Plugin-based interoperability and ecosystem management for the MolSSI Driver Interface Project.

The MolSSI Driver Interface (MDI) Project is an effort to simplify and standardize the process of enabling tight interoperability between independently developed code bases and is supported by numerous software packages across the domain of chemical physics. It enables a wide variety of use cases, including quantum mechanics/molecular mechanics, advanced sampling, path integral molecular dynamics, machine learning, ab initio molecular dynamics, etc. We describe two major developments within the MDI Project that provide novel solutions to key interoperability challenges. The first of these is the development of the MDI Plugin System, which allows MDI-supporting libraries to be used as highly modular plugins, with MDI enforcing a standardized application programming interface across plugins. Codes can use these plugins without linking against them during their build process, and end-users can select which plugin(s) they wish to use at runtime. The MDI Plugin System features a sophisticated callback system that allows codes to interact with plugins on a highly granular level and represents a significant advancement toward increased modularity among scientific codes. The second major development is MDI Mechanic, an ecosystem management tool that utilizes Docker containerization to simplify the process of developing, validating, maintaining, and deploying MDI-supporting codes. Additionally, MDI Mechanic provides a framework for launching MDI simulations in which each interoperating code is executed within a separate computational environment. This eliminates the need to compile multiple production codes within a single computational environment, reducing opportunities for dependency conflicts and lowering the barrier to entry for users of MDI-enabled codes.

Safety-in-use test of facial cosmetic products on normal and self-assessed sensitive skin subjects.

BACKGROUND: Safety-in-use (SIU) studies are commonly used by the cosmetic Industry to confirm the skin and ocular compatibility of cosmetic products under realistic in-use conditions. There are only limited case studies published about the design, outcome and interpretation of product SIU studies. OBJECTIVE: A series of SIU case studies is presented to demonstrate the considerations in study design and how the methodology can help in supporting skin and ocular safety profile of facial cosmetic products within a population of different ethnicities with normal and self-perceived sensitive skin. SUBJECTS/METHODS: In a series of four single-blinded SIU studies, more than 250 female study subjects of different ethnicities and with normal and self-assessed sensitive skin were asked to use different facial cosmetic products including lotions, essences and cleansers according to the instructed usage conditions of these products. Each study was specifically designed according to product usage scenarios and target consumer groups. The primary measures of safety were based on dermal evaluations by a dermatologist for erythema and dryness/scaling and by an ophthalmologist for any visible signs of an ocular condition on eyelids, conjunctivae and cornea. The study subjects were also asked for any self-perceived skin or eye reactions. Dermal and ocular irritation potential of the products under realistic product usage conditions was evaluated according to the measures. RESULTS: Across all studies, objectively and self-assessed mean scores for skin and eye effects did not indicate any cumulative response of the investigated products over the study period. CONCLUSIONS: As a suitable tool for assessing and establishing the skin and eye compatibility of facial cosmetic products, SIU studies can be designed according to specific consumer groups, skin types and product usage scenarios to better predict realistic in-use conditions. It can demonstrate the safe use of the investigated products for people of different ethnicities, skin types and with normal or self-assessed sensitive skin, single product use or regimen use. The test results are consistent with the inherently low irritation potential of the products.

Quantitative increases of extracellular vesicles in prolonged cold storage of platelets increases the potential to enhance fibrin clot formation.

BACKGROUND: Platelet derived extracellular vesicles (EVs) display a pro-coagulant phenotype and are generated throughout platelet concentrate (PC) storage. Cold storage (CS) of PCs is thought to provide a superior haemostatic advantage over room temperature (RT) storage and could prolong the storage time. However, the effect of storage conditions on EV generation and PC function is unknown. We investigated EV production under CS and RT conditions and assessed whether these EVs exhibited a more pro-coagulant phenotype in model experiments. MATERIALS AND METHODS: Buffy-coat-derived PCs in a platelet additive solution (PAS) to plasma ratio of approximately 65:35 were stored at RT (22 ± 2°C) or CS (4 ± 2°C) for a prolonged storage duration of 20 days. Impedance aggregometry assessed platelet function. EVs were isolated throughout storage and quantified using nanoparticle tracking analysis. EVs were applied to a coagulation assay to assess the impact on fibrin clot formation and lysis. RESULTS: CS produced significantly larger EVs from day 4 onwards. EV concentration was significantly increased in CS compared to RT from day 15. EVs, regardless of storage, significantly reduced time to clot formation and maximum optical density measured compared to the no EV control. Clot formation was proportionate to the number of EV applied but was not statistically different across storage conditions when corrected for EV number. CONCLUSION: EVs in CS and RT units showed similar clot formation capacity. However, the higher number of larger EVs generated in CS compared to RT suggests PC units derived from CS conditions may overall exhibit a haemostatically superior capacity compared to RT storage.

Assessment of adverse events for a home-use intense pulsed light hair removal device using postmarketing surveillance.

BACKGROUND AND OBJECTIVES: Home-use intense pulsed light (IPL) hair removal devices are convenient for consumers. Consumer safety associated with home-use IPL devices, however, remains a subject of interest. In this descriptive analysis, we assessed the most commonly reported adverse events (AEs) for a home-use IPL device from postmarketing surveillance and qualitatively compared these with AEs from clinical studies and medical device reports of home-use IPL treatments. MATERIALS AND METHODS: For this analysis of voluntary reports, we queried a distributor's postmarketing database for IPL devices for the period beginning January 1, 2016, to December 31, 2021. All sources of comments, for example, phone, e-mail, company-sponsored web sites, were included in the analysis. AE data were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Also, we conducted a PubMed search to identify AE profiles from existing literature on home-use IPL devices and we searched the Manufacturer and User Facility Device Experience (MAUDE) database for reports on home-use IPL devices. These results were qualitatively compared to the data in the postmarketing surveillance database. RESULTS: A total of 1692 cases involving IPL were identified from voluntary reports of AEs between 2016 and 2021. The shipment-adjusted reporting rate for AE cases (number of AE cases/100,000 shipped IPL devices) was 67/100,000 during this 6-year period. The most commonly reported AEs were pain of skin 27.8% (470/1692), "thermal burn" 18.7% (316/1692), and erythema 16.0% (271/1692). Among the top 25 AEs reported, no unexpected health events were observed. The reported AEs were qualitatively similar to the pattern seen in clinical studies and the MAUDE database associated with such home-use IPL treatments. CONCLUSION: This is the first such report documenting AEs for home-use IPL hair removal from a postmarketing surveillance program. These data are supportive of the safety of such home-use low-fluence IPL technology.

Post-exercise skimmed milk, but not a sucrose beverage decreases energy intake at the next meal compared to a placebo beverage in active males.

This study compared the appetite and energy intake effects of three post-exercise beverages at a subsequent post-exercise meal. On three occasions, ten active males: (mean ± sd) age 21.3 ± 1.2 y, V˙ O2peak 58 ± 5 mL/kg/min) performed 30-min cycling at ∼60% V˙ O2peak and five 4-min intervals at 85% V˙ O2peak. Post-exercise, placebo (PLA: 57 kJ), skimmed milk (MILK: 1002 kJ) or sucrose (CHO: 1000 kJ) beverages (615 mL) were consumed. Sixty min post-beverage, subjects consumed an ad-libitum pasta lunch in a 30 min eating period. Subjective appetite and plasma acylated ghrelin and plasma glucose were determined pre-exercise, post-exercise and pre-meal, with sensory characteristics of beverages rated. Ad-libitum energy intake in MILK (6746 ± 2035) kJ) was lower than CHO (7762 ± 1921) kJ) (P = 0.038; dz = 0.98; large effect) and tended to be lower than PLA (7672 (2005) kJ) (P = 0.078; dz = 0.76; medium effect). Including energy consumed in beverages, energy intake was greater in CHO than PLA (P = 0.010; dz = 1.24; large effect) or MILK (P = 0.026; dz = 0.98; large effect), with PLA and MILK not different (P = 0.960; dz = 0.02; trial effect). Plasma ghrelin, plasma glucose and appetite were not different between trials. MILK was perceived thicker than CHO (P = 0.020; dz = 1.11; large effect) and creamier than PLA (P = 0.026; dz = 1.06; large effect). These results suggest that when energy balance is important for an exerciser, post-exercise skimmed milk ingestion reduces energy intake compared to a sucrose beverage and might therefore help facilitate recovery/adaptation without affecting energy balance.

Sunscreens - another endangered species?

Skin cancer continues to increase in incidence year-on-year and represents the most common form of cancer across the globe. Every human undergoes premature ageing, particularly on the face, neck and hands. Both phenomena are driven primarily by chronic, daily exposure to solar ultraviolet radiation (UVR). While sunscreen products play a primary role in the prevention of UVR skin damage, the active ingredients, i.e., UVR filters, are facing unprecedented challenges in the coming 10 years and their future is by no means certain. This article, therefore, reviews afresh the facts around photoprotection and the role of sunscreen products in the prevention of acute (sunburn) and chronic (cancer, photoageing) skin damage and compares/contrasts these with various emerging questions and opinions around UVR filter technology. We present a passionate defence of this remarkable technology, but also attempt to imagine a world without it.

L'incidence du cancer de la peau continue d'augmenter année après année, et ce cancer est le plus fréquent dans le monde. Tous les êtres humains connaissent un vieillissement prématuré, en particulier au niveau du visage, du cou et des mains. Les deux phénomènes sont causés principalement par une exposition quotidienne chronique aux rayons ultraviolets (UVR) du soleil. Bien que les protections solaires jouent un rôle essentiel dans la prévention des lésions cutanées dues aux UVR, les principes actifs, c'est-à-dire les filtres UVR, seront confrontés à des difficultés sans précédent dans les 10 prochaines années, et leur avenir n'est en aucun cas certain. Cet article examine donc les faits concernant la photoprotection et le rôle des produits de protection solaire dans la prévention des lésions cutanées aiguës (coups de soleil) et chroniques (cancer, photovieillissement) ; et les compare/oppose aux différentes questions et opinions émergentes concernant la technologie des filtres UVR. Nous présentons une défense passionnée de cette technologie remarquable, mais nous essayons également d'imaginer un monde sans elle.

Absence of phototoxicity/photoirritation potential of bergamottin determined In Vitro using OECD TG 432.

The phototoxic potential of a number of furocoumarins is well established. On the other hand, studies have shown that bergamottin, a furocoumarin containing a bulky, hydrophobic side chain, has significantly less or is even absent of phototoxicity potential. The OECD Test Guideline 432 3T3/Neutral Red Uptake (NRU) in vitro phototoxicity test has shown to be a highly predictive test for identifying compounds that exhibit no phototoxicological potential. In this study using OECD 432, the established phototoxic furocoumarin 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP) and psoralen were phototoxic, whereas bergamottin showed no phototoxic potential. When compared to 5-MOP, 8-MOP and psoralen, bergamottin was clearly negative at molar-adjusted concentrations that were more than 9 times higher than those that produced phototoxicity in 8-MOP; nearly 16 times than those for psoralen and more than 36 times higher than those for 5-MOP. These data using in vitro 3T3 NRU Phototoxicity Test (OECD 432) are supportive of earlier studies showing bergamottin does not exhibit phototoxicological properties. The detection and quantification of bergamottin should therefore not contribute to the potential marker furocoumarins for risk management interventions intended to reduce the phototoxicity of natural furocoumarin containing preparations.

A Physiological-Based Pharmacokinetic Model For The Broad Spectrum Antimicrobial Zinc Pyrithione: II. Dermal Absorption And Dosimetry In The Rat.

The broad spectrum antimicrobial/antifungal zinc pyrithione (ZnPT) is used in products ranging from antifouling paint to antidandruff shampoo. The hazard profile of ZnPT was established based upon comprehensive toxicological testing, and products containing this biocide have been safely used for years. The purpose of this study was to create a dermal physiologically based pharmacokinetic (PBPK) model for ZnPT in the rat for improving dose-response analysis of ZnPT-induced toxicity where reversible hindlimb weakness was the endpoint used as the basis for ZnPT risk assessments. Previously, we developed a PBPK model which simulated the kinetics of pyrithione (PT) and its major metabolites 2-(methylsulfonyl)pyridine and S-glucuronide conjugates in blood and tissues of rats following oral ZnPT administration. The dermal model was optimized utilizing in vitro dermal penetration investigations conducted with rat skin and with historical data from a dermal repeat dose study using rats. The model replicated the observed temporal patterns and elimination kinetics of [14C]PT equivalents in blood and urine during and following repeated dermal dosing and replicated the observed dose-dependencies of absorption, blood [14C]PT equivalents and plasma PT concentrations. The model provided internal dosimetry predictions for a benchmark dose analysis of hindlimb weakness in rats that combined dermal, gavage and dietary studies into a single internal dose-response model with area-under-the-curve (AUC) for plasma PT, the toxic moiety in the rat, as the internal dose metric. This PBPK model has predictive validity for calculating internal doses of PT and/or [14C]PT equivalents from different routes of exposure in the rat.

Non-pharmacologic therapies for systemic lupus erythematosus.

BACKGROUND: Non-pharmacologic therapies have been deemed as potentially beneficial for patients with systemic lupus erythematosus. We conducted an updated review to determine the effects of these therapies to inform practice. METHODS: A literature search was performed using PubMed (MEDLINE), EMBASE, Cochrane, PsychINFO, the Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Google Scholar from inception until August 2018. We included randomized controlled trials of non-pharmacologic therapies in systemic lupus erythematosus patients with sample size ≥10. Systemic lupus erythematosus was defined by 1982 or 1997 American College of Rheumatology criteria. Studies were synthesized separately by patient-reported outcomes and disease activity. Due to the heterogeneity of interventions and comparisons, a meta-analysis was not performed. RESULTS: A total of 15 randomized controlled trials involving 846 participants met the inclusion criteria. Of the 15 trials, eight used exercise interventions, six used psychological interventions (one group psychotherapy, three cognitive behavioral therapies, one psychoeducation, one mindfulness-based cognitive therapy) and one used electro-acupuncture. Five of 15 studies utilized control groups consisting of usual medical care. Other studies included control interventions of relaxation, attention placebo, symptom monitoring support, education, minimal needling, isotonic and resistance exercise. Compared with the control conditions, non-pharmacological interventions were associated with a significant improvement in fatigue in three out of six studies. Three out of eight studies reported improved anxiety and depression, and one study reported improved pain after interventions. Seven out of 11 studies reported improvement in overall quality of life in at least one domain of the Short-Form Health Survey. Of note, no studies demonstrated an improvement in disease activity after 5-52 weeks of non-pharmacological therapies. CONCLUSION: This review showed promising results for physical exercise and psychological interventions as adjuncts to traditional medical therapy for improvement in fatigue, depression, pain and quality of life for systemic lupus erythematosus. Further high-quality randomized controlled trials with longer follow-up periods are warranted.

Formulation and Artificial Sebum Effects on the Percutaneous Absorption of Zinc Pyrithione through Excised Human Skin.

BACKGROUND: Zinc pyrithione (ZnPT) is deposited on the skin as a fine particulate and must reach microorganisms localized in the stratum corneum and hair follicles in molecular form to exert its broad-spectrum antimicrobial/antifungal activity. Dissolution of ZnPT particles followed by molecular speciation results in the organic portion, i.e. pyrithione, being more susceptible to skin penetration than the inorganic component, i.e. zinc, or the chelate itself, i.e. ZnPT. OBJECTIVES: To further test the hypothesis that ZnPT skin penetration is rate-limited by dissolution and molecular speciation, the effect of different formulations and artificial sebum on the in vitro percutaneous absorption of radiolabel associated with Zn[14C]PT was investigated. METHOD: In vitro penetration of [14C]PT into and through excised human skin was measured following application of Zn[14C]PT prepared as suspensions in distinct vehicles including water-based carboxymethylcellulose (CMC), diluted body wash comprised of surfactants, and castor oil, in the presence and absence of artificial sebum. RESULTS: The steady-state flux and cumulative absorption of Zn[14C]PT increased 4- to 5-fold when deposited from a body wash or castor oil compared to a water-based CMC suspension. Tritiated water flux measured before and after treatment showed that neither the surfactant vehicle nor castor oil significantly altered barrier function versus water alone. An artificial sebum layer on the skin potentiated Zn[14C]PT and 3H2O absorption when dosed from both aqueous formulations, but not from castor oil. CONCLUSION: These data are consistent with the hypothesis that ZnPT percutaneous absorption, as measured by [14C]PT kinetics, is controlled by particle dissolution and molecular speciation.

Language matters. Addressing the use of language in the care of people with diabetes: position statement of the English Advisory Group.

The language used by healthcare professionals can have a profound impact on how people living with diabetes, and those who care for them, experience their condition and feel about living with it day-to-day. At its best, good use of language, both verbal and written, can lower anxiety, build confidence, educate and help to improve self-care. Conversely, poor communication can be stigmatizing, hurtful and undermining of self-care and can have a detrimental effect on clinical outcomes. The language used in the care of those with diabetes has the power to reinforce negative stereotypes, but it also has the power to promote positive ones. The use of language is controversial and has many perspectives. The development of this position statement aimed to take account of these as well as the current evidence base. A working group, representing people with diabetes and key organizations with an interest in the care of people with diabetes, was established to review the use of language. The work of this group has culminated in this position statement for England. It follows the contribution of Australia and the USA to this important international debate. The group has set out practical examples of language that will encourage positive interactions with those living with diabetes and subsequently promote positive outcomes. These examples are based on a review of the evidence and are supported by a simple set of principles.

Healthy People 2020: assessment of pharmacists' priorities.

OBJECTIVE: The purpose of this study was to assess perceptions of pharmacy educators on the priorities and roles of pharmacists in meeting the Healthy People 2020 objectives. STUDY DESIGN: Cross-sectional, qualitative online national survey. METHODS: A comprehensive literature review identified documented roles and responsibilities of pharmacists in addressing the 42 topic areas in Healthy People 2020. From this, a 14-item survey was developed to identify priorities of categories to improve the health of the nation and importance of the pharmacist role to achieve the objectives. The survey was sent electronically to the members of the Public Health Special Interest Group of the American Association of Colleges of Pharmacy in May and June 2014. RESULTS: Participants identified the following Healthy People 2020 categories as most important in improving the health of the nation: chronic diseases, health care services, lifestyle, prevention/well-being, and environmental factors. They identified the following Healthy People 2020 categories as possessing the most important roles for pharmacists in working to improve the health of the nation: chronic diseases, health care services, lifestyle, prevention/well-being, and infectious disease. CONCLUSIONS: There exists great congruence between top categories of importance and those that the pharmacist can impact to improve the health of the nation. The results of this study can guide efforts to educate and activate pharmacists as interprofessional team members improving health locally and globally.

Whole-Genome Sequencing Reveals the Contribution of Long-Term Carriers in Staphylococcus aureus Outbreak Investigation.

Whole-genome sequencing (WGS) makes it possible to determine the relatedness of bacterial isolates at a high resolution, thereby helping to characterize outbreaks. However, for Staphylococcus aureus, the accumulation of within-host diversity during carriage might limit the interpretation of sequencing data. In this study, we hypothesized the converse, namely, that within-host diversity can in fact be exploited to reveal the involvement of long-term carriers (LTCs) in outbreaks. We analyzed WGS data from 20 historical outbreaks and applied phylogenetic methods to assess genetic relatedness and to estimate the time to most recent common ancestor (TMRCA). The findings were compared with the routine investigation results and epidemiological evidence. Outbreaks with epidemiological evidence for an LTC source had a mean estimated TMRCA (adjusted for outbreak duration) of 243 days (95% highest posterior density interval [HPD], 143 to 343 days) compared with 55 days (95% HPD, 28 to 81 days) for outbreaks lacking epidemiological evidence for an LTC (P = 0.004). A threshold of 156 days predicted LTC involvement with a sensitivity of 0.875 and a specificity of 1. We also found 6/20 outbreaks included isolates with differing antimicrobial susceptibility profiles; however, these had only modestly increased pairwise diversity (mean 17.5 single nucleotide variants [SNVs] [95% confidence interval {CI}, 17.3 to 17.8]) compared with isolates with identical antibiograms (12.7 SNVs [95% CI, 12.5 to 12.8]) (P < 0.0001). Additionally, for 2 outbreaks, WGS identified 1 or more isolates that were genetically distinct despite having the outbreak pulsed-field gel electrophoresis (PFGE) pulsotype. The duration-adjusted TMRCA allowed the involvement of LTCs in outbreaks to be identified and could be used to decide whether screening for long-term carriage (e.g., in health care workers) is warranted. Requiring identical antibiograms to trigger investigation could miss important contributors to outbreaks.

A physiologically based pharmacokinetic model for the broad-spectrum antimicrobial zinc pyrithione: I. Development and verification.

The broad-spectrum antimicrobial zinc pyrithione (ZnPT) is used in numerous products ranging from in-can preservative/mildicide in paints to antidandruff shampoo. Although products containing ZnPT have a long history of safe use, regulatory agencies routinely set limits of exposure based upon toxicological considerations. The objective of this study was to create a physiologically based pharmacokinetic (PBPK) model for ZnPT in the rat for improving dose-response analysis of ZnPT-induced toxicity, reversible hindlimb weakness, the endpoint that has been used as the basis for ZnPT risk assessments. A rat oral PBPK model was developed that includes compartments for plasma, liver, kidneys, muscle, brain, and rapidly and slowly perfused tissues. Pyrithione metabolism to 2-(methylsulfonyl)pyridine (MSP) and glucuronide conjugates was incorporated into the model. The model was parameterized and optimized based upon data from single-dose intravenous (iv) and oral gavage pharmacokinetic studies of radiolabeled pyrithione ([14C]PT) administered as zinc [14C]-pyrithione (Zn-[14C]PT) to adult female rats. It was further evaluated and refined using data from repeated, multidose oral gavage and dietary studies of Zn[14C]PT in the adult female rat that included measurements of plasma PT concentration, the putative toxic species. The model replicated the observed short-term elimination kinetics of PT in plasma and [14C]PT in whole blood following single doses and longer term temporal patterns of plasma and blood concentrations during repeated dosing schedules. The model also accounted for production and rapid elimination of S-glucuronide conjugates (SG) of 2-pyridinethiol and 2-pyridinethiol-1-oxide in urine, as well as production and slower elimination of MSP, the major [14C]PT species in blood within several hours following administration of ZnPT. The model provided internal dosimetry predictions for a benchmark dose (BMD) analysis of hindlimb weakness in rats, and was used to combine gavage and dietary studies into a single internal dose-response model with area under the curve (AUC) for plasma PT as the internal dose metric. This PBPK model has predictive validity for calculating internal doses of PT and/or [14C]PT from different routes of exposure in the rat.

Side effects from intense pulsed light: Importance of skin pigmentation, fluence level and ultraviolet radiation-A randomized controlled trial.

BACKGROUND AND OBJECTIVE: Intense pulsed light (IPL) is a mainstream treatment for hair removal. Side effects after IPL are known, but risk factors remain to be investigated. The objective of this study was to assess the contribution of skin pigmentation, fluence level, and ultraviolet radiation (UVR) on IPL-induced side effects. METHODS: The study was a blinded, randomized intra-individual controlled trial including 16 healthy subjects with Fitzpatrick Skin Types (FST) II-V. Three test areas were each divided into four sites, randomized to a single IPL exposure of 22, 34, 46 J/cm2 or triple stacking of 46 J/cm2 . Areas were subsequently randomized to no UVR or single solar-simulated UVR exposure of 3 Standard Erythema Dose at 30 minutes or 24 hours after IPL. Each area had a corresponding control, resulting in 15 treatment sites. Follow-up visits were scheduled up to 4 weeks after IPL. Outcome measures were: (i) blinded clinical skin reactions; (ii) objectively measured erythema and pigmentation; (iii) pain measured by visual analog scale (VAS); (iv) histology (H&E, Fontana-Masson); and (v) mRNA-expression of p53. RESULTS: Fifteen subjects with FST II-IV completed the protocol. IPL induced a wide range of skin reactions, including erythema (87% of subjects), purpura (27%), blisters (20%), edema (13%), crusting (13%), hyper- (60%), and hypopigmentation (20%). Darker skin pigmentation and increasing IPL fluence were determinants for IPL-induced side effects (P ≤ 0.002), while a single exposure of UVR did not exacerbate side effects (P ≥ 0.180). Clinical findings were confirmed objectively by reflectance spectrometry and qualitatively by histological changes in skin architecture, inflammatory infiltration, and pigmentation. Marker of cellular DNA damage, that is, p53, did not increase after IPL (P ≥ 0.24). CONCLUSIONS: Skin pigmentation and IPL fluence are major determinants of side effects after IPL exposure, while a single exposure to three SED of UVR at 30 minutes or 24 hours after IPL, does not amplify such side effects. Lasers Surg. Med. 49:88-96, 2017. © 2016 Wiley Periodicals, Inc.

Human health risk assessment of chloroxylenol in liquid hand soap and dishwashing soap used by consumers and health-care professionals.

A quantitative human risk assessment of chloroxylenol was conducted for liquid hand and dishwashing soap products used by consumers and health-care workers. The toxicological data for chloroxylenol indicate lack of genotoxicity, no evidence of carcinogenicity, and minimal systemic toxicity. No observed adverse effect levels (NOAEL) were established from chronic toxicity studies, specifically a carcinogenicity study that found no cancer excess (18 mg/kg-day) and studies of developmental and reproductive toxicity (100 mg/kg-day). Exposure to chloroxylenol for adults and children was estimated for two types of rinse-off cleaning products, one liquid hand soap, and two dishwashing products. The identified NOAELs were used together with exposure estimates to derive margin of exposure (MOE) estimates for chloroxylenol (i.e., estimates of exposure over NOAELs). These estimates were designed with conservative assumptions and likely overestimate exposure and risk (i.e., highest frequency, 100% dermal penetration). The resulting MOEs ranged from 178 to over 100, 000, 000 indicating negligibly small potential for harm related to consumer or health-care worker exposure to chloroxylenol in liquid soaps used in dish washing and hand washing.

Quantitative assessment of growing hair counts, thickness and colour during and after treatments with a low-fluence, home-device laser: a randomized controlled trial.

BACKGROUND: At-home laser and intense pulsed-light hair removal continues to grow in popularity and availability. A relatively limited body of evidence is available on the course of hair growth during and after low-fluence laser usage. OBJECTIVES: To assess growing hair counts, thickness and colour quantitatively during and after cessation of low-fluence laser treatment. METHODS: Thirty-six women with skin phototypes I-IV and light to dark-brown axillary hairs were included. Entire axillary regions were randomized to zero or eight self-administered weekly treatments with an 810-nm home-use laser at 5·0-6·4 J cm(-2). Standardized clinical photographs were taken before each treatment and up to 3 months after the final treatment for computer-aided quantification of growing hair counts, thickness and colour. RESULTS: Thirty-two women completed the study protocol. During sustained treatment, there was a reduction in growing hair that reached a plateau of up to 59%, while remaining hairs became up to 38% thinner and 5% lighter (P < 0·001). The majority of subjects (77%) reported 'moderately' to 'much less hair' in treated than untreated axilla, and assessed remaining hairs as thinner and lighter (≥ 60%). After treatment cessation, hair growth gradually returned to baseline levels, and 3 months after the final treatment the count and thickness of actively growing hair exceeded pretreatment values by 29% and 7%, respectively (P ≤ 0·04). CONCLUSIONS: Sustained usage of low-fluence laser induced a stable reduction of growing hair counts, thickness and colour. The reduction was reversible and hairs regrew beyond baseline values after cessation of usage. Computer-aided image analysis was qualified for quantification of hair counts, thickness and colour after laser epilation.

Ultraviolet radiation after exposure to a low-fluence IPL home-use device: a randomized clinical trial.

The prevailing advice is to avoid sun exposure after intense pulsed light (IPL) hair removal. However, no systematic evaluation of ultraviolet radiation (UVR) after IPL hair removal exits. Therefore, we investigated the occurrence of side effects in subjects receiving solar-simulated UVR after a low-fluence IPL treatment with a home-use device. Sixteen subjects with Fitzpatrick skin types (FST) II-V were enrolled. Three constitutive buttock blocks (4.4 × 6.4 cm) were each subdivided into four sites, randomized to one IPL exposure of 0, 7, 8, or 10 J/cm2 (spectral output 530-1100 nm). Blocks were randomized to no UVR or three standard erythema doses (SEDs) UVR either 30 min or 24 h after IPL. Follow-up visits were 48 h, 1 week, and 4 weeks after IPL. Outcome measures were (i) clinical skin reactions, (ii) reflectance measurements of erythema and pigmentation, and (iii) pain. Subjects with FST II-IV experienced no skin reactions up to 4 weeks after IPL, neither erythema, edema, blisters, crusting, textual, nor pigment changes. Reflectance confirmed no change in erythema and pigmentation (p ≥ 0.090). UVR exposure induced erythema and increased pigmentation. The combination of IPL and UVR induced skin reactions not different to responses from UVR (IPL-UVR vs. UVR, p ≥ 0.164). Pain was generally low (median 1, range 0-4) and correlated positively with fluence and pigmentation (Spearman's rho ≥ 0.394, p < 0.001). One subject with FST V experienced perifollicular hyperpigmentation after IPL and slightly more intense when exposed to UVR. A single UVR exposure of three SEDs either shortly or 1 day after low-fluence IPL causes no amplification of skin responses in constitutive skin of individuals with FST II-IV.

Relevance of UV filter/sunscreen product photostability to human safety.

Photostability or photo-instability of sunscreen products is most often discussed in undesirable terms with respect to human safety. The health risks, specifically associated with sunscreens, photostable or photo-unstable, include phototoxic/photoirritation or photoallergic responses and, longer-term, an increased risk of skin cancers or photoageing. The aims of this paper are to define photostability/photo-instability and objectively assess the acute and chronic toxicological consequences from the human exposure to UV filter/sunscreens and any probable photo-degradation products. The reported prevalence of photoirritation and photoallergic responses to sunscreens is rare compared with adverse events, for example, skin irritation or sensitization, produced by cosmetics or topically applied drugs and do not directly implicate potential photo-degradation products of UV filters. Moreover, for at least one photo-unstable combination, octyl methoxycinnamate and avobenzone, the long-term benefits to humans, i.e., reduction in skin cancers, seem to outweigh any potential adverse consequences attributed to photo-degradation. Sunscreen products are formulated to achieve maximum efficacy which, by necessity and design, incorporate measures to support and promote photostability since all organic UV filters have the potential to photo-degrade. Current performance measures, in vivo SPF and in vitro UVA, conducted under standardized conditions, in part account for photostability. The concerns expressed when considering human exposure to potential photo-unstable UV filters or sunscreen products may not manifest as health risks under conditions of use. Still, improvement in sunscreen product photostability continues to be a key strategic objective for manufacturers.

Mechanistic Skin Modeling of Plasma Concentrations of Sunscreen Active Ingredients Following Facial Application.

Sunscreen products constitute two distinct categories. Recreational sunscreens protect against high-intensity, episodic sun exposure, often applied over the entire body. In contrast, facial sunscreen products are designed for sub-erythemal, low-intensity daily sun exposure. Such different exposures necessitate distinctive product safety assessments. Building on earlier methods for predicting dermal disposition, a mechanistic model was developed to simulate plasma concentrations of seven organic sunscreen active ingredients: avobenzone, ensulizole, homosalate, octinoxate, octisalate, octocrylene, and oxybenzone, following facial application. In vitro permeation testing (IVPT) was performed with two different vehicles using a subset of the UV filters. These IVPT results, in addition to previously published IVPT data and published in vivo Maximal Usage Trial (MUsT) data for the UV filters, were used to train the mechanistic dermal model via a Bayesian Markov chain Monte Carlo (MCMC) method. An external validation of the trained model with real-world in vivo datasets demonstrated that the model's predicted UV filter plasma concentrations align well with experimental measurements and capture the observed inter-individual variability. Predictions of steady-state UV filter plasma concentrations under facial application scenarios at 5% concentration and at the maximal allowable concentrations were then generated by the trained model. Oxybenzone had the greatest predicted plasma concentration following facial application. Homosalate and octisalate predictions had high uncertainty associated with the absence of data. Several application scenarios pertaining to avobenzone, ensulizole, octocrylene and octinoxate were identified in which median plasma concentration levels were at 0.5 ng/ml or below when applied in the recreational or facial product. Model limitations include uncertainty in vehicle/water partitioning, formulation metamorphosis, and UV filter systemic clearance, all of which can be refined with additional data. For UV filters, limiting exposure to facial application reduces human safety concerns based on FDA established thresholds.