High-resolution magnetic resonance spectroscopy using a solid-state spin sensor.

Quantum systems that consist of solid-state electronic spins can be sensitive detectors of nuclear magnetic resonance (NMR) signals, particularly from very small samples. For example, nitrogen-vacancy centres in diamond have been used to record NMR signals from nanometre-scale samples, with sensitivity sufficient to detect the magnetic field produced by a single protein. However, the best reported spectral resolution for NMR of molecules using nitrogen-vacancy centres is about 100 hertz. This is insufficient to resolve the key spectral identifiers of molecular structure that are critical to NMR applications in chemistry, structural biology and materials research, such as scalar couplings (which require a resolution of less than ten hertz) and small chemical shifts (which require a resolution of around one part per million of the nuclear Larmor frequency). Conventional, inductively detected NMR can provide the necessary high spectral resolution, but its limited sensitivity typically requires millimetre-scale samples, precluding applications that involve smaller samples, such as picolitre-volume chemical analysis or correlated optical and NMR microscopy. Here we demonstrate a measurement technique that uses a solid-state spin sensor (a magnetometer) consisting of an ensemble of nitrogen-vacancy centres in combination with a narrowband synchronized readout protocol to obtain NMR spectral resolution of about one hertz. We use this technique to observe NMR scalar couplings in a micrometre-scale sample volume of approximately ten picolitres. We also use the ensemble of nitrogen-vacancy centres to apply NMR to thermally polarized nuclear spins and resolve chemical-shift spectra from small molecules. Our technique enables analytical NMR spectroscopy at the scale of single cells.

Quantum Logic Enhanced Sensing in Solid-State Spin Ensembles.

We demonstrate quantum logic enhanced sensitivity for a macroscopic ensemble of solid-state, hybrid two-qubit sensors. We achieve over a factor of 30 improvement in the single-shot signal-to-noise ratio, translating to an ac magnetic field sensitivity enhancement exceeding an order of magnitude for time-averaged measurements. Using the electronic spins of nitrogen vacancy (NV) centers in diamond as sensors, we leverage the on-site nitrogen nuclear spins of the NV centers as memory qubits, in combination with homogeneous and stable bias and control fields, ensuring that all of the ∼10^{9} two-qubit sensors are sufficiently identical to permit global control of the NV ensemble spin states. We find quantum logic sensitivity enhancement for multiple measurement protocols with varying optimal sensing intervals, including XY8 and DROID-60 dynamical decoupling, as well as correlation spectroscopy, using an applied ac magnetic field signal. The results are independent of the nature of the target signal and broadly applicable to measurements using NV centers and other solid-state spin ensembles. This work provides a benchmark for macroscopic ensembles of quantum sensors that employ quantum logic or quantum error correction algorithms for enhanced sensitivity.

Effect of mitochondrial-targeted antioxidants on glycaemic control, cardiovascular health, and oxidative stress in humans: A systematic review and meta-analysis of randomized controlled trials.

AIM: To investigate the effects of mitochondrial-targeted antioxidants (mitoAOXs) on glycaemic control, cardiovascular health, and oxidative stress outcomes in humans. MATERIALS AND METHODS: Randomized controlled trials investigating mitoAOX interventions in humans were searched for in databases (MEDLINE-PubMed, Scopus, EMBASE and Cochrane Library) and clinical trial registries up to 10 June 2021. The Cochrane Collaboration's tool for assessing risk of bias and Grading of Recommendations, Assessment, Development and Evaluations were used to assess trial quality and evidence certainty, respectively. RESULTS: Nineteen studies (n = 884 participants) using mitoAOXs (including Elamipretide, MitoQ and MitoTEMPO) were included in the systematic review. There were limited studies investigating the effects of mitoAOXs on glycaemic control; and outcomes and population groups in studies focusing on cardiovascular health were diverse. MitoAOXs significantly improved brachial flow-mediated dilation (n = 3 trials; standardized mean difference: 1.19, 95% CI: 0.28, 2.16; I2 : 67%) with very low evidence certainty. No significant effects were found for any other glycaemic, cardiovascular or oxidative stress-related outcomes with mitoAOXs in quantitative analyses, with evidence certainty rated mostly as low. There was a lack of serious treatment-emergent adverse events with mitoAOXs, although subcutaneous injection of Elamipretide increased mild-moderate injection site-related events. CONCLUSION: While short-term studies indicate that mitoAOXs are generally well tolerated, there is currently limited evidence to support the use of mitoAOXs in the management of glycaemic control and cardiovascular health. Review findings suggest that future research should focus on the effects of mitoAOXs on glycaemic control and endothelial function in target clinical population groups.

Optical magnetic detection of single-neuron action potentials using quantum defects in diamond.

Magnetic fields from neuronal action potentials (APs) pass largely unperturbed through biological tissue, allowing magnetic measurements of AP dynamics to be performed extracellularly or even outside intact organisms. To date, however, magnetic techniques for sensing neuronal activity have either operated at the macroscale with coarse spatial and/or temporal resolution-e.g., magnetic resonance imaging methods and magnetoencephalography-or been restricted to biophysics studies of excised neurons probed with cryogenic or bulky detectors that do not provide single-neuron spatial resolution and are not scalable to functional networks or intact organisms. Here, we show that AP magnetic sensing can be realized with both single-neuron sensitivity and intact organism applicability using optically probed nitrogen-vacancy (NV) quantum defects in diamond, operated under ambient conditions and with the NV diamond sensor in close proximity (∼10 µm) to the biological sample. We demonstrate this method for excised single neurons from marine worm and squid, and then exterior to intact, optically opaque marine worms for extended periods and with no observed adverse effect on the animal. NV diamond magnetometry is noninvasive and label-free and does not cause photodamage. The method provides precise measurement of AP waveforms from individual neurons, as well as magnetic field correlates of the AP conduction velocity, and directly determines the AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector.

A genetic strategy for probing the functional diversity of magnetosome formation.

Model genetic systems are invaluable, but limit us to understanding only a few organisms in detail, missing the variations in biological processes that are performed by related organisms. One such diverse process is the formation of magnetosome organelles by magnetotactic bacteria. Studies of model magnetotactic α-proteobacteria have demonstrated that magnetosomes are cubo-octahedral magnetite crystals that are synthesized within pre-existing membrane compartments derived from the inner membrane and orchestrated by a specific set of genes encoded within a genomic island. However, this model cannot explain all magnetosome formation, which is phenotypically and genetically diverse. For example, Desulfovibrio magneticus RS-1, a δ-proteobacterium for which we lack genetic tools, produces tooth-shaped magnetite crystals that may or may not be encased by a membrane with a magnetosome gene island that diverges significantly from those of the α-proteobacteria. To probe the functional diversity of magnetosome formation, we used modern sequencing technology to identify hits in RS-1 mutated with UV or chemical mutagens. We isolated and characterized mutant alleles of 10 magnetosome genes in RS-1, 7 of which are not found in the α-proteobacterial models. These findings have implications for our understanding of magnetosome formation in general and demonstrate the feasibility of applying a modern genetic approach to an organism for which classic genetic tools are not available.

Systems Addressing Frail Elder Care: Description of a Successful Model.

OBJECTIVE: The aim of this article is to describe the Systems Addressing Frail Elder (SAFE) Care model, features of the interprofessional team and reengineered workflow, and details of the intervention. BACKGROUND: Older inpatients are vulnerable to adverse events related to frailty. SAFE Care, an interprofessional team-based program, was developed and evaluated in a cluster randomized controlled trial (C-RCT). Results found reduced length of stay and complications. The purpose of this article is to support and encourage the replication of this innovation or to help facilitate implementation of a similar process of organizational change. METHODS: This was a review of model features and intervention data abstracted from electronic health records. RESULTS: Salient features of team composition, training, and workflow are presented. The C-RCT intention-to-treat sample included 792 patients, of whom 307 received the SAFE Care huddle intervention. The most frequent problem was mobility (85.7%), and most frequent recommendation was fall precautions protocol (83.1%). CONCLUSIONS: The SAFE Care model may provide a standardized framework to approach, assess, and address the risks of hospitalized older adults.

Efficiency of Cathodoluminescence Emission by Nitrogen-Vacancy Color Centers in Nanodiamonds.

Correlated electron microscopy and cathodoluminescence (CL) imaging using functionalized nanoparticles is a promising nanoscale probe of biological structure and function. Nanodiamonds (NDs) that contain CL-emitting color centers are particularly well suited for such applications. The intensity of CL emission from NDs is determined by a combination of factors, including particle size, density of color centers, efficiency of energy deposition by electrons passing through the particle, and conversion efficiency from deposited energy to CL emission. This paper reports experiments and numerical simulations that investigate the relative importance of each of these factors in determining CL emission intensity from NDs containing nitrogen-vacancy (NV) color centers. In particular, it is found that CL can be detected from NV-doped NDs with dimensions as small as ≈40 nm, although CL emission decreases significantly for smaller NDs.

Identification and team-based interprofessional management of hospitalized vulnerable older adults.

BACKGROUND: Extended hospital stays and complications are common among older adults and may lead to morbidity and loss of independence. Specialized geriatric units have been shown to improve outcomes but, with the growing numbers of older adults, may be difficult to scale to meet needs. PURPOSE: The purpose was to evaluate a quality improvement initiative that redesigned unit-based workflow and trained interprofessional teams on general medical/surgical units to create care plans for vulnerable older adults using principles of comprehensive geriatric assessment and team management. METHOD: The evaluation included a cluster randomized controlled trial of 10 medical/surgical units and intention-to-treat analysis of all patients meeting risk screening criteria. RESULTS: N = 1,384, median age = 80.9 years, and 53.5% female. Mean difference in observed vs. expected length of stay was 1.03 days shorter (p = .006); incidence of complications (odds ratio [OR] = 0.45; 95% confidence interval [CI] = 0.21-0.98) and transfer to intensive care (OR = 0.45; 95% CI = 0.25-0.79) lower among patients admitted to intervention units; incidence of discharge to institutional care was higher (OR = 1.43; 95% CI = 1.06-1.93). Mortality during hospitalization (OR = 0.64; 95% CI = 0.37-1.11) did not differ between groups. CONCLUSION: Reorganizing general medical/surgical units to provide team-based interprofessional care can improve outcomes among hospitalized older adults.

Large scale pedigree analysis leads to evidence for founder effects of Hypertrophic Cardiomyopathy in Rhesus Macaques (Macaca mulatta).

Hypertrophic Cardiomyopathy (HCM) is the abnormal thickening of the ventricles and an increase in cardiac mass. Analyses of 108 rhesus macaque probands with pronounced HCM revealed a strong genetic predisposition to this disease. Macaques are ideal for investigating HCM because of their marked similarity to humans genetically, physiologically and anatomically.

Rapid Quantum Magnetic IL-6 Point-of-Care Assay in Patients Hospitalized with COVID-19.

Interleukin-6 (IL-6) has been linked to several life-threatening disease processes. Developing a point-of-care testing platform for the immediate and accurate detection of IL-6 concentrations could present a valuable tool for improving clinical management in patients with IL-6-mediated diseases. Drawing on an available biobank of samples from 35 patients hospitalized with COVID-19, a novel quantum-magnetic sensing platform is used to determine plasma IL-6 concentrations. A strong correlation was observed between IL-6 levels measured by QDTI10x and the Luminex assay (r = 0.70, p-value < 0.001) and between QDTI80x and Luminex (r = 0.82, p-value < 0.001). To validate the non-inferiority of QDTI to Luminex in terms of the accuracy of IL-6 measurement, two clinical parameters­the need for intensive care unit admission and the need for mechanical intubation­were chosen. IL-6 concentrations measured by the two assays were compared with respect to these clinical outcomes. Results demonstrated a comparative predictive performance between the two assays with a significant correlation coefficient. Conclusion: In short, the QDTI assay holds promise for implementation as a potential tool for rapid clinical decision in patients with IL-6-mediated diseases. It could also reduce healthcare costs and enable the development of future various biomolecule point-of-care tests for different clinical scenarios.

Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy.

The vagus nerve stimulation (VNS) Therapy® System is the first FDA-approved medical device therapy for the treatment of drug-resistant epilepsy. Over the past two decades, the technology has evolved through multiple iterations resulting in software-related updates and implantable lead and generator hardware improvements. Healthcare providers today commonly encounter a range of single- and dual-pin generators (models 100, 101, 102, 102R, 103, 104, 105, 106, 1000) and related programming systems (models 250, 3000), all of which have their own subtle, but practical differences. It can therefore be a daunting task to go through the manuals of these implant models for comparison, some of which are not readily available. In this review, we highlight the technological evolution of the VNS Therapy System with respect to device approval milestones and provide a comparison of conventional open-loop vs. the latest closed-loop generator models. Battery longevity projections and an in-depth examination of stimulation mode interactions are also presented to further differentiate amongst generator models.

Behavioral Risk Factors: A Guide for Oncology Nurses Counseling Patients.

BACKGROUND: Although many genetic and environmental causes of cancer are uncontrollable, individuals can choose behaviors that significantly increase or reduce their risk for cancer. OBJECTIVES: This article discusses known cancer-protective behaviors, including exercising regularly, maintaining a healthy weight, vaccinating against cancer-associated viruses, and minimizing exposure to tobacco products, alcohol, processed meats, and ultraviolet light. METHODS: The author performed a review of guidelines and techniques for counseling patients about risky behaviors, with an emphasis on patients with cancer. FINDINGS: Much remains to be learned about the most effective clinical interventions for encouraging patients to adopt healthy behaviors, but oncology nurses should become familiar with the fundamental principles of counseling patients about health-promoting behaviors.

Quantum diamond spectrometer for nanoscale NMR and ESR spectroscopy.

Nitrogen-vacancy (NV) quantum defects in diamond are sensitive detectors of magnetic fields. Owing to their atomic size and optical readout capability, they have been used for magnetic resonance spectroscopy of nanoscale samples on diamond surfaces. Here, we present a protocol for fabricating NV diamond chips and for constructing and operating a simple, low-cost 'quantum diamond spectrometer' for performing NMR and electron spin resonance (ESR) spectroscopy in nanoscale volumes. The instrument is based on a commercially available diamond chip, into which an NV ensemble is ion-implanted at a depth of ~10 nm below the diamond surface. The spectrometer operates at low magnetic fields (~300 G) and requires standard optical and microwave (MW) components for NV spin preparation, manipulation, and readout. We demonstrate the utility of this device for nanoscale proton and fluorine NMR spectroscopy, as well as for the detection of transition metals via relaxometry. We estimate that the full protocol requires 2-3 months to implement, depending on the availability of equipment, diamond substrates, and user experience.

Mapping the microscale origins of magnetic resonance image contrast with subcellular diamond magnetometry.

Magnetic resonance imaging (MRI) is a widely used biomedical imaging modality that derives much of its contrast from microscale magnetic field patterns in tissues. However, the connection between these patterns and the appearance of macroscale MR images has not been the subject of direct experimental study due to a lack of methods to map microscopic fields in biological samples. Here, we optically probe magnetic fields in mammalian cells and tissues with submicron resolution and nanotesla sensitivity using nitrogen-vacancy diamond magnetometry, and combine these measurements with simulations of nuclear spin precession to predict the corresponding MRI contrast. We demonstrate the utility of this technology in an in vitro model of macrophage iron uptake and histological samples from a mouse model of hepatic iron overload. In addition, we follow magnetic particle endocytosis in live cells. This approach bridges a fundamental gap between an MRI voxel and its microscopic constituents.

Nanodiamond-enhanced MRI via in situ hyperpolarization.

Nanodiamonds are of interest as nontoxic substrates for targeted drug delivery and as highly biostable fluorescent markers for cellular tracking. Beyond optical techniques, however, options for noninvasive imaging of nanodiamonds in vivo are severely limited. Here, we demonstrate that the Overhauser effect, a proton-electron polarization transfer technique, can enable high-contrast magnetic resonance imaging (MRI) of nanodiamonds in water at room temperature and ultra-low magnetic field. The technique transfers spin polarization from paramagnetic impurities at nanodiamond surfaces to 1H spins in the surrounding water solution, creating MRI contrast on-demand. We examine the conditions required for maximum enhancement as well as the ultimate sensitivity of the technique. The ability to perform continuous in situ hyperpolarization via the Overhauser mechanism, in combination with the excellent in vivo stability of nanodiamond, raises the possibility of performing noninvasive in vivo tracking of nanodiamond over indefinitely long periods of time.

Big Data and Pharmacovigilance: The Role of Oncology Nurses.

When new anticancer medications are approved, their safety profiles are often not fully understood. Oncology nurses have a responsibility to file reports of adverse drug events with safety registries such as MedWatch. If these registries receive prompt, complete, and accurate data from clinicians, agencies such as the U.S. Food and Drug Administration will have a stronger ability to detect hazards and to issue safety recommendations.
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Preventing Safety Hazards Associated With Do-Not-Resuscitate Orders.

Do-not-resuscitate orders can promote patients' dignity near the end of life, but they also can carry safety hazards associated with miscommunication and inappropriate withdrawal of certain kinds of care. Oncology nurses have a responsibility to identify these potential hazards and to intervene as necessary.
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Learning from disaster: patient safety and the role of oncology nurses.

When the Oncology Nursing Society (ONS) was almost exactly half its present age, in November 1994, a Boston Globe health columnist named Betsy Lehman was admitted to the Dana-Farber Cancer Institute in Boston, Massachusetts, to receive an investigational regimen for breast cancer. Her treatment ended in disaster. In one of the most notorious patient safety failures of modern times, Lehman was given severe overdoses of cyclophosphamide during a four-day period. On each of those four days, nurses, physicians, and pharmacists at Dana-Farber failed to notice that Lehman was receiving doses four times greater than the intended amount (Aspden, Wolcott, Bootman, & Cronenwett, 2007). Lehman died of cyclophosphamide toxicity on December 3, 1994.
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The hidden impact of diabetes on male sexual dysfunction and fertility.

Diabetes affects an increasingly large number of young men of reproductive age. Erectile and ejaculatory difficulties arise due to vascular and neuropathic problems. The treatment of these may have effects on fertility potential. Erectile dysfunction can be treated with mechanical devices and intracavernosal injections. Although these have not been shown to affect fertility directly, they may result in poor compliance and hence reduced frequency of ejaculation with subsequent deterioration in sperm quality. Other medical treatments may have a more direct effect. The phosphodiesterase (PDE) inhibitor pentoxifylline has been shown to affect sperm quality and early embryo development. Therefore, Viagra, also a PDE inhibitor, may affect sperm quality. There is conflicting evidence about this in the literature. Ejaculatory difficulties are also more common in diabetics although treatments such as Trucut testicular biopsy and intracytoplasmic sperm injection have improved the outlook for these patients. There is also some evidence that spermatogenesis is affected by diabetes and that patients have a reduced sperm motility and semen volume. Therefore, diabetes has a significant impact on the fertility of men with this disease both directly and indirectly. The extent of iatrogenic influence on the reduced fertility potential of these patients needs to be researched as a matter of urgency.