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Depending on the 3D-printing orientation, the anisotropy of the elastic characteristics of the Inconel 625 alloy generated with selective laser sintering from powders is investigated. The impact of the original powder combination and the following heat treatment (post-printing treatment) on the anisotropy of the alloy elastic characteristics is assessed. As demonstrated, the suggested treatments can lessen the anisotropy of the alloy elastic characteristics. Based on knowledge of the elastic constants of the single crystal and x-ray texture features, the results of a theoretical estimation of the elastic and shear moduli, Poisson's ratio, and their anisotropy in the horizontal and vertical directions of 3D printing are provided. As demonstrated, the obtained theoretical values differ by 6-10% from the corresponding experimental values. The calculated stress-strain state can be more accurately calculated with the use of the estimated elastic characteristics and their anisotropy. The strategy for 3D-printing complicated components from Inconel 625 alloy may be made more effective. [ABSTRACT FROM AUTHOR]

The analysis and synthesis of aerodynamic properties of the wind-driven power-plant (WP) construction with a vertical axis of rotation and useful interference of the stator and the rotor, that exceeds classical type analogues on energy characteristics, were conducted. The required functional dependence of the rotor rotative moment of WP on the angular speed of its rotation and the wind speed on the basis of aerodynamic optimization and researches of optimal shape and construction of WP was obtained. Respective aerodynamic power was calculated. The example of frequency stabilization of the rotor rotation through control of variable element of optimized form WP construction was considered. Method of maintaining the given angular speed of the rotor with a given deviation for a given time was proposed. [ABSTRACT FROM AUTHOR]

The analysis and synthesis of aerodynamic properties of the wind-driven power-plant (WP) construction with a vertical axis of rotation and useful interference of the stator and the rotor, that exceeds classical type analogues on energy characteristics, were conducted. The required functional dependence of the rotor rotative moment of WP on the angular speed of its rotation and the wind speed on the basis of aerodynamic optimization and researches of optimal shape and construction of WP was obtained. Respective aerodynamic power was calculated. The example of frequency stabilization of the rotor rotation through control of variable element of optimized form WP construction was considered. Method of maintaining the given angular speed of the rotor with a given deviation for a given time was proposed. [ABSTRACT FROM AUTHOR]

Features of the twist extrusion of blanks containing pores and plane cracks are considered. The effect of flat cracks on the porosity distribution and rate of local loosening during deformation is analyzed. The analysis is conducted using a modified theory of plasticity for porous bodies and the finite-element method. It is established that the porosity distribution is sensitive to the concentration of flat defects. At a certain concentration of plane defects, the porosity distribution is inverted: the porosity is higher at the periphery than at the center. The effect of flat defects on the accumulated strain and, as a result, on the structure refinement is less significant. It is confirmed that using the counter-pressure allows suppressing the growth of defects, reducing the refinement efficiency. [ABSTRACT FROM AUTHOR]

Hemodialysis (HD) therapy is of vital importance for patients with end stage renal disease (ESRD), when there is no donor organ available for transplantation to replace their malfunctioning kidneys. In contrast to healthy kidneys which work continuously and remove a broad range of toxins, during HD, patients' blood is cleansed three times a week for 4 h and not all uremic toxins are removed. For achieving long-term and/or continuous therapies, including wearable artificial kidneys, one requires membranes with long-term blood compatibility and high fouling resistance. Most membranes currently used in the clinic are made by blending of hydrophobic polymers, such as polysulfone (PSu) or polyethersulfone (PES), with hydrophilic additives, such as polyvinylpyrrolidone (PVP). Studies however, have shown that PVP could leach out from the membranes, especially during prolonged therapy leading to membrane fouling and/or complications to patients. Here, we develop hollow fibers with no additive leaching, by blending PES with small amounts of SlipSkin™ (SS). The latter, a random copolymer consisting of N -vinylpyrrolidone (NVP) and N -butylmethacrylate (BMA), has very good blood compatibility. The developed fibers can achieve high removal of a range of uremic toxins (creatinine and protein-bound uremic toxins) combined with excellent fouling resistance. Image 1 • Development of hollow fiber membranes by blending polyethersulfone (PES) with SlipSkin™ (SS). • The PES-SS fibers with 2 wt% SS have high removal of creatinine, hippuric acid (HA) and indoxyl sulfate (IS). • The PES-SS membranes have excellent blood compatibility and fouling resistance. • No elution of SS occurs from the PES-SS fibers, making them suitable for long-term hemodialysis. [ABSTRACT FROM AUTHOR]

The central amygdala (CeA) is a crucial hub in the processing of affective itch, containing a diverse array of neuronal populations. Among these components, Neuropeptide Y (NPY) and its receptors, such as NPY2R, affect various physiological and psychological processes. Despite this broad impact, the precise role of NPY2R + CeA neurons in itch modulation remains unknown, particularly concerning any potential lateralization effects. To address this, we employed optogenetics to selectively stimulate NPY2R + CeA neurons in mice, investigating their impact on itch modulation. Optogenetic activation of NPY2R + CeA neurons reduced scratching behavior elicited by pruritogens without exhibiting any lateralization effects. Electrophysiological recordings confirmed increased neuronal activity upon stimulation. However, this modulation did not affect thermal sensitivity, mechanical sensitivity, or formalin-induced hyperalgesia. Additionally, no alterations in anxiety-like behaviors or locomotion were observed upon stimulation. Projection tracing revealed connections of NPY2R + CeA neurons to brain regions implicated in itch processing. Overall, this comprehensive study highlights the role of NPY2R + CeA neurons in itch regulation without any lateralization effects., (© 2024. The Author(s).)

Crisaborole, a phosphodiesterase 4 (PDE4) inhibitor, has been approved for the treatment of mild to moderate atopic dermatitis. Atopic dermatitis is often associated with increased pain. Using a mouse model, this study investigated whether crisaborole suppresses pain associated with atopic dermatitis and the potential mechanisms underlying it. The mouse model for atopic dermatitis was developed by repeatedly applying MC903. MC903-treated mice had increased spontaneous scratching (itch-related behaviour) and wiping behaviour (pain-related behaviour). Crisaborole was topically applied to the cheek skin of MC903-treated mice, and it reduced both itch- and pain-related behaviours in these mice. Immunofluorescence staining revealed that crisaborole reduced neutrophil infiltration and interaction of neutrophils with sensory neurones. Intradermal injection of S100A8/A9, proinflammatory neutrophil mediator, enhanced not only itch-related behaviours evoked by histamine or chloroquine, but also pain-related behaviours evoked by capsaicin. Calcium imaging of mouse dorsal root ganglion neurones revealed that pretreatment with S100A8/A9 significantly increased calcium responses to histamine and capsaicin, and the proportion of chloroquine-sensitive neurones. These findings suggest that the PDE4 inhibitor reduces itch and pain, in part by inhibiting infiltration of S100A8/A9-containing neutrophils in a mouse model of MC903-induced atopic dermatitis.

The amygdala plays a key role in the processing of itch and pain signals as well as emotion. A previous study revealed that the central nucleus of the amygdala (CeA)-parabrachial nucleus (PBN) pathway is involved in pain regulation. The same pathway might also control itch. To test this possibility, prodynorphin (Pdyn)-Cre mice were used to optogenetically manipulate Pdyn + CeA-to-PBN projections. We found that optogenetic stimulation of Pdyn + amygdala neurons or Pdyn + CeA-to-PBN projections inhibited histamine-evoked and chloroquine-evoked scratching. The number of Fos-positive neurons in the PBN increased following intradermal injection of chloroquine. Optogenetic stimulation of Pdyn + CeA-to-PBN projections suppressed the increase in Fos expression in the PBN. Optogenetic stimulation of Pdyn + CeA-to-PBN projections increased thermal and mechanical thresholds without affecting anxiety-like behavior. These results highlight the importance of dynorphinergic projections from the central amygdala to the parabrachial nucleus in the regulation of itch signaling. SIGNIFICANCE STATEMENT The central nucleus of the amygdala (CeA)-parabrachial nucleus (PBN) pathway regulates pain signaling. Using prodynorphin (Pdyn)-cre mice, we investigated the role of Pdyn + CeA-to-PBN projections in itch. Optogenetic stimulation of Pdyn + CeA-to-PBN projections inhibited pruritogen-evoked scratching and neuronal activity (c-Fos expression) in the PBN. Together, dynorphinergic projections from the central amygdala to the parabrachial nucleus are important for regulating itch information., (Copyright © 2023 the authors.)

Objective: Coronavirus disease 2019 (COVID-19) has caused high morbidity and mortality worldwide. Since there is not enough evidence of risk factors of SARS-CoV-2 transmission, this study aimed to evaluate them., Methods: This survey-based study was conducted across 66 countries from May to November 2020 among suspected and confirmed individuals with COVID-19. The stepwise AIC method was utilized to determine the optimal multivariable logistic regression to explore predictive factors of SARS-CoV-2 transmission., Results: Among 2372 respondents who participated in the study, there were 1172 valid responses. The profession of non-healthcare-worker (OR: 1.77, 95%CI: 1.04-3.00, p  = .032), history of SARS-CoV or MERS-CoV infection (OR: 4.78, 95%CI: 2.34-9.63, p  < .001), higher frequency of contact with colleagues (OR: 1.17, 95%CI: 1.01-1.37, p  = .041), and habit of hugging when greeting (OR: 1.25, 95%CI: 1.00-1.56, p  = .049) were associated with an increased risk of contracting COVID-19. Current smokers had a lower likelihood of having COVID-19 compared to former smokers (OR: 5.41, 95%CI: 1.93-17.49, p  = .002) or non-smokers (OR: 3.69, 95%CI: 1.48-11.11, p  = .01)., Conclusions: Our study suggests several risk factors for SARS-CoV-2 transmission including the profession of non-healthcare workers, history of other coronavirus infections, frequent close contact with colleagues, the habit of hugging when greeting, and smoking status.

Background: Since the COVID-19 pandemic began, there have been concerns related to the preparedness of healthcare workers (HCWs). This study aimed to describe the level of awareness and preparedness of hospital HCWs at the time of the first wave., Methods: This multinational, multicenter, cross-sectional survey was conducted among hospital HCWs from February to May 2020. We used a hierarchical logistic regression multivariate analysis to adjust the influence of variables based on awareness and preparedness. We then used association rule mining to identify relationships between HCW confidence in handling suspected COVID-19 patients and prior COVID-19 case-management training., Results: We surveyed 24,653 HCWs from 371 hospitals across 57 countries and received 17,302 responses from 70.2% HCWs overall. The median COVID-19 preparedness score was 11.0 (interquartile range [IQR] = 6.0-14.0) and the median awareness score was 29.6 (IQR = 26.6-32.6). HCWs at COVID-19 designated facilities with previous outbreak experience, or HCWs who were trained for dealing with the SARS-CoV-2 outbreak, had significantly higher levels of preparedness and awareness (p<0.001). Association rule mining suggests that nurses and doctors who had a 'great-extent-of-confidence' in handling suspected COVID-19 patients had participated in COVID-19 training courses. Male participants (mean difference = 0.34; 95% CI = 0.22, 0.46; p<0.001) and nurses (mean difference = 0.67; 95% CI = 0.53, 0.81; p<0.001) had higher preparedness scores compared to women participants and doctors., Interpretation: There was an unsurprising high level of awareness and preparedness among HCWs who participated in COVID-19 training courses. However, disparity existed along the lines of gender and type of HCW. It is unknown whether the difference in COVID-19 preparedness that we detected early in the pandemic may have translated into disproportionate SARS-CoV-2 burden of disease by gender or HCW type., Competing Interests: The authors have read the journal’s policy and declare they have no competing interests.The commercial affiliations: Lower Westchester Medical Associates, Asia Shine Trading & Service CO. LTD and P.N. Lee Statistics and Computing Ltd, UK do not alter our adherence to PLOS ONE policies on sharing data and materials.

Maintaining an intact pool of neural progenitor cells (NPCs) is crucial for generating new and functionally active neurons. Methamphetamine (METH) can exacerbate the HIV-induced deficit of adult neurogenesis; however, potential mechanisms of this influence are still poorly understood. In the present study, we present evidence that chronic exposure to METH combined with brain infection by EcoHIV results in enhanced proliferation of NPCs in the subventricular zone (SVZ) in mice. This effect was long-lasting as it was preserved ex vivo in NPCs isolated from the exposed mice over several passages in the absence of additional treatments. Increased proliferation in response to METH plus HIV was associated with dysregulation of cyclin B1 and cyclin D. Transcriptomic studies indicated that 27 out of the top 30 differentially expressed genes in response to METH plus EcoHIV were targets of the forkhead box O transcriptional factor (FOXO) and primarily FOXO3. Additional ex vivo studies and in vitro experiments using human NPCs exposed to METH and infected with HIV revealed upregulation of the CXCL12-CXCR4 axis, leading to activation of downstream pAkt and pErk, the pathways that can phosphorylate FOXO3 and force its exports from the nuclei into the cytoplasm. Indeed, nuclear expulsion of FOXO3 was demonstrated both in mice exposed to METH and infected with EcoHIV and in cell cultures of human NPCs. These results provide novel information that exposure to METH combined with HIV infection can induce aberrant proliferation of SVZ-derived NPCs and identifies CXCL12-CXCR4-Akt-1-mediated phosphorylation of FOXO3 as the mechanism responsible for this effect., (© 2021. The Author(s).)

Accumulating evidence has highlighted the essential roles of cytokines in itch processing. Although IL-23 and Th17 cytokines are elevated in inflammatory skin disorders, their role in itch is unknown. Here, we investigated the role of IL-23 and IL-17A in itch response using an in vitro calcium imaging of mouse dorsal root ganglion (DRG) neurons and an in vivo behaviour test. Calcium imaging studies revealed that a few DRG neurons (~5%) responded to either IL-23 or IL-17A. Pretreatment cells with IL-23 significantly reduced calcium responses to histamine and capsaicin but not chloroquine. Behaviour experiments showed neither IL-23 nor IL-17A evoked scratching. IL-23 significantly decreased histamine-evoked scratching without affecting chloroquine-evoked scratching. There was no difference in scratching between IL-17A- and vehicle-treated groups. These results indicate that IL-23 might play a role in regulating histaminergic itch via modulation of TRPV1 activity., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Innocuous mechanical stimuli, such as rubbing or stroking the skin, relieve itch through the activation of low-threshold mechanoreceptors. However, the mechanisms behind this inhibition remain unknown. We presently investigated whether stroking the skin reduces the responses of superficial dorsal horn neurons to pruritogens in male C57BL/6J mice. Single-unit recordings revealed that neuronal responses to chloroquine were enhanced during skin stroking, and this was followed by suppression of firing below baseline levels after the termination of stroking. Most of these neurons additionally responded to capsaicin. Stroking did not suppress neuronal responses to capsaicin, indicating state-dependent inhibition. Vesicular glutamate transporter 3 (VGLUT3)-lineage sensory nerves compose a subset of low-threshold mechanoreceptors. Stroking-related inhibition of neuronal responses to chloroquine was diminished by optogenetic inhibition of VGLUT3-lineage sensory nerves in male and female Vglut3-cre / NpHR-EYFP mice. Conversely, in male and female Vglut3-cre/ChR2-EYFP mice, optogenetic stimulation of VGLUT3-lineage sensory nerves inhibited firing responses of spinal neurons to pruritogens after the termination of stimulation. This inhibition was nearly abolished by spinal delivery of the κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride, but not the neuropeptide Y receptor Y1 antagonist BMS193885. Optogenetic stimulation of VGLUT3-lineage sensory nerves inhibited pruritogen-evoked scratching without affecting mechanical and thermal pain behaviors. Therefore, VGLUT3-lineage sensory nerves appear to mediate inhibition of itch by tactile stimuli. SIGNIFICANCE STATEMENT Rubbing or stroking the skin is known to relieve itch. We investigated the mechanisms behind touch-evoked inhibition of itch in mice. Stroking the skin reduced the activity of itch-responsive spinal neurons. Optogenetic inhibition of VGLUT3-lineage sensory nerves diminished stroking-evoked inhibition, and optogenetic stimulation of VGLUT3-lineage nerves inhibited pruritogen-evoked firing. Together, our results provide a mechanistic understanding of touch-evoked inhibition of itch., (Copyright © 2020 the authors.)

Background: The ideal treatment approach for colorectal cancer (CRC) with synchronous liver metastases (SCRLM) remains debated. We performed a network meta-analysis (NMA) comparing the 'bowel-first' approach (BFA), simultaneous resection (SIM), and the 'liver-first' approach (LFA)., Methods: A systematic search of comparative studies in CRC with SCRLM was undertaken using the Embase, PubMed, Web of Science, and CENTRAL databases. Outcome measures included postoperative complications, 30- and 90-day mortality, chemotherapy use, treatment completion rate, 3- and 5-year recurrence-free survival, and 3- and 5-year overall survival (OS). Pairwise and network meta-analysis were performed to compare strategies. Heterogeneity was assessed using the Higgins I 2 statistic., Results: One prospective and 43 retrospective studies reporting on 10 848 patients were included. Patients undergoing the LFA were more likely to have rectal primaries and a higher metastatic load. The SIM approach resulted in a higher risk of major morbidity and 30-day mortality. Compared to the BFA, the LFA more frequently resulted in failure to complete treatment as planned (34% versus 6%). Pairwise and network meta-analysis showed a similar 5-year OS between LFA and BFA and a more favorable 5-year OS after SIM compared to LFA (odds ratio 0.25-0.90, p = 0.02, I 2  = 0%), but not compared to BFA., Conclusion: Despite a higher tumor load in LFA compared to BFA patients, survival was similar. A lower rate of treatment completion was observed with LFA. Uncertainty remains substantial due to imprecise estimates of treatment effects. In the absence of prospective trials, treatment of stage IV CRC patients should be individually tailored., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)