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Acute respiratory distress syndrome (ARDS) due to COVID-19 leads to a high rate of mortality in the intensive care unit (ICU). A lung-protective mechanical ventilation strategy using low tidal volumes is a cornerstone to management, but uncontrolled hypercapnia is a life-threatening consequence among severe cases. A mechanism to prevent progressive hypercapnia may offset hemodynamic instability among patients who develop hypercapnia. We present the case of a woman in her mid-60’s with severe acute hypercapnic respiratory failure secondary to COVID-19 pneumonia who was successfully treated with early implementation of lung-protective ventilation facilitated by extracorporeal carbon dioxide removal (ECCO2R). This patient’s multiple comorbid conditions included obesity, hypertension, type 2 diabetes mellitus, and hypercholesterolemia. On her fifth day of admission at the referring hospital, her worsening hypoxemia prompted endotracheal intubation during which she developed pneumothorax. She was transferred to our institution for advanced care where upon arrival, she had profound hypercapnia and respiratory acidosis. She met the criteria for treatment with an investigational ECCO2R device (Hemolung Respiratory Assist System) available through FDA Emergency Use Authorization. ECCO2R is similar to extracorporeal membrane oxygenation (ECMO) but operates at much lower blood flows (350–550 mL/min) through a smaller 15.5 French central venous catheter. Standard heparinization was provided intravenously to achieve appropriate levels of anticoagulation during ECCO2R therapy. Unlike ECMO, ECCO2R does not provide clinically meaningful oxygenation but is simpler to implement and manage. The use of ECCO2R successfully corrected and controlled the patient’s hypercapnia and acidosis and enabled meaningful reductions in ventilator tidal volumes, respiratory rates, and mean airway pressures. The patient was weaned from ECCO2R after 17 days and from mechanical ventilation 10 days later. With low tidal volume ventilation facilitated by expeditious implementation of ECCO2R, the patient survived to discharge despite her many risk factors for a poor outcome and an extended duration of invasive mechanical ventilation.

Objective Depression and anxiety are not uncommon in Rheumatoid arthritis (RA). It is increasingly recognised that they are associated with high disease activity and worse disease outcomes. We aimed to examine the frequency of depression and anxiety in an early RA inception cohort and to explore associations with disease-related measures.Methods The Scottish Early Rheumatoid Arthritis inception cohort recruited newly diagnosed RA patients followed-up 6-monthly. Anxiety and depression were assessed using the hospital anxiety and depression scale. Associations with demographic characteristics and disease-related measures were examined at baseline, 6 months and 12 months.Results 848 RA patients were included. The prevalence of anxiety and depression at baseline was 19.0% and 12.2%, respectively. Depression and anxiety scores correlated with DAS28 at all time-points (all p

The trace element selenium (Se) contributes to redox signaling, antioxidant defense, and immune responses in critically ill neonatal and adult patients. Se is required for the synthesis and function of selenoenzymes including thioredoxin (Trx) reductase-1 (TXNRD1) and glutathione peroxidases (GPx). We have previously identified TXNRD1, primarily expressed by airway epithelia, as a promising therapeutic target to prevent lung injury, likely via nuclear factor E2-related factor 2 (Nrf2)-dependent mechanisms. The present studies utilized the TXNRD1 inhibitor auranofin (AFN) to test the hypothesis that Se positively influences Nrf2 activation and selenoenzyme responses in lung epithelial cells. Murine transformed Club cells (mtCCs) were supplemented with 0, 10, 25, or 100 nM Na2SeO3 to create a range of Se conditions and were cultured in the presence or absence of 0.5 μM AFN. TXNRD1 and GPX2 protein expression and enzymatic activity were significantly greater upon Se supplementation (p

Macromolecular complexes and organelles play crucial roles within cells, but their native architectures are often unknown. Here, we use an evolutionarily conserved germline organelle, the germ granule, as a paradigm. In Drosophila embryos, we map one of its interactomes using a novel in vivo crosslinking approach that employs two interacting granule proteins and determines their common neighbor molecules. We identified an in vivo granule assembly of Tudor, Aubergine, motor and metabolic proteins, and RNA helicases, and provide evidence for direct interactions within this assembly using purified components. Our study indicates that germ granules contain efficient biochemical reactors involved in post‐transcriptional gene regulation.

A passive spreading activation theory of incubation effects states that hints, encountered by chance after an unsolved problem has been put aside, direct spreading activation to solutions in memory. Results from three experiments reject this explanation. Pretested hints that were seen seconds before unsolved problems were retested did not aid resolution unless hints were intentionally used to help problem solving.

Most of the granite-related Sn−W deposits in Myanmar are located in the Western Granitoid Province (WGP) of Southeast Asia. The Tagu deposit in the southern part of the WGP is a granite related Sn−W deposit. The biotite granite is composed of quartz, feldspars (plagioclase, orthoclase, and microcline), and micas (muscovite and biotite) and belongs to S-type peraluminous granite. Abundances of large-ion lithophile elements (LILEs), such as Rb, K, and Pb, coupled with the deficiency of high-field-strength elements (HFSEs), such as Nb, P, and Ti, indicate that the parental magma for the Tagu granite was derived from the lower continental crust at syn-collisional setting. Mineralized veins consist of early-formed oxide ore minerals, such as cassiterite and wolframite, which were followed by the formation of sulfide minerals. Three main types of fluid inclusions were distinguished from the mineralized quartz veins hosted by granite and metasedimentary rocks: Type-A—two phases, liquid (L) + vapor (V) aqueous inclusions; Type-B—two phases, vapor (V) + liquid (L) vapor-rich inclusions; And type-C—three phases, liquid + CO2-liquid + CO2-vapor inclusions. Quartz in the veins hosted in granite corresponding with earlier deposition contains type-A, type-B, and type-C fluid inclusions, whereas that in the veins hosted in metasedimentary rocks corresponding with later deposition contains only type-A fluid inclusions. The homogenization temperatures of type-A inclusions range from 140 °C to 330 °C (mode at 230 °C), with corresponding salinities from 1.1 wt.% to 8.9 wt.% NaCl equivalent for quartz veins hosted in metasedimentary rocks, and from 230 °C to 370 °C (mode at 280 °C), with corresponding salinities from 2.9 wt.% to 10.6 wt.% NaCl equivalents for quartz veins hosted in granite. The homogenization temperatures of type-B vapor-rich inclusions in quartz veins in granite range from 310 °C to 390 °C (mode at 350 °C), with corresponding salinities from 6.7 wt.% to 12.2 wt.% NaCl equivalent. The homogenization temperatures of type-C H2O−CO2−NaCl inclusions vary from 270 °C to 405 °C (mode at 330 °C), with corresponding salinities from 1.8 wt.% to 5.6 wt.% NaCl equivalent. The original ascending ore fluid was probably CO2-bearing fluid which evolved into two phase fluid by immiscibility due to pressure drop in the mineralization channels. Furthermore, the temperature and salinities of two-phase aqueous fluids were later most likely decreased by the mixing with meteoric water. The salinities of the type-B vapor-rich inclusions are higher than those of the type-C CO2-rich inclusions, which may have resulted from CO2 separation from the fluids. The escape of gases can lead to an increase in the salinity of the residual fluids. Therefore, the main ore-forming mechanisms of the Tagu Sn−W deposit are characterized by fluid immiscibility during an early stage, and fluid mixing with meteoric water in the late stage at a lower temperature.

Chromatin immunoprecipitation and DNA sequencing (ChIP-seq) has been instrumental in inferring the roles of histone post-translational modifications in the regulation of transcription, chromatin compaction and other cellular processes that require modulation of chromatin structure. However, analysis of ChIP-seq data is challenging when the manipulation of a chromatin-modifying enzyme significantly affects global levels of histone post-translational modifications. For example, small molecule inhibition of the methyltransferase EZH2 reduces global levels of histone H3 lysine 27 trimethylation (H3K27me3). However, standard ChIP-seq normalization and analysis methods fail to detect a decrease upon EZH2 inhibitor treatment. We overcome this challenge by employing an alternative normalization approach that is based on the addition of Drosophila melanogaster chromatin and a D. melanogaster-specific antibody into standard ChIP reactions. Specifically, the use of an antibody that exclusively recognizes the D. melanogaster histone variant H2Av enables precipitation of D. melanogaster chromatin as a minor fraction of the total ChIP DNA. The D. melanogaster ChIP-seq tags are used to normalize the human ChIP-seq data from DMSO and EZH2 inhibitor-treated samples. Employing this strategy, a substantial reduction in H3K27me3 signal is now observed in ChIP-seq data from EZH2 inhibitor treated samples.

Summary During Drosophila development region-specific regulation of target genes by Hox proteins is modulated by genetic interactions with various cofactors and genetic collaborators. During embryogenesis one such modulator of Hox target specificity is the zinc-finger transcription factor Teashirt (Tsh) that is expressed in the developing trunk and cooperatively functions with trunk-specific Hox proteins to promote appropriate segment fate. This embryonic function of Tsh is characterized as homeotic since loss of embryonic Tsh activity leads to transformation of trunk segments toward head identity. In addition to this embryonic homeotic role, Tsh also performs vital Hox-independent functions through patterning numerous embryonic, larval and adult structures. Here we address whether the homeotic function of Tsh is maintained throughout development by investigating its contribution to patterning the adult abdomen. We show that Tsh is expressed throughout the developing abdomen and that this expression is dependent on the three Bithorax Hox proteins Ultrabithorax, Abdominal-A and Abdominal-B. Conditional reduction of Tsh activity during pupation reveals broad homeotic roles for this transcription factor throughout the adult abdomen. Additionally we show that, as during embryogenesis, the tsh paralog tiptop (tio) plays a partially redundant role in this homeotic activity.

Incentive salience is a motivational property with 'magnet-like' qualities. When attributed to reward-predicting stimuli (cues), incentive salience triggers a pulse of 'wanting' and an individual is pulled toward the cues and reward. A key computational question is how incentive salience is generated during a cue re-encounter, which combines both learning and the state of limbic brain mechanisms. Learning processes, such as temporal-difference models, provide one way for stimuli to acquire cached predictive values of rewards. However, empirical data show that subsequent incentive values are also modulated on the fly by dynamic fluctuation in physiological states, altering cached values in ways requiring additional motivation mechanisms. Dynamic modulation of incentive salience for a Pavlovian conditioned stimulus (CS or cue) occurs during certain states, without necessarily requiring (re)learning about the cue. In some cases, dynamic modulation of cue value occurs during states that are quite novel, never having been experienced before, and even prior to experience of the associated unconditioned reward in the new state. Such cases can include novel drug-induced mesolimbic activation and addictive incentive-sensitization, as well as natural appetite states such as salt appetite. Dynamic enhancement specifically raises the incentive salience of an appropriate CS, without necessarily changing that of other CSs. Here we suggest a new computational model that modulates incentive salience by integrating changing physiological states with prior learning. We support the model with behavioral and neurobiological data from empirical tests that demonstrate dynamic elevations in cue-triggered motivation (involving natural salt appetite, and drug-induced intoxication and sensitization). Our data call for a dynamic model of incentive salience, such as presented here. Computational models can adequately capture fluctuations in cue-triggered 'wanting' only by incorporating modulation of previously learned values by natural appetite and addiction-related states.

A graph is subeulerian if it is spanned by an eulerian supergraph. Boesch, Suffel and Tindell have characterized the class of subeulerian graphs and determined the minimum number of additional lines required to make a subeulerian graph eulerian.

Macromolecular complexes and organelles play crucial roles within cells, but their native architectures are often unknown. Here, we use an evolutionarily conserved germline organelle, the germ granule, as a paradigm. In Drosophila embryos, we map one of its interactomes using a novel in vivo crosslinking approach that employs two interacting granule proteins and determines their common neighbor molecules. We identified an in vivo granule assembly of Tudor, Aubergine, motor and metabolic proteins, and RNA helicases, and provide evidence for direct interactions within this assembly using purified components. Our study indicates that germ granules contain efficient biochemical reactors involved in post-transcriptional gene regulation. [ABSTRACT FROM AUTHOR]

Abstract: The Kago low-sulfidation Au/Ag deposit was an extensively excavated mine, primarily in the Edo-period (1684), reaching as far as 1943. Au grades ranged from 4.1-13.3g/t, while Ag ranges from 2.6-6.6g/t. The higher grades of gold made this deposit more favourable to mine, in comparison to other operating mines such as Serigano towards the north. The deposit is located approximately 5km from both the Kasuga and Iwato high-sulfidation deposits located towards the south. In this study, surficial quartz veins were measured for 18O in quartz and 34S in pyrite hosted in the veins. Where available, fluid inclusion microthermometry was carried out to establish the likely temperature of the mineralising fluids. Fluid 18O compositions were estimated using microthermometry results. Host rocks surrounding the veins were analysed for their alteration mineralogy. Within the Central Vein Group (CVT), veins typically exhibit low temperature argillic alteration grading out into a regional propylitic zone. [Copyright &y& Elsevier]