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Background: We aimed to investigate whether combined phosphorous ( 31 P) magnetic resonance spectroscopic imaging (MRSI) and quantitative T 2 ' mapping are able to detect alterations of the cerebral oxygen extraction fraction (OEF) and intracellular pH (pH i ) as markers the of cellular energy metabolism in cerebral small vessel disease (SVD)., Materials and Methods: 32 patients with SVD and 17 age-matched healthy control subjects were examined with 3-dimensional  31 P MRSI and oxygenation-sensitive quantitative T 2 ' mapping (1/ T 2 '  = 1/T 2 * - 1/T 2 ) at 3 Tesla (T). PH i  was measured within the white matter hyperintensities (WMH) in SVD patients. Quantitative T 2 ' values were averaged across the entire white matter (WM). Furthermore, T 2 ' values were extracted from normal-appearing WM (NAWM) and the WMH and compared between patients and controls., Results: Quantitative T 2 ' values were significantly increased across the entire WM and in the NAWM in patients compared to control subjects (149.51 ± 16.94 vs. 138.19 ± 12.66 ms and 147.45 ± 18.14 vs. 137.99 ± 12.19 ms, p  < 0.05). WM T 2 ' values correlated significantly with the WMH load (ρ=0.441, p  = 0.006). Increased T 2 ' was significantly associated with more alkaline pH i  (ρ=0.299, p  < 0.05). Both T 2 ' and pH i were significantly positively correlated with vascular pulsatility in the distal carotid arteries (ρ=0.596, p  = 0.001 and ρ=0.452, p  = 0.016)., Conclusions: This exploratory study found evidence of impaired cerebral OEF in SVD, which is associated with intracellular alkalosis as an adaptive mechanism. The employed techniques provide new insights into the pathophysiology of SVD with regard to disease-related consequences on the cellular metabolic state., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2023 The Author(s).)

Microbial inactivation by pulsed electric field (PEF) has been studied widely although with high operational risk, while few studies on the potential of low intensity electric fields for microbial inactivation have been reported. In this study, the feasibility of inactivating microorganisms in milk by low intensity direct current (DC) electric field was investigated. Then a kinetics model was proposed based on the inactivation curves. Finally, the effect of electric field on the microflora and physicochemical properties of milk was analyzed. Results showed that the bacterial reduction >5 log CFU/mL could be achieved at 50-55°C, 0.3 A-0.6 A, and with 5 min starting intensity of 5 V/cm-9 V/cm. The inactivation kinetics consisted of three stages, therein, the middle stage, main part of the inactivation curve, followed 1st-order reaction kinetics, and the effect of temperature on it was consistent with the Arrhenius Law, which implied that the electric field itself can inactivate bacteria without thermal inactivating effect. The microflora analysis showed that naturally occurring bacteria in the milk contained typical potential pathogenic bacteria (e.g., 56.9% of Acinetobacter spp . ) and spoilage bacteria (e.g., 27.5% of Pseudomonas spp . ), and the electric field can inactivate them. Moreover, the inactivation chemically preserved the milk's fresh-like characteristics (according to indexes of whey protein denaturation rate, furosine content), and physical stability (turbidity, zeta potential, particle size, color and so on). Therefore, a promising approach is provided for microbial inactivation in dairy industry., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Introduction: Remdesivir (GS-5734) is a nucleoside analog prodrug with antiviral activity against several single-stranded RNA viruses, including the novel severe respiratory distress syndrome virus 2 (SARS-CoV-2). It is currently the only FDA-approved antiviral agent for the treatment of individuals with COVID-19 caused by SARS-CoV-2. However, remdesivir pharmacokinetics/pharmacodynamics (PK/PD) and toxicity data in humans are extremely limited. It is imperative that precise analytical methods for the quantification of remdesivir and its active metabolite, GS-441524, are developed for use in further studies. We report, herein, the first validated anti-viral paper spray-mass spectrometry (PS-MS/MS) assay for the quantification of remdesivir and GS-441524 in human plasma. We seek to highlight the utility of PS-MS/MS technology and automation advancements for its potential future use in clinical research and the clinical laboratory setting., Methods: Calibration curves for remdesivir and GS-441524 were created utilizing seven plasma-based calibrants of varying concentrations and two isotopic internal standards of set concentrations. Four plasma-based quality controls were prepared in a similar fashion to the calibrants and utilized for validation. No sample preparation was needed. Briefly, plasma samples were spotted on a paper substrate contained within pre-manufactured plastic cassette plates, and the spots were dried for 1 h. The samples were then analyzed directly for 1.2 min utilizing PS-MS/MS. All experiments were performed on a Thermo Scientific Altis triple quadrupole mass spectrometer utilizing automated technology., Results: The calibration ranges were 20 - 5000 and 100 - 25000 ng/mL for remdesivir and GS-441524, respectively. The calibration curves for the two antiviral agents showed excellent linearity (average R 2  = 0.99-1.00). The inter- and intra-day precision (%CV) across validation runs at four QC levels for both analytes was less than 11.2% and accuracy (%bias) was within ± 15%. Plasma calibrant stability was assessed and degradation for the 4 °C and room temperature samples were seen beginning at Day 7. The plasma calibrants were stable at -20 °C. No interference, matrix effects, or carryover was discovered during the validation process., Conclusions: PS-MS/MS represents a useful methodology for rapidly quantifying remdesivir and GS-441524, which may be useful for clinical PK/PD, therapeutic drug monitoring (TDM), and toxicity assessment, particularly during the current COVID-19 pandemic and future viral outbreaks., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors report financial support from Thermo Scientific for portions of this work. Dr. Manicke is an inventor on the patent “Ion Generation using Wetted Porous Material” issued to Purdue Research Foundation., (© 2022 THE AUTHORS. Publishing services by ELSEVIER B.V. on behalf of MSACL.)

MR thermometry techniques based on the strong water 1 H signal provide high spatial and temporal resolution and have shown promise for applications such as laser surgery and RF ablation. However, these techniques have low temperature sensitivity for hyperthermia applications and are greatly influenced by local motion and susceptibility variations. 1 H NMR signals from paramagnetic lanthanide complexes of Pr 3+ , Yb 3+ and Tm 3+ show up to 300-fold stronger temperature dependence compared to the water 1 H signal. In addition, 1 H chemical shifts of many of these complexes are insensitive to other factors such as the concentration of the paramagnetic complex, pH, [Ca 2+ ], and the presence of plasma macro-molecules and ions. Applications of lanthanide complexes for temperature measurement in intact animals and the feasibility of mapping temperatures in phantoms have been demonstrated. Among all the lanthanide complexes examined so far, thulium 1,&ThickSpace;4,&ThickSpace;7,&ThickSpace;10-tetramethyl-1,&ThickSpace;4,&ThickSpace;7,&ThickSpace;10-tetraazacyclododecane-1,&ThickSpace;4,&ThickSpace;7,&ThickSpace;10-tetraacetate (TmDOTMA - ) appears to be the most attractive for in vivo MR thermometry. The 1 H signal from the methyl groups on this complex is relatively intense because of 12 equivalent protons and provides high temperature sensitivity because of the large paramagnetic shifts induced by thulium. The possibility of imaging TmDOTMA 2 —in intact animals at physiologically safe concentrations has recently been demonstrated. Overall, MR thermometry methods based on hyperfine-shifted MR signals from paramagnetic lanthanide complexes appear promising for animal applications, but further studies relating to acceptable dose and signal-to-noise ratio are necessary before clinical use. [ABSTRACT FROM AUTHOR]

The application of magnetic resonance (MR) imaging in the study of human disease using small animals has steadily evolved over the past two decades and strongly established the fields of “small animal MR imaging” and “MR microscopy.” An increasing number of neuroscience related investigations now implement MR microscopy in their experiments. Research areas of growth pertaining to MR microscopy studies are focused on (1) phenotyping of genetically engineered mice models of human neurological diseases and (2) rodent brain atlases. MR microscopy can be performed in vitro on tissue specimens, ex vivo on brain slice preparations and in vivo (typically on rodents). Like most new imaging technologies, MR microscopy is technologically demanding and requires broad expertise. Uniform guidelines or “standards” of a given MR microscopy experiment are non-existent. The main focus therefore of this review will be on biological applications of MR microscopy and the experimental requirements. We also take a critical look at the biological information that small animal (rodent) MR imaging has provided in neuroscience research. [Copyright &y& Elsevier]

Based on studies in diabetic and hypertensive populations it has been postulated that early endothelial dysfunction is the mechanism responsible for the increased cardiovascular risk in microalbuminuric subjects. We evaluated the relation between microalbuminuria and endothelial dysfunction, assessed as flow-mediated dilation of the brachial artery, in an apparently healthy population. Within the framework of the PREVEND Intervention Trial non-hypertensive and non-hypercholesterolemic subjects were recruited on the basis of reproducible microalbuminuria. Using high-resolution ultrasound, flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery was assessed to measure endothelium-dependent and endothelium-independent responses, respectively. For the current study subjects with diabetes mellitus, clinical atherosclerosis, and macroalbuminuria were excluded from the analyses. We studied 421 men and 233 women (mean age (SD) 50 (12)). Increasing levels of urinary albumin excretion were accompanied by a significant increase in age, percentage men, systolic and diastolic blood pressure, body mass index, and serum triglycerides, whereas there was no decrease of flow-mediated vasodilation or nitroglycerin-mediated vasodilation. Adjusted for age and sex, urinary albumin excretion was significantly related to systolic (r=0.19, P<0.001) and diastolic (r=0.16, P<0.001) blood pressure, body mass index (r=0.18, P<0.001), and triglycerides (r=0.13, P=0.001), but not to flow-mediated vasodilation (r=−0.01, P=0.8). In contrast to blood pressure, body mass index, and triglycerides, there was no relation between urinary albumin excretion and flow-mediated vasodilation in apparently healthy subjects. These data suggest that the presence of atherogenic risk factors precedes the development of endothelial dysfunction in microalbuminuric, but otherwise healthy subjects. [Copyright &y& Elsevier]

Ion mobility spectrometry (IMS) is an analytical technique where ions are separated in the gas phase based on their mobility through a buffer gas in the presence of an electric field. An ion passing through an IMS device has a characteristic collisional cross section (CCS) value that depends on the buffer gas used. IMS can be coupled with mass spectrometry (MS), which characterizes an ion based on a mass-to-charge ratio ( m / z ), to increase analytical specificity and provide further physicochemical information. In particular, IMS-MS is of ever-increasing interest for the analysis of lipids, which can be problematic to accurately identify and quantify in bodily fluids by liquid chromatography (LC) with MS alone due to the presence of isomers, isobars, and structurally similar analogs. IMS provides an additional layer of separation when combined with front-end LC approaches, thereby, enhancing peak capacity and analytical specificity. CCS (and also ion mobility drift time) can be plotted against m / z ion intensity and/or LC retention time in order to generate in-depth molecular profiles of a sample. Utilization of IMS-MS for routine clinical laboratory testing remains relatively unexplored, but areas do exist for potential implementation. A brief update is provided here on lipid analysis using IMS-MS with a perspective on some applications in the clinical laboratory., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could affect the work reported in this paper., (© 2021 THE AUTHOR.)

Purpose: To prospectively compare artefacts and image quality in testicular stage I cancer patients using different combinations of breathing schemes and Multi-band (MB) in whole-body DWIBS at 1.5 T.Diffusion-Weighted whole-body Imaging with Background body signal Suppression (DWIBS) using inversion recovery (IR) fat saturation is a cornerstone in oncologic whole-body MRI, but implementation is restrained by long acquisition times. The new Multi-Band (MB) technique reduces scan time which can be reinvested in respiratory compensation., Methods: Thirty testicular cancer stage I patients were included. Three variations of whole-body DWIBS were tested: Standard free Breathing (FB)-DWIBS, FB-MB-DWIBS and Respiratory triggered (RT)-MB-DWIBS. Artefacts and image quality of b = 800 s/mm 2 images were evaluated using a Likert scale. No pathology was revealed. SNR was calculated in a healthy volunteer., Results: RT-MB-DWIBS was rated significantly better than FB-DWIBS in the thorax (p < 0.001) and abdomen (p < 0.001), but not in the pelvis (p = 0.569). FB-MB-DWIBS was ranked significantly lower than both FB-DWIBS (p < 0.001) and RT-MB-DWIBS (p < 0.001) at all locations. However, FB-MB-DWIBS was scanned in half the time without being less than "satisfactory". Few artefacts were encountered. SNR was similar for low-intensity tissues, but the SNR in high-intensity and respiratory-prone tissue (spleen) was slightly lower for FB-DWIBS than the other sequences., Conclusion: Images produced by the sequences were similar. MB enables the use of respiratory trigger or can be used to produce very fast free-breathing DWI with acceptable image quality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Coronavirus disease 2019 (COVID-19) is largely threatening global public health, social stability, and economy. Efforts of the scientific community are turning to this global crisis and should present future preventative measures. With recent trends in polymer science that use plasma to activate and enhance the functionalities of polymer surfaces by surface etching, surface grafting, coating and activation combined with recent advances in understanding polymer-virus interactions at the nanoscale, it is promising to employ advanced plasma processing for smart antiviral applications. This trend article highlights the innovative and emerging directions and approaches in plasma-based surface engineering to create antiviral polymers. After introducing the unique features of plasma processing of polymers, novel plasma strategies that can be applied to engineer polymers with antiviral properties are presented and critically evaluated. The challenges and future perspectives of exploiting the unique plasma-specific effects to engineer smart polymers with virus-capture, virus-detection, virus-repelling, and/or virus-inactivation functionalities for biomedical applications are analysed and discussed., Competing Interests: The authors declare no competing interests., (© 2021 The Authors. Published by Elsevier B.V.)

Background and Aims: Histopathology is the gold standard for analysis of atherosclerotic plaques but has drawbacks due to the destructive nature of the method. Ex vivo MRI is a non-destructive method to image whole plaques. Our aim was to use quantitative high field ex vivo MRI to classify plaque components, with histology as gold standard., Methods: Surgically resected carotid plaques from 12 patients with recent TIA or stroke were imaged at 11.7 T MRI. Quantitative T1/T2* mapping sequences and qualitative T1/T2* gradient echo sequences with voxel size of 30 × 30 × 60 μm 3 were obtained prior to histological preparation, sectioning and staining for lipids, inflammation, hemorrhage, and fibrous tissue. Regions of interest (ROI) were selected based on the histological staining at multiple levels matched between histology and MRI. The MRI parameters of each ROI were then analyzed with quadratic discriminant analysis (QDA) for classification., Results: A total of 965 ROIs, at 70 levels matched between histology and MRI, were registered based on histological staining. In the nine plaques where three or more plaque components were possible to co-localize with MRI, the mean degree of misclassification by QDA was 16.5 %. One of the plaques contained mostly fibrous tissue and lipids and had no misclassifications, and two plaques mostly contained fibrous tissue. QDA generally showed good classification for fibrous tissue and lipids, whereas plaques with hemorrhage and inflammation had more misclassifications., Conclusion: 11.7 T ex vivo high field MRI shows good visual agreement with histology in carotid plaques. T1/T2* maps analyzed with QDA is a promising non-destructive method to classify plaque components, but with a higher degree of misclassifications in plaques with hemorrhage or inflammation., Competing Interests: The authors report no declarations of interest., (© 2021 The Author(s).)

Metabolic profiling, metabonomics and metabolomics are terms coined in the late 1990s as they emerged as the newest ' omics ' technology at the time. This line of research enquiry uses spectroscopic analytical platforms, which are mainly nuclear magnetic resonance spectroscopy and mass spectrometry (MS), to acquire a snapshot of metabolites, the end products of a complex biological system. Metabolic profiling enables the detection, quantification and characterisation of metabolites in biofluids, cells and tissues. The source of these compounds can be of endogenous, microbial or exogenous origin, such as dietary or xenobiotic. This results in generating extensive, multivariate spectroscopic data that require specific statistical manipulation, typically performed using chemometric and pattern recognition techniques to reduce its dimensions, facilitate its biological interpretation and allow sample classification and biomarker discovery. Consequently, it is possible to study the dynamic metabolic changes in response to disease, intervention or environmental conditions. In this review, we describe the fundamentals of MS so that clinicians can be literate in the field and are able to interrogate the right scientific questions., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Cortical bone shows as a signal void when using conventional clinical magnetic resonance imaging (MRI). Ultrashort echo time MRI (UTE-MRI) can acquire high signal from cortical bone, thus enabling quantitative assessments. Magnetization transfer (MT) imaging combined with UTE-MRI can indirectly assess protons in the organic matrix of bone. This study aimed to examine UTE-MT MRI techniques to estimate the mechanical properties of cortical bone. A total of 156 rectangular human cortical bone strips were harvested from the tibial and femoral midshafts of 43 donors (62 ± 22 years old, 62 specimens from females, 94 specimens from males). Bone specimens were scanned using UTE-MT sequences on a clinical 3 T MRI scanner and on a micro-computed tomography (μCT) scanner. A series of MT pulse saturation powers (400°, 600°, 800°) and frequency offsets (2, 5, 10, 20, 50 kHz) was used to measure the macromolecular fraction (MMF) utilizing a two-pool MT model. Failure mechanical properties of the bone specimens were measured using 4-point bending tests. MMF from MRI results showed significant strong correlations with cortical bone porosity (R = -0.72, P  < 0.01) and bone mineral density (BMD) (R = +0.71, P  < 0.01). MMF demonstrated significant moderate correlations with Young modulus, yield stress, and ultimate stress ( R  = 0.60-0.61, P < 0.01). These results suggest that the two-pool UTE-MT model focusing on the organic matrix of bone can potentially serve as a novel tool to detect the variations of bone mechanical properties and intracortical porosity.

Aim: One of the most important microvasculatures' geometrical variables is number of pores per capillary length that can be evaluated using MRI. The transportation of blood from inner to outer parts of the capillary is studied by the pores and the relationship among capillary wall thickness, size and the number of pores is examined., Background: Characterization of capillary space may obtain much valuable information on the performance of tissues as well as the angiogenesis., Methods: To estimate the number of pores, a new pseudo-liquid drop model along with appropriate quantitative physiological purposes has been investigated toward indicating a package of data on the capillary space. This model has utilized the MRI perfusion, diffusion and relaxivity parameters such as cerebral blood volume (CBV), apparent diffusion coefficient (ADC), Δ R 2 and Δ R 2 * values. To verify the model, a special protocol was designed and tested on various regions of eight male Wistar rats., Results: The maximum number of pores per capillary length in the various conditions such as recovery, core, normal-recovery, and normal-core were found to be 183 ± 146, 176 ± 160, 275 ± 166, and 283 ± 143, respectively. This ratio in the normal regions was more than that of the damaged ones. The number of pores increased with increasing mean radius of the capillary and decreasing the thickness of the wall in the capillary space., Conclusion: Determination of the number of capillary pore may most likely help to evaluate angiogenesis in the tissues and treatment planning of abnormal ones.

One of the most common mitochondrial DNA (mtDNA) mutations, the A to G transition at base pair 3243, has been linked to changes in the brain, in addition to commonly observed hearing problems, diabetes and myopathy. However, a detailed quantitative description of m.3243A>G patients' brains has not been provided so far. In this study, ultra-high field MRI at 7T and volume- and surface-based data analyses approaches were used to highlight morphology (i.e. atrophy)-, microstructure (i.e. myelin and iron concentration)- and metabolism (i.e. cerebral blood flow)-related differences between patients (N = 22) and healthy controls (N = 15). The use of quantitative MRI at 7T allowed us to detect subtle changes of biophysical processes in the brain with high accuracy and sensitivity, in addition to typically assessed lesions and atrophy. Furthermore, the effect of m.3243A>G mutation load in blood and urine epithelial cells on these MRI measures was assessed within the patient population and revealed that blood levels were most indicative of the brain's state and disease severity, based on MRI as well as on neuropsychological data. Morphometry MRI data showed a wide-spread reduction of cortical, subcortical and cerebellar gray matter volume, in addition to significantly enlarged ventricles. Moreover, surface-based analyses revealed brain area-specific changes in cortical thickness (e.g. of the auditory cortex), and in T 1 , T 2 * and cerebral blood flow as a function of mutation load, which can be linked to typically m.3243A>G-related clinical symptoms (e.g. hearing impairment). In addition, several regions linked to attentional control (e.g. middle frontal gyrus), the sensorimotor network (e.g. banks of central sulcus) and the default mode network (e.g. precuneus) were characterized by alterations in cortical thickness, T 1 , T 2 * and/or cerebral blood flow, which has not been described in previous MRI studies. Finally, several hypotheses, based either on vascular, metabolic or astroglial implications of the m.3243A>G mutation, are discussed that potentially explain the underlying pathobiology. To conclude, this is the first 7T and also the largest MRI study on this patient population that provides macroscopic brain correlates of the m.3243A>G mutation indicating potential MRI biomarkers of mitochondrial diseases and might guide future (longitudinal) studies to extensively track neuropathological and clinical changes.

The 2015 Nobel Prize in Physiology or Medicine has been awarded to avermectins and artemisinin, respectively. Avermectins produced by Streptomyces avermitilis are excellent anthelmintic and potential antibiotic agents. Because wild-type strains only produce low levels of avermectins, much research effort has focused on improvements in avermectin production to meet the ever increasing demand for such compounds. This review describes the strategies that have been widely employed and the future prospects of synthetic biology applications in avermectin yield improvement. With the help of genome sequencing of S. avermitilis and an understanding of the avermectin biosynthetic/regulatory pathways, synthetic and systems biotechnology approaches have been applied for precision engineering. We focus on the design and synthesis of biological chassis, parts, devices, and modules from diverse microbes to reconstruct and optimize their dynamic processes, as well as predict favorable effective overproduction of avermectins by a 4Ms strategy (Mine, Model, Manipulation, and Measurement).