Metal-Metal Bonding as an Electrode Design Principle in the Low-Strain Cluster Compound LiScMo3O8.

Electrode materials for Li+-ion batteries require optimization along several disparate axes related to cost, performance, and sustainability. One of the important performance axes is the ability to retain structural integrity though cycles of charge/discharge. Metal-metal bonding is a distinct feature of some refractory metal oxides that has been largely underutilized in electrochemical energy storage, but that could potentially impact structural integrity. Here LiScMo3O8, a compound containing triangular clusters of metal-metal bonded Mo atoms, is studied as a potential anode material in Li+-ion batteries. Electrons inserted though lithiation are localized across rigid Mo3 triangles (rather than on individual metal ions), resulting in minimal structural change as suggested by operando diffraction. The unusual chemical bonding allows this compound to be cycled with Mo atoms below a formally +4 valence state, resulting in an acceptable voltage regime that is appropriate for an anode material. Several characterization methods including potentiometric entropy measurements indicate two-phase regions, which are attributed through extensive first-principles modeling to Li+ ordering. This study of LiScMo3O8 provides valuable insights for design principles for structural motifs that stably and reversibly permit Li+ (de)insertion.

Widespread gaps in the quality of care for primary biliary cholangitis in UK.

OBJECTIVE: Primary biliary cholangitis (PBC) is a progressive, autoimmune, cholestatic liver disease affecting approximately 15 000 individuals in the UK. Updated guidelines for the management of PBC were published by The European Association for the Study of the Liver (EASL) in 2017. We report on the first national, pilot audit that assesses the quality of care and adherence to guidelines. DESIGN: Data were collected from 11 National Health Service hospitals in England, Wales and Scotland between 2017 and 2020. Data on patient demographics, ursodeoxycholic acid (UDCA) dosing and key guideline recommendations were captured from medical records. Results from each hospital were evaluated for target achievement and underwent χ2 analysis for variation in performance between trusts. RESULTS: 790 patients' medical records were reviewed. The data demonstrated that the majority of hospitals did not meet all of the recommended EASL standards. Standards with the lowest likelihood of being met were identified as optimal UDCA dosing, assessment of bone density and assessment of clinical symptoms (pruritus and fatigue). Significant variations in meeting these three standards were observed across UK, in addition to assessment of biochemical response to UDCA (all p<0.0001) and assessment of transplant eligibility in high-risk patients (p=0.0297). CONCLUSION: Our findings identify a broad-based deficiency in 'real-world' PBC care, suggesting the need for an intervention to improve guideline adherence, ultimately improving patient outcomes. We developed the PBC Review tool and recommend its incorporation into clinical practice. As the first audit of its kind, it will be used to inform a future wide-scale reaudit.

Probing reaction processes and reversibility in Earth-abundant Na3FeF6 for Na-ion batteries.

Sodium (Na)-ion batteries are the most explored 'beyond-Li' battery systems, yet their energy densities are still largely limited by the positive electrode material. Na3FeF6 is a promising Earth-abundant containing electrode and operates through a conversion-type charge-discharge reaction associated with a high theoretical capacity (336 mA h g-1). In practice, however, only a third of this capacity is achieved during electrochemical cycling. In this study, we demonstrate a new rapid and environmentally-friendly assisted-microwave method for the preparation of Na3FeF6. A comprehensive understanding of charge-discharge processes and of the reactivity of the cycled electrode samples is achieved using a combination of electrochemical tests, synchrotron X-ray diffraction, 57Fe Mössbauer spectroscopy, X-ray photoelectron spectroscopy, magnetometry, and 23Na/19F solid-state nuclear magnetic resonance (NMR) complemented with first principles calculations of NMR properties. We find that the primary performance limitation of the Na3FeF6 electrode is the sluggish kinetics of the conversion reaction, while the methods employed for materials synthesis and electrode preparation do not have a significant impact on the conversion efficiency and reversibility. Our work confirms that Na3FeF6 undergoes conversion into NaF and Fe(s) nanoparticles. The latter are found to be prone to oxidation prior to ex situ measurements, thus necessitating a robust analysis of the stable phases (here, NaF) formed upon conversion.

Li5VF4(SO4)2: A Prototype High-Voltage Li-Ion Cathode.

A Li-rich polyanionic compound based on V3+ with a previously unknown structure, Li5VF4(SO4)2, has been developed as a high-voltage cathode material for Li-ion batteries. The solvothermal preparation of this material, crystal structure solution, and initial electrochemical characterization are presented. An analysis based on density functional theory electronic structure calculations suggests that a high voltage close to 5 V is required to extract two Li ions and to reach the oxidation state of V5+. However, the use of conventional carbonate-based electrolytes, which exhibit increasing degradation above a potential of 4.3 V, does not permit the full capacity of this compound to be achieved at this time.

A look to the future in non-alcoholic fatty liver disease: Are glucagon-like peptide-1 analogues or sodium-glucose co-transporter-2 inhibitors the answer?

The increasing prevalence of diabetes and non-alcoholic fatty liver disease (NAFLD) is a growing public health concern associated with significant morbidity, mortality and economic cost, particularly in those who progress to cirrhosis. Medical treatment is frequently limited, with no specific licensed treatments currently available for people with NAFLD. Its association with diabetes raises the possibility of shared mechanisms of disease progression and treatment. With the ever-growing interest in the non-glycaemic effects of diabetes medications, studies and clinical trials have investigated hepatic outcomes associated with the use of drug classes used for people with type 2 diabetes (T2D), such as glucagon-like peptide-1 (GLP-1) analogues or sodium-glucose co-transporter-2 (SGLT2) inhibitors. Studies exploring the use of GLP-1 analogues or SGLT2 inhibitors in people with NAFLD have observed improved measures of hepatic inflammation, liver enzymes and radiological features over short periods. However, these studies tend to have variable study populations and inconsistent reported outcomes, limiting comparison between drugs and drug classes. As these drugs appear to improve biomarkers of NAFLD, clinicians should consider their use in patients with NAFLD and T2D. However, further evidence with greater participant numbers and longer trial durations is required to support specific licensing for people with NAFLD. Larger trials would allow reporting of major adverse hepatic events, akin to cardiovascular and renal outcome trials, to be determined. This would provide a more meaningful evaluation of the impact of these drugs in NAFLD. Nevertheless, these drugs represent a future potential therapeutic avenue in this difficult-to-treat population and may beget significant health and economic impacts.

A Quiet Firehouse: Reducing Environmental Stimuli Among Professional On-Duty Firefighters.

OBJECTIVE: Firehouse alarms are so loud that they cause a systemic response, similar to the flight-or-flight response. The purpose of the study was to reduce firehouse environmental stimuli to improve sleep quality and, thus, reduce cardiac burden. METHODS: The intervention included restricted unnecessary fire alarms, reduced light levels, and regulated temperature in the bunkroom. RESULTS: Among 24 firefighters, 11 completed the matched post-assessment. Six weeks after implementing the interventions, measures revealed the average lux level dropped from 0.75 to 0.19 lux, P < 0.05, and the presence of elevated blood pressure reduced from 86% to 15%, P < 0.05. CONCLUSION: Results support that reducing environmental stimuli in firehouses reduces blood pressure, which is much easier than targeting behavior change. RECOMMENDATIONS: On the basis of this pilot study, the practice of routinely activating unnecessary fire alarms in firehouse bunkrooms should be discouraged.

Altered DNA methylation and expression of PLAGL1 in cord blood from assisted reproductive technology pregnancies compared with natural conceptions.

OBJECTIVE: To investigate DNA methylation and expression of imprinted genes and an imprinted gene network (IGN) in neonates conceived via assisted reproductive technology (ART). DESIGN: Case control. SETTING: Research institution. PATIENT(S): Two hundred sixty-four cases of cord blood and/or placental villi from neonates (101 IVF, 81 ICSI, 82 naturally conceived). INTERVENTION(S): Placentas were obtained at birth for biopsy and cord blood extraction. MAIN OUTCOME MEASURE(S): DNA methylation and expression of imprinted genes. RESULT(S): DNA methylation at the PLAGL1 differentially methylated region (DMR) was significantly higher in IVF cord blood (48.0%) compared with controls (46.0%). No differences were found in DNA methylation between conception modes for KvDMR1 and LINE-1 in cord blood and placenta as well as PLAGL1 and PEG10 in placenta villi. PLAGL1 expression was lower in both IVF and ICSI cord blood groups than in controls (relative quantification of 0.65, 0.74, 0.89, respectively). Analyzing the expression of 3 genes in a PLAGL1 regulated IGN revealed different expression between conception modes and a significant correlation to PLAGL1 expression in only one (KCNQ1OT1). CONCLUSION(S): Our results suggest a stability of DNA methylation at imprinted DMRs; however, we show PLAGL1 methylation/expression to be altered after ART. As PLAGL1 expression correlated with only one of the three IGN genes in cord blood, we propose there is a more complex mechanism of regulating the IGN that may involve other genes and epigenetic modifications in this tissue. Further research investigating IGN-implicated genes in various neonatal tissues is warranted to elucidate the full effects ART-induced alterations to PLAGL1 and the IGN may have on fetal growth/development.

Identification and characterization of a Streptococcus pyogenes operon involved in binding of hemoproteins and acquisition of iron.

The hemolytic Streptococcus pyogenes can use a variety of heme compounds as an iron source. In this study, we investigate hemoprotein utilization by S. pyogenes. We demonstrate that surface proteins contribute to the binding of hemoproteins to S. pyogenes. We identify an ABC transporter from the iron complex family named sia for streptococcal iron acquisition, which consists of a lipoprotein (siaA), membrane permease (siaB), and ATPase (siaC). The sia transporter is part of a highly conserved, iron regulated, 10-gene operon. SiaA, which was localized to the cell membrane, could specifically bind hemoglobin. The operon's first gene encodes a novel bacterial protein that bound hemoglobin, myoglobin, heme-albumin, and hemoglobin-haptoglobin (but not apo-haptoglobin) and therefore was named Shr, for streptococcal hemoprotein receptor. PhoZ fusion and Western blot analysis showed that Shr has a leader peptide and is found in both membrane-bound and soluble forms. An M1 SF370 strain with a polar mutation in shr was more resistant to streptonigrin and hydrogen peroxide, suggesting decreased iron uptake. The addition of hemoglobin to the culture medium increased cell resistance to hydrogen peroxide in SF370 but not in the mutant, implying the sia operon may be involved in hemoglobin-dependent resistance to oxidative stress. The shr mutant demonstrated reduced hemoglobin binding, though cell growth in iron-depleted medium supplemented with hemoglobin, whole blood, or ferric citrate was not affected, suggesting additional systems are involved in hemoglobin utilization. SiaA and Shr are the first hemoprotein receptors identified in S. pyogenes; their possible role in iron capture is discussed.