NMR coupled with multivariate data analysis for monitoring the degradation of a formulated therapeutic monoclonal antibody.

The function of a protein is directly coupled to its higher-order structure (HOS). Deviations in this critical quality attribute (CQA) may be linked to a decrease in the efficacy and/or safety of the final therapeutic product. High-resolution nuclear magnetic resonance (NMR) spectroscopy has been recently highlighted for protein HOS characterization, thanks to its ability to capture small changes at the molecular and structural levels (primary, secondary, tertiary and quaternary structures).

Pediatric Sleep Respiratory Disorders: A Narrative Review of Epidemiology and Risk Factors.

Sleep is a fundamental biological necessity, the lack of which has severe repercussions on the mental and physical well-being in individuals of all ages. The phrase "sleep-disordered breathing (SDB)" indicates a wide array of conditions characterized by snoring and/or respiratory distress due to increased upper airway resistance and pharyngeal collapsibility; these range from primary snoring to obstructive sleep apnea (OSA) and occur in all age groups. In the general pediatric population, the prevalence of OSA varies between 2% and 5%, but in some particular clinical conditions, it can be much higher.

Detection of Trypanosoma cruzi DTUs TcI and TcIV in two outbreaks of orally-transmitted Chagas disease in the Northern region of Brazil.

This study describes the laboratory investigation of two acute Chagas disease outbreaks that occurred in the riverside communities of Marimarituba and Cachoeira do Arua, in the Santarem municipality, Para State, located in the Northern region of Brazil, and occurred in March 2016 and August 2017, respectively. The generation of data regarding the diversity of Trypanosoma cruzi parasites circulating in the Amazon region is key for understanding the emergence and expansion of Chagas disease. This study aimed to identify T.

Using electrical impedance tomography to characterize lung impairment of children with primary ciliary dyskinesia: A pilot cross-sectional study.

Background: In children with primary ciliary dyskinesia (PCD), measures more sensitive than spirometry are needed to characterize underlying pulmonary impairment. Electrical impedance tomography (EIT) is a promising noninvasive method for monitoring the distribution of lung ventilation, and it does not require patient collaboration. We aimed to provide an assessment of the feasibility and clinical usefulness of EIT in characterizing lung impairment in children with PCD, compared to spirometry and multiple breath nitrogen washout (MBWN ) test.

Analysis of Metabolic Pathways by C-Labeled Molecular Probes and HRMAS Nuclear Magnetic Resonance Spectroscopy: Isotopologue Identification and Quantification Methods for Medical Applications.

The use of C-labeled molecular probes is essential to explore altered metabolic pathways in human pathologies. The analysis of the different C isotopologues resulting from these changes in metabolic pathways is essential to understand the different biological processes involved. We propose an NMR methodology consisting of eight different NMR experiments performed under HRMAS conditions to explore metabolic pathways in unprocessed pathological cells and tissues.

Targeted metabolomics analyses for brain tumor margin assessment during surgery.

Motivation: Identification and removal of micro-scale residual tumor tissue during brain tumor surgery are key for survival in glioma patients. For this goal, High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) spectroscopy-based assessment of tumor margins during surgery has been an effective method. However, the time required for metabolite quantification and the need for human experts such as a pathologist to be present during surgery are major bottlenecks of this technique.

L-alanine supplementation in Pompe disease (IOPD): a potential therapeutic implementation for patients on ERT? A case report.

Background: Pompe disease (PD) is a disorder of glycogen metabolism conditioning a progressive and life conditioning myopathy. Enzyme replacement therapy (ERT) is currently the best treatment option for PD, but is not resolutive. While other potential therapeutic approaches have been reported before, these have never been tried as co- treatments.

Therapeutic Strategies for COVID-19 Lung Disease in Children.

The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection has milder presentation in children than in adults, mostly requiring only supportive therapy. The immunopathogenic course of COVID-19 can be divided in two distinct but overlapping phases: the first triggered by the virus itself and the second one by the host immune response (cytokine storm). Respiratory failure or systemic involvement as Multisystem Inflammatory Syndrome in Children (MIS-C) requiring intensive care are described only in a small portion of infected children.

Design of a Capacitance-to-Digital Converter Based on Iterative Delay-Chain Discharge in 180 nm CMOS Technology.

The design of advanced miniaturized ultra-low power interfaces for sensors is extremely important for energy-constrained monitoring applications, such as wearable, ingestible and implantable devices used in the health and medical field. Capacitive sensors, together with their correspondent digital-output readout interfaces, make no exception. Here, we analyse and design a capacitance-to-digital converter, based on the recently introduced iterative delay-chain discharge architecture, showing the circuit inner operating principles and the correspondent design trade-offs.

Suspected vertical transmission of Chagas disease caused by DTU TcIV in an infection probably transmitted orally, during anoutbreak in the Brazilian Amazon.

This study describes difficulties in the monitoring of a child born during an oral outbreak of Chagas disease, in which there are several indications that the transmission occurred through the congenital route: 1. the mother was in the third trimester of pregnancy when she was infected; 2. She presented high parasitemia at the time of delivery; 3.

Machine learning assisted intraoperative assessment of brain tumor margins using HRMAS NMR spectroscopy.

Complete resection of the tumor is important for survival in glioma patients. Even if the gross total resection was achieved, left-over micro-scale tissue in the excision cavity risks recurrence. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HRMAS NMR) technique can distinguish healthy and malign tissue efficiently using peak intensities of biomarker metabolites.

Assessment of Preoperative Endometrial Histopathological Sampling as a Predictor of Final Surgical Pathology in Endometrial Cancer.

Objective:  To evaluate the agreement between the histopathological diagnoses of preoperative endometrial samples and surgical specimens and correlate the agreement between the diagnoses with the impact on surgical management and the survival of patients with endometrial adenocarcinomas.

Methods:  Sixty-two patients treated for endometrial cancer at a university hospital from 2002 to 2011 were retrospectively evaluated. The histopathological findings of preoperative endometrial samples and of surgical specimens were analyzed.

Improved Spatial Resolution of Metabolites in Tissue Biopsies Using High-Resolution Magic-Angle-Spinning Slice Localization NMR Spectroscopy.

High-resolution magic-angle-spinning H NMR spectroscopy (HR-MAS NMR) is a well-established technique for assessing the biochemical composition of intact tissue samples. In this study, we utilized a method based on HR-MAS NMR spectroscopy with slice localization (SLS) to achieve spatial resolution of metabolites. The obtained 7 slice spectra from each of the model samples (i.

Experimental Evaluation of a 3D-Printed Fluidic System for a Directional Anemometer.

An evolution of a previously proposed anemometer capable of detecting both the magnitude and the direction of the wind on a plane is proposed. The device is based on a recently formalized principle, consisting of combining the differential pressures measured across distinct diameters of a cylinder to estimate the wind velocity and incidence angle. Differently from previous sensors based on the same principle, the proposed anemometers use 3D printing to fabricate the channel structure that calculates the pressure combination in the fluidic domain.

An integrated genomic and metabolomic approach for defining survival time in adult oligodendrogliomas patients.

Introduction: The identification of frequent acquired mutations shows that patients with oligodendrogliomas have divergent biology with differing prognoses regardless of histological classification. A better understanding of molecular features as well as their metabolic pathways is essential.

Objectives: The aim of this study was to examine the relationship between the tumor metabolome, six genomic aberrations (isocitrate dehydrogenase1 [IDH1] mutation, 1p/19q codeletion, tumor protein p53 [TP53] mutation, O-methylguanin-DNA methyltransferase [MGMT] promoter methylation, epidermal growth factor receptor [EGFR] amplification, phosphate and tensin homolog [PTEN] methylation), and the patients' survival time.

A metabolic database for biomedical studies of biopsy specimens by high-resolution magic angle spinning nuclear MR: a qualitative and quantitative tool.

Purpose: The aim of this study is to generate a metabolic database for biomedical studies of biopsy specimens by high-resolution magic angle spinning (HRMAS) nuclear MR (NMR).

Methods: Seventy-six metabolites, classically found in human biopsy samples, were prepared in aqueous solution at a known concentration and analyzed by HRMAS NMR. The spectra were recorded under the same conditions as the ones used for the analysis of biopsy specimens routinely performed in our hospital.

Precise Measurement of Gas Volumes by Means of Low-Offset MEMS Flow Sensors with μL/min Resolution.

Experiments devoted to evaluate the performance of a MEMS thermal flow sensor in measuring gas volumes are described. The sensor is a single-chip platform, including several sensing structures and a low-offset, low-noise readout interface. A recently proposed offset compensation approach is implemented obtaining low temperature drift and excellent long time stability.

F NMR transverse and longitudinal relaxation filter experiments for screening: a theoretical and experimental analysis.

Ligand-based F NMR screening represents an efficient approach for performing binding assays. The high sensitivity of the methodology to receptor binding allows the detection of weak affinity ligands. The observable NMR parameters that are typically used are the F transverse relaxation rate and isotropic chemical shift.

Ultrafast high-resolution magic-angle-spinning NMR spectroscopy.

We demonstrate the acquisition of ultrafast 2D NMR spectra of semi-solid samples, with a high-resolution magic-angle-spinning setup. Using a recent double-quantum NMR pulse sequence in optimised synchronisation conditions, high-quality 2D spectra can be recorded for a sample under magic-angle spinning. An illustration is given with a semi-solid sample of banana pulp.

Complete protocol for slow-spinning high-resolution magic-angle spinning NMR analysis of fragile tissues.

High-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) is an essential tool to characterize a variety of semisolid systems, including biological tissues, with virtually no sample preparation. The "non-destructive" nature of NMR is typically compromised, however, by the extreme centrifugal forces experienced under conventional HR-MAS frequencies of several kilohertz. These features limit the usefulness of current HR-MAS approaches for fragile samples.

Ha-ras and β-catenin oncoproteins orchestrate metabolic programs in mouse liver tumors.

The process of hepatocarcinogenesis in the diethylnitrosamine (DEN) initiation/phenobarbital (PB) promotion mouse model involves the selective clonal outgrowth of cells harboring oncogene mutations in Ctnnb1, while spontaneous or DEN-only-induced tumors are often Ha-ras- or B-raf-mutated. The molecular mechanisms and pathways underlying these different tumor sub-types are not well characterized. Their identification may help identify markers for xenobiotic promoted versus spontaneously occurring liver tumors.

Slow-spinning low-sideband HR-MAS NMR spectroscopy: delicate analysis of biological samples.

High-Resolution Magic-Angle Spinning (HR-MAS) NMR spectroscopy has become an extremely versatile analytical tool to study heterogeneous systems endowed with liquid-like dynamics. Spinning frequencies of several kHz are however required to obtain NMR spectra, devoid of spinning sidebands, with a resolution approaching that of purely isotropic liquid samples. An important limitation of the method is the large centrifugal forces that can damage the structure of the sample.

Applications of NMR screening techniques to the pharmaceutical target Checkpoint kinase 1.

Ligand screening techniques based on NMR spectroscopy are not as sensitive as other commonly used methods like fluorescence, radiolabeling and surface plasmon resonance. However, using modern NMR instrumentation, they can achieve reliable screening under near physiological condition using as little as 4.6 nmol of receptor and 100 nmol of ligand.

Serum analysis by 1H nuclear magnetic resonance spectroscopy: a new tool for distinguishing neuromyelitis optica from multiple sclerosis.

Background: Neuromyelitis optica (NMO) and multiple sclerosis (MS), two inflammatory demyelinating diseases, are characterized by different therapeutic strategies. Currently, the only biological diagnostic tool available to distinguish NMO from MS is the specific serum autoantibody that targets aquaporin 4, but its sensitivity is low.

Objective: To assess the diagnostic accuracy of metabolomic biomarker profiles in these two neurological conditions, compared to control patients.

Metabolomic profile of the adrenal gland: from physiology to pathological conditions.

In this study, we i) assessed the metabolic profile of the normal adrenal cortex and medulla of adult human subjects by means of (1)H-high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy; ii) compared the biochemical profile of adenoma (Ad), adrenal cortical carcinoma (ACC), and pheochromocytoma (PCC) samples with that of healthy adrenal tissue samples; and iii) investigated the metabolic differences between ACCs and Ads as well as between ACCs and PCCs. Sixty-six tissue samples (13 adrenal cortical tissue, eight medullary tissue, 13 Ad, 12 ACC, and 20 PCC samples) were analyzed. Adrenaline and noradrenaline were undetectable in cortical samples representing the metabolic signature of the tissue derived from neural crest.