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Recessive dystrophic epidermolysis bullosa (RDEB) and junctional epidermolysis bullosa (JEB) are lethal blistering skin disorders resulting from mutations in genes coding for type VII collagen ( COL7A1 ) and laminin 332 ( LAMA3 , LAMB3 , or LAMC2 ), respectively. In RDEB, 25% of patients harbor nonsense mutations causing premature termination codons (PTCs). In JEB, a majority of mutations in LAMB3 are nonsense mutations (80%). ELX-02, an aminoglycoside analog, has demonstrated superior PTC readthrough activity and lower toxicity compared to gentamicin in various genetic disorders. This study investigated the ability of ELX-02 to suppress PTCs and promote the expression of C7 and laminin 332 in primary RDEB keratinocytes/fibroblasts and primary JEB keratinocytes harboring nonsense mutations. ELX-02 induced a dose-dependent production of C7 or laminin β3 that surpassed the results achieved with gentamicin. ELX-02 reversed RDEB and JEB cellular hypermotility and improved poor cell-substratum adhesion in JEB cells. Importantly, ELX-02-induced C7 and laminin 332 localized to the dermal-epidermal junction. This is the first study demonstrating that ELX-02 can induce PTC readthrough and restore functional C7 and laminin 332 in RDEB and JEB caused by nonsense mutations. Therefore, ELX-02 may offer a novel and safe therapy for RDEB, JEB, and other inherited skin diseases caused by nonsense mutations., Competing Interests: V.B. is a former employee and current shareholder of Eloxx Pharmaceuticals, which owns patents related to this paper. S.A. is a former employee of Eloxx Pharmaceuticals., (© 2024 The Author(s).)

The second part of this CME article discusses sunscreen regulation and safety considerations for humans and the environment. First, we provide an overview of the history of the United States Food and Drug Administration's regulation of sunscreen. Recent Food and Drug Administration studies clearly demonstrate that organic ultraviolet filters are systemically absorbed during routine sunscreen use, but to date there is no evidence of associated negative health effects. We also review the current evidence of sunscreen's association with vitamin D levels and frontal fibrosing alopecia, and recent concerns regarding benzene contamination. Finally, we review the possible environmental effects of ultraviolet filters, particularly coral bleaching. While climate change has been shown to be the primary driver of coral bleaching, laboratory-based studies suggest that organic ultraviolet filters represent an additional contributing factor, which led several localities to ban certain organic filters., (Copyright © 2024. Published by Elsevier Inc.)

As our knowledge of the harmful effects of ultraviolet radiation continues to evolve, sunscreen remains an integral part of a comprehensive photoprotection strategy against multiple endpoints of ultraviolet-mediated damage. Part 1 of this review covers sunscreen active and additive ingredient properties, mechanisms of action and gaps in coverage. Following an overview of sunscreen's efficacy in protecting against sunburn, photocarcinogenesis, photoaging, pigmentary disorders, and idiopathic photodermatoses, we highlight considerations for product use and selection in children and individuals with skin of color., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The association between early surgical menopause and increased mortality has been well demonstrated. Prior studies have also demonstrated that ovarian conservation is not associated with worse oncologic outcomes in early-stage cervical cancer. This study examined the contemporary trends and characteristics of ovarian conservation at time of hysterectomy in young women with cervical cancer., Methods: This is a retrospective cohort study examining the National Inpatient Sample. The study population was 4900 women aged ≤50 years with cervical cancer who had hysterectomy-based surgical treatment from 10/2015 to 12/2018. The exposure allocation was the adnexal procedure status (ovarian conservation versus oophorectomy). The main outcome measures were temporal trends of ovarian conservation over time and per patient age. Multivariable binary logistic regression model was fitted to identify independent characteristics associated with ovarian conservation. A classification-tree was constructed by recursive partitioning analysis to examine the utilization patterns of ovarian conservation., Results: A total of 2,940 (60.0%) women underwent ovarian conservation at hysterectomy. Ovarian conservation rates remained stable until age 37 years, ranging from 82.5% to 77.9% (P = 0.502), after which time the rate sharply and significantly decreased by 7.4% (95% confidence interval 5.4-9.3, P < 0.001) in one-year age increments from 77.9% at age 37 years to 28.7% at age 50 years. The rate of ovarian conservation increased from 54.7% in Q4/2015 to 64.4% in Q4/2018 (P = 0.002). In multivariable analysis, recent surgery remained an independent factor for ovarian conservation (adjusted-odds ratio per year-quarter 1.04, 95% confidence interval 1.03-1.06). A classification-tree model identified 24 unique patterns of ovarian conservation based on patient factor (age, race/ethnicity, primary expected payer, and year of surgery), surgical factor (minimally invasive hysterectomy), and facility factor (hospital bed capacity and region), ranging from <20% to 90% (absolute percentage difference, >80%)., Conclusion: Increasing rates of ovarian conservation at the time of hysterectomy in women undergoing surgical management of cervical cancer is encouraging; however, the marked decrease noted in patients in their mid-30s as well as substantial variability in ovarian conservation based on patient, surgical, and hospital factors are striking and warrant further consideration in clinical practice guidelines., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: An inverse relationship between hospital volume and adverse patient outcomes has been established for many conditions, but has not yet been examined in ovarian hyperstimulation syndrome (OHSS). Given the rarity of severe OHSS, but potential for high morbidity, this study aimed to elucidate the effect of hospital volume on inpatient OHSS-related complications., Methods: This is a retrospective observational study querying the National Inpatient Sample, 1/2001-12/2011. Study population was 11,878 patients with OHSS treated at 735 hospitals. Annualized hospital OHSS treatment volume was grouped as: low-volume (1 case/year), mid-volume (>1 but < 3.5 cases/year), and high-volume (≥3.5 cases/year). Main outcome measure was major complication rates stratified by hospital treatment volume, assessed by multinomial regression and binary logistic regression models., Results: A total of 2,415 (20.3%) patients were treated at low-volume centers, 5,023 (42.3%) at mid-volume centers, and 4,440 (37.4%) at high-volume centers. Patients treated at high-volume centers were more likely to be older and less comorbid with higher incomes and lower body mass index (P < 0.05). High-volume hospitals were more likely to be urban-teaching centers with large bed capacity (P < 0.001). Overall, 1,624 (13.7%) patients experienced a major complication during hospitalization. Patients treated at high-volume hospitals had lower rates of major complications (high: 11.0%, mid: 15.2%, low: 15.6%, P < 0.001). On multivariable analysis, treatment at high-volume hospitals was independently associated with a nearly 20% lower rate of major complications (odds ratio 0.82, 95% confidence interval 0.70-0.97, P = 0.021)., Conclusion: Our study suggests that higher hospital treatment volume for OHSS may be associated with improved outcomes., (Copyright © 2022 Elsevier B.V. All rights reserved.)