Increased Heating Efficiency and Selective Thermal Ablation of Malignant Tissue with DNA-Encased Multiwalled Carbon Nanotubes

Nanoparticles, including multiwalled carbon nanotubes (MWNTs), strongly absorb near-infrared (nIR) radiation and efficiently convert absorbed energy to released heat which can be used for localized hyperthermia applications. We demonstrate for the first time that DNA-encasement increases heat emission following nIR irradiation of MWNTs, and DNA-encased MWNTs can be used to safely eradicate a tumor mass <i>in vivo</i>. Upon irradiation of DNA-encased MWNTs, heat is generated with a linear dependence on irradiation time and laser power. DNA-encasement resulted in a 3-fold reduction in the concentration of MWNTs required to impart a 10 °C temperature increase in bulk solution temperature. A single treatment consisting of intratumoral injection of MWNTs (100 μL of a 500 μg/mL solution) followed by laser irradiation at 1064 nm, 2.5 W/cm² completely eradicated PC3 xenograft tumors in 8/8 (100%) of nude mice. Tumors that received only MWNT injection or laser irradiation showed growth rates indistinguishable from nontreated control tumors. Nonmalignant tissues displayed no long-term damage from treatment. The results demonstrate that DNA-encased MWNTs are more efficient at converting nIR irradiation into heat compared to nonencased MWNTs and that DNA-encased MWNTs can be used safely and effectively for the selective thermal ablation of malignant tissue <i>in vivo</i>

Prevalence, progression and modifiable risk factors for diabetic retinopathy in youth and young adults with youth-onset type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Study

   Objective: To determine the prevalence, progression and modifiable risk factors associated with development of DR in a population-based cohort of youth-onset diabetes.  Research Design and Methods: We conducted a multicenter, population-based prospective cohort study (2002 to 2019) of youth and young adults with youth-onset type 1 (n=2519) and type 2 diabetes (n=447). Modifiable factors included baseline and change from baseline to follow-up in BMI z-score, waist/height ratio, systolic and diastolic blood pressure z-score, and A1C. DR included evidence of mild or moderate non-proliferative DR or proliferative retinopathy. Prevalence estimates were standardized to estimate the burden of DR and inverse probability weighting for censoring was applied for estimating risk factors for DR at two points of follow-up.  Results: DR in youth-onset type 1 and type 2 diabetes is highly prevalent, with 52% of those with type 1 diabetes and 56% of those with type 2 diabetes demonstrating retinal changes at follow-up (12.5 [SD: 2.2] years from diagnosis). Higher baseline A1C, increase in A1C across follow-up, and increase in diastolic and systolic blood pressure were associated with observation of DR at follow-up for both diabetes types. Increase in A1C across follow-up was associated with retinopathy progression. BMI z-score and waist/height ratio were inconsistently associated, with both positive and inverse associations noted.  Conclusions: Extrapolated to all youth-onset diabetes in the U.S., we estimate 110,051 cases of DR developing within ~12 years post-diagnosis. Tight glucose and blood pressure management may offer opportunity to mitigate development and progression of DR in youth-onset diabetes. </p

Additional file 2: Figure S1. of Circulating mutational portrait of cancer: manifestation of aggressive clonal events in both early and late stages

ctDNA mutational landscape for major cancer groups for the top 30 genes in total cohort. Figure S2. ctDNA mutational landscape of patients’ stage known for the top 30 genes in lung cancer cohort. Figure S3. Higher mutation numbers in the ctDNA are associated with decreased survival in lung cancers. Higher mutation numbers in ctDNA are associated with poor survival. “n” defines the number of mutations and survival plots are separated by mutation numbers: n = 1, 2, 3, 4, 5, and 6 mutations. Blue lines indicate more than “n” mutations and the pink lines indicate equal to or less than “n” mutations. P-values were derived using the log-rank test. Figure S4. The concordance of top mutated genes in the ctDNA and tDNA of 37 lung cancer patients. (DOC 1098 kb