Two years of a pilot virtual melanoma education program for adolescents in Texas: Assessing knowledge gaps and demographic disparities.

A formal melanoma primary prevention program was developed for a target audience of grade-school adolescents near Houston, Texas, focusing on skin cancer education and promoting long-term sun safety habits. Upon application of a multivariable regression model, adolescents of Black, non-Hispanic race, male gender, and lower grade levels were independent predictors of lower baseline skin cancer prevention knowledge. These findings reveal potential areas to prioritize when addressing knowledge gaps in the adolescent community.

Novel, pathogenic insertion variant of GSDME associates with autosomal dominant hearing loss in a large Chinese pedigree.

Nonsyndromic hearing loss (NSHL) is a genetically diverse, highly heterogeneous condition characterised by deafness, and Gasdermin E (GSDME) variants have been identified as directly inducing autosomal dominant NSHL. While many NSHL cases associated with GSDME involve the skipping of exon 8, there is another, less understood pathogenic insertion variant specifically found in Chinese pedigrees that causes deafness, known as autosomal dominant 5 (DFNA5) hearing loss. In this study, we recruited a large Chinese pedigree, conducted whole-exome and Sanger sequencing to serve as a comprehensive clinical examination, and extracted genomic DNA samples for co-segregation analysis of the members. Conservation and expression analyses for GSDME were also conducted. Our clinical examinations revealed an autosomal dominant phenotype of hearing loss in the family. Genetic analysis identified a novel insertion variant in GSDME exon 8 (GSDME: NM_004403.3: c.1113_1114insGGGGTGCAGCTTACAGGGTGGGTGT: p. P372fs*36). This variant is segregated with the deafness phenotype of this pedigree. The GSDME gene was highly conserved in the different species we analysed, and its mRNA expression was ubiquitously low in different human tissues. In conclusion, we have successfully identified a novel pathogenic insertion variant of GSDME in a Chinese pedigree that causes deafness, shedding light on the genetic basis of hearing loss within this specific family. Our findings expand the spectrum of known variants associated with GSDME-related deafness and may further support both the underlying gain-of-function mechanism and functional associations of GSDME hearing loss variants.

Novel pathogenic CERKL variant in Iranian familial with inherited retinal dystrophies: genotype-phenotype correlation.

Inherited retinal dystrophies (IRDs) include a large chronic heterogeneity genetic disease. While many disease-causing pathogenic variants were involved in the progression of IRD, the Ceramide Kinase Like (CERKL) gene variant in Iranian patients is not well characterized. In this study, a consanguineous Iranian family with three generations was recruited whom presented with the clinical diagnosis of autosomal recessive IRD. By targeted next-generation sequencing (TGS) and Sanger sequencing, the proband was found to have a novel, pathological homozygous deletion variant c.560_568del (p.187_190del) of the CERKL gene (NM_001030311.2) that co-segregated with the disease in all affected family members. The Cerkl is highly expressed in the later four developmental retinal stages, playing a vital role in retina degeneration. Therefore, the identification of a novel, homozygous deletion CERKL variant c.560_568del (p.187_190del) in an IRD familial cohort descent provides insights into the molecular pathogenesis of IRD and facilitates genetic counseling and disease prediction.

Mental health trends among medical students.

Student mental health concerns can manifest in several forms. Medical students juggling a multitude of trials (i.e., intense academic rigor, financial debt, sleep deprivation, lack of control, continual exposure to sickness and death, and training mistreatment) can help explain the higher prevalence of psychological disorders within this population. Furthermore, these mental health difficulties are not static; certain challenges move into the forefront as students face key transition points in schooling. Primary examples include the entry year of medical school, the shift from preclinical curriculum to clinical training, and the final moments prior to beginning residency. Given the existing mental health trends among medical students at baseline, it can be concluded that the COVID-19 pandemic has exacerbated the stress, anxiety, and depression associated with medical education. Solutions do indeed exist to address the moral injury medical students face, from expanded crisis management training and implementation of peer support networks to destigmatization of and improved access to professional mental health resources. It is up to the curators of the medical education system to make these solutions the new status quo.

Telehealth reform post-public health emergency: crucial next steps.

As the pandemic made it unsafe for providers and patients to meet in person, the US government implemented key temporary telehealth waivers in March 2020 that expanded Medicare telehealth coverage dramatically. Some of the most significant changes included the removal of location restrictions so that patients and providers could engage in telehealth from their homes, full provider reimbursement for telehealth visits, coverage for more medical specialties and types of practitioners such as occupational and physical therapists, and the allowance of telehealth prescription of controlled substances. The waivers will end when the government removes the federal status of a public health emergency, which is expected to occur in 2023. Nearly 64 million Medicare patients are at risk of losing most modalities of telehealth access. We present current legislation that could combat this "telehealth cliff" and defend the position that Medicare telehealth access should remain permanently expanded.

Demographics of Skin Cancer Knowledge Among Middle and High Schoolers in Texas.

INTRODUCTION: Adolescents, an age group that can reduce sun exposure early, may benefit from school-based skin cancer education programs. Literature regarding the demographics of melanoma knowledge is sparse. OBJECTIVES: This study sought to evaluate melanoma knowledge among students in Texas viewing John Wayne Cancer Foundation Block the Blaze (JWCFBTB) presentations and identify group differences with regard to sociodemographic factors. METHODS: Before JWCFBTB presentations delivered in Houston and Dallas by health professions students, a pre-presentation melanoma knowledge quiz was distributed. This survey was adapted from a 2000 study evaluating melanoma knowledge in middle and high schoolers in Houston and Dallas. Respondents were also asked to provide their gender, age, grade, race, parent education level, and whether they are first-generation American. ANOVA and Tukey tests were used to evaluate demographic group differences in scores. Logistic regression models determined predictors of answering selected true/false questions correctly. RESULTS: One-way ANOVA tests showed statistically significant group differences in pre-test scores for all demographic factors evaluated. Females, Whites/Caucasians, students whose parents hold graduate degrees, and older students had higher scores. Black students and non-first-generation Americans were more likely to answer selected commonly missed questions correctly. CONCLUSIONS: Results from 2000 and 2020-2021 indicate older students from higher grade levels know more about melanoma, suggesting adolescents may benefit from earlier skin cancer education. Racial minorities and individuals of low socioeconomic status, who suffer from disparities in melanoma treatment and mortality, showed poorer melanoma knowledge. Targeting skin cancer education to disadvantaged schools may help remedy such gaps.

Skin, hair, and nail supplements advertised on Instagram.

Teens and young adults increasingly utilize social media for health information. Dermatologic supplements, advertised on social media, may be pharmacologically active and risk adverse effects. Instagram was searched, and 100 posts from March 2021 were evaluated for ingredients, health claims, account verification status, and endorsements. Only 4% of posts were made by verified accounts, and 1% of posts contained a visible Supplement Facts label. The Food and Drug Administration does not regulate dietary supplements. Ingredients such as vitamin A found in posts can pose teratogenic risk. Other potentially dangerous ingredients included saw palmetto and biotin. To accurately counsel patients who may retrieve health information from Instagram, it is important for practitioners to be familiar with social media claims.

Revisão sistemática do benefício cosmético da aplicação tópica do filtrado de fermentação / Systematic review of cosmetic benefit of topical application of ferment filtrate

O filtrado de fermentação, (FF), um subproduto de leveduras rico em nutrientes, é usado cosmeticamente no leste da Ásia desde a década de 1970. Revisamos sistematicamente os efeitos deste ativo tópico na saúde da pele e determinamos as limitações nos estudos disponíveis. A literatura recente mostrou evidências na redução do tamanho dos poros, e tambem da aspereza, hiperpigmentação e vermelhidão. No entanto, esses estudos são limitados em eficácia devido ao pequeno tamanho da amostra, muitas variáveis e capacidade limitada de validação externa. Devido ao aumento de produtos cosméticos contendo esse ingrediente, é necessária uma análise crítica da literatura disponível e futura para evitar a desinformação do consumidor

Ferment filtrate (FF), a by-product of nutrient-rich yeast, is believed to be used cosmetically in East Asia since the 1970s. We systematically reviewed the topical effects of ferment filtrate on skin health and determined limitations in the available studies. Recent literature has shown evidence in reducing the baseline fluctuation of pore size, roughness, hyperpigmentation, and redness. However, these studies are limited in efficacy due to their small sample size, their confounding variables, and their limited generalizability. Because of the increase of cosmetic products containing this ingredient, critical analysis of the available and future literature is necessary to prevent consumer misinformation.

Isotretinoin, Vitamin A Supplements, and Unintended Pregnancies in Post Roe v. Wade America.

Isotretinoin is a potent vitamin A derivative that is used to treat acne. However, despite its utility in dermatologic care, it is also highly teratogenic and can cause severe life-threatening fetal abnormalities in the first trimester of pregnancy. As a result, existing regulations are stringent in order to prevent accidental pregnancies in women taking isotretinoin. In the unlikely case of an unintended pregnancy, while taking isotretinoin, a woman could terminate her pregnancy with an abortion. However, with the recent overturning of Roe v. Wade, we explore the consequences of this landmark United States Supreme Court ruling with special attention to those taking isotretinoin and over-the-counter (OTC) vitamin A supplements.

Impact of TMPRSS2 Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2.

As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the TMPRSS2 gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was significantly associated with a short overall survival in breast invasive carcinoma (BRCA), sarcoma (SARC), and uveal melanoma (UVM), while a low expression of TMPRSS2 was significantly associated with a short overall survival in lung adenocarcinoma (LUAD), demonstrating TMPRSS2 roles in cancer patient susceptibility and severity. Additionally, TMPRSS2 expression in COVID-19-infected lung tissues was significantly reduced compared to healthy lung tissues, indicating that a low TMPRSS2 expression may result in COVID-19 severity and death. Importantly, TMPRSS2 mutation frequency was significantly higher in prostate adenocarcinoma (PRAD), and the mutant TMPRSS2 pan-cancer group was significantly associated with long overall, progression-free, disease-specific, and disease-free survival rates compared to the wild-type (WT) TMPRSS2 pan-cancer group, demonstrating loss of functional roles due to mutation. Cancer cell lines were treated with small molecules, including cordycepin (CD), adenosine (AD), thymoquinone (TQ), and TQFL12, to mediate TMPRSS2 expression. Notably, CD, AD, TQ, and TQFL12 inhibited TMPRSS2 expression in cancer cell lines, including the PC3 prostate cancer cell line, implying a therapeutic role for preventing COVID-19 in cancer patients. Together, these findings are the first to demonstrate that small molecules, such as CD, AD, TQ, and TQFL12, inhibit TMPRSS2 expression, providing novel therapeutic strategies for preventing COVID-19 and cancers.

HSPA6 and its role in cancers and other diseases.

Heat Shock Protein Family A (Hsp70) Member 6 (HSPA6) (Online Mendelian Inheritance in Man: 140555) belongs to the HSP70 family and is a partially conserved inducible protein in mammals. The HSPA6 gene locates on the human chromosome 1q23.3 and encodes a protein containing two important structural domains: The N-terminal nucleotide-binding domain and the C-terminal substrate-binding domain. Currently, studies have found that HSPA6 not only plays a role in the tumorigenesis and tumor progresses but also causes non-tumor-related diseases. Furthermore, HSPA6 exhibits to inhibit tumorigenesis and tumor progression in some types of cancers but promotes in others. Even though HSPA6 research has increased, its exact roles and mechanisms are still unclear. This article reviews the structure, expression, function, research progress, possible mechanism, and perspective of HSPA6 in cancers and other diseases, highlighting its potential role as a targeted therapeutic and prognostic marker.

AAV8-Mediated Gene Therapy Rescues Retinal Degeneration Phenotype in a Tlcd3b Knockout Mouse Model.

Purpose: The purpose of this study was to assess the therapeutic efficacy of rAAV8-hGRK1-Tlcd3b in a Tlcd3b-/- mouse model of retinal generation and validate TLCD3B's role as a ceramide synthase in vivo. Methods: Using Tlcd3b-/- mice as an inherited retinal disease animal model, we performed subretinal injection of rAAV8-hGRK1-Tlcd3b and evaluated the efficacy of gene replacement therapy. Tlcd3b-/- mice were treated at two time points: postnatal day 21 (P21) and postnatal day 120 (P120) with various dosages. Results: Tlcd3b overexpression rescued retinal degeneration in the mutant mice, as indicated by significantly improved photoreceptor function and preservation of photoreceptor cells over the course of 1 year. Although Tlcd3b is expressed in all cell types in the retina, photoreceptor cell-specific expression of Tlcd3b is sufficient to rescue the phenotype, indicating the primary function of TLCD3B is in photoreceptors. Consistent with the idea that TLCD3B is a ceramide synthase, mass spectrometry analyses of the mutant retina indicate the reduction of C16-, C18-, and C20-ceramides in the retina, which are restored with Tlcd3b overexpression. Conclusions: Our findings demonstrated the therapeutic efficacy of gene therapy in treating Tlcd3b mutant retina, laying the foundation for developing future therapy for TLCD3B retinopathy.

A novel stop codon mutation of TSPAN12 gene in Chinese patients with familial exudative vitreoretinopathy.

BACKGROUND: Familial exudative vitreoretinopathy (FEVR) is a group of inherited eye diseases characterized by premature arrest of retinal vessel development. The purpose of our study was to characterize the genetic causes and clinical features in eight Chinese families with FEVR using next-generation sequencing (NGS) technology. MATERIALS AND METHODS: Eight families with FEVR were included in genetic and clinical analyses. We screened the proband and the parents in eight pedigrees with FEVR using targeted NGS approach and in silico analysis to determine the causative mutation for their family's phenotype. RESULTS: Four cases (4/8, 50.0%) were confirmed to harbor mutations in known genes, including 3 novel mutations and one previously reported mutation. Among the detected mutations, TSPAN12 accounted for 75% (3/4). We identified a novel stop codon of TSPAN12, a heterozygous missense mutation NM_012338.4:c.633T>A, NP_036470.1:p.Tyr211Ter involved in highly conserved residues in the proband. Retrospective analysis of its clinical manifestation showed that the mutant carrier presented mild clinical features. CONCLUSIONS: We found the novel stop codon mutation p.Tyr211Ter in the TSPAN12, which creates a milder phenotype. Discovery of this novel mutation expands the mutation spectrum of TSPAN12, and would be valuable for future genetic disease diagnosis.

COVID-19 disease and malignant cancers: The impact for the furin gene expression in susceptibility to SARS-CoV-2.

Furin is a proprotein convertase that activates different kinds of regulatory proteins, including SARS-CoV-2 spike protein which contains an additional furin-specific cleavage site. It is essential in predicting cancer patients' susceptibility to SARS-CoV-2 and the disease outcomes due to varying furin expressions in tumor tissues. In this study, we analyzed furin's expression, methylation, mutation rate, functional enrichment, survival rate and COVID-19 outcomes in normal and cancer tissues using online databases, and our IHC. As a result, furin presented with biased expression profiles in normal tissues, showing 12.25-fold higher than ACE2 in the lungs. The furin expression in tumors were significantly increased in ESCA and TGCT, and decreased in DLBC and THYM, indicating furin may play critical mechanistic functions in COVID-19 viral entry into cells in these cancer patients. Line with furin over/downexpression, furin promoter hypo-/hyper-methylation may be the regulatory cause of disease and lead to pathogenesis of ESCA and THYM. Furthermore, presence of FURIN-201 isoform with functional domains (P_proprotein, Peptidase_S8 and S8_pro-domain) is highest in all cancer types in comparison to other isoforms, demonstrating its use in tumorigenesis and SARS-Cov-2 entry into tumor tissues. Furin mutation frequency was highest in UCES, and its mutation might elevate ACE2 expression in LUAD and UCEC, reduce ACE2 expression in COAD, elevate HSPA5 expression in PAAD, and elevate TMPRSS2 expression in BRCA. These results showed that furin mutations mostly increased expression of ACE2, HSPA5, and TMPRSS2 in certain cancers, indicating furin mutations might facilitate COVID-19 cell entry in cancer patients. In addition, high expression of furin was significantly inversely correlated with long overall survival (OS) in LGG and correlated with long OS in COAD and KIRC, indicating that it could be used as a favorable prognostic marker for cancer patients' survival. GO and KEGG demonstrated that furin was mostly enriched in genes for metabolic and biosynthetic processes, retinal dehydrogenase activity, tRNA methyltransferase activity, and genes involving COVID-19, further supporting its role in COVID-19 and cancer metabolism. Moreover, Cordycepin (CD) inhibited furin expression in a dosage dependent manner. Altogether, furin's high expression might not only implies increased susceptibility to SARS-CoV-2 and higher severity of COVID-19 symptoms in cancer patients, but also it highlights the need for cancer treatment and therapy during the COVID-19 pandemic. CD might have a potential to develop an anti-SARS-CoV-2 drug through inhibiting furin expression.

TQFL12, a novel synthetic derivative of TQ, inhibits triple-negative breast cancer metastasis and invasion through activating AMPK/ACC pathway.

Thymoquinone (TQ) has been reported as an anti-tumour drug widely studied in various tumours, and its mechanism and effect of which has become a focus of current research. However, previous studies from our laboratory and other groups found that TQ showed weak anti-tumour effects in many cancer cell lines and animal models. Therefore, it is necessary to modify and optimize the structure of TQ to obtain new chemical entities with high efficiency and low toxicity as candidates for development of new drugs in treating cancer. Therefore, we designed and synthesized several TQ derivatives. Systematic analysis, including in vitro and in vivo, was conducted on a panel of triple-negative breast cancer (TNBC) cells and mouse model to demonstrate whether TQFL12, a new TQ derivative, is more efficient than TQ. We found that the anti-proliferative effect of TQFL12 against TNBC cells is significantly stronger than TQ. We also demonstrated TQFL12 affects different aspects in breast cancer development including cell proliferation, migration, invasion and apoptosis. Moreover, TQFL12 inhibited tumour growth and metastasis in cancer cell-derived xenograft mouse model, with less toxicity compared with TQ. Finally, mechanism research indicated that TQFL12 increased AMPK/ACC activity by stabilizing AMPKα, while molecular docking supported the direct interaction between TQFL12 and AMPKα. Taken together, our findings suggest that TQFL12, as a novel chemical entity, possesses a better inhibitory effect on TNBC cells and less toxicity in both in vitro and in vivo studies. As such, TQFL12 could serve as a potential therapeutic agent for breast cancer.

Transcript isoforms of Reep6 have distinct functions in the retina.

Much of the complexity of the eukaryotic cell transcriptome is due to the alternative splicing of mRNA. However, knowledge on how transcriptome complexity is translated into functional complexity remains limited. For example, although different isoforms of a gene may show distinct temporal and spatial expression patterns, it is largely unknown whether these isoforms encode proteins with distinct functions matching their expression pattern. In this report, we investigated the function and relationship of the two isoforms of Reep6, namely Reep6.1 and Reep6.2, in rod photoreceptor cells. These two isoforms result from the alternative splicing of exon 5 and show mutually exclusive expression patterns. Reep6.2 is the canonical isoform that is expressed in non-retinal tissues, whereas Reep6.1 is the only expressed isoform in the adult retina. The Reep6.1 isoform-specific knockout mouse, Reep6E5/E5, is generated by deleting exon 5 and a homozygous deletion phenotypically displayed a rod degeneration phenotype comparable to a Reep6 full knockout mouse, indicating that the Reep6.1 isoform is essential for the rod photoreceptor cell survival. Consistent with the results obtained from a loss-of-function experiment, overexpression of Reep6.2 failed to rescue the rod degeneration phenotype of Reep6 knockout mice whereas overexpression of Reep6.1 does lead to rescue. These results demonstrate that, consistent with the expression pattern of the isoform, Reep6.1 has rod-specific functions that cannot be substituted by its canonical isoform. Our findings suggested that a strict regulation of splicing is required for the maintenance of photoreceptor cells.

Technical note: multi-alleles at the DYS385ab locus with high frequency in a Han Chinese population from southwestern China.

Y-chromosome short tandem repeat (Y-STR) markers have been widely used in forensic applications and usually show monoallelic or diallelic genotypic patterns at certain double-copied loci. In this study, we have found 13 samples among 703 males with multi-alleles at the DYS385ab locus, including one with five mutant alleles, nine with four, and three with three. The frequency of abnormal DYS385ab genotypes was 1.85% (13/703), which is very high in the Han Chinese population. The percentage of samples with diallelic patterns at DYS385ab was higher than that of monoallelic patterns (80.23% vs. 17.92%). Additionally, the percentage of samples with tetra-allelic patterns at DYS385ab was higher than that of tri-allelic patterns (1.28% vs. 0.43%), suggesting that there are possibly two copies with duplicated events happening frequently on the Y chromosome. Interestingly, the peak height of allele 13 was two to three-folds higher than that of other alleles. The allele 18 peak height was also two-fold higher than others, which could potentially be explained by a duplication event mechanism. We also found that tri-allelic genotypes for alleles 13, 17, and 20, tetra-allelic genotypes for alleles 13, 14, 19, and 20, and tetra-allelic genotypes for alleles 12, 13, 19 and 21 were more common than others. Furthermore, all 13 samples had multi-alleles containing allele 13, implying a founder effect in this particular Chinese-specific ethnic group. Taken together, this study provides new information for this population and will be useful for paternal lineage identification, kinship analysis, and family relationship reconstruction using Y-STR forensic DNA analysis methods.