ABSTRACT
PURPOSE: This study investigated potential use of computed tomography (CT)-based parameters in the lumbar spine as a surrogate for magnetic resonance imaging (MRI)-based findings. METHODS: In this retrospective study, all individuals, who had a lumbar spine CT scan and MRI between 2006 and 2012 were reviewed (n = 198). Disc height (DH) and endplate degeneration (ED) were evaluated between Th12/L1-L5/S1. Statistics consisted of Spearman correlation and univariate/multivariable regression (adjusting for age and gender). RESULTS: The mean CT-DH increased kranio-caudally (8.04 millimeters (mm) at T12/L1, 9.17 mm at L1/2, 10.59 mm at L2/3, 11.34 mm at L3/4, 11.42 mm at L4/5 and 10.47 mm at L5/S1). MRI-ED was observed in 58 (29%) individuals. CT-DH and MRI-DH had strong to very strong correlations (rho 0.781-0.904, p < .001). MRI-DH showed higher absolute values than CT-DH (mean of 1.76 mm). There was a significant association between CT-DH and MRI-ED at L2/3 (p = .006), L3/4 (p = .002), L4/5 (p < .001) and L5/S1 (p < .001). A calculated cut-off point was set at 11 mm. CONCLUSIONS: In the lumbar spine, there is a correlation between disc height on CT and MRI. This can be useful in trauma and emergency cases, where CT is readily available in the lack of an MRI. In addition, in the middle and lower part of the lumbar spine, loss of disc height on CT scans is associated with more pronounced endplate degeneration on MRIs. If the disc height on CT scans is lower than 11 mm, endplate degeneration on MRIs is likely more pronounced. LEVEL AND DESIGN: Level III, a retrospective study.
Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Lumbar Vertebrae , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/pathology , Magnetic Resonance Imaging/methods , Male , Female , Tomography, X-Ray Computed/methods , Retrospective Studies , Middle Aged , Adult , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Degeneration/pathology , Aged , Intervertebral Disc/diagnostic imaging , Intervertebral Disc/pathology , Aged, 80 and over , Young AdultABSTRACT
BACKGROUND: As the number of people living with dementia rapidly increases worldwide, the support provided by their informal caregivers remains key to the sustainability of most healthcare systems, this voluntary contribution representing 40% of the costs of dementia worldwide. Informal caregiving in dementia, however, is linked to long periods of chronic stress with frequent and serious negative consequences on the health and quality of life of the caregiver. A psycho-educational group intervention focusing on coping with the daily stress of dementia caregiving ("Learning to feel better to help better"), developed in French-speaking Canada and showing broad effects on quality of life, was selected with the aim of 1) adapting it to a new cultural context (French-speaking Switzerland) based on identified facilitators and barriers, using a participative approach; and 2) conducting a feasibility study to evaluate whether the adapted programme showed similar or improved feasibility and effects compared to the original Canadian programme. METHODS: A mixed-methods concurrent nested design was used to evaluate the feasibility and the effects on five quantitative core outcomes. Additional qualitative data helped document in depth the acceptability and impact of the intervention. RESULTS: We shortened the programme from 30 to 21 h in total, which resulted in increased accessibility, in terms of facilitated recruitment of participants and inclusion of a broader range of informal caregivers. There were significant reductions in subjective burden (effect size: d = -0.32) and psychological distress (d = -0.48), as well as decreases in the stress reactions of informal caregivers related to the behaviour problems of the persons with dementia (d = -0.57). The qualitative results emphasized the usefulness of providing informal caregivers with structured procedures for efficiently tackling everyday challenges, and of enabling learning through a variety of channels and activities. CONCLUSIONS: Substantial improvements are associated with this 21-h group intervention, organised in 7 sessions of 3 h each, focused on learning more efficient strategies to cope with the daily stress of dementia caregiving. This intervention empowered informal caregivers to master their daily challenges with more confidence, satisfaction and calm. TRIAL REGISTRATION: ISRCTN13512408 (registration date 17.05.2021, retrospectively registered).
Subject(s)
Dementia , Quality of Life , Humans , Quality of Life/psychology , Feasibility Studies , Dementia/psychology , Canada , Coping Skills , Caregivers/psychologyABSTRACT
Highly concentrated antibody formulations are oftentimes required for subcutaneous, self-administered biologics. Here, we report the development of a unique formulation for our first-in-class FSH-blocking humanized antibody, MS-Hu6, which we propose to move to the clinic for osteoporosis, obesity, and Alzheimer's disease. The studies were carried out using our Good Laboratory Practice (GLP) platform, compliant with the Code of Federal Regulations (Title 21, Part 58). We first used protein thermal shift, size exclusion chromatography, and dynamic light scattering to examine MS-Hu6 concentrations between 1 and 100 mg/mL. We found that thermal, monomeric, and colloidal stability of formulated MS-Hu6 was maintained at a concentration of 100 mg/mL. The addition of the antioxidant L-methionine and chelating agent disodium EDTA improved the formulation's long-term colloidal and thermal stability. Thermal stability was further confirmed by Nano differential scanning calorimetry (DSC). Physiochemical properties of formulated MS-Hu6, including viscosity, turbidity, and clarity, confirmed with acceptable industry standards. That the structural integrity of MS-Hu6 in formulation was maintained was proven through Circular Dichroism (CD) and Fourier Transform Infrared (FTIR) Spectroscopy. Three rapid freeze-thaw cycles at -80 °C/25 °C or -80 °C/37 °C further revealed excellent thermal and colloidal stability. Furthermore, formulated MS-Hu6, particularly its Fab domain, displayed thermal and monomeric storage stability for more than 90 days at 4°C and 25°C. Finally, the unfolding temperature (Tm) for formulated MS-Hu6 increased by >4.80 °C upon binding to recombinant FSH, indicating highly specific ligand binding. Overall, we document the feasibility of developing a stable, manufacturable and transportable MS-Hu6 formulation at a ultra-high concentration at industry standards. The study should become a resource for developing biologic formulations in academic medical centers.
Subject(s)
Antibodies, Monoclonal , Follicle Stimulating Hormone , Antibodies, Monoclonal/chemistry , Temperature , Calorimetry, Differential Scanning , Viscosity , Protein StabilityABSTRACT
Non-human primates are a critical species for the identification of key biological mechanisms in normal and pathological aging. One of these primates, the mouse lemur, has been widely studied as a model of cerebral aging or Alzheimer's disease. The amplitude of low-frequency fluctuations of blood oxygenation level-dependent (BOLD) can be measured with functional MRI. Within specific frequency bands (e.g. the 0.01-0.1 Hz), these amplitudes were proposed to indirectly reflect neuronal activity as well as glucose metabolism. Here, we first created whole brain maps of the mean amplitude of low frequency fluctuations (mALFF) in young mouse lemurs (mean ± SD: 2.1 ± 0.8 years). Then, we extracted mALFF in old lemurs (mean ± SD: 8.8 ± 1.1 years) to identify age-related changes. A high level of mALFF was detected in the temporal cortex (Brodmann area 20), somatosensory areas (Brodmann area 5), insula (Brodmann areas 13-6) and the parietal cortex (Brodmann area 7) of healthy young mouse lemurs. Aging was associated with alterations of mALFF in somatosensory areas (Brodmann area 5) and the parietal cortex (Brodmann area 7).
Subject(s)
Alzheimer Disease , Cheirogaleidae , Lemur , Lemuridae , Sensorimotor Cortex , Strepsirhini , Animals , Cheirogaleidae/physiology , Magnetic Resonance Imaging , Brain/pathology , Aging , Alzheimer Disease/pathologyABSTRACT
BACKGROUND: Frozen shoulder is a common, painful, and movement-restricting condition. Although primary frozen shoulder is idiopathic, secondary frozen shoulder can occur after trauma or surgery. Prophylactic and therapeutic options are often unsatisfactory. Vitamin C (ascorbic acid) is a potent physiological antioxidant and likely inhibits the activation of nuclear factor κB, which plays a decisive role in inflammatory reactions. HYPOTHESIS: Because of its anti-inflammatory effects, vitamin C may be valuable in the prevention of secondary frozen shoulder. STUDY DESIGN: Controlled laboratory study. METHODS: An in vivo shoulder contracture model was conducted by fixation of the right proximal limb of Sprague-Dawley rats. A treatment group (n = 8) receiving vitamin C orally was compared with a control group (n = 9) without vitamin C. The primary outcome was capsular thickness at the shoulder joint measured on magnetic resonance imaging (MRI) examination. Further histological examination was performed but was not statistically analyzed because of variability of the cutting plane through the glenoid. RESULTS: Vitamin C treatment resulted in less thickening of the axillary fold of the operated shoulder at 2 of the 3 locations measured on MRI compared with untreated controls (insertion to the glenoid, P = .074; insertion to the humerus, P = .006; middle of the axillary recess, P = .008). The observed structural changes in histological examination corroborated the significant changes obtained from the MRI measurements. CONCLUSION: Prophylactic vitamin C seemed to reduce the thickening of the axillary recess in secondary frozen shoulder in this preclinical study. CLINICAL RELEVANCE: Vitamin C may be helpful as a noninvasive therapeutic measure to prevent secondary frozen shoulder (eg, within the context of surgery in the shoulder region or immobilization) or to treat primary frozen shoulder at an early stage. Further studies are required to evaluate the effect of this treatment in humans and the necessary dosage in humans.
Subject(s)
Bursitis , Contracture , Shoulder Joint , Humans , Rats , Animals , Shoulder/pathology , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Rats, Sprague-Dawley , Bursitis/drug therapy , Shoulder Joint/surgery , Models, Animal , Contracture/prevention & control , Contracture/surgeryABSTRACT
Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience.
Subject(s)
Brain Mapping , Brain , Rats , Animals , Brain Mapping/methods , Consensus , Neuroimaging , Magnetic Resonance Imaging/methodsABSTRACT
Solidly Mounted Resonators (SMRs) for high frequency RF filters and sensing applications often display spurious resonances that distort their frequency response. In this work, we try to identify the origin of spurious resonances accompanying the main series resonances in AlN-based SMRs with the help of modified Butterworth Van Dyke (BVD) and Mason's models. By manufacturing SMRs of different sizes and shapes and studying the influence of the position of the electrical probing spot, we have demonstrated both theoretically and experimentally that devices with larger areas are more likely to display these additional peaks. Our updated models accurately simulate the frequency response of the SMRs, revealing that spurious peaks are mostly related to the resistance of the electrodes. Our study clarifies the origin of the spurious resonances and offers solutions for both, the optimal design and measurement method of SMRs.
ABSTRACT
During torpor in a 13-lined ground squirrel heart rate and blood flow decrease, increasing the risk of blood clot formation. In response, cells involved in clotting called platelets are sequestered in the liver, stored in the cold for months, and released back into circulation upon arousal. This is in contrast to non-hibernating mammals, including humans, in which chilled platelets undergo cold storage lesions and phagocytosis, leading to rapid clearance from circulation post-transfusion. Because of this, human platelets must be stored at room temperature, limiting their shelf life to 7 days due to the increased risk of microbial contamination at warmer temperatures. Human and ground squirrel platelets were stored at room temperature or 4 °C before being analyzed for cold storage lesions. Human platelets stored at 4 °C displayed progressive increases in phosphatidylserine surface exposure and caspase activation, while ground squirrel platelets showed minimal change. Following cold storage, sialic acid residues on human platelets were cleaved, leading to increased phagocytosis of human platelets by HepG2 cells. Ground squirrel platelets stored in the cold showed no changes in desialylation and phagocytosis, with Taxol-treated ground squirrel platelets showing the lowest phagocytosis rates between both species and all treatments. These results suggest that ground squirrel platelets may be resistant to cold storage lesions seen in human platelets. Although these experiments were done in vitro, they suggest a mechanism by which ground squirrel platelets are adapted to be stored during hibernation and remain functional following arousal. Other hibernating species may employ similar adaptations to retain functional platelets following torpor.
Subject(s)
Hibernation , Torpor , Humans , Animals , Blood Platelets/physiology , Torpor/physiology , Temperature , Hibernation/physiology , Cold Temperature , Sciuridae/physiologyABSTRACT
Post-translational modifications (PTMs) regulate various aspects of protein function, including degradation. Mass spectrometric methods relying on pulsed metabolic labeling are popular to quantify turnover rates on a proteome-wide scale. Such data have traditionally been interpreted in the context of protein proteolytic stability. Here, we combine theoretical kinetic modeling with experimental pulsed stable isotope labeling of amino acids in cell culture (pSILAC) for the study of protein phosphorylation. We demonstrate that metabolic labeling combined with PTM-specific enrichment does not measure effects of PTMs on protein stability. Rather, it reveals the relative order of PTM addition and removal along a protein's lifetime-a fundamentally different metric. This is due to interconversion of the measured proteoform species. Using this framework, we identify temporal phosphorylation sites on cell cycle-specific factors and protein complex assembly intermediates. Our results thus allow tying PTMs to the age of the modified proteins.
Subject(s)
Peptides , Protein Processing, Post-Translational , Phosphorylation , Proteolysis , Peptide HydrolasesABSTRACT
Interferon-induced transmembrane protein 3 (IFITM3) is a restriction factor that limits viral pathogenesis and exerts poorly understood immunoregulatory functions. Here, using human and mouse models, we demonstrate that IFITM3 promotes MyD88-dependent, TLR-mediated IL-6 production following exposure to cytomegalovirus (CMV). IFITM3 also restricts IL-6 production in response to influenza and SARS-CoV-2. In dendritic cells, IFITM3 binds to the reticulon 4 isoform Nogo-B and promotes its proteasomal degradation. We reveal that Nogo-B mediates TLR-dependent pro-inflammatory cytokine production and promotes viral pathogenesis in vivo, and in the case of TLR2 responses, this process involves alteration of TLR2 cellular localization. Nogo-B deletion abrogates inflammatory cytokine responses and associated disease in virus-infected IFITM3-deficient mice. Thus, we uncover Nogo-B as a driver of viral pathogenesis and highlight an immunoregulatory pathway in which IFITM3 fine-tunes the responsiveness of myeloid cells to viral stimulation.
Subject(s)
COVID-19 , Interleukin-6 , Nogo Proteins/metabolism , Animals , Cytokines/metabolism , Humans , Interleukin-6/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , SARS-CoV-2 , Toll-Like Receptor 2/metabolismABSTRACT
Peripheral arterial disease (PAD) is the least studied complication of nephrotic syndrome (NS). Risk factors which predispose children with NS to developing PAD include hyperlipidaemia, hypertension and prolonged use of steroids. The development of PAD significantly increases the morbidity and mortality associated with NS as such children are prone to sudden cardiac death. The ankle brachial index (ABI) is a tool that has been proven to have high specificity and sensitivity in detecting PAD even in asymptomatic individuals. We aimed to determine the prevalence of PAD in children with NS and to identify risk factors that can independently predict its development. A comparative cross-sectional study was conducted involving 200 subjects (100 with NS and 100 apparently healthy comparative subjects that were matched for age, sex and socioeconomic class). Systolic blood pressures were measured in all limbs using the pocket Doppler machine (Norton Doppler scan machine). ABI was calculated as a ratio of ankle to arm systolic blood pressure. PAD was defined as ABI less than 0.9. The prevalence of PAD was significantly higher in children with NS than matched comparison group (44.0% vs 6.0%, p < 0.001). Average values of waist and hip circumference were significantly higher in subjects with PAD than those without PAD (61.68± 9.1cm and 67.6± 11.2 cm vs 57.03 ± 8.3cm and 65.60± 12.5cm respectively, p< 0.005). Serum lipids (triglyceride, very low density lipoprotein, total cholesterol and low density lipoprotein) were also significantly higher in subjects with PAD than those without PAD [106.65mg/dl (67.8-136.7) vs 45.72mg/dl (37.7-61.3), 21.33mg/dl (13.6-27.3) vs 9.14mg/dl (7.5-12.3), 164.43mg/dl (136.1-259.6) vs 120.72mg/dl (111.1-142.1) and 93.29mg/dl (63.5-157.3) vs 61.84mg/dl (32.6-83.1), respectively p< 0.05]. Increasing duration since diagnosis of NS, having a steroid resistant NS and increasing cumulative steroid dose were independent predictors of PAD in children with NS; p< 0.05 respectively. With these findings, it is recommended that screening for PAD in children with NS should be done to prevent cardiovascular complications before they arise.
Subject(s)
Nephrotic Syndrome , Peripheral Arterial Disease , Ankle Brachial Index , Child , Cross-Sectional Studies , Humans , Nephrotic Syndrome/complications , Nephrotic Syndrome/epidemiology , Peripheral Arterial Disease/complications , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/epidemiology , Prevalence , Risk FactorsABSTRACT
INTRODUCTION: XEN 45® gel stent is an ab interno aqueous humor drainage device indicated for moderate glaucoma refractory to medical management. Its efficacy has been demonstrated in primary open-angle glaucoma (POAG). However, there are few studies on secondary glaucoma, including steroid-induced glaucoma (CG), defined as optic neuropathy induced by using local or systemic corticosteroids without increased flare. METHODS: We conducted a dual-center comparative cohort study between April 2019 and January 2021. 66 operated eyes were included, divided into two groups: POAG (56 eyes) and GC (10 eyes). The primary endpoint was the relative reduction in intraocular pressure (IOP) at three months postoperatively in the GC group. Three outcomes were defined: total success, partial success and failure. RESULTS: The total success rate was 100% in the GC group and 42.6% in the POAG group. Preoperative IOP was 36.1±9.1mmHg and 19.0±7.3mmHg respectively. IOP reduction was 69.1±11.7% in the GC group and 21.8±30.3% in the POAG group. Patients were younger in the GC group (49.3±21.2 versus 71.1±8.4 years), and preoperative conjunctival preparation was longer in this group (12 versus 5 weeks). The needling rate was 17.9% in the POAG group and 10% in the GC group. CONCLUSION: The XEN 45® gel stent is effective in the treatment of steroid-induced glaucoma. Further studies will be required to identify predictive factors for success and to establish criteria for good candidacy.
Subject(s)
Glaucoma Drainage Implants , Glaucoma, Open-Angle , Glaucoma , Phacoemulsification , Adrenal Cortex Hormones , Cohort Studies , Glaucoma/surgery , Glaucoma Drainage Implants/adverse effects , Glaucoma, Open-Angle/complications , Glaucoma, Open-Angle/surgery , Humans , Intraocular Pressure , Retrospective Studies , Stents/adverse effects , Steroids , Treatment OutcomeABSTRACT
Reversible protein phosphorylation is an important mechanism for regulating (dis)assembly of biomolecular condensates. However, condensate-specific phosphosites remain largely unknown, thereby limiting our understanding of the underlying mechanisms. Here, we combine solubility proteome profiling with phosphoproteomics to quantitatively map several hundred phosphosites enriched in either soluble or condensate-bound protein subpopulations, including a subset of phosphosites modulating protein-RNA interactions. We show that multi-phosphorylation of the C-terminal disordered segment of heteronuclear ribonucleoprotein A1 (HNRNPA1), a key RNA-splicing factor, reduces its ability to locate to nuclear clusters. For nucleophosmin 1 (NPM1), an essential nucleolar protein, we show that phosphorylation of S254 and S260 is crucial for lowering its partitioning to the nucleolus and additional phosphorylation of distal sites enhances its retention in the nucleoplasm. These phosphorylation events decrease RNA and protein interactions of NPM1 to regulate its condensation. Our dataset is a rich resource for systematically uncovering the phosphoregulation of biomolecular condensates.
Subject(s)
Biomolecular Condensates , Proteome , Nuclear Proteins/metabolism , Phosphorylation , Proteome/metabolism , RNA/metabolism , RNA Splicing Factors/metabolism , Ribonucleoproteins/metabolismABSTRACT
Whether the size of the prefrontal cortex (PFC) in humans is disproportionate when compared to other species is a persistent debate in evolutionary neuroscience. This question has left the study of over/under-expansion in other structures relatively unexplored. We therefore sought to address this gap by adapting anatomical areas from the digital atlases of 18 mammalian species, to create a common interspecies classification. Our approach used data-driven analysis based on phylogenetic generalized least squares to evaluate anatomical expansion covering the whole brain. Our main finding suggests a divergence in primate evolution, orienting the stereotypical mammalian cerebral proportion toward a frontal and parietal lobe expansion in catarrhini (primate parvorder comprising old world monkeys, apes, and humans). Cerebral lobe volumes slopes plotted for catarrhini species were ranked as parietalâ¼frontal > temporal > occipital, contrasting with the ranking of other mammalian species (occipital > temporal > frontalâ¼parietal). Frontal and parietal slopes were statistically different in catarrhini when compared to other species through bootstrap analysis. Within the catarrhini's frontal lobe, the prefrontal cortex was the principal driver of frontal expansion. Across all species, expansion of the frontal lobe appeared to be systematically linked to the parietal lobe. Our findings suggest that the human frontal and parietal lobes are not disproportionately enlarged when compared to other catarrhini. Nevertheless, humans remain unique in carrying the most relatively enlarged frontal and parietal lobes in an infraorder exhibiting a disproportionate expansion of these areas.
Subject(s)
Biological Evolution , Catarrhini , Frontal Lobe , Parietal Lobe , Animals , Atlases as Topic , Catarrhini/anatomy & histology , Frontal Lobe/anatomy & histology , Humans , Organ Size , Parietal Lobe/anatomy & histology , PhylogenyABSTRACT
The human default mode network (DMN) is engaged at rest and in cognitive states such as self-directed thoughts. Interconnected homologous cortical areas in primates constitute a network considered as the equivalent. Here, based on a cross-species comparison of the DMN between humans and non-hominoid primates (macaques, marmosets, and mouse lemurs), we report major dissimilarities in connectivity profiles. Most importantly, the medial prefrontal cortex (mPFC) of non-hominoid primates is poorly engaged with the posterior cingulate cortex (PCC), though strong correlated activity between the human PCC and the mPFC is a key feature of the human DMN. Instead, a fronto-temporal resting-state network involving the mPFC was detected consistently across non-hominoid primate species. These common functional features shared between non-hominoid primates but not with humans suggest a substantial gap in the organization of the primate's DMN and its associated cognitive functions.
Subject(s)
Brain Mapping , Brain , Animals , Callithrix , Default Mode Network , Magnetic Resonance Imaging , Neural PathwaysABSTRACT
The aim of this study was the isolation and molecular characterization of fungi from untreated refinery effluent by using multiple conserved genes. The Fungi isolated were characterized based on PCR amplification and genomic sequencing of the internal transcribed spacer region (ITS), partial ß-tubulin (BenA), calmodulin (CaM), and RNA polymerase second large subunit (RPB2) genes, along with morphological characterization. The obtained sequences were subjected to BLAST analysis and the corresponding fungal isolates were assigned species names after comparison with representative sequences available in GenBank. Fifteen (15) Fungi species belonging to four genera of Aspergillus, Penicillium, Fusarium, and Trichoderma with Aspergillus as the predominant genus were identified. Therefore these genes should be used as molecular markers for species level identification of fungi (especially Aspergillus and Penicillium as proven in this study.
Subject(s)
Fungi/genetics , Oil and Gas Industry , Phylogeny , Wastewater/microbiology , Calmodulin/genetics , DNA, Intergenic , Fungi/isolation & purification , Genes, Fungal , RNA Polymerase II/genetics , Tubulin/geneticsABSTRACT
Glutamate is the amino acid with the highest cerebral concentration. It plays a central role in brain metabolism. It is also the principal excitatory neurotransmitter in the brain and is involved in multiple cognitive functions. Alterations of the glutamatergic system may contribute to the pathophysiology of many neurological disorders. For example, changes of glutamate availability are reported in rodents and humans during Alzheimer's and Huntington's diseases, epilepsy as well as during aging. Most studies evaluating cerebral glutamate have used invasive or spectroscopy approaches focusing on specific brain areas. Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) is a recently developed imaging technique that can be used to study relative changes in glutamate distribution in the entire brain with higher sensitivity and at higher resolution than previous techniques. It thus has strong potential clinical applications to assess glutamate changes in the brain. High field is a key condition to perform gluCEST images with a meaningful signal to noise ratio. Thus, even if some studies started to evaluate gluCEST in humans, most studies focused on rodent models that can be imaged at high magnetic field. In particular, systematic characterization of gluCEST contrast distribution throughout the whole brain has never been performed in humans or non-human primates. Here, we characterized for the first time the distribution of the gluCEST contrast in the whole brain and in large-scale networks of mouse lemur primates at 11.7 Tesla. Because of its small size, this primate can be imaged in high magnetic field systems. It is widely studied as a model of cerebral aging or Alzheimer's disease. We observed high gluCEST contrast in cerebral regions such as the nucleus accumbens, septum, basal forebrain, cortical areas 24 and 25. Age-related alterations of this biomarker were detected in the nucleus accumbens, septum, basal forebrain, globus pallidus, hypophysis, cortical areas 24, 21, 6 and in olfactory bulbs. An age-related gluCEST contrast decrease was also detected in specific neuronal networks, such as fronto-temporal and evaluative limbic networks. These results outline regional differences of gluCEST contrast and strengthen its potential to provide new biomarkers of cerebral function in primates.
Subject(s)
Glutamic Acid , Magnetic Resonance Imaging , Animals , Brain/diagnostic imaging , Brain/metabolism , Brain Mapping , Glutamic Acid/metabolism , Humans , Magnetic Resonance Imaging/methods , PrimatesABSTRACT
BACKGROUND: Simultaneous presence of elevated waist circumference and hypertriglyceridemia (HTGW) is a simple and low-cost measure of visceral obesity, and it is associated with a plethora of cardio-metabolic abnormalities that can increase the risk of cardiovascular diseases and incident Type 2 diabetes mellitus. We decided to study the prevalence, patterns, and predictors of metabolic abnormalities in Nigerian hypertensives with the HTGW phenotype. METHODS: The medical records of 582 hypertensives with complete data of interest were retrieved and analyzed for the study. Their socio-demographic data, anthropometric data, and booking blood pressure values were retrieved. The results of their fasting plasma glucose, lipid profile, uric acid and serum creatinine were also retrieved for analysis. RESULTS: The mean age of the study population was 56.2 ±13.6, with 53.1% being males. The prevalence of smoking and use of alcohol was 4.3% and 26.5% respectively. The prevalence of the HTGW phenotype was 23.4% and were predominantly males (61%). Subjects with the HTGW phenotype were more obese assessed by waist circumference (WC) and body mass index (BMI). Mean serum total cholesterol, triglyceride, very low-density lipoprotein, uric acid, and creatinine were significantly higher in the HTGW phenotype (p = 0.003; <0.001; <0.001; 0.002 and <0.001 respectively). The prevalence of newly diagnosed Type 2 diabetes was 28.7%. There was also a preponderance of cardio-metabolic abnormalities (obesity, dyslipidaemia, hyperuricemia) in the HTGW phenotype. In both males and females, the HGTW phenotype was significantly associated with elevated Tc, TG, VLDL, hyperuricemia and atherogenic index of plasma. CONCLUSION: The HTGW phenotype is common amongst Nigerian hypertensives, and it is associated with metabolic abnormalities.