Whole-Body Hypothermia vs Targeted Normothermia for Neonates With Mild Encephalopathy: A Multicenter Pilot Randomized Clinical Trial.

Importance: Although whole-body hypothermia is widely used after mild neonatal hypoxic-ischemic encephalopathy (HIE), safety and efficacy have not been evaluated in randomized clinical trials (RCTs), to our knowledge. Objective: To examine the effect of 48 and 72 hours of whole-body hypothermia after mild HIE on cerebral magnetic resonance (MR) biomarkers. Design, Setting, and Participants: This open-label, 3-arm RCT was conducted between October 31, 2019, and April 28, 2023, with masked outcome analysis. Participants were neonates at 6 tertiary neonatal intensive care units in the UK and Italy born at or after 36 weeks' gestation with severe birth acidosis, requiring continued resuscitation, or with an Apgar score less than 6 at 10 minutes after birth and with evidence of mild HIE on modified Sarnat staging. Statistical analysis was per intention to treat. Interventions: Random allocation to 1 of 3 groups (1:1:1) based on age: neonates younger than 6 hours were randomized to normothermia or 72-hour hypothermia (33.5 °C), and those 6 hours or older and already receiving whole-body hypothermia were randomized to rewarming after 48 or 72 hours of hypothermia. Main Outcomes and Measures: Thalamic N-acetyl aspartate (NAA) concentration (mmol/kg wet weight), assessed by cerebral MR imaging and thalamic spectroscopy between 4 and 7 days after birth using harmonized sequences. Results: Of 225 eligible neonates, 101 were recruited (54 males [53.5%]); 48 (47.5%) were younger than 6 hours and 53 (52.5%) were 6 hours or older at randomization. Mean (SD) gestational age and birth weight were 39.5 (1.1) weeks and 3378 (380) grams in the normothermia group (n = 34), 38.7 (0.5) weeks and 3017 (338) grams in the 48-hour hypothermia group (n = 31), and 39.0 (1.1) weeks and 3293 (252) grams in the 72-hour hypothermia group (n = 36). More neonates in the 48-hour (14 of 31 [45.2%]) and 72-hour (13 of 36 [36.1%]) groups required intubation at birth than in the normothermic group (3 of 34 [8.8%]). Ninety-nine neonates (98.0%) had MR imaging data and 87 (86.1%), NAA data. Injury scores on conventional MR biomarkers were similar across groups. The mean (SD) NAA level in the normothermia group was 10.98 (0.92) mmol/kg wet weight vs 8.36 (1.23) mmol/kg wet weight (mean difference [MD], -2.62 [95% CI, -3.34 to -1.89] mmol/kg wet weight) in the 48-hour and 9.02 (1.79) mmol/kg wet weight (MD, -1.96 [95% CI, -2.66 to -1.26] mmol/kg wet weight) in the 72-hour hypothermia group. Seizures occurred beyond 6 hours after birth in 4 neonates: 1 (2.9%) in the normothermia group, 1 (3.2%) in the 48-hour hypothermia group, and 2 (5.6%) in the 72-hour hypothermia group. Conclusions and Relevance: In this pilot RCT, whole-body hypothermia did not improve cerebral MR biomarkers after mild HIE, although neonates in the hypothermia groups were sicker at baseline. Safety and efficacy of whole-body hypothermia should be evaluated in RCTs. Trial Registration: ClinicalTrials.gov Identifier: NCT03409770.

Multi-biofunctional properties of three species of cicada wings and biomimetic fabrication of nanopatterned titanium pillars.

Recently, multi-biofunctional properties of cicada wings have drawn keen interest for biomedical device applications due to their superhydrophobic, self-cleaning and bactericidal effects. We present a systematic evaluation of bactericidal and cytocompatible properties of cicada wings. We also present biomimetic nanofabrication of a patterned array of titanium nanopillars using electron beam lithography. We have characterized the nanoscale architecture of the wings of three different Australian species of cicadas (Psaltoda claripennis, Aleeta curvicosta and Palapsalta eyrei) using helium ion microscopy (HIM), scanning electron microscopy, atomic force measurement (AFM) and transmission electron microscopy (TEM). The chemical nature of the nanopatterned substrates was investigated using Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). Pseudomonas aeruginosa and Staphylococcus aureus cells were attached to determine the bactericidal activity of the insect wings. Human osteoblast cells were attached to examine the biocompatibility of the insect wings. It was found that all the three cicada species have unique surface topography on their wing membranes and veins. The height, spacing, diameter, density and aspect ratio of the three species varied between the species and between the membrane and the veins. The density and aspect ratio of the nanopillars on the membranes were significantly higher than on the veins. Bacterial attachment investigation confirmed that P. aeruginosa cells and S. aureus cells were damaged by the nanopatterned array of pillars. A significant reduction in colonies of P. aeruginosa cells was found on the wings of the three species compared to the control after 18 hours. A significant reduction of S. aureus cells on the wings was observed at 2 and 4 hours but not at 18 hours compared to the control. The cell morphology of the human osteoblast cells appeared intact after 24 hours of attachment, indicating the biocompatibility of the insect wings. As a proof of concept, patterned nanopillars of titanium have been fabricated using the electron beam lithography technique directly inspired by the cicada wing architecture. The titanium nanopillars were observed to damage the bacterial cells of P. aeruginosa in a manner similar to the cicada wing species and remain compatible to osteoblast cells. The outcomes of this research can help to engineer an optimum nano-patterned surface to enhance the bioactivity and bactericidal effect on biomedical devices.

Perceptions of physician assistants regarding direct-to-consumer advertising.

Of 1,254 practicing physician assistants (PAs) who completed a survey, 91% were familiar with direct-to-consumer advertising (DTCA). When asked about their general perception, 96% of PAs were neutral or unfavorable towards DTCA. PAs felt that DTCA encouraged patients to make atypical medication requests, overlook the PA's medical opinion, and seek other health care providers.

Vascular tissue construction on poly(ε-caprolactone) scaffolds by dynamic endothelial cell seeding: effect of pore size.

In vitro tissue engineering for fabrication of small diameter vascular grafts probably undergoes a sequence of events similar to the in vivo angiogenesis process. In both cases endothelial cells (ECs) play the crucial role in generating a non-thrombogenic vessel lumen and stabilization of ECs in the lumen of new vessels requires the deposition of collagen IV and elastin. Shear stress is an important in vivo signal for inducing synthesis of extracellular matrix (ECM) components, collagen IV and elastin, which form the basement membrane in the case of new blood vessels. Stimulation of ECs may therefore produce collagen and elastin in the lumen of a polymeric scaffold during the vascular tissue-engineering process if appropriate biochemical and mechanical signals are presented. However, the morphology and physicochemical characteristics of polymer scaffolds may also be crucial for EC monolayer formation and ECM deposition. In this study, tubular scaffolds made of biodegradable poly(ε-caprolactone) (PCL) with biomimetic fibrin-based coating were evaluated to compare the effects of pore sizes on surface coverage of ECs and synthesis of ECM under dynamic culture conditions. Actin was stained for identification of cells, while specific antibodies were used for locating collagen IV and elastin deposition on the scaffolds. It was found that dynamic seeding of ECs in the lumen stabilized the cells and aligned them along the direction of flow, with better deposition of insoluble elastin and collagen IV when ∼75% of pores were < 24 µm in diameter. In addition, monolayer on the ε-PCL scaffolds with lower pore sizes was found to produce nitric oxide (NO), indicating a non-thrombogenic EC layer in the lumen.