Temporary postoperative cardiac pacing requires devices with percutaneous leads and external wired power and control systems. This hardware introduces risks for infection, limitations on patient mobility, and requirements for surgical extraction procedures. Bioresorbable pacemakers mitigate some of these disadvantages, but they demand pairing with external, wired systems and secondary mechanisms for control. We present a transient closed-loop system that combines a time-synchronized, wireless network of skin-integrated devices with an advanced bioresorbable pacemaker to control cardiac rhythms, track cardiopulmonary status, provide multihaptic feedback, and enable transient operation with minimal patient burden. The result provides a range of autonomous, rate-adaptive cardiac pacing capabilities, as demonstrated in rat, canine, and human heart studies. This work establishes an engineering framework for closed-loop temporary electrotherapy using wirelessly linked, body-integrated bioelectronic devices.

Previous studies from our group have demonstrated that oxidized 1-palmitoyl-2-arachidonyl-sn-glycerol-3-phosphocholine (Ox-PAPC) activates over 1000 genes in human aortic endothelial cell (HAEC). Prominent among these are genes regulating inflammation, cholesterol homeostasis, antioxidant enzymes, and the unfolded protein response. Previous studies from our lab and others suggested that transcriptional regulation by Ox-PAPC may be controlled, at least in part, by reactive oxygen species (ROS). We now present evidence that Ox-PAPC activation of NADPH oxidase 4 (NOX4) is responsible for the regulation of two of these important groups of genes: those controlling inflammation and sterol regulation. Our data demonstrate that Ox-PAPC increases reactive oxygen species formation in HAEC as seen by DCF fluorescence. NOX4 is the major molecule responsible for this increase since downregulation of NOX4 and its components (p22phox and rac1) blocked the Ox-PAPC effect. Our data show that Ox-PAPC did not change NOX4 transcription levels but did induce recruitment of rac1 to the membrane for NOX4 activation. We present evidence that vascular endothelial growth factor receptor 2 (VEGFR2) activation is responsible for rac1 recruitment to the membrane. Finally, we demonstrate that knockdown of NOX4 and its components rac1 and p22phox decrease Ox-PAPC induction of inflammatory and sterol regulatory genes, but do not affect Ox-PAPC transcriptional regulation of other gene of antioxidant and unfolded protein response. In summary, we have identified a VEGFR2/NOX4 regulatory pathway by which Ox-PAPC controls important endothelial functions.

No abstract

Recombinant inbred lines (RILs) are an important resource for mapping genes controlling complex traits in many species. While RIL populations have been developed for maize, a maize RIL population with multiple teosinte inbred lines as parents has been lacking. Here, we report a teosinte nested association mapping (TeoNAM) population, derived from crossing five teosinte inbreds to the maize inbred line W22. The resulting 1257 BC1S4 RILs were genotyped with 51,544 SNPs, providing a high-density genetic map with a length of 1540 cM. On average, each RIL is 15% homozygous teosinte and 8% heterozygous. We performed joint linkage mapping (JLM) and a genome-wide association study (GWAS) for 22 domestication and agronomic traits. A total of 255 QTL from JLM were identified, with many of these mapping near known genes or novel candidate genes. TeoNAM is a useful resource for QTL mapping for the discovery of novel allelic variation from teosinte. TeoNAM provides the first report that PROSTRATE GROWTH1, a rice domestication gene, is also a QTL associated with tillering in teosinte and maize. We detected multiple QTL for flowering time and other traits for which the teosinte allele contributes to a more maize-like phenotype. Such QTL could be valuable in maize improvement.

No abstract

Objectives: Although the last few years have seen an increased number of smartphone applications (apps) disseminated in the field of Otolaryngology (ORL), these apps vary widely in quality. The aim of this paper, therefore, is to systematically review ORL apps directed towards patients in mobile app stores and the current literature. Methods: The Google Play Store, Apple App Store and PubMed were searched for ORL apps for patients using various keywords pertaining to different ORL subspecialties. Apps not relevant to the scope of this research and/or duplicates, educational apps, apps promoting a business, apps requiring specific separate hardware, and apps in non-English were excluded. In PubMed, keywords pertaining to the subspecialties were combined with “mobile app” in a search query; literature reviews, editorials, case reports, conference papers, duplicate articles, and articles irrelevant to ORL apps were excluded. The quality of apps with the highest number of reviews was assessed using the “Mobile App Rating Scale” (MARS), while the quality of the articles was rated using “The Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) Statement. Results: After searching the app stores, 1074 apps were included and grouped according to their ORL subspecialties. The overall MARS score of the ten most popular apps in each category was 3.65 out of 5. A total of 636 articles were identified in the literature, and 193 were included. The mean adherence percentage of the articles to the STROBE checklist was of 84.37%. Conclusions: Although the apps currently available need further development, their application in ORL appears promising. Further dialogue between physicians and patients, as well as formal support from professional and scientific associations, should be encouraged.

Oxidized-1-palmitoyl-2-arachidonyl-sn -glycerol-3-phosphocholine (Ox-PAPC) has been demonstrated to accumulate in atherosclerotic lesions and regulates expression of more than 1,000 genes in human aortic endothelial cell (HAEC). Among the most highly induced is heme oxygenase-1 (HO-1), a cell-protective antioxidant enzyme, which is sensitively induced by oxidative stress. To identify the pathway by which Ox-PAPC induces HO-1, we focused on the plasma membrane electron transport (PMET) complex, which contains ecto-NADH oxidase 1 (eNOX1) and NADPH:quinone oxidoreductase 1 (NQO1) and affects cellular redox status by regulating levels of NAD(P)H. We demonstrated that Ox-PAPC and its active components stimulated electron transfer through the PMET complex in HAECs from inside to outside [as determined by extracellular 2-(4-iodophenyl)-3-(44-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1) reduction] and from outside to inside of the cell (as determined by intracellular NBT reduction). Chemical inhibitors of PMET system and siRNAs to PMET components (NQO1 and eNOX1) significantly decreased HO-1 induction by Ox-PAPC. We present evidence that Ox-PAPC activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in HAEC plays an important role in the induction of HO-1 and PMET inhibitors blocked Nrf2 activation by Ox-PAPC. We hypothesized that PMET activation by Ox-PAPC causes intracellular NAD(P)H depletion, which leads to the increased oxidative stress and HO-1 induction. Supporting this hypothesis, cotreatment of cells with exogenous NAD(P)H and Ox-PAPC significantly decreased oxidative stress and HO-1 induction by Ox-PAPC. Taken together, we demonstrated that the PMET system in HAEC plays an important role in the regulation of cellular redox status and HO-1 expression by Ox-PAPC.

ObjectiveNeurogenic cough related to hypersensitivity of the internal branch of the superior laryngeal nerve (SLN) is often treated with neuromodulating medications, which can cause considerable side effects. An alternative therapy is steroid and local anesthetic injection of the SLN (“SLN block”), initially proposed to benefit those with lateralizing symptoms (tenderness over the thyrohyoid membrane or unilateral cough source). Our objectives are to determine if SLN block produces subjective symptomatic improvements and if repeat injections further improve symptoms, and evaluate clinical factors potentially predictive of response.MethodsRetrospective chart review of 54 patients receiving SLN blocks at a tertiary medical academic center from January 2010 to June 2020. Medical history and anticipated predictors of positive response, including stigmata of laryngeal hypersensitivity, were recorded. Outcomes included symptomatic response, number of injections required, and side effects. Response was defined subjectively by asking patients whether the injection was beneficial and objectively by using CSI scores.ResultsFifty‐four patients met the inclusion criteria. Thirty‐eight patients (70.4%) endorsed improvement. No variables were identified as positive predictors of response. Thirty‐two of the 38 (84.2%) endorsed improvement after one injection. Six of 15 (40%) patients who failed the first injection had positive response to the second. No significant side effects were reported.ConclusionNo localizing symptoms, specific cough features, or aspects of the medical history helped predict response, suggesting that a broader range of patients may be offered the intervention. The majority of patients reported symptomatic improvement and repeat injections may benefit patients with initial nonresponse.Level of Evidence4 Laryngoscope, 133:2647–2653, 2023