Distress and worry as mediators in the relationship between psychosocial risks and upper body musculoskeletal complaints in highly automated manufacturing

As a result of changes in manufacturing including an upward trend in automation and the advent of the fourth industrial revolution, the requirement for supervisory monitoring and consequently, cognitive demand has increased in automated manufacturing. The incidence of musculoskeletal disorders has also increased in the manufacturing sector. A model was developed based on survey data to test if distress and worry mediate the relationship between psychosocial factors (job control, cognitive demand, social isolation and skill discretion), stress states and symptoms of upper body musculoskeletal disorders in highly automated manufacturing companies (n = 235). These constructs facilitated the development of a statistically significant model (RMSEA 0.057, TLI 0.924, CFI 0.935). Cognitive demand was shown to be related to higher distress in employees, and distress to a higher incidence of self-reported shoulder and lower back symptoms. The mediation model incorporating stress states (distress, worry) as mediators is a novel approach in linking psychosocial risks to musculoskeletal disorders.

Practitioners’ Summary

With little requirement for physical work in many modern automated manufacturing workplaces, there is often minimal management focus on Work-Related Musculoskeletal Disorders (WRMSDs) as important occupational health problems. Our model provides evidence that psychosocial factors are important risk factors in symptoms of WRMSD and should be managed.     

Islet Regeneration: Endogenous and Exogenous Approaches

Both type 1 and type 2 diabetes are characterized by a progressive loss of beta cell mass that contributes to impaired glucose homeostasis. Although an optimal treatment option would be to simply replace the lost cells, it is now well established that unlike many other organs, the adult pancreas has limited regenerative potential. For this reason, significant research efforts are focusing on methods to induce beta cell proliferation (replication of existing beta cells), promote beta cell formation from alternative endogenous cell sources (neogenesis), and/or generate beta cells from pluripotent stem cells. In this article, we will review (i) endogenous mechanisms of beta cell regeneration during steady state, stress and disease; (ii) efforts to stimulate endogenous regeneration and transdifferentiation; and (iii) exogenous methods of beta cell generation and transplantation.     

Plutonium Loading of Prospective Grouped Actinide Extraction (GANEX) Solvent Systems based on Diglycolamide Extractants

The Grouped Actinide Extraction (GANEX) process is being developed for actinide recycling within future nuclear fuel cycles. Interactions between potential solvents and macro-concentrations of plutonium are one of the most important issues in defining the GANEX process. Surprisingly, plutonium loading of diglycolamide (DGA) based solvents such as tetra-octyl DGA (TODGA) causes precipitation rather than a conventional third phase, in direct contrast to results with U(VI), Th(IV) or lanthanide ions. Various DGA based solvent systems have been screened for their plutonium loading capacity and 0.2 M TODGA with 0.5 M DMDOHEMA in a kerosene diluent is selected as the optimum solvent formulation of those tested. Plutonium can be relatively easily stripped from this solvent using aqueous acetohydroxamic acid but this is very acid dependent in the low acidity region.     

Structure-activity relationship refinement and further assessment of indole-3-glyoxylamides as a lead series against prion disease

Structure–activity relationships within the indole‐3‐glyoxylamide series of antiprion agents have been explored further, resulting in discovery of several new compounds demonstrating excellent activity in a cell line model of prion disease (EC₅₀ <10 nM ). After examining a range of substituents at the para‐position of the N‐phenylglyoxylamide moiety, five‐membered heterocycles containing at least two heteroatoms were found to be optimal for the antiprion effect. A number of modifications were made to probe the importance of the glyoxylamide substructure, although none were well tolerated. The most potent compounds did, however, prove largely stable towards microsomal metabolism, and the most active library member cured scrapie‐infected cells indefinitely on administration of a single treatment. The present results thereby confirm the indole‐3‐glyoxylamides as a promising lead series for continuing in vitro and in vivo evaluation against prion disease.     

4,4′BOX based catalysts: Synthesis,structure and catalytic application

The synthesis of two new 4,4′ bisoxazoline ligands is described. The use of copper complexes of these and three other recently described related ligands as catalysts in a cyclopropanation reaction is discussed. The first structural data on one such chiral copper complex is reported herein.     

Fibrinogen Replacement Therapy for Traumatic Coagulopathy: Does the Fibrinogen Source Matter?

Fibrinogen is the first coagulation protein to reach critically low levels during traumatic haemorrhage. There have been no differential effects on clinical outcomes between the two main sources of fibrinogen replacement: cryoprecipitate and fibrinogen concentrate (Fg-C). However, the constituents of these sources are very different. The aim of this study was to determine whether these give rise to any differences in clot stability that may occur during trauma haemorrhage. Fibrinogen deficient plasma (FDP) was spiked with fibrinogen from cryoprecipitate or Fg-C. A panel of coagulation factors, rotational thromboelastography (ROTEM), thrombin generation (TG), clot lysis and confocal microscopy were performed to measure clot strength and stability. Increasing concentrations of fibrinogen from Fg-C or cryoprecipitate added to FDP strongly correlated with Clauss fibrinogen, demonstrating good recovery of fibrinogen (r² = 0.99). A marked increase in Factor VIII, XIII and α₂-antiplasmin was observed in cryoprecipitate (p < 0.05). Increasing concentrations of fibrinogen from both sources were strongly correlated with ROTEM parameters (r² = 0.78–0.98). Cryoprecipitate therapy improved TG potential, increased fibrinolytic resistance and formed more homogeneous fibrin clots, compared to Fg-C. In summary, our data indicate that cryoprecipitate may be a superior source of fibrinogen to successfully control bleeding in trauma coagulopathy. However, these different products require evaluation in a clinical setting.     

Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues

A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively. Several emission-based spectroscopy methods used in the paper demonstrate an especially important role for Trp 103 in TS ligands binding. In addition, the Advanced Poisson–Boltzmann Solver (APBS) results show considerable differences in the distribution of electrostatic potential around Trp 103, as compared to distributions observed for all remaining Trp residues in the mTS family of structures. Together, spectroscopic and APBS results reveal a possible interplay between Trp 103 and His190, which contributes to a reduction in enzymatic activity in the case of H190A mutation. Comparison of electrostatic potential for mTS complexes, and their mutants, with the substrate, dUMP, and inhibitors, FdUMP and N4-OH-dCMP, suggests its weaker influence on the enzyme–ligand interactions in N4OH-dCMP-mTS compared to dUMP-mTS and FdUMP-mTS complexes. This difference may be crucial for the explanation of the ”abortive reaction” inhibitory mechanism of N4OH-dCMP towards TS. In addition, based on structural analyses and the H190A mutant capacity to form a denaturation-resistant complex with N4-OH-dCMP in the mTHF-dependent reaction, His190 is apparently responsible for a strong preference of the enzyme active center for the anti rotamer of the imino inhibitor form.     

Size-Exclusion Chromatography Separation Reveals That Vesicular and Non-Vesicular Small RNA Profiles Differ in Cell Free Urine

Urinary extracellular vesicles (EVs) and their RNA cargo are a novel source of biomarkers for various diseases. We aimed to identify the optimal method for isolating small (<200 nm) EVs from human urine prior to small RNA analysis. EVs from filtered healthy volunteer urine were concentrated using three methods: ultracentrifugation (UC); a precipitation-based kit (PR); and ultrafiltration (UF). EVs were further purified by size-exclusion chromatography (SEC). EV preparations were analysed with transmission electron microscopy (TEM), Western blotting, nanoparticle tracking analysis (NTA) and an Agilent Bioanalyzer Small RNA kit. UF yielded the highest number of particles both before and after SEC. Small RNA analysis from UF-concentrated urine identified two major peaks at 10–40 nucleotides (nt) and 40–80 nt. In contrast, EV preparations obtained after UC, PR or SEC combined with any concentrating method, contained predominantly 40–80 nt sized small RNA. Protein fractions from UF+SEC contained small RNA of 10–40 nt in size (consistent with miRNAs). These data indicate that most of the microRNA-sized RNAs in filtered urine are not associated with small-sized EVs, and highlights the importance of removing non-vesicular proteins and RNA from urine EV preparations prior to small RNA analysis.