Rhinovirus as the main co-circulating virus during the COVID-19 pandemic in children.

Objective: Changes in the epidemiology of respiratory infections during the restrictions imposed as a response to the coronavirus disease 2019 (COVID-19) pandemic have been reported elsewhere. The present study's aim was to describe the prevalence of a large array of respiratory pathogens in symptomatic children and adolescents during the pandemic in Southern Brazil.

Methods: Hospitalized and outpatients aged 2 months to 18 years with signs and symptoms of acute COVID-19 were prospectively enrolled in the study from May to November 2020 in two hospitals in a large metropolitan area in a Brazilian city.

Architecture and performance analysis of an optical metrology terminal for satellite-to-satellite laser ranging.

Interferometric laser ranging is an enabling technology for high-precision satellite-to-satellite tracking within the context of Earth observation, gravitational wave detection, or formation flying. In orbit, the measurement system is affected by environmental influences, particularly satellite attitude jitter and temperature fluctuations, imposing an instrument design with a high level of thermal stability and insensitivity to rotations around the spacecraft center of mass. The new design concept presented here combines different approaches for dynamic heterodyne laser ranging and features the inherent beam-tracking capabilities of a retroreflector in a mono-axial configuration.

Massive clonal expansion of medulloblastoma-specific T cells during adoptive cellular therapy.

In both human and murine systems, we have developed an adoptive cellular therapy platform against medulloblastoma and glioblastoma that uses dendritic cells pulsed with a tumor RNA transcriptome to expand polyclonal tumor-reactive T cells against a plurality of antigens within heterogeneous brain tumors. We demonstrate that peripheral TCR Vβ repertoire analysis after adoptive cellular therapy reveals that effective response to adoptive cellular therapy is concordant with massive in vivo expansion and persistence of tumor-specific T cell clones within the peripheral blood. In preclinical models of medulloblastoma and glioblastoma, and in a patient with relapsed medulloblastoma receiving adoptive cellular therapy, an early and massive expansion of tumor-reactive lymphocytes, coupled with prolonged persistence in the peripheral blood, is observed during effective therapeutic response to immunotherapy treatment.

Best practices for the use of intracerebroventricular drug delivery devices.

For decades, intracerebroventricular (ICV), or intraventricular, devices have been used in the treatment of a broad range of pediatric and adult central nervous system (CNS) disorders. Due to the limited permeability of the blood brain barrier, diseases with CNS involvement may require direct administration of drugs into the brain to achieve full therapeutic effect. A recent comprehensive literature review on the clinical use and complications of ICV drug delivery revealed that device-associated complication rates are variable, and may be as high as 33% for non-infectious complications and 27% for infectious complications.

Investigation of Feshbach resonances in ultracold K spin mixtures.

Magnetically tunable Feshbach resonances are an indispensable tool for experiments with atomic quantum gases. We report on 37 thus far unpublished Feshbach resonances and four further probable Feshbach resonances in spin mixtures of ultracold fermionic K with temperatures well below 100 nK. In particular, we locate a broad resonance at = 389.

ADME studies of [5-(3)H]-2'-O-methyluridine nucleoside in mice: a building block in siRNA therapeutics.

The chemical modification 2'-O-methyl of nucleosides is often used to increase siRNA stability towards nuclease activities. However, the metabolic fate of modified nucleosides remains unclear. Therefore, the aim of this study was to determine the mass balance, pharmacokinetic, and absorption, distribution, metabolism, and excretion (ADME)-properties of tritium-labeled 2'-O-methyluridine, following a single intravenous dose to male CD-1 mice.

MS565: A SPECT Tracer for Evaluating the Brain Penetration of BAF312 (Siponimod).

BAF312 (siponimod) is a sphingosine-1-phosphate (S1P) receptor modulator in clinical development for the treatment of multiple sclerosis, with faster organ/tissue distribution and elimination kinetics than its precursor FTY720 (fingolimod). Our aim was to develop a tracer to better quantify the penetration of BAF312 in the human brain, with the potential to be labeled for positron emission tomography (PET) or single-photon emission computed tomography (SPECT). Although the PET radioisotopes (11)C and (18)F could have been introduced in BAF312 without modifying its structure, they do not have decay kinetics compatible with the time required for observing the drug's organ distribution in patients.

Phenotypic and metabolic investigation of a CSF-1R kinase receptor inhibitor (BLZ945) and its pharmacologically active metabolite.

1. 4-[2((1R,2R)-2-Hydroxycyclohexylamino)-benzothiazol-6-yloxyl]-pyridine-2-carboxylic acid methylamide (BLZ945) is a small molecule inhibitor of CSF-1R kinase activity within osteoclasts designed to prevent skeletal related events in metastatic disease. Key metabolites were enzymatically and structurally characterized to understand the metabolic fate of BLZ945 and pharmacological implications.

Application of a deuterium replacement strategy to modulate the pharmacokinetics of 7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-3-(4-methoxy-2-methylphenyl)-2,6-dimethylpyrazolo[5,1-b]oxazole, a novel CRF1 antagonist.

Deuterium isotope effects were evaluated as a strategy to optimize the pharmacokinetics of 7-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-3-(4-methoxy-2-methylphenyl)-2,6-dimethylpyrazolo[5,1-b]oxazole (NVS-CRF38), a novel corticotropin-releasing factor receptor 1 (CRF1) antagonist. In an attempt to suppress O-demethylation of NVS-CRF38 without losing activity against the CRF1 receptor, the protons at the site of metabolism were replaced with deuterium. For in vitro and in vivo studies, intrinsic primary isotope effects (KH/KD) were determined by the ratio of intrinsic clearance (CLint) obtained for NVS-CRF38 and deuterated NVS-CRF38.

Giant spin oscillations in an ultracold Fermi sea.

Collective behavior in many-body systems is the origin of many fascinating phenomena in nature, ranging from the formation of clouds to magnetic properties of solids. We report on the observation of collective spin dynamics in an ultracold Fermi sea with large spin. As a key result, we observed long-lived and large-amplitude coherent spin oscillations driven by local spin interactions.

Biodistribution and metabolism studies of lipid nanoparticle-formulated internally [3H]-labeled siRNA in mice.

Absorption, distribution, metabolism, and excretion properties of a small interfering RNA (siRNA) formulated in a lipid nanoparticle (LNP) vehicle were determined in male CD-1 mice following a single intravenous administration of LNP-formulated [(3)H]-SSB siRNA, at a target dose of 2.5 mg/kg. Tissue distribution of the [(3)H]-SSB siRNA was determined using quantitative whole-body autoradiography, and the biostability was determined by both liquid chromatography mass spectrometry (LC-MS) with radiodetection and reverse-transcriptase polymerase chain reaction techniques.

A perspective on tritium versus carbon-14: ensuring optimal label selection in pharmaceutical research and development.

Tritium ((3) H) and carbon-14 ((14) C) labels applied in pharmaceutical research and development each offer their own distinctive advantages and disadvantages coupled with benefits and risks. The advantages of (3) H have a higher specific activity, shorter half-life that allows more manageable waste remediation, lower material costs, and often more direct synthetic routes. The advantages of (14) C offer certain analytical benefits and less potential for label loss.

Engineering spin waves in a high-spin ultracold Fermi gas.

We report on the detailed study of multicomponent spin waves in an s=3/2 Fermi gas where the high spin leads to novel tensorial degrees of freedom compared to s=1/2 systems. The excitations of a spin-nematic state are investigated from the linear to the nonlinear regime, where the tensorial character is particularly pronounced. By tuning the initial state we engineer the tensorial spin-wave character, such that the magnitude and the sign of the counterflow spin currents are effectively controlled.

Metabolism and disposition of the metabotropic glutamate receptor 5 antagonist (mGluR5) mavoglurant (AFQ056) in healthy subjects.

The disposition and biotransformation of (14)C-radiolabeled mavoglurant were investigated in four healthy male subjects after a single oral dose of 200 mg. Blood, plasma, urine, and feces collected over 7 days were analyzed for total radioactivity, mavoglurant was quantified in plasma by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), and metabolite profiles were generated in plasma and excreta by high-performance liquid chromatography (HPLC) and radioactivity detection. The chemical structures of mavoglurant metabolites were characterized by LC-MS/MS, wet-chemical and enzymatic methods, NMR spectroscopy, and comparison with reference compounds.

Metabolism studies of unformulated internally [3H]-labeled short interfering RNAs in mice.

Absorption, distribution, metabolism, and excretion properties of two unformulated model short interfering RNA (siRNAs) were determined using a single internal [(3)H]-radiolabeling procedure, in which the full-length oligonucleotides were radiolabeled by Br/(3)H -exchange. Tissue distribution, excretion, and mass balance of radioactivity were investigated in male CD-1 mice after a single intravenous administration of the [(3)H]siRNAs, at a target dose level of 5 mg/kg. Quantitative whole-body autoradiography and liquid scintillation counting techniques were used to determine tissue distribution.

Intrinsic photoconductivity of ultracold fermions in optical lattices.

We report on the experimental observation of an analog to a persistent alternating photocurrent in an ultracold gas of fermionic atoms in an optical lattice. The dynamics is induced and sustained by an external harmonic confinement. While particles in the excited band exhibit long-lived oscillations with a momentum-dependent frequency, a strikingly different behavior is observed for holes in the lowest band.

A unique automation platform for measuring low level radioactivity in metabolite identification studies.

Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process.

Multiband spectroscopy of ultracold fermions: observation of reduced tunneling in attractive Bose-Fermi mixtures.

We perform a detailed experimental study of the band excitations and tunneling properties of ultracold fermions in optical lattices. Employing a novel multiband spectroscopy for fermionic atoms, we can measure the full band structure and tunneling energy with high accuracy. In an attractive Bose-Fermi mixture we observe a significant reduction of the fermionic tunneling energy, which depends on the relative atom numbers.

Evaluation of an anorganic bovine-derived mineral with P-15 hydrogel bone graft: preliminary study in a rabbit cranial bone model.

Objectives: The present investigation aimed to assess the bone-regenerative potential of two formulations of anorganic bovine-derived mineral bound to a P-15 (ABM/P-15) bone graft - the particulate and the hydrogel forms - in a delayed healing rabbit cranial defect model.

Material And Methods: Ten adult male New Zealand White rabbits were used to create two 8 mm transcortical cranial defects per rabbit and each one received randomly the test material (ABM/P-15 carboxymethyl cellulose (CMC)-hydrogel graft), the standard control material (ABM/P-15 particulate graft) or remained empty as a negative control. The defects were allowed to heal for 2 and 4 weeks.

Metal complexes of modified cyclen as catalysts for hydrolytic restriction of plasmid DNA.

Simple and novel nuclease models have been synthesized. These involve metal-binding ligand 1,4,7,10-tetraazlcyclododecane (cyclen) tethered to an acridine ring (a DNA-binding group) by amide linkers of various lengths. Binding of these probes to DNA was studied by monitoring changes in their UV-visible spectra affected by the presence of DNA.

Clinical evaluation alveolar ridge preservation with a beta-tricalcium phosphate socket graft.

Purpose: To determine the efficacy of an alloplastic graft material, consisting of a pure-phase beta-tricalcium phosphate (beta-TCP), in the preservation of ridge volume after tooth extraction and before dental implant placement. Histomorphometric analysis was completed on a few samples to determine the percentage of vital bone over a fixed healing period.

Materials And Methods: Patients requiring tooth extraction and bone regeneration before implant placement were included in this study.

Efficacy of high-dose chemotherapy or standard salvage therapy in patients with recurrent medulloblastoma.

The efficacy of high-dose chemotherapy (HDC) or standard salvage therapy was evaluated in patients with recurrent medulloblastoma (MBL) using retrospective chart review of all patients with recurrent MBL treated at Duke University Medical Center between 1995 and 2005 and who had undergone HDC with or without radiotherapy (RT) or standard salvage therapy after relapse. A total of 30 patients were diagnosed with recurrent MBL after standard RT alone or chemotherapy with RT. Nineteen patients (7 who received no RT before recurrence [group A] and 12 who received definitive RT before recurrence [group B]) underwent surgery and/or induction chemotherapy followed by HDC plus autologous stem-cell rescue.

Clinical evaluation of the combination of anorganic bovine-derived hydroxyapatite matrix/cell-binding peptide (P-15) in particulate and hydrogel form as a bone replacement graft material in human periodontal osseous defects: 6-month reentry controlled clinical study.

Background: This prospective, randomized, controlled clinical trial study compared the clinical outcomes of the biomaterial anorganic bovine-derived hydroxyapatite matrix/cell-binding peptide (ABM/P-15) as a biocompatible hydrogel carrier consisting of carboxymethylcellulose and glycerol or in particulate form when used as a bone replacement graft in the treatment of human periodontal infrabony defects.

Methods: Nineteen patients with advanced chronic periodontitis were recruited. All patients had at least two non-adjacent intrabony osseous defects > or = 3 mm after completion of cause-related periodontal therapy.