Alleviating symptoms of paediatric acute rhinosinusitis and acute otitis media with otorrhea using nasal-spraying Bacillus probiotics: a randomized controlled trial.

Acute rhinosinusitis (ARS) in children may be accompanied by acute otitis media (AOM) which is often associated with bacterial co-infections. These conditions are among the primary reasons that children visit hospitals and require antibiotic treatment. This study evaluated the efficacy of the nasal-spraying probiotics (LiveSpo Navax containing 5 billion Bacillus subtilis and B.

The Morphologic and Molecular Heterogeneity of Fumarate Hydratase-deficient Leiomyomas: Integrative Molecular Profiling of Uterine Smooth Muscle Tumors With Histologic Feature Correlation.

The morphologic features of uterine smooth muscle tumors (USMTs) are subject to interobserver variability and are complicated by consideration of features of fumarate hydratase deficiency (FHd) and other morphologic subtypes, with difficult cases occasionally diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP). We compare immunohistochemical findings and detailed morphologic analysis of 45 USMTs by 4 fellowship-trained gynecologic pathologists with comprehensive molecular analysis, focusing on FHd leiomyomas (n=15), compared to a variety of other USMTs with overlapping morphologic features, including 9 STUMPs, 8 usual-type leiomyomas (ULM), 11 apoplectic leiomyomas, and 2 leiomyomas with bizarre nuclei (LMBN). FHd leiomyomas, defined by immunohistochemical (IHC) loss of FH and/or 2SC accumulation, showed FH mutations and/or FH copy loss in all cases, with concurrent TP53 mutations in 2 tumors.

Central control of dynamic gene circuits governs T cell rest and activation.

The ability of cells to maintain distinct identities and respond to transient environmental signals requires tightly controlled regulation of gene networks. These dynamic regulatory circuits that respond to extracellular cues in primary human cells remain poorly defined. The need for context-dependent regulation is prominent in T cells, where distinct lineages must respond to diverse signals to mount effective immune responses and maintain homeostasis.

Impact of Heart Transplant Allocation Change on Waitlist Mortality and Posttransplant Mortality in Patients With Left Ventricular Assist Devices.

Background: In October 2018, the US heart transplant (HT) allocation system was revised giving patients with left ventricular assist device (LVAD) intermediate priority status. Few studies have examined the impact of this policy change on outcomes among patients with LVAD. We sought to determine how the allocation change impacted waitlist and posttransplant mortality in patients with LVAD.

Rupture of intrahepatic bile duct after ERCP for common bile duct stone: A case report of rare complications.

Rationale: Complications after endoscopic retrograde cholangiopancreatography (ERCP) are diverse and usually treated with nonoperative management or percutaneous drainage; however, there are still some rare, life-threatening complications. This is an extremely rare case of biliary peritonitis caused by rupture of the intrahepatic bile duct after ERCP.

Patient Concerns: A 63-year-old male underwent ERCP for common bile duct stones.

Detecting Visual Field Worsening From Optic Nerve Head and Macular Optical Coherence Tomography Thickness Measurements.

Purpose: Compare the use of optic disc and macular optical coherence tomography measurements to predict glaucomatous visual field (VF) worsening.

Methods: Machine learning and statistical models were trained on 924 eyes (924 patients) with circumpapillary retinal nerve fiber layer (cp-RNFL) or ganglion cell inner plexiform layer (GC-IPL) thickness measurements. The probability of 24-2 VF worsening was predicted using both trend-based and event-based progression definitions of VF worsening.

Progressive Encephalopathy With New Pulmonary Opacities in an Immunocompromised Host.

A 48-year-old man with history of recent travel to central Mexico and immunosuppression sought treatment with a 1-month-long history of progressive headache, fatigue, word-finding difficulties, and night sweats. The patient had a history of end-stage renal disease; he had undergone a kidney transplantation 7 years prior with good graft function with immunosuppression with tacrolimus, everolimus, and low-dose prednisone. At an outside hospital, he recently had been treated with empiric antibiotics for meningitis, but these were discontinued given the low suspicion for a bacterial cause.

Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis.

Localized prostate cancer is frequently composed of multiple spatially distinct tumors with significant inter- and intra-tumoral molecular heterogeneity. This genomic diversity gives rise to many competing clones that may drive the biological trajectory of the disease. Previous large-scale sequencing efforts have focused on the evolutionary process in metastatic prostate cancer, revealing a potential clonal progression to castration resistance.

Treatment of infantile-onset Pompe disease in a rat model with muscle-directed AAV gene therapy.

Objective: Pompe disease (PD) is caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA), leading to progressive glycogen accumulation and severe myopathy with progressive muscle weakness. In the Infantile-Onset PD (IOPD), death generally occurs <1 year of age. There is no cure for IOPD.

Quality Improvement Report: Improving Retrieval Time for CT Supplies by Using 5S.

The CT supply room is a critical resource in the imaging workflow. However, the supply room for the two CT scanners at our cancer center, one of which is used for our busy interventional service, was disorganized, and the time spent searching for the appropriate equipment could potentially lead to delays in service and contribute to patient safety risks. The purpose of this project was to reduce the time to find supplies and to increase the satisfaction of CT technologists and medical providers by reorganizing and clearly labeling supplies using "lean" principles.

Dosimetric predictors for genitourinary toxicity in MR-guided stereotactic body radiation therapy (SBRT): Substructure with fraction-wise analysis.

Background: MR-guided radiation therapy (MRgRT) systems provide superior soft tissue contrast than x-ray based systems and can acquire real-time cine for treatment gating. These features allow treatment planning margins to be reduced, allowing for improved critical structure sparing and reduced treatment toxicity. Despite this improvement, genitourinary (GU) toxicity continues to affect many patients.

The Impact of Achieving Target Intraocular Pressure on Glaucomatous Retinal Nerve Fiber Layer Thinning in a Treated Clinical Population.

Purpose: To estimate the effect of being below and above the clinician-set target intraocular pressure (IOP) on rates of glaucomatous retinal nerve fiber layer (RNFL) thinning in a treated real-world clinical population.

Design: Retrospective cohort study.

Methods: A total of 3256 eyes (1923 patients) with ≥5 reliable optical coherence tomography scans and 1 baseline visual field test were included.

Objective Measures of Gaze Behaviors and the Visual Environment during Near-Work Tasks in Young Adult Myopes and Emmetropes.

Purpose: To objectively quantify near-work gaze behaviors and the visual environment during reading tasks performed on a smartphone and on paper in both indoor and outdoor environments in myopes and emmetropes.

Methods: A novel wearable gaze and viewing distance tracking device was used to quantify near-work gaze behaviors (focusing demand) and the visual environment (20° peripheral scene relative defocus) during a series of reading tasks. Data from nine myopes (mean age, 21 ± 1.

DNA Structure Design Is Improved Using an Artificially Expanded Alphabet of Base Pairs Including Loop and Mismatch Thermodynamic Parameters.

We show that design of DNA secondary structures is improved by extending the base pairing alphabet beyond A-T and G-C to include the pair between 2-amino-8-(1'-β-d-2'-deoxyribofuranosyl)-imidazo-[1,2-]-1,3,5-triazin-(8)-4-one and 6-amino-3-(1'-β-d-2'-deoxyribofuranosyl)-5-nitro-(1)-pyridin-2-one, abbreviated as and . To obtain the thermodynamic parameters needed to include P-Z pairs in the designs, we performed 47 optical melting experiments and combined the results with previous work to fit free energy and enthalpy nearest neighbor folding parameters for P-Z pairs and G-Z wobble pairs. We find G-Z pairs have stability comparable to that of A-T pairs and should therefore be included as base pairs in structure prediction and design algorithms.

Liposomal co-delivery of toll-like receptors 3 and 7 agonists induce a hot triple-negative breast cancer immune environment.

Triple-negative breast cancer (TNBC) is highly aggressive and has no standard treatment. Although being considered as an alternative to conventional treatments for TNBC, immunotherapy has to deal with many challenges that hinder its efficacy, particularly the poor immunogenic condition of the tumor microenvironment (TME). Herein, we designed a liposomal nanoparticle (LN) platform that delivers simultaneously toll-like receptor 7 (imiquimod, IQ) and toll-like receptor 3 (poly(I:C), IC) agonists to take advantage of the different toll-like receptor (TLR) signaling pathways, which enhances the condition of TME from a "cold" to a "hot" immunogenic state.

DNA Structure Design Is Improved Using an Artificially Expanded Alphabet of Base Pairs Including Loop and Mismatch Thermodynamic Parameters.

We show that design of DNA secondary structures is improved by extending the base pairing alphabet beyond A-T and G-C to include the pair between 2-amino-8-(1'-β-D-2'-deoxyribofuranosyl)-imidazo-[1,2- ]-1,3,5-triazin-(8 )-4-one and 6-amino-3-(1'-β-D-2'-deoxyribofuranosyl)-5-nitro-(1 )-pyridin-2-one, simply P and Z. To obtain the thermodynamic parameters needed to include P-Z pairs in the designs, we performed 47 optical melting experiments and combined the results with previous work to fit a new set of free energy and enthalpy nearest neighbor folding parameters for P-Z pairs and G-Z wobble pairs. We find that G-Z pairs have stability comparable to A-T pairs and therefore should be considered quantitatively by structure prediction and design algorithms.

Clinicoradiologic and Neuropathologic Evaluation of Corticobasal Syndrome.

Background And Objectives: Corticobasal syndrome (CBS) is a clinical phenotype characterized by asymmetric parkinsonism, rigidity, myoclonus, and apraxia. Originally believed secondary to corticobasal degeneration (CBD), mounting clinicopathologic studies have revealed heterogenous neuropathologies. The objectives of this study were to determine the pathologic heterogeneity of CBS, the clinicoradiologic findings associated with different underlying pathologies causing CBS, and the positive predictive value (PPV) of current diagnostic criteria for CBD among patients with a CBS.

High-Throughput Screening Assay for Detecting Drug-Induced Changes in Synchronized Neuronal Oscillations and Potential Seizure Risk Based on Ca Fluorescence Measurements in Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neuronal 2D and 3D Cultures.

Drug-induced seizure liability is a significant safety issue and the basis for attrition in drug development. Occurrence in late development results in increased costs, human risk, and delayed market availability of novel therapeutics. Therefore, there is an urgent need for biologically relevant, in vitro high-throughput screening assays (HTS) to predict potential risks for drug-induced seizure early in drug discovery.

assays show human gamma-delta T cells specific for common allergens are Th1-polarized in allergic donors.

Gamma-delta (γδ) T cells contribute to the pathology of many immune-related diseases; however, no assays to study their activities are currently available. Here, we established a methodology to characterize human allergen-reactive γδ T cells in peripheral blood using an activation-induced marker assay targeting upregulated 4-1BB and CD69 expression. Broad and reproducible allergen-reactive γδ T cell responses were detected in donors sensitized to mouse, cockroach, house dust mite, and timothy grass, but the response did not differ from that in non-allergic participants.

Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.

Background And Objectives: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).

Segmented 3D Echo Planar Acquisition for Rapid Susceptibility-Weighted Imaging: Application to Microhemorrhage Detection in Traumatic Brain Injury.

Background: Susceptibility-weighted imaging (SWI) provides superior image contrast of cerebral microhemorrhages (CMBs). It is based on a three-dimensional (3D) gradient echo (GRE) sequence with a relatively long imaging time.

Purpose: To evaluate whether an accelerated 3D segmented echo planar imaging SWI is comparable to GRE SWI in detecting CMBs in traumatic brain injury (TBI).

Inhibition of MNKs promotes macrophage immunosuppressive phenotype to limit CD8+ T cell antitumor immunity.

To elicit effective antitumor responses, CD8+ T cells need to infiltrate tumors and sustain their effector function within the immunosuppressive tumor microenvironment (TME). Here, we evaluate the role of MNK activity in regulating CD8+ T cell infiltration and antitumor activity in pancreatic and thyroid tumors. We first show that human pancreatic and thyroid tumors with increased MNK activity are associated with decreased infiltration by CD8+ T cells.

Revealing A-T and G-C Hoogsteen base pairs in stressed protein-bound duplex DNA.

Watson-Crick base pairs (bps) are the fundamental unit of genetic information and the building blocks of the DNA double helix. However, A-T and G-C can also form alternative 'Hoogsteen' bps, expanding the functional complexity of DNA. We developed 'Hoog-finder', which uses structural fingerprints to rapidly screen Hoogsteen bps, which may have been mismodeled as Watson-Crick in crystal structures of protein-DNA complexes.

A Dendritic Cell-Activating Rv1876 Protein Elicits Mycobacterium Bovis BCG-Prime Effect via Th1-Immune Response.

The widely administered tuberculosis (TB) vaccine, Bacillus Calmette-Guerin (BCG), is the only licensed vaccine, but has highly variable efficiency against childhood and pulmonary TB. Therefore, the BCG prime-boost strategy is a rational solution for the development of new TB vaccines. Studies have shown that (Mtb) culture filtrates contain proteins that have promising vaccine potential.

Examining the Utility and Cost of Routine Type and Screen Prior to Minimally Invasive Hysterectomy.

Background And Objectives: Pre-operative type and screen (T&S) is typically obtained if a patient is expected to require a blood transfusion; however, in cases of minimal blood loss, routine T&S may be unnecessary. The objective of our study was to examine the utility and cost of routine pre-operative T&S prior to minimally invasive hysterectomies (MIH).

Methods: We performed a retrospective chart review of all MIH from January 1, 2018 to December 31, 2019.