Sedation-free transnasal esophagoscopy to evaluate and monitor esophageal diseases in children with esophageal atresia-tracheoesophageal fistula.

Patients with esophageal atresia and tracheoesophageal fistula (EA-TEF) are at increased risk of conditions including gastroesophageal reflux, peptic esophagitis, gastric metaplasia, anastomotic strictures, eosinophilic esophagitis, and dysphagia. Patients with TEF-EA may need serial endoscopy in their lifetime given the known short- and long-term GI complications. There has been increased interest in pediatric unsedated transnasal endoscopy (TNE) as an endoscopic alternative as it is lower cost, has shorter recovery time, and eliminates potential risks associated with anesthesia. We report on the use of TNE with EA-TEF in four patients: One patient had gastroesophageal reflux disease, one patient had eosinophilic esophagitis and TNE was used for surveillance in two patients. Use of TNE allowed for close endoscopic monitoring and changes in medication management. The third and fourth patients underwent TNE as part of routine EA-TEF screening which is recommended by societal guidelines (Krishnan et al, J Pediatr Gastroenterol Nutr. 2016;63(5):550-570). Unsedated TNE is an alternative endoscopic approach in the management of patients with EA-TEF.

Transnasal endoscopy ease score "TNEase score" to evaluate patient tolerance of unsedated transnasal endoscopy.

Transnasal endoscopy (TNE) with virtual reality (VR) distraction allows for unsedated pediatric upper endoscopy. Understanding the pediatric population that is successful with TNE is imperative for patient selection and experience. We developed a "TNEase Score" to assess patient tolerance from the physician's assessment. The aim of this study was to identify factors that influence patient's acceptance and tolerability of sedation-free TNE in pediatric patients undergoing the procedure. From March 2020 to April 2021, 110 TNEs were performed on subjects 5-22 years of age. The overall completion rate was 98.1%. Of these subjects, 66 subjects (60%) were graded by the gastroenterologist as TNEase Score 1 (with ease); 27 subjects (25%) were graded as TNEase Score 2 (minimal complaints); nine subjects (8%) were graded as TNEase score 3 (moderate complaints, required frequent reassurance); six subjects were graded as TNEase Score 4 (significant complaints and resistance); two subjects (2%) were graded as TNEase Score 5 (procedure terminated). Feasibility of TNE was significantly related to age, height, and whether the patient had undergone previous TNE. Thus, young age, shorter height, and first time TNE were significant predictors of higher TNEase score or difficulty tolerating TNE. Factors examined that did not predict higher TNEase score included gender, junior versus senior endoscopist, past medical history of anxiety, autism, attention-deficit/hyperactivity disorder (ADHD), or history of using a nasal spray at home. "TNEase score" allowed grading of the subject's experience and the majority of patients tolerated TNE with minimal complaints.

In situ surface-etched bacterial spore detection using dipicolinic acid-europium-silica nanoparticle bioreporters.

A basic approach was optimized for the synthesis of highly selective and sensitive in situ mesoporous (MCM) type imprinted silica polymers for the detection of dipicolinic acid (DPA) using europium as a reporter. DPA is a ubiquitous biochemical marker available during the germination event of endospore-forming bacteria such as Bacillus . Additionally, an MCM-MIP (molecularly imprinted polymeric phenomena) detector and a companion MCM-non-surface-MIP detector were synthesized using europium reporters for the sensing of DPA under optimized laboratory conditions. Our results showed that the in situ molecular imprinting process enabled rapid, selective detection of DPA with high sensitivity compared to MCM-MIP (imprinted for DPA; no DPA present), MCM-Non-MIP (no imprint present), and MCM-SR-MIP (imprinted with DPA present) detectors. The lower detection limit observed for DPA concentration is 5.49 × 10(-10) mol dm(-3) for MCM-MIP. The performance of the sensor in high-salt-water conditions, under photo-bleaching, and its reusability were also evaluated. The synthesized in situ MCM-MIP material should permit the detection of DPA for field assays related to suspect bacterial sporulation events.

Francisella tularensis 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase: kinetic characterization and phosphoregulation.

Deliberate and natural outbreaks of infectious disease, the prevalence of antibiotic resistant strains, and the ease by which antibiotic resistant bacteria can be intentionally engineered all underscore the necessity of effective vaccines and continued development of novel antimicrobial/antiviral therapeutics. Isoprenes, a group of molecules fundamentally involved in a variety of crucial biological functions, are derived from either the mevalonic acid (MVA) or methylerythritol phosphate (MEP) pathway. While mammals utilize the MVA pathway, many bacteria utilize the MEP pathway, highlighting the latter as an attractive target for antibiotic development. In this report we describe the cloning and characterization of Francisella tularensis MEP cytidylyltransferase, a MEP pathway enzyme and potential target for antibiotic development. Size exclusion chromatography indicates the protein exists as a dimer in solution. Enzyme assays produced an apparentK(MEP)(M) = 178 µM, K(CTP)(M) = 73 µM , k(MEP)(cat) = 1(s-1), k(CTP)(cat) = 0.8( s-1), and a k(MEP)(cat)/ K(MEP)(M) = 3.4 x 10(5) M(-1) min(-1). The enzyme exhibits a strict preference for Mg(+2) as a divalent cation and CTP as the nucleotide. Titanium dioxide chromatography-tandem mass spectrometry identified Thr141 as a site of phosphorylation. T141D and T141E site-directed mutants are catalytically inactive, suggesting a mechanism for post-translational control of metabolic flux through the F. tularensis MEP pathway. Overall, our study suggests that MEP cytidylyltransferase is an excellent target for the development of novel antibiotics against F. tularensis.

Fluorescence resonance energy transfer based MCM-EDTA-Tb3+-MES sensor.

An in situ mesopourous surface imprinted polymeric (SIP) sensor was synthesized for a highly sensitive, selective, and kinetically faster detection of the high-vapor-pressure nerve gas surrogate methyl salicylate (MES). Visual detection occurred on the filtrate thin films at 25 pM. Other nerve gas surrogates, TP, DMP, DMMP, PMP, and 1,4-thioxane, were tested and showed a decrease in sensitivity compared to MES. In addition, 2,6-dipicolinic acid (DPA), a biological indicator, was also investigated and showed a decrease in sensitivity compared to MES. Finally, the detection plateau was reached at 40 s and at 1.5 x 10(-4) M from pH 6-11.

Detection of Bacillus endospores using total luminescence spectroscopy.

Detection and analysis of bacteria from environmental samples (e.g. water, air, and food) are usually accomplished by standard culture techniques or by analyses that target specific DNA sequences, antigens or chemicals. For large cell numbers in aqueous suspensions, an alternative technique that has proven useful is total luminescence spectroscopy (TLS). TLS is the acquisition of fluorescence data that records the unique excitation-emission matrix (EEM) of compound fluorophores. Past work has shown that one type of bacterial endospore, Bacillus megaterium, possessed a distinct EEM pattern useful for differentiating it in complex biological fluids and suspensions. The work described here extends those observations to establish some limits on the sensitivity and specificity of TLS for the detection and analysis of bacterial endospores versus (bacterial) vegetative cells in aqueous culture. Our findings show Bacillus endospores exhibit a dramatic blue shift of 130 nm in excitation and a smaller shift of 50 nm in emission when compared to ancillary endospore and non-endospore forming bacterial cells.

Mechanisms of acute and chronic waterborne nickel toxicity in the freshwater cladoceran, Daphnia magna.

We present evidence that Mg2+ antagonism is one mechanism for acute toxicity of waterborne Ni to Daphnia magna. Acutely, adult D. magna were exposed to either control or 694 microg Ni L(-1) as NiSO4 in moderately soft water (45 mg L(-1) as CaCO3; background Ni approximately 1 microg Ni L(-1)) for 48 h without feeding. Chronically, adults were exposed to either control or 131 microg Ni L(-1) for 14 days (fed exposure). These concentrations were approximately 65% and 12%, respectively, of the measured 48-h LC50 (1068 microg Ni L(-1)) for daphnid neonates in this water quality. The clearest effect of Ni exposure was on Mg2+ homeostasis, as whole-body [Mg2+] was significantly decreased both acutely and chronically by 18%. Additionally, unidirectional Mg2+ uptake rate (measured with the stable isotope 26Mg) was significantly decreased both acutely and chronically by 49 and 47%, respectively, strongly suggesting that Ni is toxic to D. magna due at least in part to Mg2+ antagonism. No impact was observed on the whole-body concentrations or unidirectional uptake rates of Ca2+ during either acute or chronic Ni exposure, while only minor effects were seen on Na+ and Cl- balance. No acute toxic effect was seen on respiratory parameters, as both oxygen consumption rate (MO2) and whole-body hemoglobin concentration ([Hb]) were conserved. Chronically, however, Ni impaired respiratory function, as both MO2 and [Hb] were significantly reduced by 31 and 68%, respectively. Acutely, Ni accumulation was substantial, rising to a plateau between 24 and 48 h of approximately 15 microg g(-1) wet weight--an increase of approximately 25-fold over control concentrations. Mechanisms of acute toxicity of Ni in D. magna differ from those in fish; it is likely that such mechanistic differences also exist for other metals.

Demonstration of new technology MEMS and liquid crystal adaptive optics on bright astronomical objects and satellites.

We present here results using two novel adaptive optic elements, an electro-static membrane mirror, and a dual frequency nematic liquid crystal. These devices have the advantage of low cost, low power consumption, and compact size. Possible applications of the devices are astronomical adaptive optics, laser beam control, laser cavity mode control, and real time holography. Field experiments were performed on the Air Force Research Laboratory, Directed Energy Directorate's 3.67 meter AMOS telescope on Maui, Hawaii.