Humility, Relational Spirituality, and Well-being among Religious Leaders: A Moderated Mediation Model.

Prior research has demonstrated positive associations between general humility and well-being, and posited a protective effect for intellectual humility against maladjustment among religious leaders. We tested a model that extended findings on general humility to include intellectual humility among religious leaders (N = 258; M age = 42.31; 43% female; 63.7% White; 91.9% Christian affiliation). We observed a positive general humility-well-being association. Contrary to expectations, we observed risk effects for religion-specific intellectual humility. Our findings also point to the possibility that these risk effects might be attenuated by the integration of high levels of general and intellectual humility.

Nanoelectronic Platform for Ultrasensitive Detection of Protein Biomarkers in Serum using DNA Amplification.

Silicon nanowire field effect transistors (NWFETs) are low noise, low power, ultrasensitive biosensors that are highly amenable to integration. However, using NWFETs to achieve direct protein detection in physiological buffers such as blood serum remains difficult due to Debye screening, nonspecific binding, and stringent functionalization requirements. In this work, we performed an indirect sandwich immunoassay in serum combined with exponential DNA amplification and pH measurement by ultrasensitive NWFET sensors. Measurements of model cytokine interleukin-2 concentrations from <20 fM to >200 pM were demonstrated, surpassing the conventional NWFET urease-based readout. Our approach paves way for future development of universal, highly sensitive, miniaturized, and integrated nanoelectronic devices that can be applied to a wide variety of analytes.

Investigating Internalization of Reporter-Protein-Functionalized Polyhedrin Particles by Brain Immune Cells.

Achieving sustained drug delivery to the central nervous system (CNS) is a major challenge for neurological injury and disease, and various delivery vehicles are being developed to achieve this. Self-assembling polyhedrin crystals (POlyhedrin Delivery System; PODS) are being exploited for the delivery of therapeutic protein cargo, with demonstrated efficacy in vivo. However, to establish the utility of PODS for neural applications, their handling by neural immune cells (microglia) must be documented, as these cells process and degrade many biomaterials, often preventing therapeutic efficacy. Here, primary mouse cortical microglia were cultured with a GFP-functionalized PODS for 24 h. Cell counts, cell morphology and Iba1 expression were all unaltered in treated cultures, indicating a lack of acute toxicity or microglial activation. Microglia exhibited internalisation of the PODS, with both cytosolic and perinuclear localisation. No evidence of adverse effects on cellular morphology was observed. Overall, 20-40% of microglia exhibited uptake of the PODS, but extracellular/non-internalised PODS were routinely present after 24 h, suggesting that extracellular drug delivery may persist for at least 24 h.

Therapeutic effects of systemic administration of chaperone αB-crystallin associated with binding proinflammatory plasma proteins.

The therapeutic benefit of the small heat shock protein αB-crystallin (HspB5) in animal models of multiple sclerosis and ischemia is proposed to arise from its increased capacity to bind proinflammatory proteins at the elevated temperatures within inflammatory foci. By mass spectral analysis, a common set of ∼70 ligands was precipitated by HspB5 from plasma from patients with multiple sclerosis, rheumatoid arthritis, and amyloidosis and mice with experimental allergic encephalomyelitis. These proteins were distinguished from other precipitated molecules because they were enriched in the precipitate as compared with their plasma concentrations, and they exhibited temperature-dependent binding. More than half of these ligands were acute phase proteins or members of the complement or coagulation cascades. Consistent with this proposal, plasma levels of HspB5 were increased in patients with multiple sclerosis as compared with normal individuals. The combination of the thermal sensitivity of the HspB5 combined with the high local concentration of these ligands at the site of inflammation is proposed to explain the paradox of how a protein believed to exhibit nonspecific binding can bind with some relative apparent selectivity to proinflammatory proteins and thereby modulate inflammation.

Magnetic nanoparticle mediated transfection of neural stem cell suspension cultures is enhanced by applied oscillating magnetic fields.

Safe genetic modification of neural stem cell (NSC) transplant populations is a key goal for regenerative neurology. We describe a technically simple and safe method to increase transfection in NSCs propagated in the neurosphere (suspension culture) model, using magnetic nanoparticles deployed with applied oscillating magnetic fields ('magnetofection technology'). We show that transfection efficiency was enhanced over two-fold by oscillating magnetic fields (frequency=4 Hz). The protocols had no effect on cell viability, cell number, stem cell marker expression and differentiation profiles of 'magnetofected' cultures, highlighting the safety of the technique. As far as we are aware, this is the first successful application of magnetofection technology to suspension cultures of neural cells. The procedures described offer a means to augment the therapeutic potential of NSCs propagated as neurospheres - a culture model of high clinical translational relevance - by safe genetic manipulation, with further potential for incorporation into 'magneto-multifection' (repeat transfection) protocols. FROM THE CLINICAL EDITOR: This team of investigators describe a simple and safe method to increase transfection in neural stem cells using magnetic nanoparticles deployed with oscillating magnetic fields, demonstrating a greater than two-fold transfection efficiency increase by applying low frequency magnetic oscillation.

The effect of estrogen in a man with Parkinson's disease and a review of its therapeutic potential.

Estrogen has been implicated in controlling the pathogenesis and symptoms of Parkinson's disease (PD) in women. Here, we report a 53-year-old male with PD who underwent estrogen therapy with estradiol (E2). Within a month, he exhibited increased dyskinesias. His medication was reduced by 35% from a levodopa equivalent dose (LED) of 820-535 over three months, which overall improved his motor fluctuations and dyskinesias. Therefore, E2 therapy could have therapeutic potential in males with PD.

Erythritol sprays reduce Drosophila suzukii infestation without impacting honey bee visitation nor fruit quality.

BACKGROUND: Spotted-wing drosophila, Drosophila suzukii, is an economic pest of small fruits and cherries. Insecticides primarily control this pest while alternative controls are in development. Laboratory studies show that erythritol is insecticidal to D. suzukii and other pests while approved for human consumption. Moreover, erythritol combined with sucrose or non-caloric sucralose can stimulate feeding and quicken mortality. Before growers can use erythritol, the impact on crop protection, non-target insects, and fruit quality need evaluation. RESULTS: In three blueberry and cherry field cage trials, oviposition on fruit sprayed with erythritol:sucrose or erythritol:sucralose formulations was lowered by 59%-81% compared with unsprayed controls. Fly infestation (larval or adult counts from fruit) was 90% lower in a greenhouse blueberry trial, and 49% lower in an open field blueberry trial with 2 m erythritol : 0.5 m sucrose. Infestation was also 57% lower in an open field cherry trial with 1.5 m erythritol:0.5 m sucrose. Other field trials with very low pest pressure or frequent rains revealed no differences from controls. Field trials consistently revealed that honey bees did not preferentially visit plants sprayed with either erythritol formulation, although yellow jackets visited plants sprayed with erythritol:sucrose more frequently. Erythritol formulations consistently led to more leaf spotting, but there was no reduction in the quality of treated blueberries or cherries in terms of mold development, firmness, diameter, epidermal penetration force, and Brix° (total soluble solids) at harvest. CONCLUSION: Eleven trials conducted over four years show that erythritol formulations can reduce D. suzukii pressure without attracting foraging honey bees nor negatively impacting fruit quality. © 2023 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Seasonal activity of Trechnites insidiosus (Hymenoptera: Encyrtidae) and its host Cacopsylla pyricola (Hemiptera: Psyllidae) in pear.

Cacopsylla pyricola (Förster) (Hemiptera: Psyllidae) is the most expensive and challenging insect pest of commercial pear trees in the Pacific Northwest. Integrated pest management (IPM) programs are working toward relying more heavily on natural enemies to reduce insecticide use. Trechnites insidiosus (Crawford) (Hymenoptera: Encyrtidae) is the main parasitoid of C. pyricola, but little is known about its biology in the region. Developing sampling tools is important for the deployment of IPM programs, including monitoring of natural enemies. In this study, we examined 2 conventional monitoring methods: beat trays and yellow sticky cards, in addition to screened sticky cards and 3D-printed cylinder traps. Additionally, we tested an overwintering trap for the collection of parasitized C. pyricola. The trapping methods were tested in orchards in Oregon and Washington. Unscreened cards caught the most T. insidiosus and C. pyricola, followed by screened cards, cylinder traps, and then beat trays. Beat trays sometimes failed to catch any T. insidiosus, even when it was found in abundance via other methods. Screened cards and cylinder traps reduced bycatch and increased ease of identifying T. insidiosus. Specimens from the cylinder traps were also more suitable for use in molecular analysis. The overwintering traps were effective at capturing parasitized C. pyricola, but were highly variable year to year. The ideal trapping method will vary based on research needs (e.g., DNA preservation, reducing bycatch, catching higher numbers), but both screened sticky cards and cylinder traps were viable methods for monitoring T. insidiosus and its host.

Neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4-2) regulation by 14-3-3 protein binding at canonical serum and glucocorticoid kinase 1 (SGK1) phosphorylation sites.

Regulation of epithelial Na(+) channel (ENaC)-mediated transport in the distal nephron is a critical determinant of blood pressure in humans. Aldosterone via serum and glucocorticoid kinase 1 (SGK1) stimulates ENaC by phosphorylation of the E3 ubiquitin ligase Nedd4-2, which induces interaction with 14-3-3 proteins. However, the mechanisms of SGK1- and 14-3-3-mediated regulation of Nedd4-2 are unclear. There are three canonical SGK1 target sites on Nedd4-2 that overlap phosphorylation-dependent 14-3-3 interaction motifs. Two of these are termed "minor," and one is termed "major," based on weak or strong binding to 14-3-3 proteins, respectively. By mass spectrometry, we found that aldosterone significantly stimulates phosphorylation of a minor, relative to the major, 14-3-3 binding site on Nedd4-2. Phosphorylation-deficient minor site Nedd4-2 mutants bound less 14-3-3 than did wild-type (WT) Nedd4-2, and minor site Nedd4-2 mutations were sufficient to inhibit SGK1 stimulation of ENaC cell surface expression. As measured by pulse-chase and cycloheximide chase assays, a major binding site Nedd4-2 mutant had a shorter cellular half-life than WT Nedd4-2, but this property was not dependent on binding to 14-3-3. Additionally, a dimerization-deficient 14-3-3ε mutant failed to bind Nedd4-2. We conclude that whereas phosphorylation at the Nedd4-2 major site is important for interaction with 14-3-3 dimers, minor site phosphorylation by SGK1 may be the relevant molecular switch that stabilizes Nedd4-2 interaction with 14-3-3 and thus promotes ENaC cell surface expression. We also propose that major site phosphorylation promotes cellular Nedd4-2 protein stability, which potentially represents a novel form of regulation for turnover of E3 ubiquitin ligases.

Robotic-assisted total hip arthroplasty: an economic analysis.

Aim: To evaluate 90-day episode-of-care (EOC) resource consumption in robotic-assisted total hip arthroplasty (RATHA) versus manual total hip arthroplasty (mTHA). Methods: THA procedures were identified in Medicare 100% data. After propensity score matching 1:5, 938 RATHA and 4,670 mTHA cases were included. 90-day EOC cost, index costs, length of stay and post-index rehabilitation utilization were assessed. Results: RATHA patients were significantly less likely to have post-index inpatient rehabilitation or skilled nursing facility admissions and used fewer home health agency visits, compared with mTHA patients. Total 90-day EOC costs for RATHA patients were found to be US$785 less than those of mTHA patients (p = 0.0095). Conclusion: RATHA was associated with an overall lower 90-day EOC cost when compared with mTHA. The savings associated with RATHA were driven by reduced utilization and cost of post-index rehabilitation services.