Unoccluded Retinol Penetrates Human Skin In Vivo More Effectively Than Unoccluded Retinyl Palmitate or Retinoic Acid

The formation of all-trans retinoic acid is an oxidative process whereby retinol is converted to retinaldehyde and then to retinoic acid. Because retinol causes qualitative molecular changes similar to those produced by retinoic acid, we compared potency of retinol, retinaldehyde, and retinyl palmitate to retinoic acid and assessed the effects of occlusion. Retinoids were prepared in an experimental vehicle of 95% ethanol:propylene glycol (7:3) with anti-oxidant. Induction of retinoic acid 4-hydroxylase activity was the end point for comparison. Retinoic acid concentrations from 0.001% to 0.05% under occlusion produced a linear dose-response induction of 4-hydroxylase activity. The concentrations of the other retinoids under occlusion required to achieve significant induction of enzyme activity were 0.6% retinyl palmitate, 0.025% retinol, and 0.01% retinaldehyde. The linear dose-response was lost with retinoid concentrations in excess of 0.25% retinol or 0.5% retinaldehyde. Statistical analyses showed no difference in 4-hydroxylase activity between unocciuded and occluded retinol treated sites. By contrast, however, unoccluded sites treated with retinoic acid or retinyl palmitate had less induction of 4-hydroxylase activity than occluded sites. Retinol, retinaldehyde, and retinyl palmitate did not produce erythema but did increase epidermal thickness. Although retinol is a weaker retinoid than retinoic acid, the increased penetration of unoccluded retinol in comparison to unoccluded retinoic acid with this prototypic vehicle confers on retinol a more effective delivery of a retinoidal effect than unocciuded retinoic acid. Retinol at 0.25% may be a useful retinoid for application without occlusion because it does not irritate but does induce cellular and molecular changes similar to those observed with application of 0.025% retinoic acid

Retinoic Acid Isomers Applied to Human Skin in Vivo Each Induce a 4-Hydroxylase That Inactivates Only Trans Retinoic Acid

Application of all-trans retinoic acid to human skin for 4 d under occlusion produces a marked increase in retinoic acid 4-hydroxylase activity. In this study, the possible induction of other hydroxylases in response to 9-cis and 13-cis retinoic acid applications to adult human skin in vivo was determined. Application of 0.1% all-trans, 0.1% 9-cis, and 0.1% 13-cis retinoic acid to human skin for 2 d resulted in induction of only all-trans retinoic acid 4-hydroxylase activity. The 4-hydroxylase activity in microsomes from the treated tissue ranged from 383 ± 46 to 531 ± 59pg of 4-hydroxy all-trans retinoic acid formed/min/mg protein (n = 6). These same preparations were unable to use 9-cis or 13-cis retinoic acid as substrate for the hydroxylation reaction. Extraction of the retinoic acid isomers from epidermis 48h after application of 0.1% solution of each isomer yielded significant amounts of all-trans retinoic acid (36-72%) regardless of the isomer applied. The all-trans isomer produced by isomerization of both 9-cis and 13-cis retinoic acids is the likely inducer of the 4-hydroxylase. All-trans retinol and all-trans retinal were unable to compete with all-trans retinoic acid as substrate for 4-hydroxylase enzyme. The 4-hydroxylase induced in response to pharmacological doses of retinoic acids is specific for the all-trans isomer. The inability of 9-cis or 13-cis retinoic acid to induce their own hydroxylation and inactivation or act as substrate for the 4-hydroxylase in skin may have considerable implications in light of the clinical use of retinoids in the treatment of various diseases including cancers

Photodynamic therapy for acne vulgaris: a randomized, controlled, split-face clinical trial of topical aminolevulinic acid and pulsed dye laser therapy

There remains the need for more effective therapeutic options to treat acne vulgaris. Interest in light-based acne treatments has increased, but few randomized, controlled clinical trials assessing the value of photodynamic therapy (PDT) for acne have been reported.We sought to examine the efficacy of PDT using 5-aminolevulinic acid (ALA) and pulsed dye laser therapy in the treatment of acne.We conducted a randomized, controlled, split-face, single-blind clinical trial of 44 patients with facial acne. Patients were randomized to receive three pulsed dye laser treatments to one side of the face after a 60–90 min ALA application time, while the contralateral side remained untreated and served as a control. Serial blinded lesion counts and global acne severity ratings were performed.Global acne severity ratings improved bilaterally with the improvement noted to be statistically significantly greater in treated skin than in untreated skin. Erythematous macules (remnants of previously active inflammatory lesions) decreased in number in treated skin when compared with control skin and there was a transient but significant decrease in inflammatory papules in treated skin when compared with untreated skin. There were no other statistically significant differences between treated and untreated sides of the face in terms of counts of any subtype of acne lesion. Thirty percent of patients were deemed responders to this treatment with respect to improvement in their inflammatory lesion counts, while only 7% of patients responded in terms of noninflammatory lesion counts.PDT with the treatment regimen employed here may be beneficial for a subgroup of patients with inflammatory acne.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79403/1/j.1473-2165.2010.00483.x.pd

Deducing an emergent South Korean behavioural taxonomy of perceived managerial and leadership effectiveness

This is an accepted manuscript of an article published by Emerald in European Journal of Training and Development, on 28/07/2021, available online: https://doi.org/10.1108/EJTD-04-2020-0069 The accepted version of the publication may differ from the final published version.Purpose This study aims to identify people’s perceptions of what behaviourally differentiates effective managers from ineffective managers within a South Korean (SK) public sector organization, and the extent to which the findings are similar or different to those of an equivalent previous study in the SK private sector. Design/methodology/approach Adopting the “pragmatic approach” and assuming a post-positivist ontology and constructivist–interpretivist epistemology, examples of “effective” and “ineffective” managerial behaviour were collected from managers and non-managerial employees in an SK central government Ministry using the critical incident technique. The collected critical incidents were coded, classified and reduced to a smaller number of behavioural categories. These were then compared against equivalent findings from a previous SK private sector replication study using open, axial and selective coding to identify generic behavioural criteria (GBCs) Findings High degrees of convergence point towards the emergence of a “two-factor” SK behavioural taxonomy of perceived managerial and leadership effectiveness comprised of positive (n = 11) and negative (n = 4) GBCs of effective and ineffective managerial behaviour. Practical implications The GBCs constituting the deduced SK behavioural taxonomy could be used by HRD practitioners to critically evaluate the efficacy of extant management and leadership development (MLD) programmes, or to inform/shape the creation of new MLD programmes. Additionally, they could be used by other HR professionals to critically evaluate the relevance and efficacy of the assessment criteria used for existing management selection, 360-degree feedback and formal performance appraisal systems. Originality/value The emergence of an SK behavioural taxonomy through Type 3 (emic-as-emic) and Type 4 (emic-and-etic) indigenous research is a rare example of Eastern mid-range theory development

High-Power Hybrid Solid-State Lithium-Metal Batteries Enabled by Preferred Directional Lithium Growth Mechanism

Solid electrolytes are revolutionizing the field of lithium-metal batteries; however, their practical implementa-tion has been impeded by the interfacial instability between lithium metal electrodes and solid electrolytes. While various interlayers have been suggested to address this issue in recent years, long-term stability with repeated lithium deposition/ stripping has been challenging to attain. Herein, we successfully operate a high-power lithium-metal battery by inducing the preferred directional lithium growth with a rationally designed interlayer, which employs (i) crystalline-direction-controlled carbon material providing isotropic lithium transports, with (ii) prelithium deposits that guide the lithium nucleation direction toward the current collector. This combination ensures that the morphology of the interlayer is mechanically robust while regulating the preferred lithium growth underneath the interlayer without disrupting the initial interlayer/electrolyte interface, enhancing the durability of the interface. We illustrate how these material/geometric optimizations are conducted from the thermodynamic considerations, and its applicability is demonstrated for the garnet-type Li7-xLa3-aZr2-bO12 (LLZO) solid electrolytes paired with the capacity cathode. It is shown that a lithium-metal cell with the optimized amorphous carbon interlayer with prelithium deposits exhibits outstanding room-temperature cycling performance (99. 6% capacity retention after 250 cycles), delivering 4.0 mAh cm-2 at 2.5 mA cm-2 without significant degradation of the capacity. The successful long-term operation of the hybrid solid-state cell at room temperature (approximately a cumulative deliverable capacity of over 1000 mAh cm-2) is unprecedented and records the highest performance reported for lithium-metal batteries with LLZO electrolytes until date

Neutrophil extracellular traps, B cells, and type I interferons contribute to immune dysregulation in hidradenitis suppurativa.

Hidradenitis suppurativa (HS), also known as acne inversa, is an incapacitating skin disorder of unknown etiology manifested as abscess-like nodules and boils resulting in fistulas and tissue scarring as it progresses. Given that neutrophils are the predominant leukocyte infiltrate in HS lesions, the role of neutrophil extracellular traps (NETs) in the induction of local and systemic immune dysregulation in this disease was examined. Immunofluorescence microscopy was performed in HS lesions and detected the prominent presence of NETs. NET complexes correlated with disease severity, as measured by Hurley staging. Neutrophils from the peripheral blood of patients with HS peripheral also displayed enhanced spontaneous NET formation when compared to healthy control neutrophils. Sera from patients recognized antigens present in NETs and harbored increased antibodies reactive to citrullinated peptides. B cell dysregulation, as evidenced by elevated plasma cells and IgG, was observed in the circulation and skin from patients with HS. Peptidylarginine deiminases (PADs) 1 to 4, enzymes involved in citrullination, were differentially expressed in HS skin, when compared to controls, in association with enhanced tissue citrullination. NETs in HS skin coexisted with plasmacytoid dendritic cells, in association with a type I interferon (IFN) gene signature. Enhanced NET formation and immune responses to neutrophil and NET-related antigens may promote immune dysregulation and contribute to inflammation. This, along with evidence of up-regulation of the type I IFN pathway in HS skin, suggests that the innate immune system may play important pathogenic roles in this disease

Matrix Metalloproteinase-1 is the Major Collagenolytic Enzyme Responsible for Collagen Damage in UV-irradiated Human Skin ¶

Punch biopsies of human skin were obtained 1 day after irradiation with two minimal-erythema doses (MED) from either a UVB light source or a Solar Simulator and incubated in organ culture for 72 h. Organ culture fluids obtained at 24, 48 and 72 h were analyzed for collagenolytic activity and for reactivity with antibodies to matrix metalloproteinase-1 (MMP-1; interstitial collagenase) and MMP-13 (collagenase-3). High levels of collagenolytic activity were seen in organ culture fluid from skin exposed to either light source. MMP-1 was strongly induced in parallel, increasing from less than 100 ng/ml in organ culture fluid from control skin to approximately 1.1 mg/ml in culture fluid from UV-treated skin. Whereas most of the detectable MMP-1 in control culture fluid was represented by the latent form of the enzyme, approximately 50% of the enzyme was present as the active form in organ culture fluid of UV-exposed skin. In contrast, there was no detectable MMP-13 in control organ culture fluid and very little change after UV exposure (less than 100 ng/ml in both cases). Finally, neutralization studies with a blocking antibody to MMP-1 removed 95 ± 4% of the collagenolytic activity in the organ culture fluid from UV-treated skin. These findings strongly implicate MMP-1 rather than MMP-13 as the major collagenolytic enzyme responsible for collagen damage in photoaging.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73069/1/0031-8655_2003_0780043MMITMC2.0.CO2.pd