Automated radiosynthesis of [18 F]CETO, a PET radiotracer for imaging adrenal glands, on Synthra RNplus.

Primary aldosteronism (PA) is the leading secondary cause of hypertension. Determining whether one (unilateral) or both (bilateral) adrenal glands are the source of PA in a patient remains challenging, and yet it is a critical step in the decision whether to recommend potentially curative surgery (adrenalectomy) or lifelong medical therapy (typically requiring multiple drugs). Recently, we have developed a fluorine-18 radiopharmaceutical [18 F]CETO to permit greater access to PA molecular imaging. Herein, we report an automated synthesis of this radiotracer. To manufacture the radiopharmaceutical routinely for clinical PET studies, we implemented an automated radiosynthesis method on a Synthra RNplus© synthesiser for which Cl-tosyletomidate was used as the precursor for radiolabelling via nucleophilic [18 F]fluorination. [18 F]CETO was produced with 35 ± 1% (n = 7), decay corrected and 25 ± 4% (n = 7) non-decay corrected radiochemical yield with molar activities ranging from 150 to 400 GBq/µmol. The GMP compliant manufacturing process produces a sterile formulated [18 F]CETO injectable solution for human use as demonstrated by the results of quality control. Automation of the radiosynthesis of [18 F]CETO should facilitate uptake by other adrenal centres and increase access to molecular imaging in PA.

Towards Dynamic Multi-Modal Intent Sensing Using Probabilistic Sensor Networks.

Intent sensing-the ability to sense what a user wants to happen-has many potential technological applications. Assistive medical devices, such as prosthetic limbs, could benefit from intent-based control systems, allowing for faster and more intuitive control. The accuracy of intent sensing could be improved by using multiple sensors sensing multiple environments. As users will typically pass through different sensing environments throughout the day, the system should be dynamic, with sensors dropping in and out as required. An intent-sensing algorithm that allows for this cannot rely on training from only a particular combination of sensors. It should allow any (dynamic) combination of sensors to be used. Therefore, the objective of this study is to develop and test a dynamic intent-sensing system under changing conditions. A method has been proposed that treats each sensor individually and combines them using Bayesian sensor fusion. This approach was tested on laboratory data obtained from subjects wearing Inertial Measurement Units and surface electromyography electrodes. The proposed algorithm was then used to classify functional reach activities and compare the performance to an established classifier (k-nearest-neighbours) in cases of simulated sensor dropouts. Results showed that the Bayesian sensor fusion algorithm was less affected as more sensors dropped out, supporting this intent-sensing approach as viable in dynamic real-world scenarios.

Validation of a combined image derived input function and venous sampling approach for the quantification of [18F]GE-179 PET binding in the brain.

Blood-based kinetic analysis of PET data relies on an accurate estimate of the arterial plasma input function (PIF). An alternative to invasive measurements from arterial sampling is an image-derived input function (IDIF). However, an IDIF provides the whole blood radioactivity concentration, rather than the required free tracer radioactivity concentration in plasma. To estimate the tracer PIF, we corrected an IDIF from the carotid artery with estimates of plasma parent fraction (PF) and plasma-to-whole blood (PWB) ratio obtained from five venous samples. We compared the combined IDIF+venous approach to gold standard data from arterial sampling in 10 healthy volunteers undergoing [18F]GE-179 brain PET imaging of the NMDA receptor. Arterial and venous PF and PWB ratio estimates determined from 7 patients with traumatic brain injury (TBI) were also compared to assess the potential effect of medication. There was high agreement between areas under the curves of the estimates of PF (r = 0.99, p<0.001), PWB ratio (r = 0.93, p<0.001), and the PIF (r = 0.92, p<0.001) as well as total distribution volume (VT) in 11 regions across the brain (r = 0.95, p<0.001). IDIF+venous VT had a mean bias of -1.7% and a comparable regional coefficient of variation (arterial: 21.3 ± 2.5%, IDIF+venous: 21.5 ± 2.0%). Simplification of the IDIF+venous method to use only one venous sample provided less accurate VT estimates (mean bias 9.9%; r = 0.71, p<0.001). A version of the method that avoids the need for blood sampling by combining the IDIF with population-based PF and PWB ratio estimates systematically underestimated VT (mean bias -20.9%), and produced VT estimates with a poor correlation to those obtained using arterial data (r = 0.45, p<0.001). Arterial and venous blood data from 7 TBI patients showed high correlations for PF (r = 0.92, p = 0.003) and PWB ratio (r = 0.93, p = 0.003). In conclusion, the IDIF+venous method with five venous samples provides a viable alternative to arterial sampling for quantification of [18F]GE-179 VT.

Automated radiosynthesis of [11 C]UCB-J for imaging synaptic density by positron emission tomography.

An automated radiosynthesis of carbon-11 positron emission tomography radiotracer [11 C]UCB-J for imaging the synaptic density biomarker synaptic vesicle glycoprotein SV2A was established using Synthra RNPlus synthesizer. Commercially available trifluoroborate UCB-J analogue was used as a radiolabelling precursor, and the desired radiolabelled product was isolated in 11 ± 2% (n = 7) nondecay corrected radiochemical yield and formulated as a 10% EtOH solution in saline with molar activities of 20 to 100 GBq/µmol. The method was based upon the palladium(0)-mediated Suzuki cross-coupling reaction and [11 C]CH3 I as a radiolabelling synthon. The isolated product was cGMP compliant as demonstrated by the results of quality control analysis.

A simple and efficient automated cGMP-compliant radiosynthesis of [11 C]metomidate using solid phase extraction cartridge purification.

[11 C]metomidate ([11 C]MTO) is a radiotracer widely used to detect disorders of adrenocortical origin by positron emission tomography (PET) imaging. [11 C]MTO PET/computed tomography (PET/CT) is considered a sensitive and specific noninvasive alternative to adrenal vein sampling (AVS) in the management of primary hyperaldosteronism (PHA). Herein, we report a reliable automated procedure for the routine manufacturing of [11 C]MTO in current good manufacturing practice (cGMP) conditions on the commercial Synthra MeIPlus Loop Vessel synthesizer. The method is based on a combination of the captive-solvent 11 C-methylation of the carboxylate salt 1b of the MTO precursor 1a followed by solid phase extraction (SPE) cartridge purification methodology, which substitutes HPLC purification of the crude reaction mixture. Starting from 45 GBq [11 C]CO2 at the end of bombardment (EOB), 3 GBq of pure [11 C]MTO was produced in 18 minutes with 12% decay corrected radiochemical yield (RCY) at the end of synthesis (EOS) and with the modest molar activity of 13 GBq/µmol at the time of application. Each dose produced met all established quality control (QC) criteria. The method can easily be implemented into other commercial automated radiosynthesizers for manufacturing carbon-11 labeled radiotracers.

A Meta-Analysis of Complication Rates Among Different SMAS Facelift Techniques.

BACKGROUND: Sub-superficial musculo-aponeurotic system (SMAS) rhytidectomy techniques are considered to have a higher complication profile, especially for facial nerve injury, compared with less invasive SMAS techniques. This results in surgeons avoiding sub-SMAS dissection. OBJECTIVES: The authors sought to aggregate and summarize data on complications among different SMAS facelift techniques. METHODS: A broad systematic search was performed. All included studies: (1) described a SMAS facelifting technique categorized as SMAS plication, SMASectomy/imbrication, SMAS flap, high lateral SMAS flap, deep plane, and composite; and (2) reported the number of postoperative complications in participants. Meta-analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total 183 studies were included. High lateral SMAS (1.85%) and composite rhytidectomy (1.52%) had the highest rates of temporary nerve injury and were the only techniques to show a statistically significant difference compared with SMAS plication (odds ratio [OR] = 2.71 and 2.22, respectively, P < 0.05). Risk of permanent injury did not differ among techniques. An increase in major hematoma was found for the deep plane (1.22%, OR = 1.67, P < 0.05) and SMAS imbrication (1.92%, OR = 2.65, P < 0.01). Skin necrosis was higher with the SMAS flap (1.57%, OR = 2.29, P < 0.01). CONCLUSIONS: There are statistically significant differences in complication rates between SMAS facelifting techniques for temporary facial nerve injury, hematoma, seroma, necrosis, and infection. Technique should be selected based on quality of results and not the complication profile.

Toxicity implications for early life stage Japanese medaka (Oryzias latipes) exposed to oxyfluorfen.

We investigated the potential toxic effects of Oxyfluorfen (OXY), an herbicide used in agriculture, on the embryo-larval development of Japanese medaka fish (Oryzias latipes). Embryos (1-day postfertilization) and larvae (2-day posthatch) were exposed to OXY (0.5-8 mg/L) for 96 h and evaluated for mortality and hatching on embryos, and the mortality and growth on larvae during depuration. It was observed that the embryo-mortality was inconsistently altered by OXY; only the 2 mg/L group showed significant reduction on embryo survivability. However, larval-mortality was concentration-dependent and OXY exposure induced scoliosis-like phenotypic features in the surviving larvae; the calculated LC50 was 5.238 mg/L. Our data further indicated that larval skeleton, both axial and appendicular, was the potential target site of OXY. Skeletal growth in larvae exposed to 2 mg/L was inhibited significantly until 1 week of depuration with regard to the linear lengths of neurocranium, Meckel's cartilage, caudal vertebrae (first 10) in the axial skeletons, and pectoral fin and urostyle in the appendicular skeletons. Moreover, the total protein content remained unaltered by OXY after 96 h exposure; while the RNA concentration was reduced significantly in larvae exposed to 2 mg/L. Expression analysis of several genes by quantitative real-time RT-PCR (RT-qPCR) showed significant upregulation of zic5, a zinc-finger type transcription regulator, at the transcription level. This study indicated that the scoliosis induced by OXY in Japanese medaka larvae was the result of stunted skeletal growth, probably because of deregulation of zinc-finger type transcription regulators, at the genomic level.

Gut inflammation provides a respiratory electron acceptor for Salmonella.

Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen.

Salmonella uses energy taxis to benefit from intestinal inflammation.

Chemotaxis enhances the fitness of Salmonella enterica serotype Typhimurium (S. Typhimurium) during colitis. However, the chemotaxis receptors conferring this fitness advantage and their cognate signals generated during inflammation remain unknown. Here we identify respiratory electron acceptors that are generated in the intestinal lumen as by-products of the host inflammatory response as in vivo signals for methyl-accepting chemotaxis proteins (MCPs). Three MCPs, including Trg, Tsr and Aer, enhanced the fitness of S. Typhimurium in a mouse colitis model. Aer mediated chemotaxis towards electron acceptors (energy taxis) in vitro and required tetrathionate respiration to confer a fitness advantage in vivo. Tsr mediated energy taxis towards nitrate but not towards tetrathionate in vitro and required nitrate respiration to confer a fitness advantage in vivo. These data suggest that the energy taxis receptors Tsr and Aer respond to distinct in vivo signals to confer a fitness advantage upon S. Typhimurium during inflammation by enabling this facultative anaerobic pathogen to seek out favorable spatial niches containing host-derived electron acceptors that boost its luminal growth.

Mannose supplements induce embryonic lethality and blindness in phosphomannose isomerase hypomorphic mice.

Patients with congenital disorder of glycosylation (CDG), type Ib (MPI-CDG or CDG-Ib) have mutations in phosphomannose isomerase (MPI) that impair glycosylation and lead to stunted growth, liver dysfunction, coagulopathy, hypoglycemia, and intestinal abnormalities. Mannose supplements correct hypoglycosylation and most symptoms by providing mannose-6-P (Man-6-P) via hexokinase. We generated viable Mpi hypomorphic mice with residual enzymatic activity comparable to that of patients, but surprisingly, these mice appeared completely normal except for modest (~15%) embryonic lethality. To overcome this lethality, pregnant dams were provided 1-2% mannose in their drinking water. However, mannose further reduced litter size and survival to weaning by 40 and 66%, respectively. Moreover, ~50% of survivors developed eye defects beginning around midgestation. Mannose started at birth also led to eye defects but had no effect when started after eye development was complete. Man-6-P and related metabolites accumulated in the affected adult eye and in developing embryos and placentas. Our results demonstrate that disturbing mannose metabolic flux in mice, especially during embryonic development, induces a highly specific, unanticipated pathological state. It is unknown whether mannose is harmful to human fetuses during gestation; however, mothers who are at risk for having MPI-CDG children and who consume mannose during pregnancy hoping to benefit an affected fetus in utero should be cautious.

AMAnD: an automated metagenome anomaly detection methodology utilizing DeepSVDD neural networks.

The composition of metagenomic communities within the human body often reflects localized medical conditions such as upper respiratory diseases and gastrointestinal diseases. Fast and accurate computational tools to flag anomalous metagenomic samples from typical samples are desirable to understand different phenotypes, especially in contexts where repeated, long-duration temporal sampling is done. Here, we present Automated Metagenome Anomaly Detection (AMAnD), which utilizes two types of Deep Support Vector Data Description (DeepSVDD) models; one trained on taxonomic feature space output by the Pan-Genomics for Infectious Agents (PanGIA) taxonomy classifier and one trained on kmer frequency counts. AMAnD's semi-supervised one-class approach makes no assumptions about what an anomaly may look like, allowing the flagging of potentially novel anomaly types. Three diverse datasets are profiled. The first dataset is hosted on the National Center for Biotechnology Information's (NCBI) Sequence Read Archive (SRA) and contains nasopharyngeal swabs from healthy and COVID-19-positive patients. The second dataset is also hosted on SRA and contains gut microbiome samples from normal controls and from patients with slow transit constipation (STC). AMAnD can learn a typical healthy nasopharyngeal or gut microbiome profile and reliably flag the anomalous COVID+ or STC samples in both feature spaces. The final dataset is a synthetic metagenome created by the Critical Assessment of Metagenome Annotation Simulator (CAMISIM). A control dataset of 50 well-characterized organisms was submitted to CAMISIM to generate 100 synthetic control class samples. The experimental conditions included 12 different spiked-in contaminants that are taxonomically similar to organisms present in the laboratory blank sample ranging from one strain tree branch taxonomic distance away to one family tree branch taxonomic distance away. This experiment was repeated in triplicate at three different coverage levels to probe the dependence on sample coverage. AMAnD was again able to flag the contaminant inserts as anomalous. AMAnD's assumption-free flagging of metagenomic anomalies, the real-time model training update potential of the deep learning approach, and the strong performance even with lightweight models of low sample cardinality would make AMAnD well-suited to a wide array of applied metagenomics biosurveillance use-cases, from environmental to clinical utility.

A modular, deep learning-based holistic intent sensing system tested with Parkinson's disease patients and controls.

People living with mobility-limiting conditions such as Parkinson's disease can struggle to physically complete intended tasks. Intent-sensing technology can measure and even predict these intended tasks, such that assistive technology could help a user to safely complete them. In prior research, algorithmic systems have been proposed, developed and tested for measuring user intent through a Probabilistic Sensor Network, allowing multiple sensors to be dynamically combined in a modular fashion. A time-segmented deep-learning system has also been presented to predict intent continuously. This study combines these principles, and so proposes, develops and tests a novel algorithm for multi-modal intent sensing, combining measurements from IMU sensors with those from a microphone and interpreting the outputs using time-segmented deep learning. It is tested on a new data set consisting of a mix of non-disabled control volunteers and participants with Parkinson's disease, and used to classify three activities of daily living as quickly and accurately as possible. Results showed intent could be determined with an accuracy of 97.4% within 0.5 s of inception of the idea to act, which subsequently improved monotonically to a maximum of 99.9918% over the course of the activity. This evidence supports the conclusion that intent sensing is viable as a potential input for assistive medical devices.

Development and Optimization of an Unbiased, Metagenomics-Based Pathogen Detection Workflow for Infectious Disease and Biosurveillance Applications.

Rapid, specific, and sensitive identification of microbial pathogens is critical to infectious disease diagnosis and surveillance. Classical culture-based methods can be applied to a broad range of pathogens but have long turnaround times. Molecular methods, such as PCR, are time-effective but are not comprehensive and may not detect novel strains. Metagenomic shotgun next-generation sequencing (NGS) promises specific identification and characterization of any pathogen (viruses, bacteria, fungi, and protozoa) in a less biased way. Despite its great potential, NGS has yet to be widely adopted by clinical microbiology laboratories due in part to the absence of standardized workflows. Here, we describe a sample-to-answer workflow called PanGIA (Pan-Genomics for Infectious Agents) that includes simplified, standardized wet-lab procedures and data analysis with an easy-to-use bioinformatics tool. PanGIA is an end-to-end, multi-use workflow that can be used for pathogen detection and related applications, such as biosurveillance and biothreat detection. We performed a comprehensive survey and assessment of current, commercially available wet-lab technologies and open-source bioinformatics tools for each workflow component. The workflow includes total nucleic acid extraction from clinical human whole blood and environmental microbial forensic swabs as sample inputs, host nucleic acid depletion, dual DNA and RNA library preparation, shotgun sequencing on an Illumina MiSeq, and sequencing data analysis. The PanGIA workflow can be completed within 24 h and is currently compatible with bacteria and viruses. Here, we present data from the development and application of the clinical and environmental workflows, enabling the specific detection of pathogens associated with bloodstream infections and environmental biosurveillance, without the need for targeted assay development.

Amplicon Sequencing Minimal Information (ASqMI): Quality and Reporting Guidelines for Actionable Calls in Biodefense Applications.

BACKGROUND: Accurate, high-confidence data is critical for assessing potential biothreat incidents. In a biothreat event, false-negative and -positive results have serious consequences. Worst case scenarios can result in unnecessary shutdowns or fatalities at an exorbitant monetary and psychological cost, respectively. Quantitative PCR assays for agents of interest have been successfully used for routine biosurveillance. Recently, there has been increased impetus for adoption of amplicon sequencing (AS) for biosurveillance because it enables discrimination of true positives from near-neighbor false positives, as well as broad, simultaneous detection of many targets in many pathogens in a high-throughput scheme. However, the high sensitivity of AS can lead to false positives. Appropriate controls and workflow reporting can help address these challenges. OBJECTIVES: Data reporting standards are critical to data trustworthiness. The standards presented herein aim to provide a framework for method quality assessment in biodetection. METHODS: We present a set of standards, Amplicon Sequencing Minimal Information (ASqMI), developed under the auspices of the AOAC INTERNATIONAL Stakeholder Program on Agent Detection Assays for making actionable calls in biosurveillance applications. In addition to the first minimum information guidelines for AS, we provide a controls checklist and scoring scheme to assure AS run quality and assess potential sample contamination. RESULTS: Adoption of the ASqMI guidelines will improve data quality, help track workflow performance, and ultimately provide decision makers confidence to trust the results of this new and powerful technology. CONCLUSION: AS workflows can provide robust, confident calls for biodetection; however, due diligence in reporting and controls are needed. The ASqMI guideline is the first AS minimum reporting guidance document that also provides the means for end users to evaluate their workflows to improve confidence. HIGHLIGHTS: Standardized reporting guidance for actionable calls is critical to ensuring trustworthy data.

A comparison of dehydroepiandrosterone and 7-keto dehydroepiandrosterone with other drugs that modulate ethanol intake in rats responding under a multiple schedule.

Dehydroepiandrosterone (DHEA), 7-keto DHEA, and several comparison drugs (ethanol, chlordiazepoxide, rauwolscine, and RO15-4513) were administered to male rats responding under a multiple schedule of food and ethanol presentation to determine their selectivity for decreasing ethanol-maintained responding. DHEA and 7-keto DHEA significantly decreased both ethanol-maintained and food-maintained responding, compared with the control, while also decreasing the blood ethanol concentration (BEC). Acute ethanol administration also decreased responding for both food and ethanol; however, ethanol-maintained responding was more potently decreased than food-maintained responding. BEC remained relatively stable after increasing ethanol doses. Among the other drugs tested, RO15-4513 was the most selective for decreasing ethanol-maintained responding compared with food-maintained responding, and it decreased BECs as ethanol-maintained responding decreased. The largest dose of rauwolscine significantly decreased responding for food, whereas it did not affect ethanol-maintained responding compared with the control. Low to intermediate doses of rauwolscine produced small, nonsignificant increases in ethanol-maintained responding and BECs. Chlordiazepoxide produced significant decreases in food-maintained responding and the dose of ethanol presented, but only at the highest dose tested. Although DHEA and 7-keto DHEA did not decrease ethanol-maintained responding as selectively as ethanol or RO15-4513 under the multiple schedule, these neurosteroids may be valuable pharmacological tools in the development of new treatments for alcohol abuse and dependence.

Left Ventricular Thrombus of Unknown Etiology in a Patient With COVID-19 Disease With No Significant Medical History.

The incidence of left ventricular thrombus is relatively low. Ventricular thrombi typically manifest in patients with reduced ejection fraction and post myocardial infarction [1]. The impact of COVID-19's hypercoagulability state is presented here. A 44 year old male who contracted COVID-19, progressed to moderate disease requiring inpatient treatment with supplemental oxygen. During the course of the hospital stay, while receiving National Institutes of Health guideline directed thromboembolism prophylaxis for COVID-19 infected patients [2], the patient developed a left ventricular thrombus which consequently embolized and occluded the left anterior descending and left circumflex coronary arteries requiring rheolytic thrombectomy.

Cryotherapy for treatment of chronic rhinitis: 3-month outcomes of a randomized, sham-controlled trial.

BACKGROUND: The purpose of this study was to test whether cryotherapy is superior to a sham procedure for reducing symptoms of chronic rhinitis. METHODS: This study was a prospective, multicenter, 1:1 randomized, sham-controlled, patient-blinded trial. The predetermined sample size was 61 participants per arm. Adults with moderate/severe symptoms of chronic rhinitis who were candidates for cryotherapy under local anesthesia were enrolled. Participants were required to have minimum reflective Total Nasal Symptom Scores (rTNSSs) of 4 for total, 2 for rhinorrhea, and 1 for nasal congestion. Follow-up visits occurred at 30 and 90 days postprocedure. Patient-reported outcome measures included the rTNSS, standardized Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ(S)], and Nasal Obstruction Symptom Evaluation (NOSE) questionnaires. Adverse events were also recorded. The primary endpoint was the comparison between the treatment and sham arms for the percentage of responders at 90 days. Responders were defined as participants with a 30% or greater reduction in rTNSS relative to baseline. RESULTS: Twelve US investigational centers enrolled 133 participants. The primary endpoint analysis included 127 participants (64 active, 63 sham) with 90-day results. The treatment arm was superior at the 90-day follow-up with 73.4% (47 of 64) responders compared with 36.5% (23 of 63) in the sham arm (p < 0.001). There were greater improvements in the rTNSS, RQLQ(S), and NOSE scores for the active arm over the sham arm at the 90-day follow-up (p < 0.001). One serious procedure-related adverse event of anxiety/panic attack was reported. CONCLUSION: Cryotherapy is superior to a sham procedure for improving chronic rhinitis symptoms and patient quality of life.

Balloon dilation of the Eustachian tube with a seeker-based device: A registry of 169 patients.

OBJECTIVE: To collect real-world data on the safety and effectiveness of balloon dilation of the Eustachian tube using a seeker-based device in patients with persistent/chronic symptoms of Eustachian tube dysfunction. METHODS: A multicenter, prospective, single-arm registry was conducted from June 2018 through August 2020 at 10 US centers, including tertiary care and private practices. Primary endpoints included mean change from baseline in the 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and the serious related adverse event rate. Secondary endpoints include changes in middle ear assessments, surgical intervention rate, and changes in Sino-Nasal Outcome Test and Work and Activity Impairment (WPAI) questionnaires. RESULTS: A total of 169 participants were treated with balloon dilation of the Eustachian tube, with 166 and 154 participants completing the 6-week and 6-month follow-ups, respectively. Repeated measures analysis of the change in ETDQ-7 scores indicated statistically significant improvement (-2.1; 95% CI -2.40, -1.84; P < .0001) at 6-month follow-up. The minimum clinically important difference of improvement was achieved by 85% of participants at 6 months. Four nonserious adverse events were reported. Middle ear functional assessments were improved in the majority of participants with abnormal baseline findings. There were no statistically significant differences in the change from baseline ETDQ-7 scores between participants who had concurrent procedures and those who did not. WPAI scores demonstrated significant improvement. CONCLUSION: Real-world evidence supports the clinical studies demonstrating that balloon dilation of the Eustachian tube with a seeker-based device is a safe and effective procedure to treat ETD symptoms. LEVEL OF EVIDENCE: 3.

Gastric Xanthoma in the Pediatric Population: A Possible Herald for Malignancy?

Gastric xanthoma is frequently an incidental finding on upper endoscopy in adults. Gastric xanthomas (GX) can be mistaken for malignancies and warrant prompt histologic diagnosis. The underlying etiology is not fully understood; however, it has been linked to Helicobacter pylori gastritis and gastric cancer. GX in the pediatric population is largely unreported in the literature. Because of the relative rarity, documentation with case reports are essential to provide as much data as possible to see if there is a correlation between GX and malignant potential in the pediatric population. Our group is reporting two cases, a 10-year-old male and a 7-year-old male, both who presented with chronic dysphagia, upper abdominal pain, nausea, vomiting, and loss of appetite. Upper endoscopies for both patients revealed small polypoid lesions located in the antrum with foamy histiocytes on histology, leading to the diagnosis of gastric xanthoma.

Ultra-sensitive and rapid detection of nucleic acids and microorganisms in body fluids using single-molecule tethering.

Detection of microbial nucleic acids in body fluids has become the preferred method for rapid diagnosis of many infectious diseases. However, culture-based diagnostics that are time-consuming remain the gold standard approach in certain cases, such as sepsis. New culture-free methods are urgently needed. Here, we describe Single MOLecule Tethering or SMOLT, an amplification-free and purification-free molecular assay that can detect microorganisms in body fluids with high sensitivity without the need of culturing. The signal of SMOLT is generated by the displacement of micron-size beads tethered by DNA probes that are between 1 and 7 microns long. The molecular extension of thousands of DNA probes is determined with sub-micron precision using a robust and rapid optical approach. We demonstrate that SMOLT can detect nucleic acids directly in blood, urine and sputum at sub-femtomolar concentrations, and microorganisms in blood at 1 CFU mL-1 (colony forming unit per milliliter) threefold faster, with higher multiplexing capacity and with a more straight-forward protocol than amplified methodologies. SMOLT's clinical utility is further demonstrated by developing a multiplex assay for simultaneous detection of sepsis-causing Candida species directly in whole blood.