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Presents a brief history of the events leading to the characterization of the compound thought to be ditellurium decafluoride. Notes reasons why this was inaccurate and suggests methods by which the compound might be prepared. (SLH)

Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA+ mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after next-generation androgen receptor–directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA+ identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA+ by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

Nitric oxide (NO) chemiluminescence detectors (CLDs) are specialized and sensitive spectroscopic instruments capable of directly measuring NO flux rates. NO CLDs have been instrumental in the characterization of mammalian nitrite-dependent NO synthases. However, no detailed description of NO flux analysis using NO CLD is available. Herein, a detailed review of the NO CL methodology is provided with guidelines for measuring NO-production rates from aqueous samples, such as isolated enzymes or protein homogenates. Detailed description of the types of signals one can encounter, data processing, and potential pitfalls related to NO flux measurements will also be covered.

The influenza A M2 channel, a prototype for the viroporin class of viral channels, is an acid-activated viroporin that conducts protons across the viral membrane, a critical step in the viral life cycle. As the protons enter from the viral exterior, four central His37 residues control the channel activation by binding subsequent protons, which opens the Trp41 gate and allows proton flux to the viral interior. Asp44 is essential for maintaining the Trp41 gate in a closed state at high pH, which results in asymmetric conduction. The prevalent D44N mutant disrupts this gate and opens the C-terminal end of the channel, resulting in overall increased conduction in the physiologically relevant pH range and a loss of this asymmetric conduction. Here, we use extensive Multiscale Reactive Molecular Dynamics (MS-RMD) and Quantum Mechanics/Molecular mechanics (QM/MM) simulations with an explicit, reactive excess proton to calculate the free energy of proton transport in the M2 mutant and to study the dynamic molecular-level behavior of D44N M2. We find that this mutation significantly lowers the barrier of His37 deprotonation in the activated state and shifts the barrier for entry up to the Val27 tetrad. These free energy changes are reflected in structural shifts. Additionally, we show that the increased hydration around the His37 tetrad diminishes the effect of the His37 charge on the channel’s water structure, facilitating proton transport and enabling activation from the viral interior. Altogether, this work provides key insight into the fundamental characteristics of PT in WT M2 and how the D44N mutation alters this PT mechanism, and it expands our understanding of the role of emergent mutations in viroporins.

Shortwave infrared (SWIR)-emitting small molecules are desirable for biological imaging applications. In this study, four novel pentamethine indolizine cyanine dyes were synthesized with N,N-dimethylaniline-based substituents on the indolizine periphery at varied substitution sites. The dyes are studied via computational chemistry and optical spectroscopy both in solution and when encapsulated. Dramatic spectral shifts in the absorption and emission spectrum wavelengths with added donor groups are observed. Significant absorption and emission with an emissive quantum yield as high as 3.6% in the SWIR region is possible through the addition of multiple donor groups per indolizine.

A high dose of whey protein hydrolysate fed with milk minerals rich in calcium (Capolac®) results in enhanced glucagon-like peptide-1 (GLP-1) concentrations in lean individuals; however, the effect of different calcium doses ingested alongside protein is unknown. The present study assessed the dose response of calcium fed alongside 25 g whey protein hydrolysate on GLP-1 concentrations in individuals with overweight/obesity. Eighteen adults (mean ± sd: 8M/10F, 34 ± 18 years, 28·2 ± 2·9 kgm−2) completed four trials in a randomised, double-blind, crossover design. Participants consumed test solutions consisting of 25 g whey protein hydrolysate (CON), supplemented with 3179 mg (LOW), 6363 mg (MED) or 9547 mg (HIGH) Capolac® on different occasions, separated by at least 48 h. The calcium content of test solutions equated to 65, 892, 1719 and 2547 mg, respectively. Arterialised-venous blood was sampled over 180 min to determine plasma concentrations of GLP-1TOTAL, GLP-17–36amide, insulin, glucose, NEFA, and serum concentrations of calcium and albumin. Ad libitum energy intake was measured at 180 min. Time–averaged incremental AUC (iAUC) for GLP-1TOTAL (pmol·l−1·min−1) did not differ between CON (23 ± 4), LOW (25 ± 6), MED (24 ± 5) and HIGH (24 ± 6). Energy intake (kcal) did not differ between CON (940 ± 387), LOW (884 ± 345), MED (920 ± 334) and HIGH (973 ± 390). Co-ingestion of whey protein hydrolysate with Capolac® does not potentiate GLP-1 release in comparison with whey protein hydrolysate alone. The study was registered at clinical trials (NCT03819972).

Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease in tRNA m5C levels, resulting in deficits in expression of 70% of tRNAGly isodecoders. Altogether, 1488/5820 proteins changed upon neuronal Nsun2-deficiency, in conjunction with glycine codon-specific defects in translational efficiencies. Loss of Gly-rich proteins critical for glutamatergic neurotransmission was associated with impaired synaptic signaling at PFC pyramidal neurons and defective contextual fear memory. Changes in the neuronal translatome were also associated with a 146% increase in glycine biosynthesis. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC. Furthermore, they link synaptic plasticity and complex behaviors to epitranscriptomic modifications of cognate tRNAs and the proteomic homeostasis associated with specific amino acids., The link between tRNA modifications, protein translation, and behavior is unclear. Here, the authors show that neuronal Nsun2 deficiency results in codon-specific epitranscriptomic changes of Gly-tRNAs and proteomic changes affecting synaptic signaling and behavior in mice.

Background Fetal docosahexaenoic acid (DHA) supply relies on preferential transplacental transfer, which is regulated by placental DHA lipid metabolism. Maternal hyperglycemia and obesity associate with higher birthweight and fetal DHA insufficiency but the role of placental DHA metabolism is unclear. Methods Explants from 17 term placenta were incubated with 13C-labeled DHA for 48 h, at 5 or 10 mmol/L glucose treatment, and the production of 17 individual newly synthesized 13C-DHA labeled lipids quantified by liquid chromatography mass spectrometry. Results Maternal BMI positively associated with 13C-DHA-labeled diacylglycerols, triacylglycerols, lysophospholipids, phosphatidylcholine and phosphatidylethanolamine plasmalogens, while maternal fasting glycemia positively associated with five 13C-DHA triacylglycerols. In turn, 13C-DHA-labeled phospholipids and triacylglycerols positively associated with birthweight centile. In-vitro glucose treatment increased most 13C-DHA-lipids, but decreased 13C-DHA phosphatidylethanolamine plasmalogens. However, with increasing maternal BMI, the magnitude of the glucose treatment induced increase in 13C-DHA phosphatidylcholine and 13C-DHA lysophospholipids was curtailed, with further decline in 13C-DHA phosphatidylethanolamine plasmalogens. Conversely, with increasing birthweight centile glucose treatment induced increases in 13C-DHA triacylglycerols were exaggerated, while glucose treatment induced decreases in 13C-DHA phosphatidylethanolamine plasmalogens were diminished. Conclusions Maternal BMI and glycemia increased the production of different placental DHA lipids implying impact on different metabolic pathways. Glucose-induced elevation in placental DHA metabolism is moderated with higher maternal BMI. In turn, findings of associations between many DHA lipids with birthweight suggest that BMI and glycemia promote fetal growth partly through changes in placental DHA metabolism.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is inversely associated with type 2 diabetes mellitus (T2DM) risk. Metabolic changes due to DASH adherence and their potential relationship with incident T2DM have not been described. The objective is to determine metabolite clusters associated with adherence to a DASH-like diet in the Insulin Resistance Atherosclerosis Study cohort and explore if the clusters predicted 5-year incidence of T2DM. The current study included 570 non-diabetic multi-ethnic participants aged 40–69 years. Adherence to a DASH-like diet was determined a priori through an eighty-point scale for absolute intakes of the eight DASH food groups. Quantitative measurements of eighty-seven metabolites (acylcarnitines, amino acids, bile acids, sterols and fatty acids) were obtained at baseline. Metabolite clusters related to DASH adherence were determined through partial least squares (PLS) analysis using R. Multivariable-adjusted logistic regression was used to explore the associations between metabolite clusters and incident T2DM. A group of acylcarnitines and fatty acids loaded strongly on the two components retained under PLS. Among strongly loading metabolites, a select group of acylcarnitines had over 50 % of their individual variance explained by the PLS model. Component 2 was inversely associated with incident T2DM (OR: 0·89; (95 % CI 0·80, 0·99), P-value = 0·043) after adjustment for demographic and metabolic covariates. Component 1 was not associated with T2DM risk (OR: 1·02; (95 % CI 0·88, 1·19), P-value = 0·74). Adherence to a DASH-type diet may contribute to reduced T2DM risk in part through modulations in acylcarnitine and fatty acid physiology.

BACKGROUND AND PURPOSE: Dual-layer spectral CT is a novel technology that utilized conventional single-tube CT acquisition with a dual-layer detector for the separation of high and low-energy photons to create spectral data for material decomposition. We evaluated the spectral parameters of iodine density and Z-effective values in primary head and neck squamous cell carcinoma and determined its impact on local tumor staging. MATERIALS AND METHODS: Twenty-one patients with primary head and neck squamous cell carcinoma and 15 healthy controls were retrospectively evaluated. Iodine density (milligram/milliliter) and Z-effective values were compared quantitatively between head and neck squamous cell carcinoma and normal neck mucosa. The receiver operating characteristic area under the curve determined the diagnostic performance of the spectral data for local staging. We compared conventional CT images without and with iodine density and Z-effective images to determine its impact on local tumor staging. RESULTS: Primary head and neck squamous cell carcinoma showed higher mean iodine density (2.01 [SD, 0.26] mg/mL, P

The histological distinction between acute and chronic liver injury is a challenging aspect of liver histopathology. It is traditionally based on the interpretation of morphological changes to the extracellular matrix (ECM) at sites of hepatocyte loss using histochemical stains. Our aim was to investigate whether immunohistochemistry and multiplexing for collagen type (I & III) and elastic fibres and a modified Victoria blue method could be helpful. We studied 43 livers removed at transplantation for acute liver failure (ALF, 20 cases) or cirrhosis (23) plus 8 normal controls. In ALF the periportal ECM was normal in 2 cases, contained mainly collagen I associated with a ductular reaction in 6 cases, and delicate elastic strands in 11 cases. Periportal deposition of mainly collagen I and mature elastic fibres was observed in cirrhosis. In ALF the perisinusoidal ECM was intact in 4 cases, collapsed or condensed but of normal composition (predominantly collagen III) in 2 cases, and collapsed and condensed containing mostly collagen I in 17 cases (7 including delicate immature elastic strands). In contrast, bridging fibrous septa of cirrhosis contained abundant collagen 1 and bundles of mature elastin. We propose the use of a scale and the use of immunohistochemistry and multiplexing in additional to histochemical stains to characterise the ECM changes in acute and chronic liver injury.

The COVID-19 pandemic underscores the need for rapid, safe, and effective vaccines. In contrast to some traditional vaccines, nanoparticle-based subunit vaccines are particularly efficient in trafficking antigens to lymph nodes, where they induce potent immune cell activation. Here, we developed a strategy to decorate the surface of oxidation-sensitive polymersomes with multiple copies of the SARS-CoV-2 spike protein receptor-binding domain (RBD) to mimic the physical form of a virus particle. We evaluated the vaccination efficacy of these surface-decorated polymersomes (RBDsurf) in mice compared to RBD-encapsulated polymersomes (RBDencap) and unformulated RBD (RBDfree), using monophosphoryl-lipid-A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBDsurf elicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBDsurf was the only group to significantly increase the proportion of RBD-specific germinal center B cells in the vaccination-site draining lymph nodes. Both RBDsurf and RBDencap drove similarly robust CD4+ and CD8+ T cell responses that produced multiple Th1-type cytokines. We conclude that a multivalent surface display of spike RBD on polymersomes promotes a potent neutralizing antibody response to SARS-CoV-2, while both antigen formulations promote robust T cell immunity., We developed nanoscale polymer vesicles (polymersomes) decorated with multiple copies of SARS-CoV-2 antigen as a COVID-19 vaccine that elicits neutralizing antibodies and cellular immunity.

Aims: \ud Identifying novel mediators of lethal myocardial reperfusion injury that can be targeted during primary percutaneous coronary intervention (PPCI) is key to limiting the progression of patients with ST-elevated myocardial infarction (STEMI) to heart failure. Here we show through parallel clinical and integrative preclinical studies the significance of the protease cathepsin-L on cardiac function during reperfusion injury.\ud \ud Methods and Results: \ud We found that direct cardiac release of cathepsin-L in STEMI patients (n = 76) immediately post-PPCI leads to elevated serum cathepsin-L levels and that serum levels of cathepsin-L in the first 24 hour post-reperfusion are associated with reduced cardiac contractile function and increased infarct size. Preclinical studies, demonstrate that inhibition of cathepsin-L release following reperfusion injury with CAA0225 reduces infarct size and improves cardiac contractile function by limiting abnormal cardiomyocyte calcium handling and apoptosis.\ud \ud Conclusion: \ud Our findings suggest that cathepsin-L is a novel therapeutic target that could be exploited clinically to counteract the deleterious effects of acute reperfusion injury after an acute STEMI.\ud \ud Translational perspective: \ud New therapeutic targets are urgently required to limit myocardial damage after reperfusion injury. We identified cardiac release of the protease cathepsin-L among patients following primary percutaneous coronary intervention (PPCI). Elevated serum levels of cathepsin-L were associated with reduced contractile function and increased infarct size at 24 hour and 6 months post-PPCI. Work conducted using animal models indicated that cardiac release of cathepsin-L mediated cardiac dysfunction following reperfusion injury. Specific inhibition of cathepsin-L prevented abnormal calcium handling, reduced infarct size and improved contractile function. These novel findings offer the prospect of targeting cathepsin-L-mediated cardiac dysfunction after PPCI.

The Naples Botanical Garden, located in Collier County, Florida, attracts over 220,000 visitors each year. The gardens house a collection of plants from around the world, including a featured area for over 100 species of exotic and native bromeliads. Ornamental bromeliads have previously been investigated to define their “tank” structure as a haven for mosquito eggs and larvae. The Naples Botanical Gardens was investigated for the presence of juvenile mosquitoes inhabiting large-tanked bromeliads. A survey of mosquito species inhabiting bromeliads in the gardens indicated that the most abundant species was Culex quinquefasciatus. With the ongoing threat of vector borne diseases such as West Nile virus, the abundance of vector mosquitoes and heavy tourist traffic in the gardens, insecticide resistance testing was performed on Cx. quinquefasciatus originating in the gardens in order to assess the ability of pyrethroid-based insecticides used by the local vector control agency to successfully target this species in the event of a disease outbreak. We identified pyrethroid resistance in Cx. quinquefasciatus collected from Naples Botanical Gardens, and that oxidase activity was the primary mechanism responsible for its pyrethroid resistance status.

Summary Objective Molecular information derived from dynamic [18F]sodium fluoride ([18F]NaF) PET imaging holds promise as a quantitative marker of bone metabolism. The objective of this work was to evaluate physiological mechanisms of [18F]NaF uptake in subchondral bone of individuals with and without knee osteoarthritis (OA). Methods Eleven healthy volunteers and twenty OA subjects were included. Both knees of all subjects were scanned simultaneously using a 3T hybrid PET/MRI system. MRI MOAKS assessment was performed to score the presence and size of osteophytes, bone marrow lesions, and cartilage lesions. Subchondral bone kinetic parameters of bone perfusion (K1), tracer extraction fraction, and total tracer uptake into bone (Ki) were evaluated using the Hawkins 3-compartment model. Measures were compared between structurally normal-appearing bone regions and those with structural findings. Results Mean and maximum SUV and kinetic parameters Ki, K1, and extraction fraction were significantly different between Healthy subjects and subjects with OA. Between-group differences in metabolic parameters were observed both in regions where the OA group had degenerative changes as well as in regions that appeared structurally normal. Conclusions Results suggest that bone metabolism is altered in OA subjects, including bone regions with and without structural findings, compared to healthy subjects. Kinetic parameters of [18F]NaF uptake in subchondral bone show potential to quantitatively evaluate the role of bone physiology in OA initiation and progression. Objective measures of bone metabolism from [18F]NaF PET imaging can complement assessments of structural abnormalities observed on MRI.

Dairy fat is rich in SFA such as palmitic acid (16:0) but low in linoleic acid (18:2n-6). The natural carbon 13 enrichment (δ13C) of 16:0 is higher in dairy fat than in most of the food supply. In adults, serum levels of pentadecanoic acid (15:0) and heptadecanoic acid (17:0) are recognised as biomarkers of dairy intake. In adolescents, no study has evaluated serum fatty acid levels or δ13C in response to chronic dairy consumption. The objectives of this study were to evaluate whether increased dairy product consumption can modulate (1) serum fatty acid levels and (2) 16:0 δ13C in adolescents with overweight/obesity who followed a 12-week weight management programme. This secondary analysis of a randomised control trial included two groups of adolescent females: recommended dairy (RDa; n 23) and low dairy (LDa; n 23). The RDa group was given 4 servings/d of dairy products while the LDa group maintained dairy intakes at ≤ 2 servings/d. Blood was sampled before and after the intervention. Lipids were extracted and separated, and fatty acids were quantified by GC. Isotope ratio MS was used to assess 16:0 δ13C. There were no group differences on serum changes of 15:0 or 17:0. Within TAG, 18:2n-6 was lowered by 7·4 % only in the RDa group (P = 0·040). The difference in delta 16:0 δ13C between the LDa and RDa groups did not reach statistical significance (P = 0·070). Reductions in serum 18:2n-6 by dairy consumption could have positive health implications, but more studies are needed to confirm this assertion.

The synthesis, characterization and antimicrobial activity of Cu(II) complexes of some p-substituted aniline Schiff base ligands have been carried out. The Schiff bases were obtained from salicylaldehyde and o-vanillin. The Cu(II) complexes have been characterized by elemental analysis, conductivity measurement, infrared and electronic spectral data. The complexes were obtained either as metal chelates [Cu(L)2] or Schiff base adducts (CuCl2.2LH).xH2O. The metal chelates were non-electrolytes while the Schiff base adducts exhibited 1:1 or 2:1 electrolytes in methanol. The Cu(II) complexes exhibited slight antimicrobial activity against Escherichia coli ATCC® 8739™*, Staphylococcus aureus subsp. aureus ATCC® 6538™*, Bacillus subtilis subsp. spizizenii ATCC® 6633™* and Candida albicans ATCC® 2091™*. The complexes exhibited significant antifungal activity. KEY WORDS: Metal Chelates, Schiff bases, Adducts, Cu(II) complexes, Salicylaldimines Bull. Chem. Soc. Ethiop. 2021, 35(1), 33-42. DOI: https://dx.doi.org/10.4314/bcse.v35i1.3

The Cedars ultramafic block hosts alkaline springs (pH > 11) in which calcium carbonate forms upon uptake of atmospheric CO2 and at times via mixing with surface water. These processes lead to distinct carbonate morphologies with “floes” forming at the atmosphere-water interface, “snow” of fine particles accumulating at the bottom of pools and terraced constructions of travertine. Floe material is mainly composed of aragonite needles despite CaCO3 precipitation occurring in waters with low Mg/Ca ( The calcium carbonates exhibit an extreme range and approximately 1:1 covariation in δ13C (−9 to −28‰ VPDB) and δ18O (0 to −20‰ VPDB) that is characteristic of travertine formed in high pH waters. The large isotopic fractionations have previously been attributed to kinetic isotope effects accompanying CO2 hydroxylation but the controls on the δ13C-δ18O endmembers and slope have not been fully resolved, limiting the use of travertine as a paleoenvironmental archive. The limited areal extent of the springs (∼0.5 km2) and the limited range of water sources and temperatures, combined with our sampling strategy, allow us to place tight constraints on the processes involved in generating the systematic C and O isotope variations. We develop an isotopic reaction–diffusion model and an isotopic box model for a CO2-fed solution that tracks the isotopic composition of each dissolved inorganic carbon (DIC) species and CaCO3. The box model includes four sources or sinks of DIC (atmospheric CO2, high pH spring water, fresh creek water, and CaCO3 precipitation). Model parameters are informed by new floe Δ44Ca data (−0.75 ± 0.07‰), direct mineral growth rate measurements (4.8 to 8 × 10−7 mol/m2/s) and by previously published elemental and isotopic data of local water and DIC sources. Model results suggest two processes control the extremes of the array: (1) the isotopically light end member is controlled by the isotopic composition of atmospheric CO2 and the kinetic isotope fractionation factor (KFF (‰) = (α − 1) × 1000) accompanying CO2 hydroxylation, estimated here to be −17.1 ± 0.8‰ (vs. CO2(aq)) for carbon and −7.1 ± 1.1‰ (vs. ‘CO2(aq) + H2O’) for oxygen at 17.4 ± 1.0 °C. Combining our results with revised CO2 hydroxylation KFF values based on previous work suggests consistent KFF values of −17.0 ± 0.3‰ (vs. CO2(aq)) for carbon and −6.8 ± 0.8‰ for oxygen (vs. ‘CO2(aq) + H2O’) over the 17–28 °C temperature range. (2) The isotopically heavy endmember of calcium carbonates at The Cedars reflects the composition of isotopically equilibrated DIC from creek or surface water (mostly HC O 3 - , pH = 7.8–8.7) that occasionally mixes with the high-pH spring water. The bulk carbonate δ13C and δ18O values of modern and ancient travertines therefore reflect the proportion of calcium carbonate formed by processes (1) and (2), with process (2) dominating the carbonate precipitation budget at The Cedars. These results show that recent advances in understanding kinetic isotope effects allow us to model complicated but common natural processes, and suggest ancient travertine may be used to retrieve past meteoric water δ18O and atmospheric δ13C values. There is evidence that older travertine at The Cedars recorded atmospheric δ13C that predates large-scale combustion of fossil fuels.

Background Lameness is a debilitating condition in equine athletes that leads to more performance limitation and loss of use than any other medical condition. There are a limited number of non-terminal experimental models that can be used to study early inflammatory and synovial fluid biophysical changes that occur in the equine joint. Here, we compare the well-established carpal IL-1β-induced synovitis model to a tarsal intra-articular lavage model, focusing on serial changes in synovial fluid inflammatory cytokines/chemokines and the synovial fluid lubricating molecules lubricin/proteoglycan 4 and hyaluronic acid. The objectives of this study were to evaluate clinical signs; synovial membrane and synovial fluid inflammation; and synovial fluid lubricants and biophysical properties in response to carpal IL-1β synovitis and tarsal intra-articular lavage. Results Hyaluronic acid (HA) concentrations, especially high molecular weight HA, and synovial fluid viscosity decreased after both synovitis and lavage interventions. Synovial fluid lubricin concentrations increased 17–20-fold for both synovitis and lavage models, with similar changes in both affected and contralateral joints, suggesting that repeated arthrocentesis alone resulted in elevated synovial fluid lubricin concentrations. Synovitis resulted in a more severe inflammatory response based on clinical signs (temperature, heart rate, respiratory rate, lameness and joint effusion) and clinicopathological and biochemical parameters (white blood cell count, total protein, prostaglandin E2, sulfated glycosaminoglycans, tumor necrosis factor-α and CC chemokine ligands − 2, − 3, − 5 and − 11) as compared to lavage. Conclusions Synovial fluid lubricin increased in response to IL-1β synovitis and joint lavage but also as a result of repeated arthrocentesis. Frequent repeated arthrocentesis is associated with inflammatory changes, including increased sulfated glycosaminoglycan concentrations and decreased hyaluronic acid concentrations. Synovitis results in more significant inflammatory changes than joint lavage. Our data suggests that synovial fluid lubricin, TNF-α, CCL2, CCL3, CCL5, CCL11 and sGAG may be useful biomarkers for synovitis and post-lavage joint inflammation. Caution should be exercised when performing repeated arthrocentesis clinically or in experimental studies due to the inflammatory response and loss of HA and synovial fluid viscosity.

Glass carbon electrodes (GCE) were modified with metal organic frameworks (MOFs) containing molybdenum polyoxometallates (Mo POMs) in a copper benzene tricarboxylate framework (HKUST-1). The Mo POM...

Binder-free mesoporous graphitic carbon composite films on polymer or metal substrates are attractive for high-surface-area electrodes to achieve superior device performances. However, rapid and large-area fabrication of such materials remains a significant challenge due to the harsh conditions required for the carbonization process. We report an efficient method that combines bottom-up precursor film assembly with photothermal processing using sub-millisecond light pulses generated from a xenon flash lamp. This approach enables the rapid carbonization and graphitization of precursor films over large areas at ambient bulk temperature to yield functional films while avoiding damage to the substrates. The films contain light-absorbing nanoparticles to convert light energy into heat, a block copolymer to template the porous structures via self-assembly, and phenol-fomaldehyde resin to form the carbon skeleton. Graphitic carbon nanoribbons embedded in a porous carbon matrix are created under mild conditions using iron nanoparticles as the catalyst during the millisecond photothermal process. The resulting composite films show excellent electrochemical properties and are demonstrated for use as high capacity lithium ion battery anodes.

As part of the United States Environmental Protection Agency’s 2010 Nitrogen Dioxide (NO(2)) National Ambient Air Quality Standards (NAAQS) review, a national network of near-road sites was established to characterize pollutant behavior, interaction, and dispersion in the ambient near-road environment. Using spatial interpolation to estimate the near-road concentration increments of NO(2) and particulate matter with an aerodynamic diameter of 2.5 micrometers and less (PM(2.5)) relative to nearby non-near-road monitors, we found that the 2013–2018 national average increment is 6.9 ppb and 1.0 μg m(−3) for NO(2) and PM(2.5), respectively. Analyses of the hourly near-road NO(2,) nitric oxide (NO), and PM(2.5) increments showed distinct diurnal cycles; the NO(2) increment peaks at ~9 ppb during the early afternoon (2–4pm local time) while the NO and PM(2.5) increments peak during the morning rush hour (5–8am local time) at 25 ppb and 1.8 μg m(−3) for NO and PM(2.5), respectively. Although long term trends are not yet available for this network of sites, a similar analysis of the NO(2) and PM(2.5) increment at a quasi-near-road site outside of the official network in Elizabeth, NJ showed gradual decreases in the increment over time since the mid-2000s.

RationaleRumination is a repetitive, negative, self-focused thinking style associated with various forms of psychopathology. Recent studies suggest that rumination increases craving for alcohol and predicts harmful drinking and alcohol-related problems. However, the acute effects of alcohol on rumination have not been previously studied. It is proposed that alcohol may reduce ruminative thinking through decreasing negative mood.ObjectivesIn the present study, we aimed to test the previously unexplored effects of acute alcohol consumption on rumination in a hazardous drinking population.MethodsWe conducted a randomised placebo-controlled laboratory study to examine the effect of low (0.4 g kg−1) and high doses (0.8 g kg−1) of alcohol on state rumination compared to placebo. Participants completed a rumination induction task prior to receiving drinks. We then measured state rumination and mood at repeated time points; 30 min, 60 min and 90 min post-drinks consumption.ResultsWe found a significant decrease in state rumination in the low-dose alcohol group compared to placebo at 30 min post-alcohol consumption, but no difference was observed between the high-dose alcohol and placebo groups. Mediation analysis provided evidence for an indirect effect of alcohol on state rumination through concurrent changes in negative mood.ConclusionsThese findings suggest that acute alcohol consumption can regulate negative mood and concurrently rumination, providing preliminary evidence for the role of rumination in alcohol use disorders. Rumination may be a treatment target in alcohol use disorders.