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Introduction: Recent evidence of a causal link between Phosphodiesterase-5-inhibitor (PDE-5i) use and melanoma has caused concern in PDE-5i use and was even addressed in the 2018 American Urological Association guideline on erectile dysfunction (ED). Given that several studies have affirmed this low probability but statistically significant association, one might expect a shift in melanoma diagnoses since PDE-5is were introduced in 1998. We sought to determine if the introduction of PDE-5i drugs for ED treatment increased incidence of melanoma., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to compare the incidence of melanoma diagnosis in American men between 1973 and 2015, providing over a decade of data before and after PDE-5i introduction in 1998. Interrupted time-series and logistic regression were used to assess this relationship., Results: Over 43 years, the SEER database has reported 292,166 cases of Melanoma, with males accounting for 53.7% of cases (Standard deviation [SD] 3%, Range 47.5-58.3%). After the introduction of PDE-5i, there was no proportional increase in melanoma diagnoses, in fact demonstrating a 2% lower incidence from prediction models (p < 0.05)., Conclusion: Our analysis of the SEER database demonstrates that the trend in incidence of melanoma has fallen in the era of PDE-5i use for ED. These findings may be of value in counseling patients anxious about the potential association between PDE-5i use and skin cancer; however, continued research analyzing individual-level risk are needed., Competing Interests: Declaration of Competing Interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cosmetic oils are used to dissolve crystalline lipophilic UV filters; however, little knowledge exists about the effect of other formulation ingredients. This study investigates the influence of emulsifiers on the recrystallization speed of 4 UV filters and the impact of UV-filter crystal formation on delivered performance. The crystallization pattern of studied UV filters was assessed using X-ray diffractometry, whereas their recrystallization speed in formulations with various emulsifiers was monitored microscopically. UV-filter concentration was above the saturation level to promote recrystallization. Furthermore, to understand the kinetics of recrystallization, the conformer number of each UV-filter was calculated. For the impact on performance, the absorbance of a sunscreen was measured before and after recrystallization of the contained UV filter. This study confirmed the crystallinity of tested UV filters. The emulsifier was shown to influence the UV-filter recrystallization speed in emulsions. Continuous oil phase sunscreens were critical; all UV filters recrystallized promptly in oils and water-in-oil emulsions. Large molecule UV filters showed slowest recrystallization speed explained by a higher number of possible conformers. Finally, this work confirmed the negative impact of crystal formation on the delivered photoprotection of a sunscreen., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

An important property of sunscreens is their water resistance after the application on human skin. In this work, the hypothesis that UV absorber molecules which are able to form liposomes, so-called liposomogenic UV absorbers, show better water resistance on a pig skin model than UV-absorbing molecules lacking this ability was tested. The assumption behind is that molecules which can form liposomes are able to integrate into the stratum corneum lipids of the skin. Three different liposomogenic UV absorbers were synthesized and their behavior investigated, leading to the confirmation of the hypothesis. With one of the liposomogenic UV absorbers, it was possible to show the integration of the UV absorber molecules into the bilayers of another liposome consisting of phosphatidylcholine, supporting the assumption that liposomogenic UV absorbers exhibit improved water resistance because they integrate into the skin lipids., (Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

O-glycosylation of podoplanin (PDPN) on lymphatic endothelial cells is critical for the separation of blood and lymphatic systems by interacting with platelet C-type lectin-like receptor 2 during development. However, how O-glycosylation controls endothelial PDPN function and expression remains unclear. In this study, we report that core 1 O-glycan-deficient or desialylated PDPN was highly susceptible to proteolytic degradation by various proteases, including metalloproteinases (MMP)-2/9. We found that the lymph contained activated MMP-2/9 and incubation of the lymph reduced surface levels of PDPN on core 1 O-glycan-deficient endothelial cells, but not on wild-type ECs. The lymph from mice with sepsis induced by cecal ligation and puncture, which contained bacteria-derived sialidase, reduced PDPN levels on wild-type ECs. The MMP inhibitor, GM6001, rescued these reductions. Additionally, GM6001 treatment rescued the reduction of PDPN level on lymphatic endothelial cells in mice lacking endothelial core 1 O-glycan or cecal ligation and puncture-treated mice. Furthermore, core 1 O-glycan-deficient or desialylated PDPN impaired platelet interaction under physiological flow. These data indicate that sialylated O-glycans of PDPN are essential for platelet adhesion and prevent PDPN from proteolytic degradation primarily mediated by MMPs in the lymph., (© 2014 by The American Society of Hematology.)

The aerobic biodegradation of 5-methyl-benzotriazole (5-TTri) was optimized using lab-scale setups and activated sludge communities (ASC) collected from three wastewater treatment plants (WWTP) MBR-MH, CAS-E and CAS-M being different in their treatment technologies. ASC inocula were diluted to rule out non-biodegrading species and incubated under two nutrient conditions: A) mineral salt media (MSM) and B) carbon and nitrogen supplied MSM giving MSM-CN. 5-TTri removal with the ASC ranged from 60% to 100% in only 10 days. 100 μL suspended biomass from the biodegrading setups was subsequently plated on solid media to eliminate possible activated sludge remnants. After growth occurred, mixed colonies were harvested and inoculated in fresh liquid MSM containing 20 mg L(-1) 5-TTri. These bacterial consortia showed good 5-TTri removal in MSM-CN rather than in MSM, indicating nutrient supply being required for efficient biodegradation. In addition, experiments with high 5-TTri concentrations ranging from 20 to 1,000 mg L(-1) were conducted in both, MSM and MSM-CN and the maximal 5-TTri removal capacity of the ASC evaluated. 50 mg L(-1) 5-TTri was still removed in both media whereas 100 mg L(-1) was solely removed in MSM-CN. 5-TTri biodegradation patterns also indicated that 5-TTri might be co-metabolized by microbial consortia. Furthermore, experiments with gradient-solid-media-plates showed 5-TTri to be inhibitory for the ASC in concentrations above 50 mg L(-1) and revealed the optimal conditions regarding carbon and nitrogen concentration and pH value for effective 5-TTri biodegradation by ASC. Nitrogen proved a crucial factor for enhancing organisms' biodegradation capacity with an optimal pH around 7 while carbon showed no such effect., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The basic zipper Gcn4 protein activates transcription in the yeast Saccharomyces cerevisiae in response to amino acid starvation. This includes numerous metabolic genes of amino acid or purine biosynthesis and the developmental cell-surface flocculin gene FLO11, which is required for diploid pseudohyphae formation and for adhesion upon nutrient starvation. We separated the metabolic from the developmental response by screening for GCN4 alleles that allow growth during amino acid starvation but are impaired in adhesion and are unable to form pseudohyphae. The identified Gcn4(L267S) variant carries an amino acid substitution in the third of the four conserved leucines of the zipper dimerization domain. This mutation abolished FLO11 expression and results in reduced but sufficient transcriptional activity for amino acid biosynthetic genes. The Leu267Ser substitution impairs Gcn4 homodimer formation and is a significantly more stable protein than the wild-type protein. A helix-breaker substitution in Leu253 results in a transcriptionally inactive but highly stable protein variant. This is due to a feedback circuit between transcriptional activity of Gcn4 and its own stability, which depends on the Gcn4-controlled cyclin PCL5. Gcn4(L253G) reduces the expression of Pcl5 and therefore reduces its own degradation. This self-controlled buffer system to restrict transcriptional activity results in a reciprocal correlation between Gcn4 transcriptional activity and protein stability., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

We lack comparative data on sunscreens with comparable sun protection factors (SPFs), but with different levels of UVA protection, especially against cumulative erythema from repeated suberythemal exposure. Thus, we compared the protection from cumulative sunburn with two sunscreens labeled SPF 6, but with different UVR-absorbing properties, one that absorbs the UVB waveband and the other that absorbs UVB+UVA wavebands. We simulated sunlight typical of temperate latitudes to expose skin daily to suberythemal doses for 13 consecutive days. The study population consisted of eight fair-skinned sun-sensitive healthy young adults. Erythema was assessed by eye and objectively, and the SPF of each sunscreen was modeled with changes in solar UVR with time of day and latitude. The broad-spectrum sunscreen gave much better protection against cumulative erythema than the UVB sunscreen. The explanation for this is that UVA makes a greater contribution toward sunburn at temperate latitudes than under the laboratory conditions in which SPF is tested and assigned. The data support the current trend toward broad-spectrum sunscreen protection. They also show that labeled SPF is much more reliable with broad-spectrum sunscreens because SPF with primarily UVB sunscreens is dependent on time of day and latitude.

At the stage of screening of new sun protection formulations, quick and inexpensive methods for estimation of the ultraviolet (UV) screening performance are highly desirable. It has been shown recently that apart from measurements of sun protection factors in vitro, calculations using a calibrated step film model are also a possibility. In the present investigation, further evidence for the usefulness of the step film model in terms of prediction of the sun protection factor is shown. In addition, it is demonstrated that parameters, which characterize the protection in the UVA range such as the UVA/UVB ratio and the critical wavelength can be calculated in good accordance with experimental data. Although with less accuracy, the estimation of UVA protection factors is also possible, if the photodegradation some filters undergo upon irradiation is taken into consideration., (Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1780-1795, 2004)