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The application of extracellular vesicles, particularly exosomes (EXs), is rapidly expanding in the field of medicine, owing to their remarkable properties as natural carriers of biological cargo. This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues (NAF-EXs) for personalized medicine, which can be derived at the time of diagnosis by endoscopic ultrasound. Herein, we show that exosomes (EXs) derived from NAFs demonstrate differential bio-physical characteristics, efficient cellular internalization, drug loading efficiency, pancreatic tumor targeting and delivery of payloads. NAF-derived EXs (NAF-EXs) were used for loading ormeloxifene (ORM), a potent anti-cancer and desmoplasia inhibitor as a model drug. We found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype, which may be due to regulation of Ca2+ influx in fibroblast cells. NAF-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition (EMT) and repressed tumor growth in xenograft mouse model. In conclusion, our data suggests preferential tropism of NAF-EXs for PDAC tumors, thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer drugs. Additionally, it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.
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BACKGROUND: While the prevalence of vitiligo is similar across racial and ethnic groups, the effects of vitiligo vary by demographic group, culture, and skin color, with darker-skinned individuals facing greater stigma due to increased visibility of the disease.1,2 The recruitment of diverse participants that are representative of the United States (US) population is crucial to ensuring the generalizability of findings and understanding the impacts of vitiligo across diverse patient groups. Objectives: This study aimed to determine demographic reporting trends in US vitiligo clinical trials and to determine whether participants are representative of the US population. METHODS: A search for US vitiligo clinical trials was conducted on clinicaltrials.gov. Trials conducted between 2006 to September 5, 2023, were included if they intended to treat vitiligo, were conducted in the US, and were completed or terminated. Results: Of the 15 trials meeting inclusion criteria, only 60% (n=9) reported participant race/ethnicity. These 9 studies included 1,510 participants, of which only 25.43% (n=384) were non-White and 20.40% were Hispanic. There was disproportionately low representation of racial minorities, particularly Black, Native American, and Native Hawaiian groups. Limitations: Limitations of our study include small sample size, variations in demographic reporting between trials, and undercounting of minority groups by the US Census. Conclusions: Racial and ethnic minority groups remain underrepresented in US vitiligo clinical trials. Given that the impact of vitiligo can vary by the affected individual’s demographic group and skin color, investigators must be intentional about including a more diverse and representative population in vitiligo clinical trials. J Drugs Dermatol. 2024;23(7):e164-e166. doi:10.36849/JDD.8117e.
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Ensaios Clínicos como Assunto , Vitiligo , Humanos , Vitiligo/etnologia , Vitiligo/terapia , Estudos Transversais , Estudos Retrospectivos , Ensaios Clínicos como Assunto/estatística & dados numéricos , Estados Unidos , Etnicidade/estatística & dados numéricos , Masculino , Feminino , Grupos Raciais/estatística & dados numéricos , Minorias Étnicas e Raciais/estatística & dados numéricosRESUMO
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.
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Vitamin A in high doses has been found to be highly teratogenic, leading to severe fetal abnormalities if exposure occurs during pregnancy. Hence, prescription vitamin A acne medications like isotretinoin are highly regulated via programs such as iPledge, which intend to avert fetal exposure to isotretinoin and to educate healthcare providers, pharmacists, and patients about the significant risks associated with isotretinoin and its appropriate usage conditions. However, over-the-counter (OTC) vitamin A supplements are not subject to these requirements, and calculating the vitamin A content of these supplements can be difficult due to the lack of Food and Drug Administration (FDA) regulations and inconsistencies in labeling. If the necessary information is provided, ChatGPT, a generative artificial intelligence (AI) tool, can help the general public calculate the vitamin A content of supplements. Nonetheless, supplement manufacturers do not always provide the data necessary for these calculations.
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INTRODUCTION: Podiatric infections are common in patients with and without diabetes. Biofilm detection would aid in determining the severity of foot infections and preventive strategies to manage them. OBJECTIVE: The authors studied the clinicomicrobiological profile of podiatric infections. MATERIALS AND METHODS: Organisms from podiatric specimens were identified and the antibiotic susceptibility of the organisms determined using standard microbiological methods. Organisms were screened for biofilm production using the microtiter plate method. Staphylococcus aureus isolates were screened for ica, cna, and hlg genes by multiplex PCR. RESULTS: A total of 117 patients were included in the study, and specimens from 71 patients were culture positive (60.6%). Gram-negative bacteria were predominant (n = 88 [73.3%]). S aureus (n = 32 [26.7%]) was the most common isolate. The rate of biofilm production was 54.2%. Pseudomonas aeruginosa was the most prevalent biofilm producer (82.8%). The study revealed a statistically significant association of biofilm formation with MDR, MRSA, and prior antibiotic therapy with multiple (≥4) antibiotics. CONCLUSION: Isolation of MRSA or MDR strain from diabetic foot infections could alert the clinician to the possibility of treatment failure with a single drug regimen owing to associated biofilm production. Detection of biofilm producers and subsequent early debridement and/or cleaning of wounds might prevent chronic infection.