Efficacy and Safety of Intense Pulsed Light With a KTP/PDLlike Filter for the Treatment of Facial Telangiectasias.

BACKGROUND: An intense pulsed light (IPL) narrowband "KTP/PDL-like" filter (525–585 nm) may combine the tolerability of the IPL with the precision of KTP and PDL lasers. This study evaluated the impact of IPL with a KTP/PDL-like filter on telangiectasias. METHODS: This was a single-center, prospective study of 17 subjects with facial telangiectasias and skin types I–III. Three monthly treatments were performed using this specific filter, with follow-up visits at 1, 3, and 6 months. Telangiectasia improvement was assessed by the investigator and subjects using a 5-point scale. Facial photographs and safety assessments were obtained at each visit. Subject discomfort was evaluated using a visual analog scale (VAS) immediately posttreatment, and subject downtime was recorded at each subsequent visit. RESULTS: All facial telangiectasias significantly improved. At 1-month follow-up, >50% lesion clearance was noted in 97.1% of facial (n=36) and 85.7% of non-facial (n=7) lesions, with 73% of subjects satisfied or very satisfied. An increase in mean social downtime (0, 2.3, and 3 days) and VAS scores (3.5, 4.5, and 4.8) with treatments 1, 2, and 3, respectively, mirrored a stepwise increase in fluence with subsequent sessions. CONCLUSIONS: The use of a novel IPL narrowband KTP/PDL-like filter can significantly improve facial and non-facial telangiectasias with minimal downtime. J Drugs Dermatol. 2020;19(9):844-850. doi:10.36849/JDD.2020.4834.

Pioglitazone improves hepatic mitochondrial function in a mouse model of nonalcoholic steatohepatitis.

Pioglitazone is effective in improving insulin resistance and liver histology in patients with nonalcoholic steatohepatitis (NASH). Because dysfunctional mitochondrial metabolism is a central feature of NASH, we hypothesized that an important target of pioglitazone would be alleviating mitochondrial oxidative dysfunction. To this end, we studied hepatic mitochondrial metabolism in mice fed high-fructose high-transfat diet (TFD) supplemented with pioglitazone for 20 wk, using nuclear magnetic resonance-based 13C isotopomer analysis. Pioglitazone improved whole body and adipose insulin sensitivity in TFD-fed mice. Furthermore, pioglitazone reduced intrahepatic triglyceride content and fed plasma ketones and hepatic TCA cycle flux, anaplerosis, and pyruvate cycling in mice with NASH. This was associated with a marked reduction in most intrahepatic diacylglycerol classes and, to a lesser extent, some ceramide species (C22:1, C23:0). Considering the cross-talk between mitochondrial function and branched-chain amino acid (BCAA) metabolism, pioglitazone's impact on plasma BCAA profile was determined in a cohort of human subjects. Pioglitazone improved the plasma BCAA concentration profile in patients with NASH. This appeared to be related to an improvement in BCAA degradation in multiple tissues. These results provide evidence that pioglitazone-induced changes in NASH are related to improvements in hepatic mitochondrial oxidative dysfunction and changes in whole body BCAA metabolism.

Charge Distribution Fine-Tunes the Translocation of α-Helical Amphipathic Peptides across Membranes.

Hundreds of cationic antimicrobial and cell-penetrating peptides (CPPs) form amphipathic α-helices when bound to lipid membranes. Here, we test two hypotheses for the differences in the ability of these peptides to translocate across membranes. The first, which we now call the hydrophobicity hypothesis, is that peptide translocation is determined by the Gibbs energy of insertion into the bilayer from the membrane interface. The second, which we call the charge-distribution hypothesis, is that translocation is determined by whether the distribution of cationic residues in the peptide can transiently stabilize a high-energy inserted intermediate by forming salt bridges to the phosphates of lipid headgroups. To test these hypotheses, we measured translocation of two series of peptide variants. The first series was based on TP10W, a peptide derived from the amphipathic CPP transportan 10; the second was based on DL1a, a synthetic peptide derived from staphylococcal δ-lysin. The peptides in those two series had small sequence changes relative to TP10W and DL1a: either single-residue substitutions or two-residue switches, which were designed to increase or decrease translocation differently according to the two hypotheses. We found that with regard to the changes introduced in the sequences, five out of six peptide variants translocated in agreement with the charge-distribution hypothesis, whereas none showed agreement with the hydrophobicity hypothesis. We conclude that large effects on translocation are probably determined by hydrophobicity, but the fine tuning appears to arise from the distribution of cationic residues along the peptide sequence.

Persistence of choking injuries in children.

BACKGROUND: Choking injuries are a significant cause of morbidity and mortality in children and represent a significant public health concern. Evaluating trends and the impact of interventions are essential to highlight whether progress has been made and to target public health efforts. OBJECTIVE: To investigate how rates of nonfatal and fatal choking injuries have changed before and after 2010 when policy recommendations were made by the American Academy of Pediatrics. METHODS: A descriptive study investigating unintentional nonfatal and fatal choking injuries in children aged 0-19 years using national data from 2001 to 2016 through the Centers for Disease Control and Prevention's WISQARS™ and WONDER databases, focusing on the 6 years prior and 6 years after release of the AAP's recommendations. The data was categorized by age, gender, year, and race/ethnicity for descriptive and statistical analyses. RESULTS: From 2001 to 2016, there were a total of 305,814 nonfatal injuries and 2347 choking deaths in children from 0 to 19 years. Children under five years of age accounted for 73% of nonfatal injuries and 75% of choking fatalities. There was a statistically significant increase in the nonfatal injuries rate when comparing 2005-2010 and 2011-2016 (19/100,000 versus 26/100,000, respectively). There was a decrease in the choking fatalities rate in all children (0.18/100,000 versus 0.16/100,000, respectively) but no change in fatalities rate for children under five. White and Black children experience nonfatal choking injuries at a higher rate than Hispanics. Black children had highest rates of choking fatalities over Hispanic, White, Asian, and Alaskan or American Indian ethnicities. The lowest rates of death occurred in Asians. CONCLUSIONS: Overall rate of nonfatal choking injuries increased, while rate of choking fatalities in children decreased after 2010. However, the choking fatalities rate in 0-4 years olds, the highest risk group, did not change. Racial gaps exist with highest rates of injury in Black children. We must continue to educate and raise awareness of choking injuries, with targeted efforts to address racial disparities.

ML-MEDIC: A Preliminary Study of an Interactive Visual Analysis Tool Facilitating Clinical Applications of Machine Learning for Precision Medicine.

Accessible interactive tools that integrate machine learning methods with clinical research and reduce the programming experience required are needed to move science forward. Here, we present Machine Learning for Medical Exploration and Data-Inspired Care (ML-MEDIC), a point-and-click, interactive tool with a visual interface for facilitating machine learning and statistical analyses in clinical research. We deployed ML-MEDIC in the American Heart Association (AHA) Precision Medicine Platform to provide secure internet access and facilitate collaboration. ML-MEDIC's efficacy for facilitating the adoption of machine learning was evaluated through two case studies in collaboration with clinical domain experts. A domain expert review was also conducted to obtain an impression of the usability and potential limitations.