Concentric Ring Trajectory Sampling With k-Space Reordering Enables Assessment of Tissue-Specific T and T Relaxation for H-Labeled Substrates in the Human Brain at 7 T.

Deuterium metabolic imaging (DMI) is an emerging Magnetic Resonance technique providing valuable insight into the dynamics of cellular glucose (Glc) metabolism of the human brain in vivo using deuterium-labeled (H) glucose as non-invasive tracer. Reliable concentration estimation of H-Glc and downstream synthesized neurotransmitters glutamate + glutamine (Glx) requires accurate knowledge of relaxation times, but so far tissue-specific T and T relaxation times (e.g.

Insurmountable antagonism of human mu opioid receptors by buprenorphine is due to hemi-equilibrium.

Buprenorphine is an FDA approved drug for the treatment of opioid use disorder and is a long-lasting, low efficacy (partial) agonist of the μ opioid receptor. As a partial agonist, buprenorphine can act as either an agonist or an antagonist depending on the efficiency of the cellular signaling system. Here we investigated the antagonist properties of buprenorphine using a genetically-encoded biosensor to monitor cAMP levels in real time in HEK293 cells expressing a relatively low density of the human μ receptor.

Regulated GATA1 expression as a universal gene therapy for Diamond-Blackfan anemia.

Gene therapy using hematopoietic stem and progenitor cells is altering the therapeutic landscape for patients with hematologic, immunologic, and metabolic disorders but has not yet been successfully developed for individuals with the bone marrow failure syndrome Diamond-Blackfan anemia (DBA). More than 30 mutations cause DBA through impaired ribosome function and lead to inefficient translation of the erythroid master regulator GATA1, providing a potential avenue for therapeutic intervention applicable to all patients with DBA, irrespective of the underlying genotype. Here, we report the development of a clinical-grade lentiviral gene therapy that achieves erythroid lineage-restricted expression of GATA1.

Predictors of future overdose among people who inject drugs in Baltimore, Maryland.

Background: Longitudinal studies of future overdose risk among people who inject drugs (PWID) are needed to inform planning of targeted overdose preventions in the United States.

Methods: The Integrating Services to Improve Treatment and Engagement (INSITE) study followed 720 PWID between June 2018 and August 2019 to evaluate the delivery of mobilized healthcare services in Baltimore, Maryland. The present analyses used logistic regression to identify baseline characteristics predictive of non-fatal or fatal overdose during the 6-month follow-up among 507 participants with overdose information.

Neurochemistry and functional connectivity in the brain of people with Charles Bonnet syndrome.

Background: Charles Bonnet syndrome (CBS) is a condition in which people with vision loss experience complex visual hallucinations. These complex visual hallucinations may be caused by increased excitability in the visual cortex that are present in some people with vision loss but not others.

Objectives: We aimed to evaluate the association between γ-aminobutyric acid (GABA) in the visual cortex and CBS.

Quantifying brain development in the HEALthy Brain and Child Development (HBCD) Study: The magnetic resonance imaging and spectroscopy protocol.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The acquisition of multimodal magnetic resonance-based brain development data is central to the study's core protocol. However, application of Magnetic Resonance Imaging (MRI) methods in this population is complicated by technical challenges and difficulties of imaging in early life.

Identification of antibody targets associated with lower HIV viral load and viremic control.

Background: High HIV viral loads (VL) are associated with increased morbidity, mortality, and on-going transmission. HIV controllers maintain low VLs in the absence of antiretroviral therapy (ART). We previously used a massively multiplexed antibody profiling assay (VirScan) to compare antibody profiles in HIV controllers and persons living with HIV (PWH) who were virally suppressed on ART.

Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution.

Background: High priority efforts are underway to support the development of novel mucosal COVID-19 vaccines, such as the US Government's Project NextGen and the Center for Epidemic Preparedness Innovations' goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration.

Glutamate dynamics and BOLD response during OCD symptom provocation in the lateral occipital cortex: A 7 Tesla fMRI-fMRS study.

Obsessive-compulsive disorder (OCD) is linked with dysfunction in frontal-striatal, fronto-limbic, and visual brain regions. Research using proton magnetic resonance spectroscopy (H-MRS) suggests that altered neurometabolite levels, like glutamate, may contribute to this dysfunction. However, static neurometabolite levels in OCD patients have shown inconsistent results, likely due to previous studies' limited focus on neurometabolite dynamics.

3D ultra-short echo time P-MRSI with rosette k-space pattern: Feasibility and comparison with conventional weighted CSI.

Phosphorus-31 magnetic resonance spectroscopic imaging (P-MRSI) provides valuable non-invasive information on tissue metabolism but is burdened by poor sensitivity and prolonged scan duration. Ultra-short echo time (UTE) acquisitions minimize signal loss when probing signals with relatively short spin-spin relaxation time (T), while also preventing first-order dephasing. Here, a three-dimensional (3D) UTE sequence with a rosette k-space trajectory is applied to P-MRSI at 3T.

Whole-brain deuterium metabolic imaging via concentric ring trajectory readout enables assessment of regional variations in neuronal glucose metabolism.

Deuterium metabolic imaging (DMI) is an emerging magnetic resonance technique, for non-invasive mapping of human brain glucose metabolism following oral or intravenous administration of deuterium-labeled glucose. Regional differences in glucose metabolism can be observed in various brain pathologies, such as Alzheimer's disease, cancer, epilepsy or schizophrenia, but the achievable spatial resolution of conventional phase-encoded DMI methods is limited due to prolonged acquisition times rendering submilliliter isotropic spatial resolution for dynamic whole brain DMI not feasible. The purpose of this study was to implement non-Cartesian spatial-spectral sampling schemes for whole-brain H FID-MR Spectroscopic Imaging to assess time-resolved metabolic maps with sufficient spatial resolution to reliably detect metabolic differences between healthy gray and white matter regions.

A synthetic biology approach for the treatment of pollutants with microalgae.

The increase in global population and industrial development has led to a significant release of organic and inorganic pollutants into water streams, threatening human health and ecosystems. Microalgae, encompassing eukaryotic protists and prokaryotic cyanobacteria, have emerged as a sustainable and cost-effective solution for removing these pollutants and mitigating carbon emissions. Various microalgae species, such as and have demonstrated their ability to eliminate heavy metals, salinity, plastics, and pesticides.

Implementation of a Self-Audit Tool Improves Regulatory Compliance for Point-of-Care Respiratory Virus Testing in the Emergency Department.

Background: Point-of-care testing in the emergency department decreases wait times and supports evidence-based patient care. However, hurdles to successful implementation include management of interdisciplinary work flows and establishment of an effective quality control program. As COVID-19 testing is now integrated into screening protocols in emergency and urgent care settings, hospital systems must maintain flexible and adaptable respiratory virus testing to adapt to regional trends in transmission.

Integrated care van delivery of evidence-based services for people who inject drugs: A cluster-randomized trial.

Background And Aims: People who inject drugs (PWID) are at risk for adverse outcomes across multiple dimensions. While evidence-based interventions are available, services are often fragmented and difficult to access. We measured the effectiveness of an integrated care van (ICV) that offered services for PWID.

Elucidating Local Structure and Positional Effect of Dopants in Colloidal Transition Metal Dichalcogenide Nanosheets for Catalytic Hydrogenolysis.

Tailoring nanoscale catalysts to targeted applications is a vital component in reducing the carbon footprint of industrial processes; however, understanding and controlling the nanostructure influence on catalysts is challenging. Molybdenum disulfide (MoS), a transition metal dichalcogenide (TMD) material, is a popular example of a nonplatinum-group-metal catalyst with tunable nanoscale properties. Doping with transition metal atoms, such as cobalt, is one method of enhancing its catalytic properties.

Effect of feeding frequency on the anaerobic digestion of berry fruit waste.

On-site anaerobic digesters for small agricultural farms typically have feeding schedules that fluctuate according to farm operations. Shocks in feeding, particularly for putrescible waste can disrupt the stable operation of a digester. The effect of intermittent feeding on the anaerobic digestion of rejected raspberries was investigated in four 3L reactors operated in semicontinuous mode for 350 days at 38 °C with a hydraulic retention time of 25 days and an organic loading rate (OLR) of 1gVS/L/d.

Universal dynamic fitting of magnetic resonance spectroscopy.

Purpose: Dynamic (2D) MRS is a collection of techniques where acquisitions of spectra are repeated under varying experimental or physiological conditions. Dynamic MRS comprises a rich set of contrasts, including diffusion-weighted, relaxation-weighted, functional, edited, or hyperpolarized spectroscopy, leading to quantitative insights into multiple physiological or microstructural processes. Conventional approaches to dynamic MRS analysis ignore the shared information between spectra, and instead proceed by independently fitting noisy individual spectra before modeling temporal changes in the parameters.

Analytical Validation of Aptamer-Based Serum Vancomycin Monitoring Relative to Automated Immunoassays.

The practice of monitoring therapeutic drug concentrations in patient biofluids can significantly improve clinical outcomes while simultaneously minimizing adverse side effects. A model example of this practice is vancomycin dosing in intensive care units. If dosed correctly, vancomycin can effectively treat methicillin-resistant streptococcus aureus (MRSA) infections.

Diffusion-weighted MR spectroscopy: Consensus, recommendations, and resources from acquisition to modeling.

Brain cell structure and function reflect neurodevelopment, plasticity, and aging; and changes can help flag pathological processes such as neurodegeneration and neuroinflammation. Accurate and quantitative methods to noninvasively disentangle cellular structural features are needed and are a substantial focus of brain research. Diffusion-weighted MRS (dMRS) gives access to diffusion properties of endogenous intracellular brain metabolites that are preferentially located inside specific brain cell populations.

Comprehensive profiling of pre-infection antibodies identifies HIV targets associated with viremic control and viral load.

Background: High HIV viral load (VL) is associated with increased transmission risk and faster disease progression. HIV controllers achieve viral suppression without antiretroviral (ARV) treatment. We evaluated viremic control in a community-randomized trial with >48,000 participants.

Toward point-of-care diagnostics: Running enzymatic assays on a photonic waveguide-based sensor chip with a portable, benchtop measurement system.

We demonstrate a portable, compact system to perform absorption-based enzymatic assays at a visible wavelength of 639 nm on a photonic waveguide-based sensor chip, suitable for lab-on-a-chip applications. The photonic design and fabrication of the sensor are described, and a detailed overview of the portable measurement system is presented. In this publication, we use an integrated photonic waveguide-based absorbance sensor to run a full enzymatic assay.