Creatine Ratio Research Articles

Correlation of Pre-Operative Myo-Inositol/Creatine Ratio with Histopathological Grade of Glioma

Background: Introduction: Gliomas are the most frequent primary intracerebral tumors in adults & constitute 35–50% of all intracranial neoplasms. In determining a treatment plan, tumor grade is a key consideration for minimizing the risk of unnecessary morbidity and mortality. Objective: To evaluate Correlation of pre-operative Myo-inositol/Creatine ratio with histopathological grade of glioma. Materials and method: This was a cross sectional experimental study. Total 33 patients consistent with selection criteria were enrolled in this study. Myo-inositol/ Creatine ratio was obtained from MRS. Histopathological grade of glioma was obtained from biopsy (hematoxylin and eosin stain or HE stain) report. The obtained results were then grouped categorically. Result: Out of 33 patients, 22 were male and 11 were female. According to histopathology, 14 gliomas were confirmed as high grade and 19 gliomas were confirmed as low grade. Spearman Rank Correlation Test showed a moderate negative association between Myo-inositol/Creatine ratio with glioma grading with coefficient value of r = -0.611 with a statistically significant p-value (p<0.001). We were able to differentiate between low grade (II) and high grade (III + IV) gliomas using the Myoinositol/ Creatine ratio. The levels of MI/Cr were higher (e”0.48) in patients with lowgrade glioma, and lower (<0.48) in patients high grade glioma Conclusion: This study has shown a significant correlation between pre-operative Myo-inositol/Creatine ratio with histopathological grade of glioma. It may help neurosurgeons in taking clinical decisions about patient management and counselling. Bang. J Neurosurgery 2024; 13(2): 57-63

The Abnormal N-Acetylaspartate to Creatine Ratio of the Right Putamen is Linked to Wakefulness in Patients with Insomnia Disorder.

Converging evidence implicates the putamen in sleep-wake regulation. However, its role remains unclear. We hypothesized that metabolic abnormalities in the putamen are linked to insomnia disorder, which has not been previously addressed, and investigated putaminal N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in patients with insomnia disorder compared to healthy controls. In the present study, the concentrations of NAA, Cho, and Cr in the putamen of 23 patients with insomnia disorder and 18 healthy controls were determined using proton magnetic resonance spectroscopy. Sociodemographic, psychometric, and polysomnography data were obtained from all participants. We found that the mean NAA/Cr ratio of the right putamen was significantly greater in the insomnia group compared to the control group and also greater than the left putamen within the insomnia group. The NAA/Cr ratio of the right putamen distinguished insomnia disorder from normal sleep with 78.3% sensitivity and 61.1% specificity. Furthermore, this ratio positively correlated with both objective and subjective insomnia severity and sleep quality. Our findings provide critical evidence for the dysfunctional putaminal metabolism of NAA/Cr in insomnia disorder, suggesting that the abnormal NAA/Cr ratio of the right putamen is linked to wakefulness in patients with insomnia disorder and may serve as a potential biomarker of insomnia disorder.

Amino acid metabolism in glioma: in vivo MR-spectroscopic detection of alanine as a potential biomarker of poor survival in glioma patients.

Reprogramming of amino acid metabolism is relevant for initiating and fueling tumor formation and growth. Therefore, there has been growing interest in anticancer therapies targeting amino acid metabolism. While developing personalized therapeutic approaches to glioma, in vivo proton magnetic resonance spectroscopy (MRS) is a valuable tool for non-invasive monitoring of tumor metabolism. Here, we evaluated MRS-detected brain amino acids and myo-inositol as potential diagnostic and prognostic biomarkers in glioma. We measured alanine, glycine, glutamate, glutamine, and myo-inositol in 38 patients with MRI-suspected glioma using short and long echo-time single-voxel PRESS MRS sequences. The detectability of alanine, glycine, and myo-inositol and the (glutamate + glutamine)/total creatine ratio were evaluated against the patients' IDH mutation status, CNS WHO grade, and overall survival. While the detection of alanine and non-detection of myo-inositol significantly correlated with IDH wildtype (p = 0.0008, p = 0.007, respectively) and WHO grade 4 (p = 0.01, p = 0.04, respectively), glycine detection was not significantly associated with either. The ratio of (glutamate + glutamine)/total creatine was significantly higher in WHO grade 4 than in 2 and 3. We found that the overall survival was significantly shorter in glioma patients with alanine detection (p = 0.00002). Focusing on amino acids in MRS can improve its diagnostic and prognostic value in glioma. Alanine, which is visible at long TE even in the presence of lipids, could be a relevant indicator for overall survival.

Metabolic profiling of atypical meningioma and recurrent meningioma: a comparative analysis with proton magnetic resonance spectroscopy.

Meningiomas are predominantly benign, but some cases exhibit recurrent growth after surgery and undergo malignant transformation to WHO grade 2 or grade 3. Despite progress in genetic analyses, advancements in metabolomic analysis remain less established. Herein, the authors investigated metabolic activity differences between WHO grade 1 meningiomas and WHO grade 2 or 3 meningiomas by noninvasively using proton magnetic resonance spectroscopy (1H-MRS), aiming to preoperatively estimate malignancy. They also reviewed the literature to elucidate this aspect of meningioma research. At Ryukyu University Hospital, the authors focused on 93 patients diagnosed with meningioma between 2011 and 2021. The inclusion criteria encompassed prior surgery, pathological diagnoses of meningioma, and preoperative 1H-MRS. Group I included 71 patients with WHO grade 1 meningioma and group II included 22 patients, comprising 19 and 3 with WHO grade 2 and 3 meningioma, respectively. The authors retrospectively conducted a comparative analysis of patient backgrounds and tumor metabolites. Group I and II did not differ significantly in terms of patient demographic characteristics (age and sex). Group II demonstrated a significantly lower extent of tumor resection (p < 0.01), higher MIB-1 labeling index (LI) (p < 0.05), higher incidence of prior irradiation (p < 0.001), and increased rate of tumor recurrence (p = 0.005) compared to group I. According to 1H-MRS, all metabolites, except lactate, displayed significantly higher median creatine (Cr) ratios in group II than group I: glutamine/Cr was 8.46, glutamate/Cr was 9.49, lipid/Cr was 11.36, and choline/Cr was 2.77. According to the receiver operating characteristic (ROC) analysis, glutamine had the largest area under the curve of 0.765 among 10 metabolites, and the cutoff value for distinguishing between group I and II was 5.76. In cases pathologically graded as WHO grade 2 or 3 meningiomas, metabolic products such as glutamine, glutamate, lipids, and choline increased significantly. These changes were correlated with elevation of the MIB-1 LI. In group II, the mean MIB-1 LI was 8.58, significantly higher than in group I, suggesting a strong association with pathological malignancy. Therefore, 1H-MRS may help to noninvasively predict tumor metabolic activity and tumor recurrence. Furthermore, the authors concluded from the ROC analysis that glutamine may be a potential indicator of future growth of meningioma and benefits of early surgery.

Spectrophotometric and chromatographic analysis of creatine:creatinine crystals in urine

Creatinine is the end product of the catabolism of creatine and creatine phosphate. Creatine phosphate serves as a reservoir of high-energy phosphate, especially in skeletal and cardiac muscle. Besides typical known changes in serum and urinary creatinine concentrations, rare cases associated with changes in serum and urinary creatine levels have been described in the literature in humans. These cases are mostly linked to an excessive intake of creatine ethyl ester or creatine monohydrate, often resulting in increased urine creatinine concentrations. In addition, it is known that at such elevated creatinine concentrations, creatinine crystallisation may occur in the urine. Analysis of crystals and urinary concrements, often of heterogenous chemical composition, may provide diagnostic and therapeutic hints to the benefit of the patient. The aim of the present work was to analyze urine crystals of unclear composition with microscopic and spectroscopic techniques.On routine microscopic analysis of urine, a preliminary suspicion of uric acid or creatinine crystals was expressed. The crystals were of a cuboid shape and showed polarization effects in microscopy. The dried urine sample was whitish-orange in colour, odourless and dissolved well in water. Protein concentration in dry weight (DW) urine was about 0.3 mg/mg. The measured zinc content in the studied sample was approximately 660 µg/g DW sample and copper content was approximately 64 µg/g DW sample. A lead signal of around 10 µg/g DW sample was also observed. UV–Vis analysis showed a maximum creatine peak around 220 nm, compatible with the spectrum of creatinine with a maximum peak of 230 nm. Using HPLC technique, an extreme high ratio of creatine to creatinine of about 38 was measured, which led to the conclusion of the occurrence of rare creatine crystals in urine.

The Ethyl Acetate Extract of Phyllanthus emblica L. Alleviates Diabetic Nephropathy in a Murine Model of Diabetes.

Oil-Gan is the fruit of the genus Phyllanthus emblica L. The fruits have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN throughout the disease course. The primary aim of this study was to examine the protective effects (including analyses of urine and blood, and inflammatory cytokine levels) and mechanisms of the ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy; the secondary aim was to examine the expression levels of p- protein kinase Cα (PKCα)/t-PKCα in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included a vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. The administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing 3 (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. A histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.

Gender-related alterations of serum trace elements and neurometabolism in the anterior cingulate cortex of patients with major depressive disorder

BackgroundIt is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. Methods109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. ResultsIn individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. ConclusionsOur findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC.

The influence of anterior cingulateGABA+ and glutamateon emotion regulation and reactivity in adolescents and adults.

During adolescence, emotion regulation and reactivity are still developing and are in many ways qualitatively different from adulthood. However, the neurobiological processes underpinning these differences remain poorly understood, including the role of maturing neurotransmitter systems. We combined magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (dACC) and self-reported emotion regulation and reactivity in a sample of typically developed adolescents (n=37; 13-16 years) and adults (n=39; 30-40 years), and found that adolescents had higher levels of glutamate to total creatine (tCr) ratio in the dACC than adults. A glutamate Í age group interaction indicated a differential relation between dACC glutamate levels and emotion regulation in adolescents and adults, and within-group follow-up analyses showed that higher levels of glutamate/tCr were related to worse emotion regulation skills in adolescents. We found no age-group differences in gamma-aminobutyric acid+macromolecules (GABA+) levels; however, emotion reactivity was positively related to GABA+/tCr in the adult group, but not in the adolescent group. The results demonstrate that there are developmental changes in the concentration of glutamate, but not GABA+, within the dACC from adolescence to adulthood, in accordance with previous findings indicating earlier maturation of the GABA-ergic than the glutamatergic system. Functionally, glutamate and GABA+ are positively related to emotion regulation and reactivity, respectively, in the mature brain. In the adolescent brain, however, glutamate is negatively related to emotion regulation, and GABA+ is not related to emotion reactivity. The findings are consistent with synaptic pruning of glutamatergic synapses from adolescence to adulthood and highlight the importance of brain maturational processes underlying age-related differences in emotion processing.

Study of variables in the ratio of creatine in the blood of short, medium and long distance for runners

The study of the effect of training on jogging on serum creatine levels is important to identify the level of developmental and functional development, as well as understanding the process of developing appropriate training programs for short, medium- and long-term effectiveness. Creatine is an important indicator in the human body by calculating the blood quantities in the day following the race or training in order to know the work of the kidneys or any damage in them, and to establish a sound path and right to our coaches and our players relying on the analysis that helps them in the development of their achievement. The aim of the study was to study the variables in the ratio of creatine in the blood of short, medium and long distances of 10 players. The experimental approach - equal groups due to its relevance to the subject of the research. The researchers concluded: The presence of effects of significant significance for the athletes in the various energy systems in the ratio of creatine in the blood of the players and according to the high intensity and effort in the functional work of the two kidneys. Short-range athletes were more susceptible to high blood creatinine, as they needed higher voltage than medium and short hips.

Estimating the synaptic density deficit in Alzheimer's disease using multi-contrast CEST imaging.

In vivo noninvasive imaging of neurometabolites is crucial to improve our understanding of the underlying pathophysiological mechanism in neurodegenerative diseases. Abnormal changes in synaptic organization leading to synaptic degradation and neuronal loss is considered as one of the primary factors driving Alzheimer's disease pathology. Magnetic resonance based molecular imaging techniques such as chemical exchange saturation transfer (CEST) and magnetic resonance spectroscopy (MRS) can provide neurometabolite specific information which may relate to underlying pathological and compensatory mechanisms. In this study, CEST and short echo time single voxel MRS was performed to evaluate the sensitivity of cerebral metabolites to beta-amyloid (Aβ) induced synaptic deficit in the hippocampus of a mouse model of Alzheimer's disease. The CEST based spectra (Z-spectra) were acquired on a 9.4 Tesla small animal MR imaging system with two radiofrequency (RF) saturation amplitudes (1.47 μT and 5.9 μT) to obtain creatine-weighted and glutamate-weighted CEST contrasts, respectively. Multi-pool Lorentzian fitting and quantitative T1 longitudinal relaxation maps were used to obtain metabolic specific apparent exchange-dependent relaxation (AREX) maps. Short echo time (TE = 12 ms) single voxel MRS was acquired to quantify multiple neurometabolites from the right hippocampus region. AREX contrasts and MRS based metabolite concentration levels were examined in the ARTE10 animal model for Alzheimer's disease and their wild type (WT) littermate counterparts (age = 10 months). Using MRS voxel as a region of interest, group-wise analysis showed significant reduction in Glu-AREX and Cr-AREX in ARTE10, compared to WT animals. The MRS based results in the ARTE10 mice showed significant decrease in glutamate (Glu) and glutamate-total creatine (Glu/tCr) ratio, compared to WT animals. The MRS results also showed significant increase in total creatine (tCr), phosphocreatine (PCr) and glutathione (GSH) concentration levels in ARTE10, compared to WT animals. In the same ROI, Glu-AREX and Cr-AREX demonstrated positive associations with Glu/tCr ratio. These results indicate the involvement of neurotransmitter metabolites and energy metabolism in Aβ-mediated synaptic degradation in the hippocampus region. The study also highlights the feasibility of CEST and MRS to identify and track multiple competing and compensatory mechanisms involved in heterogeneous pathophysiology of Alzheimer's disease in vivo.

The effects of sandplay therapy on the limbic system and prefrontal cortex in women with generalized anxiety disorder

Generalized Anxiety Disorder (GAD) is a common disorder characterized by psychological and neurophysiological impairments. Previous studies show that Jungian Sandplay Therapy (SPT) effectively improves anxiety symptoms in individuals with GAD. This study explores whether clinical symptom improvement from using SPT also involves changes in brain functioning. The study focused on the brain regions implicated in GAD, including the hippocampus, amygdala, thalamus, and prefrontal cortex (PFC). Magnetic resonance spectroscopy was used to target these brain regions to measure metabolite changes, specifically in the N-Acetylaspartate to creatine (NAA/Cr) ratio—a measure of neuronal viability. A within-subject pre-post design was utilized with adult females from Indonesia diagnosed with GAD (n = 6, ages 21 to 40). Thirty sessions of SPT were provided weekly. Results from both clinical measures of anxiety (HAM-A and GAD-7) indicated mean pretest scores in the clinical range, with average posttest scores below the clinical range for GAD. Likewise, the NAA/Cr ratio mean scores for the hippocampus, amygdala, and PFC were outside the healthy range before and trended toward or into the healthy range after treatment. The NAA/Cr ratio mean scores in the thalamus were in the healthy range before treatment and remained in the healthy range after treatment. This study concludes that SPT effectively improves clinical anxiety symptoms in individuals with GAD and may also improve metabolic brain functioning in the limbic system and PFC. Limitations, implications, and further research are discussed.

Diagnostic algorithm for glioma grading using dynamic susceptibility contrast‑enhanced magnetic resonance perfusion and proton magnetic resonance spectroscopy.

The present retrospective study aimed to investigate the diagnostic capacity of and design a diagnostic algorithm for dynamic susceptibility contrast-enhanced MRI (DSCE-MRI) and proton magnetic resonance spectroscopy (1H-MRS) in grading low-grade glioma (LGG) and high-grade glioma (HGG). This retrospective study enrolled 57 patients, of which 14 had LGG and 43 had HGG, five had World Health Organization grade 1, nine had grade 2, 20 had grade 3 and 23 had grade 4 glioma. All subjects underwent a standard 3T MRI brain tumor protocol with conventional MRI (cMRI) and advanced techniques, including DSCE-MRI and 1H-MRS. The associations of grade categorization with parameters in tumor and peritumor regions in the DSCE-MRI were examined, including tumor relative cerebral blood volume (TrCBV) and peripheral relative (Pr)CBV, as well as Tr and Pr cerebral blood flow (CBF) and 1H-MRS, including the creatine (Cr) and N-acetyl aspartate (NAA) ratios of choline (Cho), i.e. the TCho/NAA, PCho/NAA, TCho/Cr and PCho/Cr metabolite ratios. The data were compared using the Mann-Whitney U-test, independent samples t-test, Chi-square test, Fisher's exact test and receiver operating characteristic curve analyses. Decision tree analysis established an algorithm based on cutoffs for specified significant parameters. The PrCBF had the highest performance in the preoperative prediction of histological glioma grading, followed by the TrCBV, PrCBF, TrCBV, PCho/NAA, PCho/Cr, TCho/NAA and TCho/Cr. An algorithm based on TrCBV, PrCBF and TCho/Cr had a diagnostic accuracy of 100% for LGG and 90.7% for HGG and a misclassification risk of 7%. The cutoffs (sensitivity and specificity) were 2.48 (86 and 100%) for TrCBV, 1.26 (83.7 and 100%) for PrCBF and 3.18 (69.8 and 78.6%) for TCho/Cr. In conclusion, the diagnostic algorithm using TrCBV, PrCBF and TCho/Cr values, which were obtained from DSCE-MRI and 1H-MRS, increased diagnostic accuracy to 100% for LGGs and 90.7% for HGGs compared to previous studies using conventional MRI. This non-invasive advanced MRI diagnostic algorithm is recommended for clinical application for constructing preoperative strategies and prognosis of patients with glioma.

The impact of weekly semaglutide, a glucagon-like peptide-1 agonist, on kidney outcomes in adults with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with kidney complications. This study aims to investigate the effects of weekly subcutaneous semaglutide, a GLP-1 agonist, on kidney outcomes. This retrospective cohort study was conducted in nephrology and endocrinology clinics at KFAFH from March 2022 to February 2023. The sample size was determined based on hospital records, and randomly selected patients who met the inclusion criteria were included. The inclusion criteria included adults with T2DM who were on weekly subcutaneous semaglutide for 6 months or longer. Patients with type 1 diabetes mellitus, pregnant or gestational diabetes patients, individuals who added other antidiabetic medications during the study period, and participants who refused to be involved were excluded from the study. The study included participants aged between 42 and 85 years, with a mean age of 65.38 years, and the majority (58.7%) were males. There was a significant weight and BMI reduction observed in all patients, with P values <0.001 for both. The average weight reduction was 2.97 kg (SD = 2.34, 95% CI 1.65-3.30), and the average Body (BMI) reduction was 1.16 (SD = 0.91, 95% CI 1.03-1.29). A vast majority of participants (98.5%) reported a weight loss of at least 1 kg, and 13.8% of participants experienced a change in BMI category from higher to lower. No patients reported an increase in the BMI category. There was a significant reduction in glycohemoglobin (HbA1c) measurements from 9.18 pretreatment to 8.13 posttreatment, with an average reduction of 1.05 units (SD = 1.84, 95% CI 0.79-1.31). The majority of participants (70.9%) reported a reduction in HbA1c of at least 0.1 unit. Although there was a slight decrease in estimated glomerular filtration rate (eGFR) values on average (1.35 units), the change was not statistically significant (P = 0.059). More than half of the participants (51.5%) reported an increase in eGFR, 45.4% reported a decrease, and 3.1% reported no change. There was a statistically significant reduction in urinary albumin-to-creatinine ratio (UACR) values from a median of 5.97 pretreatment to a median of 5.60 post-treatment. The median decrease was 0.72 units, with one-third (33.3%) reporting an increase and two-thirds (66.7%) reporting a decrease in values. The correlation analysis revealed no significant association between the total quantity of semaglutide taken and the magnitude of changes. Our study on the impact of weekly semaglutide in adults with T2DM reveals positive effects on kidney outcomes, including weight loss, glycemic control and improved urine albumin creatine ratio, and a reduced risk of nephropathy. These findings highlight the potential of semaglutide as a safe and effective treatment option for improving renal health in individuals with T2DM.

Sparsentan is superior to losartan in the gddY mouse model of IgA nephropathy.

The mechanism leading to the development of immunoglobulin A nephropathy (IgAN) remains to be completely understood. Endothelin-1 (ET-1) as well as angiotensin II (AngII) promote glomerular injury, tubulointerstitial inflammation and fibrosis leading to chronic kidney disease. Sparsentan, a dual endothelin angiotensin receptor antagonist, recently received accelerated approval in the USA for the reduction of proteinuria in adults with IgAN at high risk of disease progression. To elucidate the mechanisms by which sparsentan is efficacious in IgAN, we examined the effect of treatment in gddY mice, a spontaneous IgAN mouse model, versus the monoselective angiotensin II type 1 receptor (AT1R) antagonist, losartan, on the development of renal injury at doses resulting in similar blood pressure lowering. Four-week-old gddY mice were given control chow, chow containing sparsentan or drinking water containing losartan until 12 or 20 weeks old. Remarkably, the albumin:creatine ratio (ACR) was attenuated more rapidly and to a greater extent in mice treated with sparsentan than those treated with losartan. The decrease in ACR from baseline after 4 weeks of treatment correlated with beneficial effects of sparsentan on glomerulosclerosis and protection of podocytes and glycocalyx after 16 weeks of treatment across treatment groups; thus, sparsentan treatment delayed development of renal injury to a greater extent than losartan. Expression of mRNA for ET-1, endothelin type A receptor and AT1R and proinflammatory genes was upregulated in 12-week-old gddY mice and was prevented by sparsentan and losartan to a comparable extent. The results of this study, and in light of the results of the phase 3 PROTECT trial, provide a novel perspective and understanding of the mechanisms by which sparsentan has a beneficial renoprotective effect against IgAN compared with AT1R antagonism alone.

Altered metabolites in the periaqueductal gray of COVID-19 patients experiencing headaches: a longitudinal MRS study.

Headache is one of the most common symptoms of acute COVID-19 infection. However, its mechanisms remain poorly understood, and there is a lack of studies investigating changes in the periaqueductal gray (PAG) in COVID-19 patients exhibiting headaches. The study aimed to explore the alterations in metabolites of the PAG pre- and post-COVID-19 infection in individuals who suffered from headaches during the acute phase of the disease using proton magnetic resonance spectroscopy (1H-MRS). Fifteen participants who experienced headaches during the acute phase of COVID-19 were recruited. All subjects underwent two proton magnetic resonance spectroscopy (1H-MRS) examinations focusing on the PAG before and after they were infected. Metabolite changes were assessed between the pre- and post-infection groups. The combined glutamine and glutamate/total creatine ratio (Glx/tCr) was increased in the PAG following COVID-19 infection. The total choline/total creatine ratio (tCho/tCr) in the pre-infection group was negatively correlated with the duration of headache during the COVID-19 acute phase. The present study indicates that PAG plays a pivotal role in COVID-19 headaches, thereby supporting the involvement of trigeminovascular system activation in the pathophysiology of COVID-19 headaches.

Study on the Relationship Between MRI Functional Imaging and Multiple Immunohistochemical Features of Glioma: A Noninvasive and More Precise Glioma Management.

To investigate the performance of diffusion-tensor imaging (DTI) and hydrogen proton magnetic resonance spectroscopy (1H-MRS) parameters in predicting the immunohistochemistry (IHC) biomarkers of glioma. Patients with glioma confirmed by pathology from March 2015 to September 2019 were analyzed, the preoperative DTI and 1H-MRS images were collected, apparent diffusion coefficient (ADC) and fractional anisotropy (FA), in the lesion area were measured, the relative values relative ADC (rADC) and relative FA (rFA) were obtained by the ratio of them in the lesion area to the contralateral normal area. The peak of each metabolite in the lesion area of 1H-MRS image: N-acetylaspartate (NAA), choline (Cho), and creatine (Cr), and metabolite ratio: NAA/Cho, NAA/(Cho + Cr) were selected and calculated. The preoperative IHC data were collected including CD34, Ki-67, p53, S-100, syn, vimentin, NeuN, Nestin, and glial fibrillary acidic protein. One predicting parameter of DTI was screened, the rADC of the Ki-67 positive group was lower than that of the negative group. Two parameters of 1H-MRS were found to have significant reference values for glioma grades, the NAA and Cr decreased as the grade of glioma increased, moreover, Ki-67 Li was negatively correlated with NAA and Cr. NAA and Cr have potential application value in predicting glioma grades and tumor proliferation activity. Only rADC has predictive value for Ki-67 expression among DTI parameters.

Investigating neural dysfunction with abnormal protein deposition in Alzheimer’s disease through magnetic resonance spectroscopic imaging, plasma biomarkers, and positron emission tomography

In Alzheimer’s disease (AD), aggregated abnormal proteins induce neuronal dysfunction. Despite the evidence supporting the association between tau proteins and brain atrophy, further studies are needed to explore their link to neuronal dysfunction in the human brain. To clarify the relationship between neuronal dysfunction and abnormal proteins in AD-affected brains, we conducted magnetic resonance spectroscopic imaging (MRSI) and assessed the neurofilament light chain plasma levels (NfL). We evaluated tau and amyloid-β depositions using standardized uptake value ratios (SUVRs) of florzolotau (18F) for tau and 11C-PiB for amyloid-β positron emission tomography in the same patients. Heatmaps were generated to visualize Z scores of glutamate to creatine (Glu/Cr) and N-acetylaspartate to creatine (NAA/Cr) ratios using data from healthy controls. In AD brains, Z score maps revealed reduced Glu/Cr and NAA/Cr ratios in the gray matter, particularly in the right dorsolateral prefrontal cortex (rDLPFC) and posterior cingulate cortex (PCC). Glu/Cr ratios were negatively correlated with florzolotau (18F) SUVRs in the PCC, and plasma NfL levels were elevated and negatively correlated with Glu/Cr (P = 0.040, r = −0.50) and NAA/Cr ratios (P = 0.003, r = −0.68) in the rDLPFC. This suggests that the abnormal tau proteins in AD-affected brains play a role in diminishing glutamate levels. Furthermore, neuronal dysfunction markers including Glu/tCr and NAA/tCr could potentially indicate favorable clinical outcomes. Using MRSI provided spatial information about neural dysfunction in AD, enabling the identification of vulnerabilities in the rDLPFC and PCC within the AD’s pathological context.

Magnetic Resonance Spectroscopy metabolites as biomarkers of Alzheimer’s Disease

AbstractBackgroundMagnetic resonance spectroscopy (MRS) is a non‐invasive method of evaluating metabolite levels in the cerebral cortex. Measurable metabolites can provide markers of neuronal damage, glial activation and, neurotransmission, pathological features of Alzheimer’s disease. Here we sought to establish the effectiveness of several metabolites as biomarkers for Alzheimer’s disease.Method198 participants with a single‐voxel 1H MRS scan were enrolled (n = 170 participants living with Alzheimer’s disease, n = 28 healthy controls). All participants underwent 3‐tesla magnetic resonance imaging and cognitive assessment with the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS‐cog). An experienced radiographer placed an 8cm3 voxel within the posterior cingulate cortex for single‐voxel 1H MRS acquisition. Scans were then processed to evaluate levels of N‐acetylaspartate, myo‐inositol, choline, and glutamate. Creatine peak was additionally evaluated as a reference. N‐acetylaspartate/creatine, myo‐inositol /creatine, choline/creatine ratios and glutamate were compared between Alzheimer’s participants and controls to calculate the effect size. Correlations were then performed between metabolite ratios and ADAS‐cog scores.ResultN‐acetylaspartate/creatine effectively distinguished between Alzheimer’s patients and healthy controls (Cohens D = 0.83) with a lowered ratio in Alzheimer’s participants. Elevated glutamate signal and myo‐inositol/creatine ratios were also displayed in Alzheimer’s patients (Cohens D = 0.62 and 0.69, respectively). Choline/creatine ratio displayed no significant difference between groups (Cohens D = 0.26). Lower N‐acetylaspartate /creatine and glutamate correlated with higher ADAS‐cog scores (r = ‐0.29, p &lt; 0.001, CIs: ‐0.42 to ‐0.14 and r = ‐0.30, p &lt; 0.001, CIs: ‐0.44 to ‐0.16, respectively). Myo‐inositol and choline failed to correlate with cognitive impairment.ConclusionN‐acetylaspartate, a signature of neuronal damage, is an effective biomarker of Alzheimer’s disease and associated cognitive decline. Enhanced glial activity, measured with myo‐inositol, was shown in Alzheimer’s disease, suggesting that glial‐reactivity markers deserve consideration in the diagnosis of Alzheimer’s disease. Glutamate demonstrated the strongest association with cognitive impairment, despite showing a smaller effect size than N‐acetylaspartate and myo‐inositol in distinguishing between Alzheimer’s patients and controls. Together we establish MRS is a useful, non‐invasive biomarker of several pathological processes involved in the development of Alzheimer’s. Evaluation of N‐acetylaspartate, glutamate, and myo‐inositol may aid in the diagnosis of neurodegenerative disease, detecting markers undetectable by conventional MRI methodology.

Genetic evidence supporting the causal role of gut microbiota in chronic kidney disease and chronic systemic inflammation in CKD: a bilateral two-sample Mendelian randomization study.

The association of gut microbiota (GM) and chronic kidney disease (CKD), and the relevancy of GM and chronic systemic inflammation in CKD, were revealed on the basis of researches on gut-kidney axis in previous studies. However, their causal relationships are still unclear. To uncover the causal relationships between GM and CKD, as well as all known GM from eligible statistics and chronic systemic inflammation in CKD, we performed two-sample Mendelian randomization (MR) analysis. We acquired the latest and most comprehensive summary statistics of genome-wide association study (GWAS) from the published materials of GWAS involving GM, CKD, estimated glomerular filtration rate (eGFR), c-reactive protein (CRP) and urine albumin creatine ratio (UACR). Subsequently, two-sample MR analysis using the inverse-variance weighted (IVW) method was used to determine the causality of exposure and outcome. Based on it, additional analysis and sensitivity analysis verified the significant results, and the possibility of reverse causality was also assessed by reverse MR analysis during this study. At the locus-wide significance threshold, IVW method and additional analysis suggested that the protective factors for CKD included family Lachnospiraceae (P=0.049), genus Eubacterium eligens group (P=0.002), genus Intestinimonas (P=0.009), genus Streptococcu (P=0.003) and order Desulfovibrionales (P=0.001). Simultaneously, results showed that genus LachnospiraceaeUCG010 (P=0.029) was a risk factor for CKD. Higher abundance of genus Desulfovibrio (P=0.048) was correlated with higher eGFR; higher abundance of genus Parasutterella (P=0.018) was correlated with higher UACR; higher abundance of class Negativicutes (P=0.003), genus Eisenbergiella (P=0.021), order Selenomonadales (P=0.003) were correlated with higher CRP levels; higher abundance of class Mollicutes (0.024), family Prevotellaceae (P=0.030), phylum Tenericutes (P=0.024) were correlated with lower levels of CRP. No significant pleiotropy or heterogeneity was found in the results of sensitivity analysis, and no significant causality was found in reverse MR analysis. This study highlighted associations within gut-kidney axis, and the causal relationships between GM and CKD, as well as GM and chronic systemic inflammation in CKD were also revealed. Meanwhile, we expanded specific causal gut microbiota through comprehensive searches. With further studies for causal gut microbiota, they may have the potential to be new biomarkers for targeted prevention of CKD and chronic systemic inflammation in CKD.

1H-MRS neurometabolite profiles and motor development in school-aged children who are HIV-exposed uninfected: a birth cohort study.

Alterations in regional neurometabolite levels as well as impaired neurodevelopmental outcomes have previously been observed in children who are HIV-exposed uninfected (CHEU). However, little is known about how neurometabolite profiles may relate to their developmental impairment. This study aimed to compare neurometabolite concentrations in school-aged CHEU and children who are HIV-unexposed (CHU) and to explore associations of neurometabolite profiles with functional neurodevelopment in the context of perinatal HIV exposure. We used 3 T single voxel proton magnetic resonance spectroscopy (1H-MRS) to quantify absolute and relative neurometabolites in the parietal gray and parietal white matter in school-aged CHEU and aged- and community-matched CHU. Functional neurodevelopmental outcomes were assessed using the early learning outcome measure (ELOM) tool at 6 years of age. Our study included 152 school-aged children (50% males), 110 CHEU and 42 CHU, with an average age of 74 months at the neuroimaging visit. In an adjusted multiple linear regression analysis, significantly lower glutamate (Glu) concentrations were found in CHEU as compared to CHU in the parietal gray matter (absolute Glu, p = 0.046; Glu/total creatine (Cr+PCr) ratios, p = 0.035) and lower total choline to creatine ratios (GPC+PCh/Cr+PCr) in the parietal white matter (p = 0.039). Using factor analysis and adjusted logistic regression analysis, a parietal gray matter Glu and myo-inositol (Ins) dominated factor was associated with HIV exposure status in both unadjusted (OR 0.55, 95% CI 0.17-0.45, p = 0.013) and adjusted analyses (OR 0.59, 95% CI 0.35-0.94, p = 0.031). With Ins as one of the dominating metabolites, this neurometabolic factor was similar to that found at the age of two years. Furthermore, this factor was also found to be correlated with ELOM scores of gross motor development in CHEU (Pearson's r = -0.48, p = 0.044). In addition, in CHEU, there was a significant association between Ins/Cr+PCr ratios in the parietal white matter and ELOM scores of fine motor coordination and visual motor integration in CHEU (Pearson's r = 0.51, p = 0.032). Reduced Glu concentrations in the parietal gray matter may suggest regional alterations in excitatory glutamatergic transmission pathways in the context of perinatal HIV and/or antiretroviral therapy (ART) exposure, while reduced Cho ratios in the parietal white matter suggest regional myelin loss. Identified associations between neurometabolite profiles and gross and fine motor developmental outcomes in CHEU are suggestive of a neurometabolic mechanism that may underlie impaired motor neurodevelopmental outcomes observed in CHEU.