent nec3 mutants identified a single candidate cytochrome P450 gene (HORVU.MOREX.r2.6HG0460850) that was validated as nec3 by independent mutations that result in predicted nonfunctional proteins. Histology studies determined that nec3 mutants had an unstable cutin layer that disrupted normal Bipolaris sorokiniana germ tube development.