DermTok: Who's Talking Sun? A Cross-Sectional Analysis of Sun Protection Content on TikTok.

Despite the widespread interest in dermatology on TikTok, studies have shown most related videos are not produced by board-certified dermatologists (BCDs) or other health professionals. To see if this trend extended to sun protection, we examined TikTok videos associated with sun safety to determine the proportion produced by BCDs. From August 25, 2023, to August 27, 2023, investigators input the following hashtags into the TikTok search bar: #sunscreen, #sunprotection, #spf, #skincancer, and #skinprotection. The top 100 videos in each category were analyzed and categorized based on the content creator. Additionally, we assessed whether videos explicitly addressed skin of color (SOC). Of the analyzed videos, only 16.6% originated from BCDs. Beauty bloggers/bloggers were the most prevalent creators in this category (38.7%), followed by patients/consumers (33.7%). Only 2.8% of the videos pertained to SOC patients. This highlights a gap in the type of educational content generated by dermatologists on TikTok, with sun safety being a potential subject to target within social media. Additionally, the small representation of videos addressing SOC patients underscores the need for more diverse and inclusive educational skincare content on TikTok.J Drugs Dermatol. 2024;23(7):571-574. doi:10.36849/JDD.8179.

Rural Health Disparities in Skin Cancer Amplified Among Skin of Color.

Limited studies explore the role social determinants of health have on urban-rural health disparities, particularly for Skin of Color. To further evaluate this relationship, a cross-sectional study was conducted on data from five states using the 2018 to 2021 Behavior Risk Factor Surveillance Survey, a national state-run health survey. Prevalence of skin cancer history and urban/rural status were evaluated across these social determinants of health: sex, age, race, insurance status, number of personal healthcare providers, and household income. Overall, rural counterparts were significantly more likely to have a positive skin cancer history across most social determinants of health. Rural populations had a higher prevalence of skin cancer history across all races (P<.001). Rural non-Hispanic Whites had greater odds than their urban counterparts (OR=1.40; 95% CI 1.34 - 1.46). The odds were approximately twice as high for rural Black (OR=1.74; 95% CI 1.14 - 2.65), Hispanic (OR=2.31; 95% CI 1.56 - 3.41), and Other Race, non-Hispanic (OR=1.99; 95% CI 1.51 - 2.61), and twenty times higher for Asians (OR=20.46; 95% CI 8.63 - 48.54), although no significant difference was seen for American Indian/Alaskan Native (OR=1.5; 95% CI 0.99 - 2.28). However, when household income exceeded $100,000 no significant difference in prevalence or odds was seen between urban and rural settings. Despite increasing awareness of metropolitan-based health inequity, urban-rural disparities in skin cancer prevalence continue to persist and may be magnified by social determinants such as income and race. J Drugs Dermatol. 2024;23(6):480-484.    doi:10.36849/JDD.8094.

Opposite perceptual biases in analogous auditory and visual tasks are unique to consonant-vowel strings and are unlikely a consequence of repetition.

Despite wide reporting of a right ear (RE) advantage on dichotic listening tasks and a right visual field (RVF) advantage on visual half-field tasks, we know very little about the relationship between these perceptual biases. Previous studies that have investigated perceptual asymmetries for analogous auditory and visual consonant-vowel tasks have indicated a serendipitous finding: a RE advantage and a left visual field (LVF) advantage with poor cross-modal correlations. In this study, we examined the possibility that this LVF advantage for visual processing of consonant-vowel strings may be a consequence of repetition by examining perceptual biases in analogous auditory and visual tasks for both consonant-vowel strings and words. We replicated opposite perceptual biases for consonant-vowel strings (RE and LVF advantages). This did not extend to word stimuli where we found RE and RVF advantages. Furthermore, these perceptual biases did not differ across the three experimental blocks. Thus, we can firmly conclude that this LVF advantage is unique to consonant-vowel strings and is not a consequence of the repetition of a relatively limited number of stimuli. Finally, a test of covariances indicated no cross-modal relationships between laterality indices suggesting that perceptual biases are dissociable within individuals and cluster on mode of presentation.

Toxic Ingredients in Personal Care Products: A Dermatological Perspective.

Environmental dermatology is the study of how environmental factors affect the integumentary system. The environment includes natural and built habitats, encompassing ambient exposure, occupational exposures, and lifestyle exposures secondary to dietary and personal care choices. This review explores common toxins found in personal care products and packaging, such as bisphenols, parabens, phthalates, per- and poly-fluoroalkyl substances, p-phenylenediamine, and formaldehyde. Exposure to these toxins has been associated with carcinogenic, obesogenic, or proinflammatory effects that can potentiate disease. In addition, these compounds have been implicated as endocrine-disrupting chemicals that can worsen dermatological conditions such as acne vulgaris, or dermatitis. Certain pollutants found in personal care products are not biodegradable and have the potential to bioaccumulate in humans. Therefore, even short-term exposure can cause long-lasting issues for communities. The skin is often the first point of contact for environmental exposures and serves as the conduit between environmental toxins and the human body. Therefore, it is important for dermatologists to understand common pollutants and their acute, subacute, and chronic impact on dermatological conditions to better diagnose and manage disease.

Immune checkpoint inhibitor associated epidermal necrosis, beyond SJS and TEN: a review of 98 cases.

Immune checkpoint inhibitor (ICI) therapies carry the risk of major immune-related adverse events (irAEs). Among the most severe irAEs is epidermal necrosis that may clinically mimic Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN). The aim of this study was to provide a summary of the clinical and histological features of ICI-associated epidermal necrosis, with a special focus on factors associated with fatal outcomes in cases of extensive disease. A total of 98 cases, 2 new cases and 96 reported on PubMed and in the literature, of ICI-associated epidermal necrosis were assessed. Development of epidermal necrosis occurred between 1 day and 3 years after starting ICI therapy, with an average onset of 13.8 weeks for patients with limited (< 30% BSA) and 11.3 weeks for those with extensive (≥ 30% BSA) involvement, and a median onset of 5.8 weeks and 4 weeks respectively. A preceding rash was seen in 52 cases and was more common in extensive cases. Mucosal involvement was only reported in 65% of extensive cases but was significantly associated with fatal reactions. Co-administration of cytotoxic chemotherapy was associated with more extensive disease. Recovery was observed in 96% and 65% of those with limited and extensive involvement respectively and no specific therapy was associated with improved survival. Young age was significantly associated with poor outcomes in extensive disease, the average age of surviving patients was 64.5 years old versus 55.1 years old for deceased patients, p < 0.01. Both superficial perivascular and interface/lichenoid inflammatory infiltrates were commonly seen. These findings suggest that ICI-associated epidermal necrosis should be considered a distinct clinical entity from drug-induced SJS/TEN.

Prevalence and molecular epidemiology of carbapenemase-producing Enterobacterales isolated from dog and cat faeces submitted to veterinary laboratories in the USA.

AIMS: To estimate the prevalence of carbapenemase-producing Enterobacterales (CPE) carriage among pets using faecal specimens submitted to veterinary diagnostic laboratories throughout the US. A secondary aim was to employ whole-genome sequencing (WGS) to characterize isolates of CPE from companion animals and compare them to publicly available CPE genomes. METHODS AND RESULTS: To estimate the prevalence of CPE in companion animals in the USA, a multicenter surveillance study including 8 different veterinary diagnostic laboratories from across the USA was conducted. Briefly, remnant faecal specimens from dogs and cats were screened using two selective agar plates (CHROMID Carba and MacConkey with 1 mg/L cefotaxime and 0.125 mg/L meropenem) and presumptive CPE isolates screened by the modified carbapenemase inactivation method for carbapenemase production. A total of 2393 specimens were screened and yielded 196 isolates for carbapenemase screening. A total of 5 isolates from 4 dogs and 1 cat at 3 different veterinary diagnostic laboratories were confirmed to produce a carbapenemase (0.21%). Whole-genome sequencing (WGS) revealed two E. coli (ST167) isolates that both produced an NDM-5 carbapenemase, two Enterobacter hormaechei (ST171) isolates that produced an NDM-5 carbapenemase and a KPC-4 carbapenemase respectively and one Klebsiella oxytoca (ST199) that produced an Oxa-48-type carbapenemase. Both E. coli isolates were found to be within at least 22 SNPs of previously characterized canine and human CPE isolates. CONCLUSIONS: This study demonstrates that the prevalence of CPE among companion animals is relatively low (0.21%) but that given the genetic relatedness of animal isolates to human isolates, additional surveillance is needed.

Methionine aminopeptidase 2 is required for HSC initiation and proliferation.

In a chemical screening, we tested the antiangiogenic effects of fumagillin derivatives and identified fumagillin as an inhibitor of definitive hematopoiesis in zebrafish embryos. Fumagillin is known to target methionine aminopeptidase II (MetAP2), an enzyme whose function in hematopoiesis is unknown. We investigated the role of MetAP2 in hematopoiesis by using zebrafish embryo and human umbilical cord blood models. Zebrafish metap2 was expressed ubiquitously during early embryogenesis and later in the somitic region, the caudal hematopoietic tissue, and pronephric duct. metap2 was inhibited by morpholino and fumagillin treatment, resulting in increased mpo expression at 18 hours postfertilization and reduced c-myb expression along the ventral wall of dorsal aorta at 36 hours postfertilization. It also disrupted intersegmental vessels in Tg(fli1:gfp) embryos without affecting development of major axial vasculatures. Inhibition of MetAP2 in CB CD34(+) cells by fumagillin had no effect on overall clonogenic activity but significantly reduced their engraftment into immunodeficient nonobese diabetes/severe combined immunodeficiency mice. metap2 knock-down in zebrafish and inhibition by fumagillin in zebrafish and human CB CD34(+) cells inhibited Calmodulin Kinase II activity and induced ERK phosphorylation. This study demonstrated a hitherto-undescribed role of MetAP2 in definitive hematopoiesis and a possible link to noncanonical Wnt and ERK signaling.

Colorectal Cancer Screening Disparities Among Race: A Zip Code Level Analysis.

BACKGROUND: Colorectal cancer (CRC) screening can prevent disease by early identification. Existing disparities in CRC screening have been associated with factors including race, socioeconomic status, insurance, and even geography. Our study takes a deeper look into how social determinants related to zip code tabulation areas affect CRC screenings. MATERIALS AND METHODS: We conducted a retrospective cross-sectional study of CRC screenings by race at a zip code level, evaluating for impactful social determinant factors such as the social deprivation index (SDI). We used publicly available data from CDC 500 Cities Project (2016-2019), PLACES Project (2020), and the American Community Survey (2019). We conducted multivariate and confirmatory factor analyses among race, income, health insurance, check-up visits, and SDI. RESULTS: Increasing the tertile of SDI was associated with a higher likelihood of being Black or Hispanic, as well as decreased median household income (P < .01). Lower rates of regular checkup visits were found in the third tertile of SDI (P < .01). The multivariate analysis showed that being Black, Hispanic, lower income, being uninsured, lack of regular check-ups, and increased SDI were related to decreased CRC screening. In the confirmatory factor analysis, we found that SDI and access to insurance were the variables most related to decreased CRC screening. CONCLUSION: Our results reveal the top 2 factors that impact a locality's CRC screening rates are the social deprivation index and access to health care. This data may help implement interventions targeting social barriers to further promote CRC screenings within disadvantaged communities and decrease overall mortality via early screening.

Pharmacokinetic and pharmacodynamic modeling of opioid-induced gastrointestinal side effects in patients receiving tapentadol IR and oxycodone IR.

PURPOSE: To understand the relationship between the risk of opioid-related gastrointestinal adverse effects (AEs) and exposure to tapentadol and oxycodone as well as its active metabolite, oxymorphone, using pharmacokinetic/pharmacodynamic models. METHODS: The analysis was based on a study in patients with moderate-to-severe pain following bunionectomy. Population PK modeling was conducted to estimate population PK parameters for tapentadol, oxycodone, and oxymorphone. Time to AEs was analyzed using Cox proportional-hazards models. RESULTS: Risk of nausea, vomiting, and constipation significantly increased with exposure to tapentadol or oxycodone/oxymorphone. However, elevated risk per drug exposure of AEs for tapentadol was ~3-4 times lower than that of oxycodone, while elevated AE risk per drug exposure of oxycodone was ~60 times lower than that for oxymorphone, consistent with reported in vitro receptor binding affinities for these compounds. Simulations show that AE incidence following administration of tapentadol IR is lower than that following oxycodone IR intake within the investigated range of analgesic noninferiority dose ratios. CONCLUSIONS: This PK/PD analysis supports the clinical findings of reduced nausea, vomiting and constipation reported by patients treated with tapentadol, compared to patients treated with oxycodone.

Population pharmacokinetics of doripenem based on data from phase 1 studies with healthy volunteers and phase 2 and 3 studies with critically ill patients.

A population pharmacokinetic model of doripenem was constructed using data pooled from phase 1, 2, and 3 studies utilizing nonlinear mixed effects modeling. A 2-compartment model with zero-order input and first-order elimination best described the log-transformed concentration-versus-time profile of doripenem. The model was parameterized in terms of total clearance (CL), central volume of distribution (V(c)), peripheral volume of distribution (V(p)), and distribution clearance between the central and peripheral compartments (Q). The final model was described by the following equations (for jth subject): CL(j) (liters/h) = 13.6.(CL(CR)(j)/98 ml/min)(0.659).(1 + CL(race)(j) [0 for Caucasian]); V(c)(j) (liters) = 11.6.(weight(j)/73 kg)(0.596); Q(j) (liters/h) = 4.74.(weight(j)/73)(1.06); and V(p)(j) (liters) = 6.04.(CL(CR)(j)/98 ml/min)(0.417).(weight(j)/73 kg)(0.840).(age(j)/40 years)(0.307). According to the final model, population mean parameter estimates and interindividual variability (percent coefficient of variation [% CV]) for CL (liters/h), V(c) (liters), V(p) (liters), and Q (liters/h) were 13.6 (19%), 11.6 (19%), 6.0 (25%), and 4.7 (42%), respectively. Residual variability, estimated using three separate additive residual error models, was 0.17 standard deviation (SD), 0.55 SD, and 0.92 SD for phase 1, 2, and 3 data, respectively. Creatinine clearance was the most significant predictor of doripenem clearance. Mean Bayesian clearance was approximately 33%, 55%, and 76% lower for individuals with mild, moderate, or severe renal impairment, respectively, than for those with normal renal function. The population pharmacokinetic model based on healthy volunteer data and patient data informs us of doripenem disposition in a more general population as well as of the important measurable intrinsic and extrinsic factors that significantly influence interindividual pharmacokinetic differences.

Finger-powered fluidic actuation and mixing via MultiJet 3D printing.

Additive manufacturing, or three-dimensional (3D) printing, has garnered significant interest in recent years towards the fabrication of sub-millimeter scale devices for an ever-widening array of chemical, biological and biomedical applications. Conventional 3D printed fluidic systems, however, still necessitate the use of non-portable, high-powered external off-chip sources of fluidic actuation, such as electro-mechanical pumps and complex pressure-driven controllers, thus limiting their scope towards point-of-need applications. This work proposes entirely 3D printed sources of human-powered fluidic actuation which can be directly incorporated into the design of any 3D printable sub-millifluidic or microfluidic system where electrical power-free operation is desired. Multiple modular, single-fluid finger-powered actuator (FPA) designs were fabricated and experimentally characterized. Furthermore, a new 3D fluidic one-way valve concept employing a dynamic bracing mechanism was developed, demonstrating a high diodicity of ∼1117.4 and significant reduction in back-flow from the state-of-the-art. As a result, fabricated FPA prototypes achieved tailorable experimental fluid flow rates from ∼100 to ∼3000 µL min-1 without the use of electricity. Moreover, a portable human-powered two-fluid pulsatile fluidic mixer, capable of generating fully-mixed fluids in 10 seconds, is presented, demonstrating the application of FPAs towards on-chip integration into more complex 3D printed fluidic networks.

An integrated microfluidic device for large-scale in situ click chemistry screening.

An integrated microfluidic device has been developed to perform 1024 in situ click chemistry reactions in parallel using the bovine carbonic anhydrous II (bCAII) click chemistry system as a proof-of-concept study and a rapid hit identification approach using SPE purification and electrospray-ionization mass spectrometry, multiple reaction monitoring (MRM) analysis, all of which improves the sensitivity and throughput of the downstream analysis.

Assessing Time of Onset for Interstitial Lung Disease in Anti-MDA5 Antibody-Positive Dermatomyositis.

This cohort study seeks to describe the time interval between interstitial lung disease and anti­melanoma differentiation-associated gene 5 antibody-positive dermatomyositis diagnoses.

Chondroitinase ABC has a long-lasting effect on chondroitin sulphate glycosaminoglycan content in the injured rat brain.

Chondroitin sulphate proteoglycans (CSPGs) are axon growth inhibitory molecules present in the glial scar that play a part in regeneration failure after damage to the CNS and which restrict CNS plasticity. Removal of chondroitin sulphate glycosaminoglycan (GAG) chains with chondroitinase-ABC (chABC) in models of CNS injury promotes both axon regeneration and plasticity. We have analysed the immediate and long-term effects of a single injection of chABC on CSPGs, GAGs and axon regeneration. We made unilateral nigrostriatal lesions in adult rats accompanied by an adjacent infusion of either chABC or a bacterial-derived control enzyme (penicillinase). Within 24 h of chABC treatment there was digestion of GAGs, including hyaluronan, and a reduction in neurocan in an area extending 1.5 mm around the injection site. Around 50% of GAG is inaccessible to chABC digestion, even in tissue digested in vitro, which probably represents intracellular stores. In control penicillinase treated animals, total GAGs recovered from the lesioned brains were up-regulated by 4-fold 7 days after injury and gradually decreased to normal at 28 days post-lesion. In chondroitinase-treated animals, the total GAG remained at low level throughout the 28-day experimental period. This suggests the persistence of active chABC for at least 10 days after injection which is able to digest CSPGs released from cells during this time. This was confirmed by immunological detection of enzyme for 10 days and by retrieval of active enzyme from the brain at 10 days after injection. Our results suggest that a single injection of chABC can produce an environment conducive to CNS repair for over 10 days.

Heparan sulphate proteoglycans in glia and in the normal and injured CNS: expression of sulphotransferases and changes in sulphation.

Heparan sulphate proteoglycans (HSPGs) have multiple functions relevant to the control of the CNS injury response, particularly in modulating the effects of growth factors and localizing molecules that affect axon growth. We examined the pattern of expression and glycanation of HSPGs in the normal and damaged CNS, and in astrocytes and oligodendrocyte precursors because of their participation in the injury reaction. The composition of HS glycosaminoglycan (GAG) chains was analysed by biochemical analysis and by the binding of antibodies that recognize sulphated epitopes. We also measured levels of HS sulphotransferases and syndecans. Compared with oligodendrocytes, oligodendrocyte precursors have more 2-O-sulphation in their HS GAG. This is accompanied by higher expression of the enzyme responsible for 2-O-sulphation, HS 2-O-sulphotransferase (HS2ST) and a fall in syndecan-1. Astrocytes treated with tumour growth factor (TGF)alpha or TGFbeta to mimic the injury response showed upregulation of syndecan-1 and HS2ST correlating with an increase in 2-O-sulphate residues in their HS GAGs. This also correlated with increased staining with AO4B08 anti-GAG antibody that recognizes high sulphation, and reduced staining with RB4EA12 recognizing low sulphation. After injury to the adult rat brain there was an overall increase in the quantity of HSPG around the injury site, mRNA for HS2ST was increased, and the changes in staining with sulphation-specific antibodies were consistent with an increase in 2-O-sulphated HS. Syndecan-1 was upregulated in astrocytes. The major injury-related change, seen in injured brain and cultured glia, was an increase in 2-O-sulphated HS and increased syndecan-1, suggesting novel approaches to modulating scar formation.

The role of survivin in angiogenesis during zebrafish embryonic development.

BACKGROUND: Survivin is the smallest member of the inhibitor of apoptosis (IAP) gene family. Recently, the zebrafish survivin-1 gene has been cloned, showing remarkable sequence identity and similarity over the BIR domain compared with human and mouse survivin gene. Here we investigated the role of survivin in angiogenesis during zebrafish development. Morpholinos (MOs) targeting the 5' untranslated region (UTR) (SurUTR) and sequences flanking the initiation codon (SurATG) of zebrafish survivin-1 gene were injected into embryos at 1-4 cell stage. Vasculature was examined by microangiography and GFP expression in Tg(fli1:EGFP)y1 embryos. RESULTS: In embryos co-injected with SurUTR and SurATG-MOs, vasculogenesis was intact but angiogenesis was markedly perturbed, especially in the inter-segmental vessels (ISV) and dorsal longitudinal anastomotic vessels (DLAV) of the trunk, the inner optic circle and optic veins of developing eyes and the sub-intestinal vessels. Apoptosis was increased, as shown by TUNEL staining and increase in caspase-3 activity. Efficacy of SurUTR and SurATG-MOs was demonstrated by translation inhibition of co-injected 5'UTR survivin:GFP plasmids. The phenotypes could be recapitulated by splice-site MO targeting the exon2-intron junction of survivin gene and rescued by survivin mRNA. Injection of human vascular endothelial growth factor (VEGF) protein induced ectopic angiogenesis and increased survivin expression, whereas treatment with a VEGF receptor inhibitor markedly reduced angiogenesis and suppressed survivin expression. CONCLUSION: Survivin is involved in angiogenesis during zebrafish development and may be under VEGF regulation.