Point-of-Care Ultrasound Diagnosis of Ureteropelvic Junction Obstruction in a Child With Recurrent Abdominal Pain and Vomiting.

A case is described of a 4 year-old girl who presented with chronic episodic abdominal pain with vomiting. Physical examination was unremarkable aside from hypertension. Point-of-care renal ultrasound showed hydronephrosis, leading to a diagnosis of ureteropelvic junction obstruction presenting with Dietl crisis (episodic abdominal pain secondary to urinary tract obstruction). The clinical utility of point-of-care renal ultrasound in the evaluation of abdominal pain and ultrasound findings of ureteropelvic junction obstruction are highlighted.

Propagating annotations of molecular networks using in silico fragmentation.

The annotation of small molecules is one of the most challenging and important steps in untargeted mass spectrometry analysis, as most of our biological interpretations rely on structural annotations. Molecular networking has emerged as a structured way to organize and mine data from untargeted tandem mass spectrometry (MS/MS) experiments and has been widely applied to propagate annotations. However, propagation is done through manual inspection of MS/MS spectra connected in the spectral networks and is only possible when a reference library spectrum is available. One of the alternative approaches used to annotate an unknown fragmentation mass spectrum is through the use of in silico predictions. One of the challenges of in silico annotation is the uncertainty around the correct structure among the predicted candidate lists. Here we show how molecular networking can be used to improve the accuracy of in silico predictions through propagation of structural annotations, even when there is no match to a MS/MS spectrum in spectral libraries. This is accomplished through creating a network consensus of re-ranked structural candidates using the molecular network topology and structural similarity to improve in silico annotations. The Network Annotation Propagation (NAP) tool is accessible through the GNPS web-platform https://gnps.ucsd.edu/ProteoSAFe/static/gnps-theoretical.jsp.

Abscopal effect following checkpoint inhibitor therapy and localized radiotherapy for metastatic clear cell renal cell carcinoma: A case report.

We present the case of a 64-year-old patient with metastatic renal cell carcinoma, who experienced disease progression despite undergoing multiple lines of systemic therapy, including immune checkpoint inhibitors (ICI). Two months after stereotactic radiosurgery to his brain lesions and while the patient was not on any systemic therapy, restaging scans demonstrated a dramatic near complete regression of the primary renal lesion and metastatic sites, which was attributed to the abscopal effect, mediated by the exposure to ICI and radiotherapy. While its mechanisms are not fully understood, it is believed to stem from the tumor immunosuppression and immunogenicity induced by radiation.

Charge Transfer in Spatially Defined Organic Radical Polymers.

Charge transfer in nonconjugated redox-active polymers is influenced by redox site proximity and polymer flexibility, but it is challenging to observe these effects independently. In this work, spatially defined radical-containing polymers are synthesized by using acyclic diene metathesis (ADMET) polymerization of α,ω-dienes bearing a central activated ester. Postpolymerization functionalization with 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO) introduces TEMPO radical groups onto the polymer backbone through amide linkages to yield spatially defined polymers with radical units every 9, 11, 15, and 21 carbons. Increased radical spacing leads to reduced spin-spin coupling and increased chain flexibility. The glass transition temperatures (Tg) range from 47.6 to -13.8 °C, depending on the radical spacing. The spatially defined TEMPO-substituted polymer with a spacing length of 15 carbons displays the lowest Tg and the shortest hopping distance, as shown through molecular dynamics simulations. Also, this polymer displays kinetics 1000 times faster than the commonly studied TEMPO-containing polymer poly(2,2,6,6-tetramethylpiperidinyloxy-4-ylacrylamide) (PTAm). Remarkably, comparison of the diffusion and kinetics attributed to the redox reaction reveals that both the apparent diffusion coefficient and the self-exchange reaction rate constant are correlated to the polymer's Tg as log[Dapp] and log[kex,app] ∼ Tg, respectively. Critically, these data demonstrate that controlling the spacing of redox-active groups along a polymer backbone strongly influences backbone flexibility and radical packing, which leads to synergetic improvements in the charge transfer kinetics of nonconjugated redox-active polymers.

Evaluation of Endotracheal Tube Depth in the Out-of-Hospital Setting.

Introduction Endobronchial intubation is a known complication of endotracheal intubation with significant associated morbidity and a reported incidence of up to 15%. In the out-of-hospital setting, paramedics must rely on bedside techniques to confirm appropriate endotracheal tube (ETT) depth. The present real-world practices of paramedics have not been described in this regard. Methods A multi-point survey was distributed to paramedics within the state of Pennsylvania. Participants were scored on the basis of their use of techniques to confirm ETT depth with the highest sensitivity to exclude endobronchial intubation. Results Four-hundred nine (409) responses from 111 emergency medical services (EMS) agencies were recorded. Participants were found to evaluate endotracheal tube depth via auscultation of bilateral breath sounds (91.7% of participants), visualization of the endotracheal tube as it advances 1-2 cm beyond the vocal cords (82.9%), observation of symmetrical chest rise (80.0%), and by securing the ETT at 21 and 23 cm at the incisors for women and men (18.6%). Experienced paramedics were more likely to use the 21/23 cm rule (p=0.039). Participants did not employ the cumulative use of these techniques (p < 0.001) as per a method that has been previously described to exclude endobronchial intubation with 100% sensitivity. Conclusion These data suggest that paramedics are not presently employing the most sensitive techniques to exclude endobronchial intubation. An educational initiative and protocol update may be beneficial.

Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis.

BACKGROUND: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. RESULTS: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. CONCLUSIONS: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis.