Stepwise Decreases Research Articles

Dendritically localized RNAs are packaged as diversely composed ribonucleoprotein particles with heterogeneous copy number states.

Localization of mRNAs to dendrites is a fundamental mechanism by which neurons achieve spatiotemporal control of gene expression. Translationally repressed neuronal mRNA transport granules, also referred to as ribonucleoprotein particles (RNPs), have been shown to be trafficked as single or low copy number RNPs and as larger complexes with multiple copies and/or species of mRNAs. However, there is little evidence of either population in intact neuronal circuits. Using single molecule fluorescence in situ hybridization studies in the dendrites of adult rat and mouse hippocampus, we provide evidence that supports the existence of multi-transcript RNPs with the constituents varying in amounts for each RNA species. By competing-off fluorescently labeled probe with serial increases of unlabeled probe, we detected stepwise decreases in Arc RNP number and fluorescence intensity, suggesting Arc RNAs localize to dendrites in both low- and multiple-copy number RNPs. When probing for multiple mRNAs, we find that localized RNPs are heterogeneous in size and colocalization patterns that vary per RNA. Further, localized RNAs that are targeted by the same trans-acting element (FMRP) display greater levels of colocalization compared to an RNA not targeted by FMRP. Simultaneous visualization of a dozen FMRP-targeted mRNA species using highly multiplexed imaging demonstrates that dendritic RNAs are mostly trafficked as heteromeric cargoes of multiple types of RNAs (at least one or more RNAs). Moreover, the composition of these RNA cargoes, as assessed by colocalization, correlates with the abundance of the transcripts even after accounting for the expected differences in colocalization based on expression. Collectively, these results suggest that dendritic RNPs are packaged as heterogeneous co-assemblies of different mRNAs and that RNP contents may be driven, at least partially, by highly abundant dendritic RNAs; a model that favors efficiency over fine-tuned control for sustaining long-distance trafficking of thousands of messenger molecules.

Assessment of Autoregulation of the Cerebral Circulation during Acute Lung Injury in a Neonatal Porcine Model.

In neonates with acute lung injury (ALI), targeting lower oxygenation saturations is suggested to limit oxygen toxicity while maintaining vital organ function. Although thresholds for cerebral autoregulation are studied for the management of premature infants, the impact of hypoxia on hemodynamics, tissue oxygen consumption and extraction is not well understood in term infants with ALI. We examined hemodynamics, cerebral autoregulation and fractional oxygen extraction, as measured by near-infrared spectroscopy (NIRS) and blood gases, in a neonatal porcine oleic acid injury model of moderate ALI. We hypothesized that in ALI animals, cerebral oxygen extraction would be increased to a greater degree than kidney or gut oxygen extraction as indicative of the brain's adaptive efforts to increase cerebral oxygen extraction at the expense of splanchnic end organs. Fifteen anesthetized, ventilated 5-day-old neonatal piglets were divided into moderate lung injury by treatment with oleic acid or control (sham injection). The degree of lung injury was quantified at baseline and after establishment of ALI by blood gases, ventilation parameters and calculated oxygenation deficit, hemodynamic indices by echocardiography and lung injury score by ultrasound. PaCO2 was maintained constant during ventilation. Cerebral, renal and gut oxygenation was determined by NIRS during stepwise decreases in inspired oxygen from 50% to 21%, correlated with PaO2 and PvO2; changes in fractional oxygen extraction (ΔFOE) were calculated from NIRS and from regional blood gas samples. The proportion of cerebral autoregulation impairment attributable to blood pressure, and to hypoxemia, was calculated from autoregulation nomograms. ALI manifested as hypoxemia with increasing intrapulmonary shunt fraction, decreased lung compliance and increased resistance, and marked increase in lung ultrasound score. Brain, gut and renal NIRS, obtained from probes placed over the anterior skull, central abdomen and flank, respectively, correlated with concurrent SVC (brain) or IVC (gut, renal) PvO2 and SvO2. Cerebral autoregulation was impaired after ALI as a function of blood pressure at all FiO2 steps, but predominantly by hypoxemia at FiO2 < 40%. Cerebral ΔFOE was higher in ALI animals at all FiO2 steps. We conclude that in an animal model of neonatal ALI, cerebrovascular blood flow regulation is primarily dependent on oxygenation. There is not a defined oxygenation threshold below which cerebral autoregulation is impaired in ALI. Cerebral oxygen extraction is enhanced in ALI, reflecting compensation for exhausted cerebral autoregulation due to the degree of hypoxemia and/or hypotension, thereby protecting against tissue hypoxia.

Examining Racial and Gender Diversity in the Plastic Surgery Pipeline: Where is the Leak?

There is limited information about minority representation throughout the plastic and reconstructive surgery (PRS) pipeline. The aim of this study was to examine trends in representation among minorities at different stages of the PRS training pathway, starting with potential candidates in high school through practicing physicians. The PRS pipeline was defined as high school; college; medical school applicants, matriculants, and graduates; PRS residency applicants, matriculants, and active residents; and PRS practicing physicians. Racial data for each stage were obtained from the US Census and Association of American Medical Colleges. The proportion of races at each stage were divided by their US population counterpart proportions to produce representation quotients (RQs). Medians and interquartile ranges (IQRs) are reported. Mann-Whitney U tests compared RQ values within identities between successive stages. Black students had high representation in high school (RQ = 1.26 [IQR: 1.21-1.29]) but had significant, stepwise decreases in representation in subsequent stages. A similar trend was observed for Hispanic individuals, who had their highest representation in high school (1.43 [1.37-1.50]), followed by significant decreases in RQ at nearly every subsequent stage up to and including practicing physicians (0.30 [0.28-0.31). Asian individuals were overrepresented at every stage (high school RQ: 1.01 [1.00-1.03]; practicing physician RQ: 2.30 [2.27-2.32]). White individuals were underrepresented before residency but had an RQ that approximated 1 in subsequent stages. Racial minorities experienced decreases in representation at each successive stage in the PRS pipeline following high school. Ongoing diversity efforts should focus on premedical recruitment and professional support for minority students.

Exercise capacity following SARS-CoV-2 infection is related to changes in cardiovascular and lung function in military personnel

BackgroundSince the COVID-19 pandemic, post-COVID syndrome (persistent symptoms/complications lasting >12 weeks) continues to pose medical and economic challenges. In military personnel, where optimal fitness is crucial, prolonged limitations affecting their ability to perform duties has occupational and psychological implications, impacting deployability and retention. Research investigating post-COVID syndrome exercise capacity and cardiopulmonary effects in military personnel is limited. MethodsUK military personnel were recruited from the Defence Medical Services COVID-19 Recovery Service. Participants were separated into healthy controls without prior SARS-CoV-2 infection (group one), and participants with prolonged symptoms (>12 weeks) after mild-moderate (community-treated) and severe (hospitalised) COVID-19 illness (group 2 and 3, respectively). Participants underwent cardiac magnetic resonance imaging (CMR) and spectroscopy, echocardiography, pulmonary function testing and cardiopulmonary exercise testing (CPET). Results113 participants were recruited. When compared in ordered groups (one to three), CPET showed stepwise decreases in peak work, work at VT1 and VO2 max (all p < 0.01). There were stepwise decreases in FVC (p = 0.002), FEV1 (p = 0.005), TLC (p = 0.002), VA (p < 0.001), and DLCO (p < 0.002), and a stepwise increase in A-a gradient (p < 0.001). CMR showed stepwise decreases in LV/RV volumes, stroke volumes and LV mass (LVEDVi/RVEDVi p < 0.001; LVSV p = 0.003; RVSV p = 0.001; LV mass index p = 0.049). ConclusionIn an active military population, post-COVID syndrome is linked to subclinical changes in maximal exercise capacity. Alongside disease specific changes, many of these findings share the phenotype of deconditioning following prolonged illness or bedrest. Partitioning of the relative contribution of pathological changes from COVID-19 and deconditioning is challenging in post-COVID syndrome recovery.

Electrochemical Li+ Insertion/Extraction Reactions at LiPON/Epitaxial Graphene Interfaces.

Redox reactions of the Li+ insertion/extraction from one to two interlayers of graphene (Gr) on area-defined single-crystalline SiC substrates are investigated using lithium phosphorus oxynitride glass (LiPON) as the solid-state electrolyte. Unlike an organic liquid electrolyte, this glassy electrolyte does not induce a reduction current and excludes the desolvation reaction of Li+. Gr electrodes with less than two Gr layers show a single reduction peak and one or two oxidation peaks below +0.21 V (vs Li+/Li), differing distinctly from those of graphite and multilayer Gr, which display multiple peaks (multiple stage transitions). However, this finding aligns with the conventional understanding that graphite stage structure transitions proceed with stepwise increases or decreases in the number of Gr layers between adjacent Li-inserted interlayers. Cyclic voltammetry measurements indicate the presence of surface capacity due to Li+ adsorption/desorption at the LiPON/Gr interface. Moreover, Li+ insertion and extraction induce different charge transfer resistances at the level of a single interlayer. These sensitive measurements are achieved using high-quality epitaxial Gr and LiPON electrolyte, which prevent the formation of a solid electrolyte interphase and the desolvation reaction of Li+. Similar measurements using bilayer Gr produced by chemical vapor deposition coupled with a Gr transfer method and an ethylene carbonate/dimethyl carbonate liquid electrolyte are not reliable. Thus, the proposed method is effective for electrochemical measurement of Gr electrodes with a controlled number of layers.

From hybrid process to pure biofilm anammox process: Suspended sludge biomass management contributing to high-level anammox enrichment in biofilms

The application of mainstream anammox is highly desirable for municipal wastewater treatment. However, enrichment of anammox bacteria (AnAOB) is challenging, particularly given the vicious competition from denitrifying bacteria (DB). Here, suspended sludge biomass management, a novel operational strategy for hybrid process (suspended sludge/biofilm), was investigated for 570 days based on a modified anaerobic–anoxic–oxic system treating municipal wastewater. By successively decreasing the suspended sludge concentration, the traditional hybrid process was successfully upgraded to a pure biofilm anammox process. During this process, both the nitrogen removal efficiency (NRE) and rate (NRR) were significantly improved (P < 0.001), from 62.1 ± 4.5% to 79.2 ± 3.9% and from 48.7 ± 9.7 to 62.3 ± 9.0 g N/(m3·d), respectively. Mainstream anammox was improved in the following: Candidatus Brocadia was enriched from 0.70% to 5.99% in anoxic biofilms [from (9.94 ± 0.99) × 108 to (1.16 ± 0.01) × 1010 copies/g VSS, P < 0.001]; the in situ anammox reaction rate increased from 8.8 ± 1.9 to 45.5 ± 3.2 g N/(m3·d) (P < 0.001); the anammox contribution to nitrogen removal rose from 9.2 ± 2.8% to 67.1 ± 8.3% (P < 0.001). Core bacterial microbiome analysis, functional gene quantification, and a series of ex situ batch experiments demonstrated that the stepwise decreases in suspended sludge concentration effectively mitigated the vicious competition of DB against AnAOB, enabling high-level AnAOB enrichment. This study presents a straightforward and effective strategy for enriching AnAOB in municipal wastewater, shedding fresh light on the application and upgradation of mainstream anammox.

Longitudinal Validation of Right Ventricular Pressure Monitoring for the Assessment of Right Ventricular Systolic Dysfunction in a Large Animal Ischemic Model.

RV pressure monitoring can detect changes in RV systolic performance assess by RV Ees following the development of an acute RV ischemic model. Acute ischemic RV dysfunction was induced by progressive embolization of microsphere in the right coronary artery to mimic RV dysfunction clinically experienced during cardiopulmonary bypass separation caused by air microemboli. RV hemodynamic performance was assessed using RV pressure waveform-derived parameters and RV Ees obtained using a conductance catheter during inferior vena cava occlusions. Acute ischemia resulted in a significant reduction in RV Ees from 0.26 mm Hg/mL (interquartile range, 0.16-0.32 mm Hg/mL) to 0.14 mm Hg/mL (0.11-0.19 mm Hg/mL; p < 0.010), cardiac output from 6.3 L/min (5.7-7 L/min) to 4.5 (3.9-5.2 L/min; p = 0.007), mean systemic arterial pressure from 72 mm Hg (66-74 mm Hg) to 51 mm Hg (46-56 mm Hg; p < 0.001), and mixed venous oxygen saturation from 65% (57-72%) to 41% (35-45%; p < 0.001). Linear mixed-effect model analysis was used to assess the relationship between Ees and RV pressure-derived parameters. The reduction in RV Ees best correlated with a reduction in RV maximum first derivative of pressure during isovolumetric contraction (dP/dtmax) and single-beat RV Ees. Adjusting RV dP/dtmax for heart rate resulted in an improved surrogate of RV Ees. Stepwise decreases in RV Ees during acute ischemic RV dysfunction were accurately tracked by RV dP/dtmax derived from the RV pressure waveform.

PS-C30-7: THE ASSOCIATION BETWEEN INSULIN RESISTANCE AND DECLINE IN ORGAN FUNCTION IN NON-OBESE JAPANESE INDIVIDUALS

Background: Obesity-induced insulin resistance is a critical metabolic abnormality involved in the decline in various organ functions, which likely contributes to the development of serious diseases, such as type 2 diabetes, hypertension, and cardiovascular disease. However, little information is available on the association between insulin resistance and organ function in non-obese people. The major purpose of this study was to investigate the relationship between insulin resistance (estimated by the homeostasis model assessment for insulin resistance, HOMA-IR) and selected indicators of organ-specific functions in non-obese individuals. Materials and Methods: We analyzed data obtained from non-obese (body mass index [BMI], 18.5 to &lt; 25 kg/m2), non-diabetic 3546 Japanese individuals (2034 men and 1512 women) who received health checkups in 2018 at Keio University Hospital. Individuals were divided into quartiles according to their HOMA-IR values. Multiple regression analysis was performed to further investigate the relationship between HOMA-IR values and organ parameters after adjustment for covariates, such as age, gender, and BMI. Results: Those with HOMA-IR in the highest quartile had a higher incidence of metabolic syndrome, hypertension, stroke, and chronic kidney disease. There were significant stepwise (P &lt; 0.05) increases in metabolic syndrome indicators (BMI, visceral adipose tissue area, triglyceride, uric acid), liver enzymes (AST, ALT, γGTP, ChE), systemic inflammatory markers (white blood cell count, CRP), systolic and diastolic blood pressure, and ocular pressure, from the first quartile to fourth quartile of HOMA-IR, whereas there were stepwise decreases in HDL-C and parameters of renal function (eGFR) and pulmonary function (forced expiratory volume, vital capacity). Multiple regression analyses revealed that HOMA-IR values were significantly (P &lt; 0.05) associated with these parameters expect eGFR even after adjusting for covariates. Conclusion: Our results suggest that insulin resistance is associated with decline in the function of multiple organs in non-obese, non-diabetic Japanese individuals. Further studies are required to establish cause and effect in this relationship.

Tc-99m DMSA SPECT for Follow-Up of Non-Operative Treatments in Renal Injuries: A Prospective Single-Center Study.

The assessment of cortical integrity following renal injuries with planar Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy depends on measuring relatively decreased cortical uptake (i.e., split renal function [SRF]). We analyzed the additive values of the volumetric and quantitative analyses of the residual cortical integrity using single-photon emission computed tomography (SPECT) compared to the planar scintigraphy. This prospective study included 47 patients (male:female, 32:15; age, 47 ± 22 years) who had non-operatively managed renal injuries and underwent DMSA planar and SPECT imaging 3-6 months after the index injury. In addition to planar SRF, SPECT SRF, cortical volume, and absolute cortical uptake were measured for the injured kidney and both kidneys together. The correlations of planar SRF with SPECT SRF and those of SRF with volumetric/quantitative parameters obtained with SPECT were analyzed. The association of SPECT parameters with renal function, grades of renal injuries, and the risk of renal failure was also analyzed. SPECT SRF was significantly lower than planar SRF, with particularly higher biases in severe renal injuries. Planar and SPECT SRF (dichotomized with a cutoff of 45%) showed 19%-36% of discrepancies with volumetric and quantitative DMSA indices (when dichotomized as either high or low). Absolute cortical uptake of the injured kidney best correlated with glomerular filtration rate (GFR) at follow-up (ρ = 0.687, P < 0.001) with significant stepwise decreases by GFR strata (90 and 60 mL/min/1.73 m²). Total renal cortical uptake was significantly lower in patients with moderate-to-high risk of renal failure than those with low risk. However, SRF did not reflect GFR decrease below 60 mL/min/1.73 m² or the risk of renal failure, regardless of planar or SPECT (count- or volume-based SRF) imaging. Quantitative measurements of renal cortical integrity assessed with DMSA SPECT can provide more clinically relevant and comprehensive information than planar imaging or SRF alone.

Suffusion of a sand–clay mixture: impact of the ionic-concentration gradient, clay type, sand-grain size and hydraulic gradient

Internal erosion by suffusion within a sand–clay mixture may occur as detachment of clay particles, which is induced by a decrease in ionic concentration (IC) along with application of a high hydraulic gradient. Through designed laboratory soil-column experiments, this study investigates the impact of the IC gradient (stepwise or gradual decrease), clay mineralogy, sand particle size and hydraulic gradient on the suffusion of a sand–clay mixture. The observed breakthrough concentration of clay particles revealed the substantial suffusion of a sand–clay mixture caused by a stepwise decrease in the IC for kaolinite and illite, while similar filtrated quantities of bentonite were observed for stepwise and gradual decreases in IC. In addition, the small-grained sand showed a relatively high susceptibility to suffusion by a stepwise decrease in IC, most likely because of the low reattachment of detached clay particles. The mass of filtrated clay particles evaluated from the area of the observed breakthrough curves in this study provides a clear insight into the need to incorporate the IC gradient when assessing the susceptibility to the suffusion of clay-containing soils.

Arsenic extraction from seriously contaminated paddy soils with ferrihydrite-loaded sand columns

Reductive dissolution of iron oxides in flooded paddy soils is the most important cause of arsenic (As) release into soil aqueous solution and thus entry into rice. From the perspective of soil cleanup, however, As release under flooded condition could facilitate labile As removal. In this study, a porous column pre-loaded with ferrihydrite (Fh) was constructed, and its efficiency of soil As extraction was investigated using a purpose-designed mesocosm coupled with diffusive gradients in thin films (DGT) for in situ visualization. With Fh-column deployed in aqueous solution, >90% removal of As(III) was achieved within 5 days at initial As (100 mg L−1) of two orders of magnitude higher than in most paddy soil solutions (1–1538 μg L−1). By applying Fh-column in a seriously contaminated paddy soil (102 mg As kg−1), porewater As showed stepwise decreases from 2727 μg L−1 to 129–1455 μg L−1 at a distance-dependent manner over four intermittent extractions during 91 days. Soil DGT-As exhibited similar spatiotemporal changes to porewater As. After four extractions, 17.8% of total soil As was removed by Fh-column in a 10 cm radius range on average and ∼1/3 of As bound to amorphous and crystalline Fe/Al oxides was depleted, which accounted for 88.7% of decline in total soil As. With the post-extracted soil, a 48% lower As accumulation in rice seedlings and a 65% decline in bulk soil DGT-As were attained. This study provides a conceptual foundation for rapid removal of high soluble As by Fh-columns from flooded soils, improving seriously As-contaminated paddies to sustainable resources for safe food production.

Diabetic family history in young Japanese persons with normal glucose tolerance associates with k-means clustering of glucose response to oral glucose load, insulinogenic index and Matsuda index

AimsThe present study aimed to clarify the relationships between diabetic family history (FH), and dysglycemic response to the oral glucose tolerance test (OGTT), insulin secretion, and insulin sensitivity in young Japanese persons with normal glucose tolerance (NGT). MethodsWe measured plasma glucose (PG) and immunoreactive insulin levels in 1,309 young Japanese persons (age <40 years) with NGT before and at 30, 60, and 120 min during a 75-g OGTT. Dysglycemia during OGTT was analyzed by k-means clustering analysis. Body mass index (BMI), blood pressure (BP), and lipids were measured. Insulin secretion and sensitivity indices were calculated. ResultsPG levels during OGTT were classified by k-means clustering analysis into three groups with stepwise decreases in glucose tolerance even among individuals with NGT. In these clusters, proportion of males, BMI, BP and frequency of FH were higher, and lipid levels were worse, together with decreasing glucose tolerance. Subjects with a diabetic FH showed increases in PG after glucose loading and decreases in insulinogenic index and Matsuda index. ConclusionsDysglycemic response to OGTT by k-means clustering analysis was associated with FH in young Japanese persons with NGT. FH was also associated with post-loading glucose, insulinogenic index, and Matsuda index.

Longitudinal course and phenotypes of health-related quality of life in adults with atopic dermatitis.

The real-world course of health-related quality of life (HRQoL) in atopic dermatitis (AD) is not well established. To examine predictors, longitudinal course and phenotypes of HRQoL in adult patients with AD. This was a prospective dermatology-practice based study of 955 patients with AD (age 18-97 years). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. HRQoL was assessed using the 10-item short-form Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health (PGH). AD severity and impact was assessed by patient-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Eczema Area and Severity Index (EASI), Objective SCORing Atopic Dermatitis (O-SCORAD), Investigator's Global Assessment (IGA), Numerical Rating Scale (NRS) average and worst itch, PROMIS sleep-related impairment (SRI), and nine-item Patient Health Questionnaire (PHQ)-9. Repeated-measures regression models were constructed to examine itch over time. In multivariable linear regression models controlling for age, race/ethnicity, history of asthma, hay fever and food allergy, baseline PGH-physical (PGH-P4) T scores were inversely associated with patient-reported global AD severity, POEM, EASI, objective SCORAD, IGA, NRS average and worst itch, PROMIS SRI and PHQ-9, with stepwise decreases of physical health with worsening severity. PGH-mental health (PGH-M4) T scores were associated with all aforementioned severity measures aside from POEM. In multivariable repeated measures linear regression models, decreased PGH-P4 and PGH-M4 T scores and mapped five-dimension EuroQoL over time were associated with self-reported global AD severity, NRS worst and mean itch, POEM, PROMIS sleep disturbance and SRI, EASI, objective SCORAD, IGA and PHQ-9. Latent class analysis identified six classes of HRQoL, which were associated with measures of AD severity, nonwhite race, Hispanic ethnicity and having only public health insurance, but not age or sex. Patients with AD have a heterogeneous longitudinal course and distinct patterns of HRQoL. Many patients had fluctuating HRQoL over time. Most patients with moderate to severe disease at baseline had persistent HRQoL impairment over time.

The Impact of HbA1c level on heart failure with recovered rjection fraction in patients with Type 2 Diabetes

Abstract Background Heart failure (HF) with improved or recovered ejection fraction (EF, HFrecEF) has been recognized as a new type of HF with different underlying clinical phenotype, pathophysiology and prognosis. However, few studies have analyzed the relationship between type 2 diabetes and HFrecEF, and the impact of glycemic level on myocardial function recovery. Purpose In the present study, we sought to investigate the relation between HbA1c level and HFrecEF in patients with type 2 diabetes. Methods A total of 796 HF patients with reduced left-ventricular ejection fraction (LVEF, &amp;lt;40%) and type 2 diabetes were consecutively enrolled from August 2012 to July 2020. During follow-up for up to 24 months, patients were classified into HFrecEF for whom developed recovered LVEF (≥40% and absolute increase ≥5%) and HFrEF for whose LVEF was persistently reduced (&amp;lt;40%). The relation between HbA1c and the recovery of LV function was analyzed. Results HF patients with type 2 diabetes had significantly lower rates of LVEF recovery when having higher versus lower HbA1c levels in the baseline (the lowest tertile: 62.4%, intermediate tertile: 50.4%, the highest tertile: 46.8%; P&amp;lt;0.001). There were stepwise decreases in changes of LVEF (P&amp;lt;0.001) and increases in changes of LV end-systolic diameter (LVESD; P=0.093) with increasing tertiles of LVEF during follow-up. In the subgroup analysis, the impact of HbA1c on LVEF recovery was more prominent in patients with ischemic heart disease (P&amp;lt;0.001) than those with dilated cardiomyopathy (P=0.536). A significant interaction term was present between HbA1c and etiology of heart failure with regard to LVEF recovery (P=0.012). After multivariate adjustment of conventional confounding factors, high HbA1c level remained to be an independent risk factor lower incidence of HFrecEF in patients type 2 diabetes. Conclusions Our study suggests that optimal glycemic control is an independent predictor for incidence of HFrecEF in patients with type 2 diabetes. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation of China, Shanghai Municipal Commission of Health and Family Planning

Remodeling of Arctic char (Salvelinus alpinus) lipidome under a stimulated scenario of Arctic warming.

Arctic warming associated with global climate change poses a significant threat to populations of wildlife in the Arctic. Since lipids play a vital role in adaptation of organisms to variations in temperature, high-resolution mass-spectrometry-based lipidomics can provide insights into adaptive responses of organisms to a warmer environment in the Arctic and help to illustrate potential novel roles of lipids in the process of thermal adaption. In this study, we studied an ecologically and economically important species-Arctic char (Salvelinus alpinus)-with a detailed multi-tissue analysis of the lipidome in response to chronic shifts in temperature using a validated lipidomics workflow. In addition, dynamic alterations in the hepatic lipidome during the time course of shifts in temperature were also characterized. Our results showed that early life stages of Arctic char were more susceptible to variations in temperature. One-year-old Arctic char responded to chronic increases in temperature with coordinated regulation of lipids, including headgroup-specific remodeling of acyl chains in glycerophospholipids (GP) and extensive alterations in composition of lipids in membranes, such as less lyso-GPs, and more ether-GPs and sphingomyelin. Glycerolipids (e.g., triacylglycerol, TG) also participated in adaptive responses of the lipidome of Arctic char. Eight-week-old Arctic char exhibited rapid adaptive alterations of the hepatic lipidome to stepwise decreases in temperature while showing blunted responses to gradual increases in temperature, implying an inability to adapt rapidly to warmer environments. Three common phosphatidylethanolamines (PEs) (PE 36:6|PE 16:1_20:5, PE 38:7|PE 16:1_22:6, and PE 40:7|PE 18:1_22:6) were finally identified as candidate lipid biomarkers for temperature shifts via machine learning approach. Overall, this work provides additional information to a better understanding of underlying regulatory mechanisms of the lipidome of Arctic organisms in the face of near-future warming.

Right Ventricular Pulmonary Artery Coupling and Mortality in Cardiac Intensive Care Unit Patients.

BackgroundImpaired right ventricular (RV) pulmonary artery coupling has been associated with higher mortality in patients with chronic heart disease, but few studies have examined this metric in critically ill patients. We sought to evaluate the association between RV pulmonary artery coupling, defined by the ratio of tricuspid annular peak systolic tissue Doppler velocity (TASV)/estimated RV systolic pressure (RVSP), and mortality in cardiac intensive care unit patients.Methods and ResultsUsing a database of unique cardiac intensive care unit admissions from 2007 to 2018, we included patients with TASV/RVSP ratio measured within 1 day of hospitalization. Hospital mortality was analyzed using multivariable logistic regression, and 1‐year mortality was analyzed using multivariable Cox proportional‐hazards analysis. We included 4259 patients with a mean age of 69±15 years (40.1% women). Admission diagnoses included acute coronary syndrome in 56%, heart failure in 52%, respiratory failure in 24%, and cardiogenic shock in 12%. The mean TASV/RVSP ratio was 0.31±0.14, and in‐hospital mortality occurred in 7% of patients. Higher TASV/RVSP ratio was associated with lower in‐hospital mortality (adjusted unit odds ratio, 0.68 per each 0.1‐unit higher ratio; 95% CI, 0.58–0.79; P<0.001) and lower 1‐year mortality among hospital survivors (adjusted unit hazard ratio, 0.83 per each 0.1‐unit higher ratio; 95% CI, 0.77–0.90; P<0.001). Stepwise decreases in hospital and 1‐year mortality were observed in each higher TASV/RVSP quintile. The TASV/RVSP ratio remained associated with mortality after adjusting for left ventricular systolic and diastolic function.ConclusionsA low TASV/RVSP ratio is associated with increased short‐term and long‐term mortality among cardiac intensive care unit patients, emphasizing importance of impaired RV pulmonary artery coupling as a determinant of poor prognosis. Further study is required to determine whether interventions to optimize RV pulmonary artery coupling can improve outcomes.

1712. Epidemiology, Clinical Characteristics, and Outcomes of Influenza-Associated Hospitalizations in Children in the post-2009 Pandemic Era

BackgroundSignificant changes in influenza vaccination coverage and antiviral treatment guidance occurred following the 2009 influenza pandemic in children. However, data are limited describing recent epidemiology, clinical characteristics, antiviral use, vaccine coverage, and outcomes of influenza-related hospitalizations in children.MethodsChildren < 18 years hospitalized with influenza during seasons 2010–2011 through 2018–2019 were included through the US Influenza Hospitalization Surveillance Network (FluSurv-NET). Age-stratified hospitalization rates were calculated using the number of catchment-area residents with laboratory-confirmed influenza within 14 days prior to or ≤3 days after hospital admission during October 1-April 30 of each influenza season. Data on underlying medical history, influenza vaccination, antiviral use, and outcomes were abstracted from medical records using standard case report forms by trained surveillance officers.ResultsOver 9 seasons, 13,235 children were identified. Stepwise decreases in unadjusted hospitalization rates with age occurred, with the highest rates in infants < 6 months (ranging 56–184 per 100,000 persons) (Fig.1). Among these children, 56% were male, 34% were non-Hispanic White, 55% had a preexisting medical condition, and 8% were immunocompromised (Table 1). Use of antiviral treatment substantially increased from 56% to 85%, and influenza vaccination rates among hospitalized children increased from 34% to 43% over time. Regarding severe outcomes, 2,676 (20%) were admitted to ICU, 2,262 (17%) had pneumonia, 690 (5%) required mechanical ventilation, and 72 (0.5%) died. In univariable analysis, compared to hospitalized infants < 6 months, children >13 years had higher odds of ICU admission (odds ratio (OR), 2.0; 95% CI, 1.7–2.4), mechanical ventilation (OR, 1.7; 95% CI, 1.2–2.3), and pneumonia (OR, 2.6; 95% CI, 2.1–3.3) (Table 2).Figure 1 Table 1 Table 2 ConclusionAlthough influenza-related hospitalization rates decreased with increasing age, severe outcomes were more common among hospitalized older children. Room for improvement exists in influenza vaccination coverage and antiviral use. While 20% of children were admitted to ICU, death was uncommon.DisclosuresSue Kim, MPH, Council of State and Territorial Epidemiologists (CSTE) (Grant/Research Support) Melissa Sutton, MD, MPH, CDC funding (Emerging Infections Program) (Grant/Research Support) Evan J. Anderson, MD, Sanofi Pasteur (Scientific Research Study Investigator)

Effect of crystal orientation on droplet wetting behavior on single-crystal Al2O3 substrates: An experimental study

The wetting property of liquids on a solid surface is of key relevance to many areas ranging from biological systems to industrial applications. The wetting behavior of water, glycerin, and castor oil (featuring varying viscosities and surface energies) on single-crystal α-Al2O3 substrates with various crystal orientations of (0001), (112¯0), (101¯0), and (011¯2) was studied using the improved sessile drop method at room temperature and a closed environment. The effects of substrate crystal orientation on the liquid wetting behavior and its dependence on the liquid type were investigated. The contact angle of all three liquids on the (0001)-orientated substrates was obviously smaller than those of the other substrate orientations. The effects of α-Al2O3 substrate crystal orientation on the liquid wetting behavior on the substrates can be attributed to the liquid and substrate surface energies, the liquid viscosity, and the substrate atomic arrangement. The wetting process of water on α-Al2O3 could be divided into two stages. The contact angle was basically unchanged in stage I, and evaporation of droplets causes stepwise decreases of the contact angle in stage II. The height and contact angle of glycerin and castor oil on the substrates change very slowly in 1800 s. The findings of this study help provide a better understanding of the wetting behavior of liquids on solids and its mechanism.

Noninvasive Echocardiographic Left Ventricular Stroke Work Index Predicts Mortality in Cardiac Intensive Care Unit Patients.

Reduced left ventricular stroke work index (LVSWI) has been associated with adverse outcomes in several populations of patients with chronic heart disease, but no prior studies have examined this metric in cardiac intensive care unit (CICU) patients. We sought to determine whether a low LVSWI, as measured noninvasively using transthoracic echocardiography, is associated with higher mortality in CICU patients. Using a database of unique Mayo Clinic CICU admissions from 2007 to 2018, we identified patients with LVSWI measured by transthoracic echocardiography within 1 day of CICU admission. Hospital mortality was analyzed using multivariable logistic regression, and 1-year mortality was analyzed using multivariable Cox proportional-hazards analysis, adjusted for left ventricular ejection fraction and known predictors of hospital mortality. We included 4536 patients with a mean age of 68±14 years (36% women). Admission diagnoses (not mutually exclusive) included acute coronary syndrome in 62%, heart failure in 46%, and cardiogenic shock in 11%. The mean LVSWI was 38±14 g×min/m2, and in-hospital mortality occurred in 6% of patients. LVSWI had better discrimination for hospital mortality than left ventricular ejection fraction (P<0.001 by De Long test). Higher LVSWI was associated with lower in-hospital mortality (adjusted odds ratio, 0.72 per 10 g×min/m2 higher [95% CI, 0.61-0.84]; P<0.001) and lower 1-year mortality (adjusted hazard ratio, 0.812 per 1 g×min/m2 higher [95% CI, 0.759-0.868]; P<0.001). Stepwise decreases in hospital and 1-year mortality were observed with higher LVSWI. Low LVSWI, reflecting poor left ventricular systolic and diastolic performance, is associated with increased short-term and long-term mortality among CICU patients. This emphasizes the importance of Doppler transthoracic echocardiography as a predictor of outcomes among critically ill patients. Further study is required to determine whether early interventions to optimize LVSWI can improve outcomes in the CICU setting.

Microbial ecology of a lactate-driven dark fermentation process producing hydrogen under carbohydrate-limiting conditions

Despite the high prevalence of lactic acid bacteria in dark fermentation (DF) processes, their ecological role is not yet completely elucidated, preventing their systematic use as “helpers” for hydrogen production. The aim of this study was to investigate the microbial community structure of a lactate-driven DF process that successfully produced hydrogen under carbohydrate-limiting conditions using tequila vinasse as a substrate. Microbial responses to stepwise decreases in hydraulic retention time (HRT) from 24 to 4 h were assessed by using Illumina MiSeq sequencing. HRTs above 12 h and below 6 h led to a lower hydrogen production rate (HPR; 0.2–3.3 L/L-d) and process stability (HPR variations within 25–65%), which were associated with the presence of Acetobacter lovaniensis, Clostridium luticellari, Blautia coccoides, and the high abundance of propionate and lactate. Interestingly, transient conditions from unsteady-to-steady state occurred at an HRT of 12 h, where species richness and evenness decreased remarkably. Accordingly, HRTs between 12 and 6 h resulted in higher HPRs of up to 11.7 ± 0.7 L/L-d with HPR variations of less than 10%, which closely matched with the dominance of Clostridium sp., and butyrate and acetate as the main aqueous products. Overall, the results indicate that the successfulness of exploiting the ‘unwanted’ LAB proliferation through lactate-driven DF processes requires the enrichment of lactate-consuming and hydrogen-producing bacteria, which entails the selection of proper biocatalysts and operating conditions/strategies such as the operation of DF reactors under carbohydrate-limiting conditions and low HRTs.