β1 Integrin-Mediated Adhesion Signalling Is Essential for Epidermal Progenitor Cell Expansion

Background: There is a major discrepancy between the in vitro and in vivo results regarding the role of b1 integrins in the maintenance of epidermal stem/progenitor cells. Studies of mice with skin-specific ablation of b1 integrins suggested that epidermis can form and be maintained in their absence, while in vitro data have shown a fundamental role for these adhesion receptors in stem/progenitor cell expansion and differentiation. Methodology/Principal Findings: To elucidate this discrepancy we generated hypomorphic mice expressing reduced b1 integrin levels on keratinocytes that developed similar, but less severe defects than mice with b1-deficient keratinocytes. Surprisingly we found that upon aging these abnormalities attenuated due to a rapid expansion of cells, which escaped or compensated for the down-regulation of b1 integrin expression. A similar phenomenon was observed in aged mice with a complete, skin-specific ablation of the b1 integrin gene, where cells that escaped Cre-mediated recombination repopulated the mutant skin in a very short time period. The expansion of b1 integrin expressing keratinocytes was even further accelerated in situations of increased keratinocyte proliferation such as wound healing. Conclusions/Significance: These data demonstrate that expression of b1 integrins is critically important for the expansion of epidermal progenitor cells to maintain epidermal homeostasis

Hair regrowth treatment efficacy and resistance in androgenetic alopecia: A systematic review and continuous Bayesian network meta-analysis

BackgroundAndrogenetic alopecia (AGA) affects almost half the population, and several treatments intending to regenerate a normal scalp hair phenotype are used. This is the first study comparing treatment efficacy response and resistance using standardized continuous outcomes.ObjectiveTo systematically compare the relative efficacy of treatments used for terminal hair (TH) regrowth in women and men with AGA.MethodsA systematic literature review was conducted (from inception to August 11, 2021) to identify randomized, Placebo-controlled trials with ≥ 20 patients and reporting changes in TH density after 24 weeks. Efficacy was analyzed by sex at 12 and 24 weeks using Bayesian network meta-analysis (B-NMA) and compared to frequentist and continuous outcomes profiles.ResultsThe search identified 2,314 unique articles. Ninety-eight were included for full-text review, and 17 articles met the inclusion criteria for data extraction and analyses. Eligible treatments included ALRV5XR, Dutasteride 0.5 mg/day, Finasteride 1 mg/day, low-level laser comb treatment (LLLT), Minoxidil 2% and 5%, Nutrafol, and Viviscal. At 24 weeks, the B-NMA regrowth efficacy in TH/cm2 and significance (**) in women were ALRV5XR: 30.09**, LLLT: 16.62**, Minoxidil 2%: 12.13**, Minoxidil 5%: 10.82**, and Nutrafol: 7.32**, and in men; ALRV5XR: 21.03**, LLLT: 18.75**, Dutasteride: 18.37**, Viviscal: 13.23, Minoxidil 5%: 13.13**, Finasteride: 12.38, and Minoxidil 2%: 10.54. Two distinct TH regrowth response profiles were found; Continuous: ALRV5XR regrowth rates were linear in men and accelerated in women; Resistant: after 12 weeks, LLLT, Nutrafol, and Viviscal regrowth rates attenuated while Dutasteride and Finasteride plateaued; Minoxidil 2% and 5% lost some regrowth. There were no statistical differences for the same treatment between women and men. B-NMA provided more accurate, statistically relevant, and conservative results than the frequentist-NMA.ConclusionSome TH regrowth can be expected from most AGA treatments with less variability in women than men. Responses to drug treatments were rapid, showing strong early efficacy followed by the greatest resistance effects from flatlining to loss of regrowth after 12–16 weeks. Finasteride, Minoxidil 2% and Viviscal in men were not statistically different from Placebo. LLLT appeared more efficacious than pharmaceuticals. The natural product formulation ALRV5XR showed better efficacy in all tested parameters without signs of treatment resistance (see Graphical abstract).Systematic review registrationwww.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42021268040, identifier CRD42021268040

Managing hyperemesis gravidarum: a multimodal challenge

Up to 90% of pregnant women experience nausea and vomiting. When prolonged or severe, this is known as hyperemesis gravidarum (HG), which can, in individual cases, be life threatening. In this article the aetiology, diagnosis and treatment strategies will be presented based on a selective literature review. Treatment strategies range from outpatient dietary advice and antiemetic drugs to hospitalization and intravenous (IV) fluid replacement in persistent or severe cases. Alternative methods, such as acupuncture, are not yet evidence based but sometimes have a therapeutic effect

Modulation and SSR tests performed on the BPA 500 kV thyristor controlled series capacitor unit at Slatt substation

Field experience is reported for a thyristor controlled series capacitor (TCSC) recently commissioned at BPA`s Slatt substation. Subsynchronous resonance tests show that TCSC interactions with shaft dynamics of PGE`s Boardman steam generator are well understood and are effectively avoided by normal TCSC valve firing logic. Modulation tests, performed with the Boardman plant off line, show that the TCSC can be a powerful and responsive actuator for swing damping. Security considerations did not permit lightly damped operation of the controlled plant. Close analysis indicates that the TCSC damping contribution, though small, was measurable. The best estimate is that damping for the McNary mode is 7.33% and 8.55%, for the TCSC damper loop open and closed respectively. TCSC testing and monitoring is facilitated by an advanced interactive measurement network representing BPA`s approach to the information requirements of major control systems

Ecological risk as a component of the credit risk of financial liabilities of manufacturing companies

Artykuł podejmuje zagadnienie ryzyka ekologicznego związanego z działalnością przedsiębiorstw produkcyjnych i jego wpływu na ocenę ich ryzyka kredytowego dokonywaną przez instytucje finansowe w przypadku ubiegania się przez te firmy o pożyczkę pieniężną. Przedstawiono w nim wybrane modele oceny ryzyka kredytowego oraz omówiono znaczenia aspektów ekologicznych związanych z działalnością produkcyjną w procedurze jego oceny. Na podstawie analizy piśmiennictwa wskazano również na podstawowe relacje pomiędzy tymi rodzajami ryzyka w praktyce działalności sektora bankowego.The paper discusses the issue of ecological risk connected with the business activity of manufacturing companies and its impact on credit risk assessment performed by financial institutions, in case the companies submit applications for bank loans. The paper presents selected models of credit risk assessment and analyses the significance of ecological aspects related to the production activity in the assessment procedure. On the basis of the analysis of background literature, principle relations between these types of risk in the practice of functioning of the banking sector

Analysis of the Impact of Balancing Area Cooperation on the Operation of the Western Interconnection with Wind and Solar Generation

This presentation describes the analysis of the impact of balancing area cooperation on the operation of the Western Interconnection with wind and solar generation, including a discussion of operating reserves, ramping, production simulation, and conclusions