In situ study of the effect of endogenous and exogenous agents on color stability, hardness, and surface roughness of an elastomer for facial prostheses.

PURPOSE: To evaluate in situ the influence of sweat, oil, sunscreen, and disinfectant solution on the color stability, hardness, and roughness of elastomer for facial prostheses. MATERIALS AND METHODS: Standardized and intrinsically pigmented specimens remained in contact with human skin from the same person for 30 days, considering exposures (n = 36 per group), absent of exposition (Control, C); sweat and oiliness contact (SO); sweat and oiliness associated with sunscreen (SOS); 0.12% chlorhexidine digluconate immersion (CD0.12%); and all agents exposed (SOSCD). The main variables were color change (CIELab and National Standard Bureau system, NBS), Shore A hardness, and surface roughness, measured at baseline and 30 days. Qualitative analyses were performed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). The data were analyzed by Kruskal-Wallis tests (color) and two-way ANOVA (hardness and roughness) with Sidak post-test (α = 0.05). RESULTS: CD0.12% (1.54 ± 0.49) and SOSCD (2.10 ± 1.03) had similar effects and caused the smallest color changes, considered mild and noticeable (NBS), respectively. SOS promoted the greatest color change (6.99 ± 1.43, NBS: large) and hardness (17.97 ± 0.56); SOS promoted intermediate roughness (3.48 ± 1.05) between SOSCD (2.25 ± 0.53), and two similar groups: C (4.46 ± 0.95), and CD0.12% (4.39 ± 1.26). The qualitative analysis showed an irregular, dense, dry, and whitish layer on the surface of the specimens exposed to sunscreen, which was reduced when in contact with 0.12% chlorhexidine digluconate. CONCLUSIONS: Endogenous and exogenous factors are capable of altering elastomer properties. The 0.12% chlorhexidine digluconate minimized the changes caused by sweat, oil, and sunscreen.

EuIII and TbIII upconversion intermediated by interparticle energy transfer in functionalized NaLnF4 nanoparticles.

Lanthanide (LnIII)-doped sodium gadolinium tetrafluoride (NaGdF4) nanoparticles have been excelled as attractive upconversion systems for anti-counterfeiting or energy conversion for instance, with a special interest in the visible upconversion of EuIII and TbIII. The core@shell architecture has enabled the bright upconversion of EuIII and TbIII in this matrix by interfacial energy transfer sensibilized by the TmIII/YbIII pair. Another approach to enable EuIII and TbIII upconversion could be the interparticle energy transfer (IPET) between LnIII-doped sensitizer and acceptor nanoparticles. Yet, the low molar absorptivity of the LnIII through 4f ↔ 4f electronic transitions and the large distance between the nanoparticles are shortcomings that should decrease the energy transfer efficiency. On the other hand, it is feasible to predict that the association of organic ligands displaying large molar absorptivity on the acceptor nanoparticle surface could help to overcome the absorption limitation. Inspired by this exciting possibility, herein, we present the EuIII/TbIII upconversion intermediated by IPET between the donor TmIII, YbIII-doped NaGdF4 nanoparticle and the acceptor LnIII-doped NaGdF4 (Ln = Eu and/or Tb) nanoparticles functionalized with a series organic ligands on the surface (tta- = thenoyltrifluoroacetonate, acac- = acetylacetonate, or 3,5-bbza- = 3,5-dibromebenzoate). Either in solid state or in suspension, upon excitation at 980 nm, visible EuIII/TbIII upconversion could be observed. This emission comes from the absorption of the TmIII, YbIII pair in the donor nanoparticle, followed by IPET from the TmIII excited levels to the ligand singlet/triplet states on the acceptor nanoparticle surface, ligand-to-EuIII/TbIII energy transfer, and upconversion emission. Spectroscopic evidences from the analysis of the donor level lifetimes indicate the contribution of non-radiative energy transfer for the IPET mechanism; the radiative mechanism also contributes for the IPET. Moreover, the design herein introduced enables the development of luminescence temperature probes with relative thermal sensitivity as high as 1.67% K-1 at 373 K. Therefore, this new upconversion pathway opens an avenue of possibilities in an uncharted territory to tune the visible upconversion of LnIII ions.

Intensity and lifetime ratiometric luminescent thermometer based on a Tb(III) coordination polymer.

A three-dimensional terbium(III) coordination polymer of formula [Tb(bttb)0.5(2,5-pzdc)0.5]n (1) [H4bttb = 1,2,4,5-tetrakis(4'-carboxyphenyl)benzene and H2-2,5-pzdc = 2,5-pyrazinedicarboxylic acid] was obtained under hydrothermal conditions. The bttb4- tetraanion in 1 adopts the bridging and chelating-bridging pseudo-oxo coordination modes while the 2,5-pzdc2- dianion exhibits a rather unusual bis-bidentate bridging pseudo-oxo coordination mode, both ligands being responsible for the stiffness of the resulting 3D structure. Solid-state photoluminescent measurements illustrate that 1 exhibits remarkable green luminescence emission, the most intense band occurring in the region of 550 nm (5D4 → 7F5) with lifetimes at the millisecond scale. Thermometric performances of 1 reveal a maximum relative sensitivity (Sm) of 0.76% K-1 at 295 K (δT = 0.05 K), constituting a TbIII ratiometric solid luminescent thermometer over the physiological temperature range. Variable-temperature static (dc) magnetic susceptibility measurements for 1 in the temperature range 2.0-300 K show the expected behavior for the depopulation of the splitted mJ levels of the 7F7 ground state of the magnetically anisotropic terbium(III) ion plus a weak antiferromagnetic interaction through the carboxylate bridges. No significant out-of-phase magnetic susceptibility signals were observed for 1 in the temperature range 2.0-10.0 K, either in the absence or presence of a static dc magnetic field.

Effect of radiation therapy on fracture resistance of simulated immature teeth submitted to root reinforcement.

BACKGROUND: The literature is scanty regarding the effect of radiation therapy (RT) on the mechanical properties of immature permanent teeth. AIM: To evaluate the effect of RT on the fracture resistance of simulated immature teeth submitted to different types of root reinforcement. DESIGN: Sixty-four human teeth simulating the Cvek stage 3 of root development were distributed into eight groups (n = 8), according to exposure or not to RT (70 Gy) and the root reinforcement method: Group NR (control)-no reinforcement/no RT; Group NR + RT (control)-no reinforcement/RT; Group PO-tricalcium silicate-based cement (TS) apical plug/canal obturation/no RT; Group PO + RT-TS apical plug/canal obturation/RT; Group TS-canal filling with TS/no RT; Group TS + RT-canal filling with TS/RT; Group FP-TS apical plug/fibreglass post/no RT; and Group FP + RT-TS apical plug/fibreglass post/RT. Fracture resistance was determined using a universal testing machine (0.5 mm/min). RESULTS: In the intergroup comparison, nonirradiated teeth had higher fracture resistance (p < .05). Groups FP and FP + RT had higher fracture resistance (p < .001). CONCLUSION: Radiotherapy affected the fracture resistance of simulated immature teeth. Reinforcement with fibreglass posts increased the fracture resistance, regardless of the radiation.

Tuning the Thermometric Features in 1D Luminescent EuIII and TbIII Coordination Polymers through Different Bridge Phosphine Oxide Ligands.

TbIII and EuIII systems have been investigated as ratiometric luminescent temperature probes in luminescent coordination polymers due to TbIII → EuIII energy transfer (ET). To help understand how ion-ion separation, chain conformation as well as excitation channel impact their thermometric properties, herein, [Eu(tfaa)3(µ-L)Tb(tfaa)3]n one-dimensional (1D) coordination polymers (tfaa- = trifluoroacetylacetonate, and L = [(diphenylphosphoryl)R](diphenyl)phosphine oxide, R = ethyl - dppeo - or butyl - dppbo) were synthesized. The short µ-dppeo bridge ligand leads to a more linear 1D polymeric chain, while the longer µ-dppbo bridge leads to tighter packed chains. As the temperature rises from 80 K, upon direct TbIII excitation at 488 nm, the TbIII emission intensity decreases, while the EuIII emission intensity increases after 160 and 200 K when L = dppeo or dppbo, respectively. The temperature-dependent emission intensities, due to TbIII → EuIII ET, enable the development of ratiometric luminescent temperature probes featuring maximum relative thermal sensitivity up to 3.8% K-1 (250 K, L = dppbo, excitation at 488 nm). On the other hand, the same system displays maximum thermal sensitivity up to 3.5% K-1 (323 K) upon ligand excitation at 300 nm. Thus, by changing the excitation channel and bridge ligand that leads to modification of the polymer conformations, the maximum relative thermal sensitivity can be tuned.

Functional Shoulder Evaluation after Osteosynthesis of Greater Tuberosity Fracture: Is There any Influence of Glenohumeral Dislocation?

Objective To evaluate the postoperative functional and radiographic outcomes of the shoulder of patients submitted to transosseous suturing of a greater tuberosity fracture (GTF) through an anterolateral route and the influence of the glenohumeral dislocation on these outcomes. Methods We conducted a retrospective study and functional assessment using the Constant-Murley score. The distance between the greater tuberosity and the joint surface of the proximal humerus (in true anteroposterior radiographs) after the union was calculated. We used the Fisher exact test for the categorical independent variables, and the Student t or Mann-Whitney test for the non-categorical variables. Results In total, 26 patients met the inclusion criteria, and 38% of the sample presented an association between glenohumeral dislocation and GTF. The mean Constant-Murley score was of 82.5 + 8.02 points. The presence of an associated dislocation did not alter the functional outcome. The mean distance between the greater tuberosity of the humerus and the joint surface of the humeral head after the union was of 9 ± 4.3 mm below the articular line of the humeral head. The dislocation led to a lower level of reduction, but this did not influence the Constant-Murley score. Conclusion The cases of GTF submitted to surgical treatment with transosseous sutures had good functional outcomes. The presence of dislocation made the anatomical reduction of the greater tuberosity difficult. However, it did not influence the Constant-Murley score.

Functional Shoulder Evaluation after Osteosynthesis of Greater Tuberosity Fracture: Is There any Influence of Glenohumeral Dislocation? / Avaliação funcional do ombro após osteossíntese da fratura da tuberosidade maior: Há influência da luxação glenoumeral?

Abstract Objective To evaluate the postoperative functional and radiographic outcomes of the shoulder of patients submitted to transosseous suturing of a greater tuberosity fracture (GTF) through an anterolateral route and the influence of the glenohumeral dislocation on these outcomes. Methods We conducted a retrospective study and functional assessment using the Constant-Murley score. The distance between the greater tuberosity and the joint surface of the proximal humerus (in true anteroposterior radiographs) after the union was calculated. We used the Fisher exact test for the categorical independent variables, and the Student t or Mann-Whitney test for the non-categorical variables. Results In total, 26 patients met the inclusion criteria, and 38% of the sample presented an association between glenohumeral dislocation and GTF. The mean Constant-Murley score was of 82.5 + 8.02 points. The presence of an associated dislocation did not alter the functional outcome. The mean distance between the greater tuberosity of the humerus and the joint surface of the humeral head after the union was of 9 + 4.3 mm below the articular line of the humeral head. The dislocation led to a lower level of reduction, but this did not influence the Constant-Murley score. Conclusion The cases of GTF submitted to surgical treatment with transosseous sutures had good functional outcomes. The presence of dislocation made the anatomical reduction of the greater tuberosity difficult. However, it did not influence the Constant-Murley score.

Resumo Objetivo Avaliar os resultados funcional e radiográfico pós-operatórios do ombro, em pacientes submetidos a sutura transóssea de fratura da tuberosidade maior (FTM) por acesso anterolateral, e a influência da luxação glenoumeral nesses resultados. Métodos Realizou-se estudo retrospectivo e avaliação funcional (pela escala de Constant-Murley). Calculou-se a distância entre a tuberosidade maior e a superfície articular do úmero proximal (por meio de radiografia em incidência anteroposterior verdadeira) após a consolidação. Usou-se o teste Exato de Fisher para as variáveis independentes categóricas, e os testes tde Student ou de Mann-Whitney para as não categóricas. Resultados Ao todo, 26 pacientes preencheram os critérios de inclusão. A associação de luxação glenoumeral com FTM foi observada em 38% da amostra. A média da pontuação na escala de Constant-Murley foi de 82,5 + 8,02. A presença de luxação associada não alterou o resultado funcional. A distância média da consolidação da tuberosidade maior do úmero em relação à superfície articular da cabeça umeral foi de 9 + 4,3 mm abaixo da linha articular da cabeça umeral. Pacientes com luxação associada evoluíram com redução menor, mas isso não influenciou na pontuação na escala de Constant-Murley. Conclusão As FTMs submetidas ao tratamento cirúrgico com sutura transóssea evoluíram com bom resultado funcional. A presença de luxação dificultou a redução anatômica da tuberosidade maior. Entretanto, isso não influenciou na pontuação na escala de Constant-Murley.

The Hertel classification can't predict the risk of humeral head osteonecrosis after osteosynthesis using an anterolateral approach.

BACKGROUND: Proximal humeral fractures can progress to osteonecrosis of the humeral head. Hertel developed a binary classification system (12 subtypes) and demonstrated that some patterns have more risk to develop osteonecrosis. Hertel described the prevalence and the risk factors for Humeral head osteonecrosis after osteosynthesis using a Deltopectoral approach. Few studies have evaluated the prevalence and the capacity of Hertel's classification to predict Humeral Head osteonecrosis following osteosynthesis of proximal Humeral fractures through the anterolateral approach. The objectives of this study were to correlate osteonecrosis predictors established by the Hertel classification with the risk of developing osteonecrosis and its prevalence after osteosynthesis using the anterolateral approach. METHODS: This was a retrospective study of patients who underwent osteosynthesis of proximal humerus fractures using an anterolateral approach. Patients were divided into two groups: high risk for necrosis (group 1) and low risk for necrosis (group 2) according to Hertel's criteria. The overall prevalence of osteonecrosis and the prevalence in each group were calculated. A radiological examination was performed in the true anteroposterior (Grashey), scapular, and axillary views, before and after the operation (minimum 1 year after surgery). A Kaplan-Meier curve was used to assess the pattern of the temporal evolution of osteonecrosis. The groups were compared using the Chi-square test or Fisher's exact test. The unpaired t-test (parametric variables - age) and the Mann-Whitney test (non-parametric time between trauma and surgery) were used. RESULTS: In total, 39 patients were evaluated. The postoperative follow-up time was 14.5 ± 3.3 months. The time to onset of necrosis was 14.1 ± 3.9 months. Sex, age, and time between trauma and surgery did not influence the risk of necrosis. Type 2, 9, 10, 11, and 12, or fractures with posteromedial head extension less than or equal to 8 mm, or diaphysis deviation greater than 2 mm, as well as grouping did not influence the risk for osteonecrosis. CONCLUSIONS: Hertel's criteria were not able to predict the development of osteonecrosis after osteosynthesis of proximal humerus fractures performed through the anterolateral approach. The total prevalence of osteonecrosis was 17.9% with a tendency toward an increased incidence after 1 year of surgical treatment.

The Hertel classification can't predict the risk of humeral head osteonecrosis after osteosynthesis using an anterolateral approach

ABSTRACT Background: Proximal humeral fractures can progress to osteonecrosis of the humeral head. Hertel developed a binary classification system (12 subtypes) and demonstrated that some patterns have more risk to develop osteonecrosis. Hertel described the prevalence and the risk factors for Humeral head osteonecrosis after osteosynthesis using a Deltopectoral approach. Few studies have evaluated the prevalence and the capacity of Hertel's classification to predict Humeral Head osteonecrosis following osteosynthesis of proximal Humeral fractures through the anterolateral approach. The objectives of this study were to correlate osteonecrosis predictors established by the Hertel classification with the risk of developing osteonecrosis and its prevalence after osteosynthesis using the anterolateral approach. Methods: This was a retrospective study of patients who underwent osteosynthesis of proximal humerus fractures using an anterolateral approach. Patients were divided into two groups: high risk for necrosis (group 1) and low risk for necrosis (group 2) according to Hertel's criteria. The overall prevalence of osteonecrosis and the prevalence in each group were calculated. A radiological examination was performed in the true anteroposterior (Grashey), scapular, and axillary views, before and after the operation (minimum 1 year after surgery). A KaplanMeier curve was used to assess the pattern of the temporal evolution of osteonecrosis. The groups were compared using the Chi-square test or Fisher's exact test. The unpaired t-test (parametric variables - age) and the MannWhitney test (non-parametric time between trauma and surgery) were used. Results: In total, 39 patients were evaluated. The postoperative follow-up time was 14.5 ± 3.3 months. The time to onset of necrosis was 14.1 ± 3.9 months. Sex, age, and time between trauma and surgery did not influence the risk of necrosis. Type 2, 9, 10, 11, and 12, or fractures with posteromedial head extension less than or equal to 8 mm, or diaphysis deviation greater than 2 mm, as well as grouping did not influence the risk for osteonecrosis. Conclusions: Hertel's criteria were not able to predict the development of osteonecrosis after osteosynthesis of proximal humerus fractures performed through the anterolateral approach. The total prevalence of osteonecrosis was 17.9% with a tendency toward an increased incidence after 1 year of surgical treatment.

Prevalence and risk factors for pseudarthrosis in humeral shaft fractures treated by minimally invasive plate osteosynthesis: A 10-year review.

Introduction: Fractures of the humeral shaft account for about 3% to 5% of all fractures. Although conservative treatment remains the first choice, there are a number of surgical indications. Minimally invasive plate osteosynthesis shows good functional results. However, complications have been reported, such as non-union. Objective: To assess the prevalence and risk factors for non-union after treatment of humeral shaft fractures using minimally invasive plate osteosynthesis. Materials and methods: This retrospective study was carried out in patients treated by minimally invasive plate osteosynthesis between 2009 and 2019. Demographic data and variables related to the fracture that could influence bone healing were analysed. The unpaired t-test and Mann-Whitney test were used for the statistical analyses. Categorical variables were analysed using the chi-square test or Fisher's exact test. Results: The study population showed a male predominance (53 of 75, 70.7%). The average time for fracture healing was 19.8 ± 15.3 weeks. Seven patients developed non-union. Only the presence of an open fracture increased the likelihood of non-union. Conclusions: The prevalence of non-union in patients treated by minimally invasive plate osteosynthesis was 9.3%. Patients with open fractures were six times more likely to progress to non-union. Fracture characteristics (Arbeitsgemeinschaft für Osteosynthesefragen classification, fracture location and plate working length) did not influence progression to non-union.

In Vitro Testing of Sunscreens for Dermal Absorption: Method Comparison and Rank Order Correlation with In Vivo Absorption.

Evaluating the dermal absorption of sunscreen UV filters requires the development of a bio-predictable in vitro permeation test (IVPT). This work describes the comparison of two IVPT methods and rank order correlations of in vitro absorption (skin permeation and retention) with the in vivo absorption (AUC and skin retention) of sunscreens. The IVPT was compared regarding the following elements: (1) application of a single finite dose vs. an infinite dose and (2) the use of heat-separated human epidermis vs. dermatomed skin models. The IVPT was used to evaluate dermal absorption of six UV filters (avobenzone, homosalate, octinoxate, octisalate, octocrylene, and oxybenzone) in commercial sunscreens. Both the in vivo and in vitro permeation studies demonstrated that all UV filters were absorbed following a single-dose application. Sunscreens were rank ordered by the amount of the UV filters absorbed. Data obtained from the IVPT method using a single finite dose and heat-separated human epidermis was found to correlate with the clinical data. Rank orders of the cumulative in vitro skin permeation and the in vivo AUC were found comparable for oxybenzone, homosalate, octisalate, and octinoxate. Rank orders of the in vitro and in vivo skin retention of oxybenzone and octinoxate were also comparable. Additional IVPT parameters may be optimized to enhance the discriminatory power for UV filters with low skin permeation potential (e.g., avobenzone and octocrylene).

In Vitro Testing of Sunscreens for Dermal Absorption: A Platform for Product Selection for Maximal Usage Clinical Trials.

Sunscreen products contain UV filters as active ingredients for the protection of the skin against UVR. The US Food and Drug Administration (FDA) issued a new proposed rule in 2019 (84.FR.6204) for sunscreens and identified the need for additional safety data for certain UV filters including their dermal absorption data. Dermal absorption data reveal systemic exposure of UV filters in humans, which can be obtained from clinical maximal usage trials. FDA guidance recommends conducting in vitro skin permeation tests (IVPTs) to help select formulations for maximal usage clinical trials as IVPT results may be indicative of in vivo absorption. This case study reports in vitro methodologies used for the selection of sunscreen products for an FDA-sponsored proof-of-concept maximal usage clinical trial. An IVPT method was developed using human cadaver skin. Commercially available sunscreen products were tested to determine the skin absorption potential of common UV filters using the IVPT. All the studied sunscreen products demonstrated a certain degree of skin absorption of UV filters using IVPT, and a formulation rank order was obtained. These sunscreen products were also characterized for several formulation properties including the globule size in emulsions, which was found to be an indicator for the rank order.

Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial.

Importance: A prior pilot study demonstrated the systemic absorption of 4 sunscreen active ingredients; additional studies are needed to determine the systemic absorption of additional active ingredients and how quickly systemic exposure exceeds 0.5 ng/mL as recommended by the US Food and Drug Administration (FDA). Objective: To assess the systemic absorption and pharmacokinetics of the 6 active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate) in 4 sunscreen products under single- and maximal-use conditions. Design, Setting, and Participants: Randomized clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) was conducted in 48 healthy participants. The study was conducted between January and February 2019. Interventions: Participants were randomized to 1 of 4 sunscreen products, formulated as lotion (n = 12), aerosol spray (n = 12), nonaerosol spray (n = 12), and pump spray (n = 12). Sunscreen product was applied at 2 mg/cm2 to 75% of body surface area at 0 hours on day 1 and 4 times on day 2 through day 4 at 2-hour intervals, and 34 blood samples were collected over 21 days from each participant. Main Outcomes and Measures: The primary outcome was the maximum plasma concentration of avobenzone over days 1 through 21. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, homosalate, octisalate, and octinoxate over days 1 through 21. Results: Among 48 randomized participants (mean [SD] age, 38.7 [13.2] years; 24 women [50%]; 23 white [48%], 23 African American [48%], 1 Asian [2%], and 1 of unknown race/ethnicity [2%]), 44 (92%) completed the trial. Geometric mean maximum plasma concentrations of all 6 active ingredients were greater than 0.5 ng/mL, and this threshold was surpassed on day 1 after a single application for all active ingredients. For avobenzone, the overall maximum plasma concentrations were 7.1 ng/mL (coefficient of variation [CV], 73.9%) for lotion, 3.5 ng/mL (CV, 70.9%) for aerosol spray, 3.5 ng/mL (CV, 73.0%) for nonaerosol spray, and 3.3 ng/mL (CV, 47.8%) for pump spray. For oxybenzone, the concentrations were 258.1 ng/mL (CV, 53.0%) for lotion and 180.1 ng/mL (CV, 57.3%) for aerosol spray. For octocrylene, the concentrations were 7.8 ng/mL (CV, 87.1%) for lotion, 6.6 ng/mL (CV, 78.1%) for aerosol spray, and 6.6 ng/mL (CV, 103.9%) for nonaerosol spray. For homosalate, concentrations were 23.1 ng/mL (CV, 68.0%) for aerosol spray, 17.9 ng/mL (CV, 61.7%) for nonaerosol spray, and 13.9 ng/mL (CV, 70.2%) for pump spray. For octisalate, concentrations were 5.1 ng/mL (CV, 81.6%) for aerosol spray, 5.8 ng/mL (CV, 77.4%) for nonaerosol spray, and 4.6 ng/mL (CV, 97.6%) for pump spray. For octinoxate, concentrations were 7.9 ng/mL (CV, 86.5%) for nonaerosol spray and 5.2 ng/mL (CV, 68.2%) for pump spray. The most common adverse event was rash, which developed in 14 participants. Conclusions and Relevance: In this study conducted in a clinical pharmacology unit and examining sunscreen application among healthy participants, all 6 of the tested active ingredients administered in 4 different sunscreen formulations were systemically absorbed and had plasma concentrations that surpassed the FDA threshold for potentially waiving some of the additional safety studies for sunscreens. These findings do not indicate that individuals should refrain from the use of sunscreen. Trial Registration: ClinicalTrials.gov Identifier: NCT03582215.

Suboptimal UVA attenuation by broad spectrum sunscreens under outdoor solar conditions contributes to lifetime UVA burden.

BACKGROUND: Broad spectrum sunscreens with a sun protection factor (SPF) of 15 or greater are indicated to decrease the risk of skin cancer and early skin aging caused by the sun if used as directed with other sun protection measures. To determine whether sunscreen product performance is compromised under solar exposure and to test spectral uniformity of protection across the UVA spectrum, we tested broad spectrum sunscreens with a variety of active pharmaceutical ingredients (APIs) and in a variety of dosage forms. METHODS: A cross-sectional market survey of 32 sunscreen drug products containing either organic or inorganic APIs with SPFs of 15, 30, 50, and 70 was tested. UV doses were delivered via natural sun in Silver Spring, Maryland between June and September of 2017. RESULTS: Of the 32 sunscreen drug products, 6 products failed to meet their broad spectrum claim under solar exposure. Using FDA's new proposal to strengthen sunscreen broad spectrum requirements, spectral uniformity based on the mean sunscreen absorbance of UVA1(340-400 nm)/UV (290-400 nm) indicated that ~40% of sunscreen drug products tested had suboptimal UVA protection. CONCLUSION: US consumers may unknowingly be receiving up to 36% more transmitted UVA when selecting between similarly labeled broad spectrum sunscreen drug products with equivalent SPF values. FDA's new proposal may help decrease consumers' overall lifetime UVA burden. Spectral absorbance data on sunscreen performance can be used to further improve the coupling of broad spectrum protection to a product's SPF value so that consumers have improved proportional increases in UV protection.

Effect of Sunscreen Application Under Maximal Use Conditions on Plasma Concentration of Sunscreen Active Ingredients: A Randomized Clinical Trial.

Importance: The US Food and Drug Administration (FDA) has provided guidance that sunscreen active ingredients with systemic absorption greater than 0.5 ng/mL or with safety concerns should undergo nonclinical toxicology assessment including systemic carcinogenicity and additional developmental and reproductive studies. Objective: To determine whether the active ingredients (avobenzone, oxybenzone, octocrylene, and ecamsule) of 4 commercially available sunscreens are absorbed into systemic circulation. Design, Setting, and Participants: Randomized clinical trial conducted at a phase 1 clinical pharmacology unit in the United States and enrolling 24 healthy volunteers. Enrollment started in July 2018 and ended in August 2018. Interventions: Participants were randomized to 1 of 4 sunscreens: spray 1 (n = 6 participants), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two milligrams of sunscreen per 1 cm2 was applied to 75% of body surface area 4 times per day for 4 days, and 30 blood samples were collected over 7 days from each participant. Main Outcomes and Measures: The primary outcome was the maximum plasma concentration of avobenzone. Secondary outcomes were the maximum plasma concentrations of oxybenzone, octocrylene, and ecamsule. Results: Among 24 participants randomized (mean age, 35.5 [SD, 1.5] years; 12 (50%] women; 14 [58%] black or African American; 14 [58%]), 23 (96%) completed the trial. For avobenzone, geometric mean maximum plasma concentrations were 4.0 ng/mL (coefficient of variation, 6.9%) for spray 1; 3.4 ng/mL (coefficient of variation, 77.3%) for spray 2; 4.3 ng/mL (coefficient of variation, 46.1%) for lotion; and 1.8 ng/mL (coefficient of variation, 32.1%). For oxybenzone, the corresponding values were 209.6 ng/mL (66.8%) for spray 1, 194.9 ng/mL (52.4%) for spray 2, and 169.3 ng/mL (44.5%) for lotion; for octocrylene, 2.9 ng/mL (102%) for spray 1, 7.8 ng/mL (113.3%) for spray 2, 5.7 ng/mL (66.3%) for lotion, and 5.7 ng/mL (47.1%) for cream; and for ecamsule, 1.5 ng/mL (166.1%) for cream. Systemic concentrations greater than 0.5 ng/mL were reached for all 4 products after 4 applications on day 1. The most common adverse event was rash, which developed in 1 participant with each sunscreen. Conclusions and Relevance: In this preliminary study involving healthy volunteers, application of 4 commercially available sunscreens under maximal use conditions resulted in plasma concentrations that exceeded the threshold established by the FDA for potentially waiving some nonclinical toxicology studies for sunscreens. The systemic absorption of sunscreen ingredients supports the need for further studies to determine the clinical significance of these findings. These results do not indicate that individuals should refrain from the use of sunscreen. Trial Registration: ClinicalTrials.gov Identifier: NCT03582215.

The Evaluation of Noninvasive Measurements of Erythema as a Potential Surrogate for DNA Damage in Repetitively UV-exposed Human Skin.

Erythema (i.e. visible redness) and DNA damage caused by ultraviolet radiation (UVR) in human skin have similar action spectra and show good correlation after a single exposure to UVR. We explored the potential to use instrumental assessments of erythema as a surrogate for DNA damage after repeated exposures to UVR. We exposed 40 human subjects to three different exposure schedules using two different UVR sources. Cyclobutane-pyrimidine dimers (CPDs) in skin biopsies were measured by immunofluorescence, and erythema was assessed by both the Erythemal Index (EI) and the Oxy-hemoglobin (Oxy-Hb) content. Surprisingly, the skin with the highest cumulative dose ended up with the lowest level of DNA damage, and with the least erythema, as assessed by Oxy-Hb (but not EI) 24 h after the last UV exposure. Although the level of CPDs, on average, paralleled Oxy-Hb (R2 = 0.80-0.94, P = 0.03-0.11), the correlation did not hold for the pooled individual measurements (R2 = 0.009, P = 0.37) due to potential individual differences in UV-induced photoadaptation. We suggest that the methodology may be optimized to improve the correlation between DNA damage level and erythema to enable noninvasive risk assessment based on erythema/Oxy-Hb content for individual human subjects.

Functional evaluation of patients with surgically treated terrible triad of the elbow.

OBJECTIVES: To evaluate the functional outcome of patients with surgically treated terrible triad of the elbow. METHODS: A retrospective evaluation was performed using the MEPS score (Mayo Elbow Performance Score) of patients diagnosed with terrible triad of the elbow who underwent surgical treatment. RESULTS: 14 patients (nine men and five women) and 15 elbows (one bilateral case) were evaluated. A MEPS average score of 78 points and 86% good and excellent results was obtained. As complications, we had one case of infection and three of neuropraxia of the ulnar nerve. CONCLUSION: The patients had stable elbow with good function, however with reduced range of motion. Level of Evidence IV, Case Series.

Avaliação funcional de pacientes com tríade terrível do cotovelo tratados cirurgicamente / Functional evaluation of patients with surgically treated terrible triad of the elbow

Objetivo: Avaliar os resultados funcionais de pacientes com tríade terrível do cotovelo tratados cirurgicamente. Métodos: Avaliação retrospectiva com utilização da escala MEPS (Mayo Elbow Performance Score) de pacientes diagnosticados com tríade terrível do cotovelo e submetidos a tratamento cirúrgico. Resultados: Foram avaliados 14 pacientes (nove homens e cinco mulheres) e 15cotovelos (um caso bilateral). Obtivemos a média de 78 pontos e86% de bons e excelentes resultados com a utilização da escala MEPS. Como complicações, tivemos um caso de infecção e três de neurapraxia do nervo ulnar. Conclusão: Os pacientes evoluíram com cotovelo estável, com boa função, porém, com diminuição do arco de movimento. Nível de Evidência IV, Série de Casos.

Objectives: To evaluate the functional outcome of patients with surgically treated terrible triad of the elbow. Methods: A retrospective evaluation was performed using the MEPS score (Mayo Elbow Performance Score) of patients diagnosed with terrible triad of the elbow who underwent surgical treatment. Results: 14 patients (nine men and five women) and 15 elbows (one bilateral case) were evaluated. A MEPS average score of 78 points and 86%good and excellent results was obtained. As complications, we had one case of infection and three of neuropraxia of the ulnarnerve. Conclusion: The patients had stable elbow with good function, however with reduced range of motion. Level of Evidence IV, Case Series.

Identification of Genes Expressed in Hyperpigmented Skin Using Meta-Analysis of Microarray Data Sets.

More than 375 genes have been identified that are involved in regulating skin pigmentation and these act during development, survival, differentiation, and/or responses of melanocytes to the environment. Many of these genes have been cloned, and disruptions of their functions are associated with various pigmentary diseases; however, many remain to be identified. We have performed a series of microarray analyses of hyperpigmented compared with less pigmented skin to identify genes responsible for these differences. The rationale and goal for this study was to perform a meta-analysis on these microarray databases to identify genes that may be significantly involved in regulating skin phenotype either directly or indirectly that might not have been identified due to subtle differences by any of these individual studies alone. The meta-analysis demonstrates that 1,271 probes representing 921 genes are differentially expressed at significant levels in the 5 microarray data sets compared, providing new insights into the variety of genes involved in determining skin phenotype. Immunohistochemistry was used to validate two of these markers at the protein level (TRIM63 and QPCT), and we discuss the possible functions of these genes in regulating skin physiology.