Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism

Patients with alcoholism and type 2 diabetes manifest altered metabolism, including elevated aldehyde levels and unusually low asparagine levels. We show that asparagine synthetase B (ASNS), the only human asparagine-forming enzyme, is inhibited by disease-relevant reactive aldehydes, including formaldehyde and acetaldehyde. Cellular studies show non-cytotoxic amounts of reactive aldehydes induce a decrease in asparagine levels. Biochemical analyses reveal inhibition results from reaction of the aldehydes with the catalytically important N-terminal cysteine of ASNS. The combined cellular and biochemical results suggest a possible mechanism underlying the low asparagine levels in alcoholism and diabetes. The results will stimulate research on the biological consequences of the reactions of aldehydes with nucleophilic residues

Symmetric Grothendieck polynomials, skew Cauchy identities, and dual filtered Young graphs

Symmetric Grothendieck polynomials are analogues of Schur polynomials in the K-theory of Grassmannians. We build dual families of symmetric Grothendieck polynomials using Schur operators. With this approach we prove skew Cauchy identity and then derive various applications: skew Pieri rules, dual filtrations of Young's lattice, generating series and enumerative identities. We also give a new explanation of the finite expansion property for products of Grothendieck polynomials

Mars Aeronomy Observer: Report of the Science Working Team

The Mars Aeronomy Observer (MAO) is a candidate follow-on mission to Mars Observer (MO) in the Planetary Observer Program. The four Mariner and two Viking spacecraft sent to Mars between 1965 and 1976 have provided a wealth of information concerning Martian planetology. The Mars Observer, to be launched in 1990, will build on their results by further examining the elemental and mineralogical composition of the surface, the strength and multipolar composition of the planetary magnetic field, the gravitational field and topography, and the circulation of the lower atmosphere. The Mars Aeronomy Observer is intended to address the last major aspects of Martian environment which have yet to be investigated: the upper atmosphere, the ionsphere, and the solar wind interaction region

Validity of Ultra-Short-Term Heart Rate Variability Derived from Femoral Arterial Pulse Waveform in a British Military Cohort.

Various non-electrocardiogram (ECG) based methods are considered reliable sources of heart rate variability (HRV) measurement. However, the ultra-short recording of a femoral arterial waveform has never been validated against the gold-standard ECG-based 300s HRV and was the aim of this study.A validity study was conducted using a sample from the first follow-up of the longitudinal ADVANCE study UK. The participants were adult servicemen (n = 100); similar in age, rank, and deployment period (Afghanistan 2003-2014). The femoral arterial waveforms (14s) from the pulse wave velocity (PWV) assessment, and ECG (300s) were recorded at rest in the supine position using the Vicorder™ and Bittium Faros™ devices, respectively, in the same session. HRV analysis was performed using Kubios Premium. Resting heart rate (HR) and root mean square of successive differences (RMSSD) were reported. The Bland-Altman %plots were constructed to explore the PWV-ECG agreement in HRV measurement. A further exploratory analysis was conducted across methods and durations.The participants' mean age was 38.0 ± 5.3 years. Both PWV-derived HR (r = 0.85) and RMSSD (rs=0.84) showed strong correlations with their 300s-ECG counterparts (p < 0.001). Mean HR was significantly higher with ECG than PWV (mean bias: -12.71 ± 7.73%, 95%CI: -14.25%, -11.18%). In contrast, the difference in RMSSD between the two methods was non-significant [mean bias: -2.90 ± 37.82% (95%CI: -10.40%, 4.60%)] indicating good agreement. An exploratory analysis of 14s ECG-vs-300s ECG measurement revealed strong agreement in both RMSSD and HR.The 14s PWV-derived RMSSD strongly agrees with the gold-standard (300s-ECG-based) RMSSD at rest. Conversely, HR appears method sensitive

Mental health outcomes of male UK military personnel deployed to Afghanistan and the role of combat injury: analysis of baseline data from the ADVANCE cohort study

Background: The long-term psychosocial outcomes of UK armed forces personnel who sustained serious combat injuries during deployment to Afghanistan are largely unknown. We aimed to assess rates of probable post-traumatic stress disorder (PTSD), depression, anxiety, and mental health-associated multimorbidity in a representative sample of serving and ex-serving UK military personnel with combat injuries, compared with rates in a matched sample of uninjured personnel. Methods: This analysis used baseline data from the ADVANCE cohort study, in which injured individuals were recruited from a sample of UK armed forces personnel who were deployed to Afghanistan and had physical combat injuries, according to records provided by the UK Ministry of Defence. Participants from the uninjured group were frequency-matched by age, rank, regiment, deployment, and role on deployment. Participants were recruited through postal, email, and telephone invitations. Participants completed a comprehensive health assessment, including physical health assessment and self-reported mental health measures (PTSD Checklist, Patient Health Questionnaire-9, and Generalised Anxiety Disorder-7). The mental health outcomes were rates of PTSD, depression, anxiety, and mental health-associated multimorbidity in the injured and uninjured groups. The ADVANCE study is ongoing and is registered with the ISRCTN registry, ISRCTN57285353. Findings: 579 combat-injured participants (161 with amputation injuries and 418 with non-amputation injuries) and 565 uninjured participants were included in the analysis. Participants had a median age of 33 years (IQR 30–37 years) at the time of assessment. 90·3% identified as White and 9·7% were from all other ethnic groups. The rates of PTSD (16·9% [n=89] vs 10·5% [n=53]; adjusted odds ratio [AOR] 1·67 [95% CI 1·16–2·41], depression (23·6% [n=129] vs 16·8% [n=87]; AOR 1·46 [1·08–2·03]), anxiety (20·8% [n=111] vs 13·5% [n=71]; AOR 1·56 [1·13–2·24]) and mental health-associated multimorbidity (15·3% [n=81] vs 9·8% [n=49]; AOR 1·62 [1·12–2·49]) were greater in the injured group than the uninjured group. Minimal differences in odds of reporting any poor mental health outcome were noted between the amputation injury subgroup and the uninjured group (AOR range 0·77–0·97), whereas up to double the odds were noted for the non-amputation injury subgroup compared with the uninjured group (AOR range 1·74–2·02). Interpretation: Serious physical combat injuries were associated with poor mental health outcomes. However, the type of injury sustained influenced this relationship. Regardless of injury, this cohort represents a group who present with greater rates of PTSD than the general population, as well as increased psychological burden from multimorbidity. Funding: The ADVANCE Charity

Hospital length of stay for COVID-19 patients: Data-driven methods for forward planning.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-07-01, epub 2021-07-22Publication status: PublishedFunder: Medical Research Council; Grant(s): MR/R502236/1Funder: Royal Society; Grant(s): 202562/Z/16/Z, INF/R2/180067BackgroundPredicting hospital length of stay (LoS) for patients with COVID-19 infection is essential to ensure that adequate bed capacity can be provided without unnecessarily restricting care for patients with other conditions. Here, we demonstrate the utility of three complementary methods for predicting LoS using UK national- and hospital-level data.MethodOn a national scale, relevant patients were identified from the COVID-19 Hospitalisation in England Surveillance System (CHESS) reports. An Accelerated Failure Time (AFT) survival model and a truncation corrected method (TC), both with underlying Weibull distributions, were fitted to the data to estimate LoS from hospital admission date to an outcome (death or discharge) and from hospital admission date to Intensive Care Unit (ICU) admission date. In a second approach we fit a multi-state (MS) survival model to data directly from the Manchester University NHS Foundation Trust (MFT). We develop a planning tool that uses LoS estimates from these models to predict bed occupancy.ResultsAll methods produced similar overall estimates of LoS for overall hospital stay, given a patient is not admitted to ICU (8.4, 9.1 and 8.0 days for AFT, TC and MS, respectively). Estimates differ more significantly between the local and national level when considering ICU. National estimates for ICU LoS from AFT and TC were 12.4 and 13.4 days, whereas in local data the MS method produced estimates of 18.9 days.ConclusionsGiven the complexity and partiality of different data sources and the rapidly evolving nature of the COVID-19 pandemic, it is most appropriate to use multiple analysis methods on multiple datasets. The AFT method accounts for censored cases, but does not allow for simultaneous consideration of different outcomes. The TC method does not include censored cases, instead correcting for truncation in the data, but does consider these different outcomes. The MS method can model complex pathways to different outcomes whilst accounting for censoring, but cannot handle non-random case missingness. Overall, we conclude that data-driven modelling approaches of LoS using these methods is useful in epidemic planning and management, and should be considered for widespread adoption throughout healthcare systems internationally where similar data resources exist

The underlying mechanisms by which Post-Traumatic Growth is associated with cardiovascular health in male UK military personnel: The ADVANCE cohort study

Post-Traumatic Growth (PTG) is associated with good cardiovascular health, but the mechanisms of this are poorly understood. This cross-sectional analysis assessed whether factors of PTG (Appreciation of Life (AOL), New Possibilities (NP), Personal Strength (PS), Relating to Others (RTO) and Spiritual Change (SC)) are associated with cardiovascular health in a cohort of 1006 male UK military personnel (median age 34). The findings suggest AOL, PS and RTO are associated with better cardiovascular health through cardiometabolic effects (lower levels of triglycerides, and total cholesterol) and haemodynamic functioning (lower diastolic blood pressure), but not inflammation. However, NP and SC were associated with poorer cardiovascular health through cardiometabolic effects (lower levels of high-density lipoproteins and higher levels of total cholesterol) and AOL had a non-linear association with low-density lipoproteins. These findings suggest that the relationship between PTG and cardiovascular functioning is complex and in need of further scrutiny