Raymays6244

Post-tracheotomy swallowing function has not been well described in the pediatric population. This study aims to (1) determine differences in swallowing functioning pre- and post-tracheotomy and (2) examine the association between postoperative dysphagia and indication for tracheotomy, age at the time of tracheotomy, and time between tracheotomy and modified barium swallow (MBS).

A retrospective chart review was performed on 752 patients who underwent a tracheotomy from 2003 to 2018 and had adequate documentation for review. Patients were included if they received a post-operative MBS. Descriptive statistics, logistic regression, and Fisher's exact test were used to analyze the data.

The cohort included 233 patients. The mean age at the time of tracheotomy was 25 months (±50.5). The indications for the tracheotomy were upper airway obstruction (110/233, 47.2%), chronic respiratory failure (104/233, 44.6%), and neurologic disease (19/233, 8.2%). The mean time from tracheotomy to post-operative MBS was 224 days (±297.7). Of the patients who had documented pre- and post-tracheotomy diets, nearly half of patients had improvement in their swallowing function after tracheotomy placement (82/195; 42.1%). Post-tracheotomy MBS recommended thickened liquids in 30.9% of the patients (72/233) and 42.5% (99/233) were recommended thin liquids. The remainder (62/233, 26.6%) remained nothing by mouth (NPO). Patients with neurological disease as the indication for the tracheotomy were more likely to remain NPO (

 = .039).

A tracheotomy can functionally and anatomically affect swallowing in pediatric patients. The majority of our studied cohort was able to resume some form of an oral diet postoperatively based on MBS. This study highlights the need for objective measurements of swallowing in the postoperative tracheotomy patient to allow for safe and timely commencement of an oral diet.

Level 3.

Level 3.Aim Numerous drugs are being widely prescribed for COVID-19 treatment without any direct evidence for the drug safety/efficacy in patients across diverse ethnic populations. Materials & methods We analyzed whole genomes of 1029 Indian individuals (IndiGen) to understand the extent of drug-gene (pharmacogenetic), drug-drug and drug-drug-gene interactions associated with COVID-19 therapy in the Indian population. Results We identified 30 clinically significant pharmacogenetic variants and 73 predicted deleterious pharmacogenetic variants. COVID-19-associated pharmacogenes were substantially overlapped with those of metabolic disorder therapeutics. CYP3A4, ABCB1 and ALB are the most shared pharmacogenes. Fifteen COVID-19 therapeutics were predicted as likely drug-drug interaction candidates when used with four CYP inhibitor drugs. Conclusion Our findings provide actionable insights for future validation studies and improved clinical decisions for COVID-19 therapy in Indians.Natural hyperbolic materials with dielectric permittivities of opposite signs along different principal axes can confine long-wavelength electromagnetic waves down to the nanoscale, well below the diffraction limit. Confined electromagnetic waves coupled to phonons in hyperbolic dielectrics including hexagonal boron nitride (hBN) and α-MoO3 are referred to as hyperbolic phonon polaritons (HPPs). HPP dissipation at ambient conditions is substantial, and its fundamental limits remain unexplored. Here, we exploit cryogenic nanoinfrared imaging to investigate propagating HPPs in isotopically pure hBN and naturally abundant α-MoO3 crystals. Close to liquid-nitrogen temperatures, losses for HPPs in isotopic hBN drop significantly, resulting in propagation lengths in excess of 8 μm, with lifetimes exceeding 5 ps, thereby surpassing prior reports on such highly confined polaritonic modes. Our nanoscale, temperature-dependent imaging reveals the relevance of acoustic phonons in HPP damping and will be instrumental in mitigating such losses for miniaturized mid-infrared technologies operating at liquid-nitrogen temperatures.Over the last 5 years, metal halide perovskites (MHPs) have emerged as promising photocatalysts for CO2 reduction because of their extraodinary visible-light-harvesting capabilities and appropriate band structure. However, the CO2 photoreduction activity of pristine MHPs is still unsatisfactory because of the phase instability, serious radiative recombination, and insufficient surface-active sites. This Perspective summarizes the strategies employed in recent studies for enhancing the photocatalytic CO2 reduction performance of MHPs from the standpoint of structure engineering, which includes composition/dimension regulation, surface modification, and heterostructure construction. The relationship between the structure (composition, dimension, and shape) and photocatalytic performance is established, which is instructive for exploiting highly efficient perovskite-based photocatalysts in artificial photosynthesis applications. Further, some important challenges and future prospects of MHPs in this field are proposed and discussed.Fluoride-based compounds doped with rare-earth cations are the preferred choice of materials to achieve efficient upconversion, of interest for a plethora of applications ranging from bioimaging to energy harvesting. Herein, we demonstrate a simple route to fabricate bright upconverting films that are transparent, self-standing, flexible, and emit different colors. Starting from the solvothermal synthesis of uniform and colloidally stable yttrium fluoride nanoparticles doped with Yb3+ and Er3+, Ho3+, or Tm3+, we find the experimental conditions to process the nanophosphors as optical quality films of controlled thickness between few hundreds of nanometers and several micrometers. A thorough analysis of both structural and photophysical properties of films annealed at different temperatures reveals a tradeoff between the oxidation of the matrix, which transitions through an oxyfluoride crystal phase, and the efficiency of the upconversion photoluminescence process. It represents a significant step forward in the understanding of the fundamental properties of upconverting materials and can be leveraged for the optimization of upconversion systems in general. We prove bright multicolor upconversion photoluminescence in oxyfluoride-based phosphor transparent films upon excitation with a 980 nm laser for both rigid and flexible versions of the layers, being possible to use the latter to coat surfaces of arbitrary shape. Our results pave the way toward the development of upconverting coatings that can be conveniently integrated in applications that demand a large degree of versatility.Hepatic fibrosis commonly exists in chronic liver disease and would eventually develop to cirrhosis and liver cancer with high fatality. Phosphodiesterase-9 (PDE9) has attracted profound attention as a drug target because of its highest binding affinity among phosphodiesterases (PDEs) with cyclic guanosine monophosphate. NADPH tetrasodium salt purchase However, no published study has reported PDE9 inhibitors as potential agents against hepatic fibrosis yet. Herein, structural modification from a starting hit LL01 led to lead 4a, which exhibited an IC50 value of 7.3 nM against PDE9, excellent selectivity against other PDE subfamilies, and remarkable microsomal stability. The cocrystal structure of PDE9 with 4a revealed an important residue, Phe441, capable of improving the selectivity of PDE9 inhibitors. Administration of 4a exerted a significant antifibrotic effect in bile duct-ligation-induced rats with hepatic fibrosis and transforming growth factor-β-induced fibrogenesis. This therapeutic effect was indeed achieved by selectively inhibiting PDE9 rather than other PDE isoforms, identifying PDE9 inhibitors as potential agents against hepatic fibrosis.Several toll-like receptors (TLRs) reside inside endosomes of specific immune cells-among them, aberrant activation of TLR7 and TLR9 is implicated in myriad contexts of autoimmune diseases, making them promising therapeutic targets. However, small-molecule TLR7 and TLR9 antagonists are not yet available for clinical use. We illustrate here the importance of C2, C6, and N9 substitutions in the purine scaffold for antagonism to TLR7 and TLR9 through structure-activity relationship studies using cellular reporter assays and functional studies on primary human immune cells. Further in vitro and in vivo pharmacokinetic studies identified an orally bioavailable lead compound 29, with IC50 values of 0.08 and 2.66 μM against TLR9 and TLR7, respectively. Isothermal titration calorimetry excluded direct TLR ligand-antagonist interactions. In vivo antagonism efficacy against mouse TLR9 and therapeutic efficacy in a preclinical murine model of psoriasis highlighted the potential of compound 29 as a therapeutic candidate in relevant autoimmune contexts.TFF3 regulates essential gastro- and neuroprotective functions, but its molecular mode of action remains poorly understood. Synthetic intractability and lack of reliable bioassays and validated receptors are bottlenecks for mechanistic and structure-activity relationship studies. Here, we report the chemical synthesis of TFF3 and its homodimer via native chemical ligation followed by oxidative folding. Correct folding was confirmed by NMR and circular dichroism, and TFF3 and its homodimer were not cytotoxic or hemolytic. TFF3, its homodimer, and the trefoil domain (TFF310-50) were susceptible to gastrointestinal degradation, revealing a gut-stable metabolite (TFF37-54; t1/2 > 24 h) that retained its trefoil structure and antiapoptotic bioactivity. We tried to validate the putative TFF3 receptors CXCR4 and LINGO2, but neither TFF3 nor its homodimer displayed any activity up to 10 μM. The discovery of a gut-stable bioactive metabolite and reliable synthetic accessibility to TFF3 and its analogues are cornerstones for future molecular probe development and structure-activity relationship studies.Microalgae are among the most genetically and metabolically diverse organisms on earth, yet their identification and metabolic profiling have generally been slow and tedious. Here, we established a reference ramanome database consisting of single-cell Raman spectra (SCRS) from >9000 cells of 27 phylogenetically diverse microalgal species, each under stationary and exponential states. When combined, prequenching ("pigment spectrum" (PS)) and postquenching ("whole spectrum" (WS)) signals can classify species and states with 97% accuracy via ensemble machine learning. Moreover, the biosynthetic profile of Raman-sensitive metabolites was unveiled at single cells, and their interconversion was detected via intra-ramanome correlation analysis. Furthermore, not-yet-cultured cells from the environment were functionally characterized via PS and WS and then phylogenetically identified by Raman-activated sorting and sequencing. This PS-WS combined approach for rapidly identifying and metabolically profiling single cells, either cultured or uncultured, greatly accelerates the mining of microalgae and their products.Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) has aroused public concerns as it can pose multiple health threats to pregnant women and cause adverse birth outcomes for fetuses. In previous studies, the prenatal exposure levels and transplacental transfer efficiencies (TTE) of PFASs have been reported and discussed. Specifically, the binding affinities between PFASs and some transporters were determined, demonstrating that the TTE values of PFASs are highly dependent on their binding behaviors. To summarize primary findings of previous studies and propose potential guidance for future research, this article provides a systematic overview on levels and characteristics of prenatal exposure to PFASs worldwide, summarizes relationships between TTE values and structures of PFASs, and discusses possible transplacental transfer mechanisms, especially for the combination between PFASs and transporters. Given the critical roles of transporters in the transplacental transfer of PFASs, we conducted molecular docking to further clarify the binding behaviors between PFASs and the selected transporters.