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Today, depression is a usual mental disorder that is associated with a depressed mood and loss of interest. Therefore, considering these problems, the main goal of the present research work was to develop a new multifunctional cost-effective citric acid-based dendritic structure (CAD) with the capability of antidepressant drug delivery. For this, at first, three different generations of citric acid dendrimer (CAD G1, CAD G2, and CAD G3) were synthesized through divergent methods. Afterward, each of the synthesized dendrimers was functionalized with lauryl alcohol (LAU), and CAD Gn-LAU was obtained. The fabricated samples were characterized for acute synthesis employing the Fourier transform infrared spectroscopy and proton nuclear magnetic resonance (1H NMR). The ratio of the PEG protons to LAU protons specified the percentage of LAU grafting on the dendrimer surface. The outcome displayed that the CAD G1, CAD G2, and CAD G3 were functionalized with LAU groups respectively at about 60, 60, and 33%. All CAD Gn (1–3) were able to encapsulate the fluoxetine (FXN) in its pristine or LAU functionalized form via high-affinity interactions. The highest FXN loading percentage was observed for CAD G3-LAU, at about 52%. The FXN release study approved the pH sensitivity of the prepared systems, which is the main criterion in a specific therapy. All in all, the findings met the aim and can suggest that the synthesized CAD Gn-LAU dendrimers are efficient carriers for FXN delivery in the desired way. [ABSTRACT FROM AUTHOR]

We study single-voxel in vivo proton magnetic resonance spectroscopy (MRS) of white matter in the brain of a 25 year old healthy male volunteer. The free induction decay (FID) data of short length (0.5KB) are encoded at a long echo time (272 ms) with and without water suppression at a clinical scanner of a weak magnetic field (1.5T). For these FIDs, the fast Fourier transform (FFT) gives sparse, rough and metabolically uninformative spectra. In such spectra, resolution and signal to noise ratio (SNR) are poor. Exponential or Gaussian filters applied to the FIDs can improve SNR in the FFT spectra, but only at the expense of the worsened resolution. This impacts adversely on in vivo MRS for which both resolution and SNR of spectra need to be very good or excellent, without necessarily resorting to stronger magnetic fields. Such a long sought goal is at last within reach by means of the optimized derivative fast Fourier transform (dFFT), which dramatically outperforms the FFT in every facet of signal estimations. The optimized dFFT simultaneously improves resolution and SNR in derivative spectra. They are presently shown to be of comparably high quality irrespective of whether water is suppressed or not in the course of FID encodings. The ensuing benefits of utmost relevance in the clinic include a substantial shortening of the patient examination time. The implied significantly better cost-effectiveness should make in vivo MRS at low-field clinical scanners (1.5T) more affordable to ever larger circles of hospitals worldwide. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a poor prognostic factor in cancer patients. In recent years, there have been reports that serum creatinine and cystatin C (Cr/CysC) ratio is associated with sarcopenia. However, the prognostic value of the Cr/CysC ratio in biliary tract cancer is unclear. We evaluated the impact of the Cr/CysC ratio on sarcopenia and prognosis in biliary tract cancer. Methods: We retrospectively reviewed the records of 190 patients with biliary tract cancer who had undergone surgical resection from January 2017 to March 2023. Frozen serum samples collected at the time of surgery were used to measure CysC. We calculated the Cr/CysC ratio and investigated the relationship with sarcopenia and the prognostic significance. Results: We calculated the cutoff value of the Cr/CysC ratio for low skeletal muscle index (SMI) (< 42 cm2/m2 for males and < 38 cm2/m2 for females). The optimal cutoff value of the Cr/CysC ratio was 0.848. The low Cr/CysC ratio group was significantly associated with higher preoperative CRP and lower albumin, lower SMI, lower handgrip strength, and higher intramuscular adipose tissue content. In multivariate analysis, patients with a low Cr/CysC ratio showed poorer overall survival (hazard ratio 2.60, 95% confidence interval 1.07–6.29, p = 0.033), which was significantly worse than in those with a high Cr/CysC ratio. Conclusions: In patients with biliary tract cancer, the Cr/CysC ratio showed weak correlation with sarcopenic indicators. However, the Cr/CysC ratio could be strong prognostic factor in biliary tract cancer. [ABSTRACT FROM AUTHOR]

N -acetylasparate and lactate are two prominent brain metabolites closely related to mitochondrial functioning. Prior research revealing lower levels of NAA and higher levels of lactate in the cerebral cortex of patients with schizophrenia suggest possible abnormalities in the energy supply pathway necessary for brain function. Given that stress and adversity are a strong risk factor for a variety of mental health problems, including psychotic disorders, we investigated the hypothesis that stress contributes to abnormal neuroenergetics in patients with schizophrenia. To test this hypothesis, we used the Stress and Adversity Inventory (STRAIN) to comprehensively assess the lifetime stressor exposure profiles of 35 patients with schizophrenia spectrum disorders and 33 healthy controls who were also assessed with proton magnetic resonance spectroscopy at the anterior cingulate cortex using 3 Tesla scanner. Consistent with the hypothesis, greater lifetime stressor exposure was significantly associated with lower levels of N -acetylasparate (β = −0.36, p =.005) and higher levels of lactate (β = 0.43, p =.001). Moreover, these results were driven by patients, as these associations were significant for the patient but not control group. Though preliminary, these findings suggest a possible role for stress processes in the pathophysiology of abnormal neuroenergetics in schizophrenia. [ABSTRACT FROM AUTHOR]

Posttraumatic stress disorder (PTSD) is a psychiatric condition characterized by a prolonged stress response to potentially life-threatening events long after the event has passed. Understanding factors related to recovery from traumatic life events may inform novel targets for intervention. There is emerging preclinical evidence that creatine (Cr), a molecule critical to brain bioenergetics, may be a neurobiological marker of stress reactivity and recovery. 25 US Veterans (8 female) completed the Life Events Checklist for DSM-5, which assessed different types of traumatic events. Veterans were also asked to rate the subjective stress of each traumatic event on a 1–10 scale currently (Current Stress) and at the time the event occurred (Past Stress). Stress recovery was quantified as the difference between Current and Past Stress. Current PTSD symptoms were also assessed using the PTSD Checklist for DSM-5. Cr concentrations in the anterior cingulate cortex (ACC) were measured in the anterior cingulate cortex using proton magnetic resonance spectroscopy (1H-MRS). Higher levels of Cr were associated with self-reported stress recovery from participants' most traumatic life event. Cr was not related to number of different types of traumatic life events or current PTSD symptoms. The sample size was relatively small. Stress recovery was measured via retrospective self-report. Future experimental work in humans should clarify the protective role of Cr in recovery from trauma. ACC concentrations of Cr may be an important neurochemical factor related to stress recovery. Future work should investigate Cr as a possible protective factor against the effects of traumatic stress. • Creatine is necessary for healthy brain metabolism and changes with stress. • Creatine levels were measured in trauma-exposed veterans. • Higher creatine levels were associated with greater recovery from trauma. • The role of creatine in posttraumatic stress disorder should be further studied. [ABSTRACT FROM AUTHOR]

N -acetyl aspartate (NAA) is a marker of neuronal integrity and metabolism. Deficiency in neuronal plasticity and hypometabolism are implicated in Major Depressive Disorder (MDD) pathophysiology. To test if cerebral NAA concentrations decrease progressively over the MDD course, we conducted a pre-registered meta-analysis of Proton Magnetic Resonance Spectroscopy (1H-MRS) studies comparing NAA concentrations in chronic MDD (n = 1308) and first episode of depression (n = 242) patients to healthy controls (HC, n = 1242). Sixty-two studies were meta-analyzed using a random-effect model for each brain region. NAA concentrations were significantly reduced in chronic MDD compared to HC within the frontal lobe (Hedges' g = −0.330; p = 0.018), the occipital lobe (Hedges' g = −0.677; p = 0.007), thalamus (Hedges' g = −0.673; p = 0.016), and frontal (Hedges' g = −0.471; p = 0.034) and periventricular white matter (Hedges' g = −0.478; p = 0.047). We highlighted a gap of knowledge regarding NAA levels in first episode of depression patients. Sensitivity analyses indicated that antidepressant treatment may reverse NAA alterations in the frontal lobe. We highlighted field strength and correction for voxel grey matter as moderators of NAA levels detection. Future studies should assess NAA alterations in the early stages of the illness and their longitudinal progression. • We compared 1H-MRS NAA levels between Major Depressive Disorder (MDD) and controls. • Only 8 studies reported NAA levels in first episode of depression. • Thalamic, frontal, occipital NAA was lower in chronic MDD compared to controls. • Antidepressants may reverse frontal NAA deficits, but further research is needed. • Field strength and correction for voxel grey matter fraction modify NAA detection. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Metabolites in biofluids can serve as biomarkers for diagnosing diseases and monitoring body conditions. Among the available biofluids, interstitial fluid (ISF) in the skin has garnered considerable attention owing to its advantages, which include inability to clot, easy access to the skin, and possibility of incorporating wearable devices. However, the scientific understanding of skin ISF composition is limited. In this study, we aimed to compare metabolites between skin dialysate containing metabolites from the skin ISF and venous blood (plasma) samples, both collected under resting states. We collected forearm skin dialysate using intradermal microdialysis alongside venous blood (plasma) samples from 12 healthy young adults. We analyzed these samples using capillary electrophoresis–fourier transform mass spectrometry–based metabolomics (CE–FTMS). Significant positive correlations were observed in 39 metabolites between the skin dialysate and plasma, including creatine (a mitochondrial disease biomarker), 1-methyladenosine (an early detection of cancer biomarker), and trimethylamine N-oxide (a posterior predictor of heart failure biomarker). Based on the Human Metabolome Technologies database, we identified 12 metabolites unique to forearm skin dialysate including nucleic acids, benzoate acids, fatty acids, amino acids, ascorbic acid, 3-methoxy-4-hydroxyphenylethyleneglycol (an Alzheimer's disease biomarker), and cysteic acid (an acute myocardial infarction biomarker). We show that some venous blood biomarkers may be predicted from skin dialysate or skin ISF, and that these fluids may serve as diagnostic and monitoring tools for health and clinical conditions. • Skin interstitial fluid offers non-clotting, easy access from the skin surface. • Identified 12 key metabolites in skin dialysate by using CE–FTMS–based metabolomics. • Skin dialysate positively correlates with plasma in 39 metabolites. [ABSTRACT FROM AUTHOR]

Although magnetic resonance spectroscopy (MRS) has provided in vivo measurements of brain chemical profiles in bipolar disorder (BD), there are no data on clinically and therapeutically important onset polarity (OP) and predominant polarity (PP). We conducted a proton MRS study in BD polarity subphenotypes, focusing on emotion regulation brain regions. Forty-one euthymic BD patients stratified according to OP and PP and sixteen healthy controls (HC) were compared. 1H-MRS spectra of the anterior and posterior cingulate cortex (ACC, PCC), left and right hippocampus (LHIPPO, RHIPPO) were acquired at 3.0T to determine metabolite concentrations. We found significant main effects of OP in ACC mI, mI/tNAA, mI/tCr, mI/tCho, PCC tCho, and RHIPPO tNAA/tCho and tCho/tCr. Although PP had no significant main effects, several medium and large effect sizes emerged. Compared to HC, manic subphenotypes (i.e., manic-OP, manic-PP) showed greater differences in RHIPPO and PCC, whereas depressive suphenotypes (i.e., depressive-OP, depressive-PP) in ACC. Effect sizes were consistent between OP and PP as high intraclass correlation coefficients (ICC) were confirmed. Our findings support the utility of MRS in the study of the neurobiological underpinnings of OP and PP, highlighting that the regional specificity of metabolite changes within the emotion regulation network consistently marks both polarity subphenotypes. [ABSTRACT FROM AUTHOR]

Neurological complications of the COVID-19 infection may be caused in part by local neurochemical and structural abnormalities that could not be detected during routine medical examinations. We examined within subject neurometabolic and structural brain alterations from pre-to post-COVID-19 in the hippocampal region of three elderly individuals (aged 63–68 years) who had a COVID-19 infection with mild symptoms. Patients were participating in an interventional study in which they were closely monitored at the time they were diagnosed with COVID-19. Patients 1 and 2 just completed 18–20 resistance training sessions prior to their diagnosis. Patient 3 was assigned to a non-training condition in the same study. Whole brain magnetic resonance imaging (MRI) images and proton magnetic resonance spectroscopy (1H-MRS) of the left hippocampus were collected before and after infection. Structural and spectroscopic imaging measures post-COVID-19 were contrasted to the pre-COVID-19 measures and were compared with values for Minimal Detectable Change at 95% (MDC 95) and 90% (MDC 90) confidence from a group of six elderly (aged 60–79 years) without COVID-19 that participated in the same study. After SARS-COV-2 infection, we observed a reduction of glutamate-glutamine (Glx) in Patients 1 and 2 (≥ 42.0%) and elevation of myo-inositol (mIns) and N -acetyl-aspartate (NAA) in Patient 3 (≥ 36.4%); all > MDC 90. MRI findings showed increased (Patients 1 and 2) or unchanged (Patient 3) hippocampal volume. Overall, findings from this exploratory study suggest that mild COVID-19 infection could be associated with development of local neuroinflammation and reduced glutamate levels in the hippocampus. Our 1H-MRS findings may have clinical value for explaining chronic neurological and psychological complaints in COVID-19 long-haulers. • 1H-MRS spectra and MRI images were collected from hippocampus of 3 COVID-19 patients. • COVID-19 disease was associated with increased myoinositol and reduced Glx levels. • Resistance trained patients showed hippocampal volume increase despite COVID-19. • COVID-19 disease was associated with increased anxiety and depression levels. • 1H-MRS may be applied to detect neurochemical abnormalities in COVID-19 long-haulers. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the response patterns of circulating lipids to exercise and diet interventions in nonalcoholic fatty liver disease (NAFLD). Methods: The 8.6-month four-arm randomized controlled study comprised 115 NAFLD patients with prediabetes who were assigned to aerobic exercise (AEx; n = 29), low-carbohydrate diet (Diet; n = 28), AEx plus low-carbohydrate diet (AED; n = 29), and nonintervention (NI, n = 29) groups. Hepatic fat content (HFC) was quantified by proton magnetic resonance spectroscopy. Serum lipidomic analytes were measured using liquid chromatography-mass spectrometry. Results: After intervention, the total level of phosphatidylcholine (PC) increased significantly in the AEx group (P = 0.043), whereas phosphatidylethanolamine (PE) and triacylglycerol decreased significantly in the AED group (P = 0.046 and P = 0.036, respectively), and phosphatidylserine decreased in the NI group (P = 0.002). Changes of 21 lipid metabolites were significantly associated with changes of HFC, among which half belonged to PC. Most of the molecules related to insulin sensitivity belonged to sphingomyelin (40 of 79). Controlling for the change of visceral fat, the significant associations between lipid metabolites and HFC remained. In addition, baseline serum lipids could predict the response of HFC to exercise and/or diet interventions (PE15:0/18:0 for AED, area under the curve (AUC) = 0.97; PE22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0 for AEx, AUC = 0.90; and PC14:1(9Z)/19:1(9Z) for Diet, AUC = 0.92). Conclusions: Changes of lipidome after exercise and/or diet interventions were associated with HFC reductions, which are independent of visceral fat reduction, particularly in metabolites belonging to PC. Importantly, baseline PE could predict the HFC response to exercise, and PC predicted the response to diet. These results indicate that a circulating metabolomics panel can be used to facilitate clinical implementation of lifestyle interventions for NAFLD management. [ABSTRACT FROM AUTHOR]

Combining proton and phosphorus magnetic resonance spectroscopy offers a unique opportunity to study the oxidative and glycolytic components of metabolism in working muscle. This paper presents a 7 T proton calf coil design that combines dipole and loop elements to achieve the high performance necessary for detecting metabolites with low abundance and restricted visibility, specifically lactate, while including the option of adding a phosphorus array. We investigated the transmit, receive, and parallel imaging performance of three transceiver dipoles with six pair-wise overlap-decoupled standard or twisted pair receive-only coils. With a higher SNR and more efficient transmission decoupling, standard loops outperformed twisted pair coils. The dipoles with standard loops provided a four-fold-higher image SNR than a multinuclear reference coil comprising two proton channels and 32% more than a commercially available 28-channel proton knee coil. The setup enabled up to three-fold acceleration in the right–left direction, with acceptable g-factors and no visible aliasing artefacts. Spectroscopic phantom measurements revealed a higher spectral SNR for lactate with the developed setup than with either reference coil and fewer restrictions in voxel placement due to improved transmit homogeneity. This paper presents a new use case for dipoles and highlights their advantages for the integration in multinuclear calf coils. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance spectroscopy (1H MRS) presents a powerful tool for revealing molecular-level metabolite information, complementary to the anatomical insight delivered by magnetic resonance imaging (MRI), thus playing a significant role in in vivo/in vitro biological studies. However, its further applications are generally confined by spectral congestion caused by numerous biological metabolites contained within the limited proton frequency range. Herein, we propose a pure-shift-based 1H localized MRS method as a proof of concept for high-resolution studies of biological samples. Benefitting from the spectral simplification from multiplets to singlet peaks, this method addresses the challenge of spectral congestion encountered in conventional MRS experiments and facilitates metabolite analysis from crowded NMR resonances. The performance of the proposed pure-shift 1H MRS method is demonstrated on different kinds of samples, including brain metabolite phantom and in vitro biological samples of intact pig brain tissue and grape tissue, using a 7.0 T animal MRI scanner. This proposed MRS method is readily implemented in common commercial NMR/MRI instruments because of its generally adopted pulse-sequence modules. Therefore, this study takes a meaningful step for MRS studies toward potential applications in metabolite analysis and disease diagnosis. [ABSTRACT FROM AUTHOR]

There is a need to develop therapies for neonatal encephalopathy (NE) in low‐ and middle‐income countries (LMICs) where the burden of disease is greatest and therapeutic hypothermia (HT) is not effective. We aimed to assess the efficacy of melatonin following inflammation‐amplified hypoxia–ischaemia (IA‐HI) in the newborn piglet. The IA‐HI model accounts for the contribution of infection/inflammation in this setting and HT is not cytoprotective. We hypothesised that intravenous melatonin (5% ethanol, at 20 mg/kg over 2 h at 1 h after HI + 10 mg/kg/12 h between 24 and 60 h) is safe and associated with: (i) reduction in magnetic resonance spectroscopy lactate/N‐acetylaspartate (MRS Lac/sNAA); (ii) preservation of phosphorus MRS phosphocreatine/phosphate exchange pool (PCr/Epp); (iii) improved aEEG/EEG recovery and (iv) cytoprotection on immunohistochemistry. Male and female piglets underwent IA‐HI by carotid artery occlusion and reduction in FiO2 to 6% at 4 h into Escherichia coli lipopolysaccharide sensitisation (2 μg/kg bolus + 1 μg/kg/h over 12 h). At 1 h after IA‐HI, piglets were randomised to HI‐saline (n = 12) or melatonin (n = 11). There were no differences in insult severity between groups. Target melatonin levels (15–30 mg/L) were achieved within 3 h and blood ethanol levels were <0.25 g/L. At 60 h, compared to HI‐saline, melatonin was associated with a reduction of 0.197 log10 units (95% CrI [−0.366, −0.028], Pr(sup) 98.8%) in basal‐ganglia and thalamic Lac/NAA, and 0.257 (95% CrI [−0.676, 0.164], Pr(sup) 89.3%) in white matter Lac/NAA. PCr/Epp was higher in melatonin versus HI‐saline (Pr(sup) 97.6%). Melatonin was associated with earlier aEEG/EEG recovery from 19 to 24 h (Pr(sup) 95.4%). Compared to HI‐saline, melatonin was associated with increased NeuN+ cell density (Pr(sup) 99.3%) across five of eight regions and reduction in TUNEL‐positive cell death (Pr(sup) 89.7%). This study supports the translation of melatonin to early‐phase clinical trials. Melatonin is protective following IA‐HI where HT is not effective. These data guide the design of future dose‐escalation studies in the next phase of the translational pipeline. [ABSTRACT FROM AUTHOR]

Purpose: Urinary biomarkers are known to be able to diagnose renal damage caused by obstruction at an early stage. We evaluated the usefulness of urine N-acetyl-beta-D-glucosaminidase (NAG) to determine the prognosis of antenatal hydronephrosis. Materials and Methods: From January 2019 to December 2021, a retrospective study was performed on patients with grade 3 or 4 hydronephrosis. We analyzed the ultrasonographic findings and the urinary NAG/Cr ratio between the laparoscopic pyeloplasty (LP) group and active surveillance (AS) group. Results: A total of 21 children underwent LP for ureteropelvic junction (UPJ) obstruction and 14 children underwent AS. The mean age at the time of examination was 3.7 months (1.7-7.5 months) in the LP and 5.2 months (0.5-21.5 months) in the AS (p=0.564). The mean anteroposterior pelvic diameter was 30.0 mm (15.0-49.0 mm) in the LP and 16.7 mm (9.0-31.3 mm) in the AS (p=0.003). The mean renal parenchymal thickness was 2.6 mm (1.2-3.7 mm) in the LP and 3.8 mm (2.9-5.5 mm) in the AS (p=0.017). The urinary NAG/Cr ratio was 26.1 IU/g (9.8-47.4 IU/g) in the LP and 11.1 IU/g (2.6-18.1 IU/g) in the AS (p=0.003). After LP, the urinary NAG/Cr ratio was significantly reduced to 10.4 IU/g (3.4-14.2 IU/g) (p=0.023). Conclusions: The urinary NAG/Cr ratio, one of the biomarkers of acute renal injury, is closely related to the degree of hydronephrosis. Therefore, it may be useful to determine whether to perform surgery on the UPJ obstruction and to predict the prognosis. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the differences between resting and active thalamic neurometabolite levels and inhibitory function in obsessive compulsive disorder (OCD) patients with poor sleep quality (PSQ was defined as Pittsburgh Sleep Quality Index >5 and sleep efficiency ≤85%) compared to OCD patients with good sleep quality (GSQ) and healthy controls (HCs), as well as the relationship of these indices to obsessive compulsive symptoms. Functional magnetic resonance spectroscopy (fMRS) was used to measure resting and active thalamic neurometabolite levels in 72 subjects (20 HCs and 38 OCD patients included in study analysis). Response inhibition function was measured by the Go-Nogo task before and during MRS recording. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The symptoms of OCD, anxiety and depression were evaluated using relevant clinical scales. OCD patients exhibited significantly reduced Glx/Cr levels in the resting thalamus. The levels of resting thalamic Glu/Cr and Glx/Cr in OCD patients with PSQ were significantly lowest. OCD patients had significantly lower correct rates on Go tasks, higher error rates on Nogo tasks, and longer error average response times (EART) to the Nogo task. OCD patients with PSQ demonstrated the highest Nogo task error rate and the longest EART to Nogo task. Furthermore, PSQI scores exhibited negative correlations with Glu/Cr and Glx/Cr in the resting thalamus. OCD patients with PSQ demonstrated reduced levels of thalamic resting Glx and more pronounced response inhibitory function impairment. Aberrant neurometabolite levels in critical brain regions, coupled with heightened response inhibition function deficits, may be a neurobiological basis for the PSQ that OCD patients generally exhibit. [ABSTRACT FROM AUTHOR]

It 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. 109 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. In 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. Our 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. • Serum levels of Cu and CER decreased in men with MDD, while the Cu/Zn ratio increased in women with MDD. • In males with MDD, a gender-specific decrease in the NAA/PCr + Cr ratio was noted in the left ACC. • The Cu/Zn ratio and Fe levels in male MDD patients are associated with changes in neurometabolism in the ACC. [ABSTRACT FROM AUTHOR]

• MG patients were accompanied by cognitive decline. • MG patients have a combination of abnormal brain function and neurometabolites. • First study of investigating neurometabolites in vivo in patients with MG. Whether patients with myasthenia gravis (MG) exhibit cognitive impairment is controversial. Also the underlying mechanisms are unknown. We aimed to investigate alterations in cognitive function, neurometabolite levels, and brain function in patients with MG and to explore the associations between abnormal regional brain functional activity, neurometabolite concentrations in the MPFC and left thalamus, and cognitive activity in patients with MG. Neuropsychological tests, proton magnetic resonance spectroscopy, and resting-state functional magnetic resonance imaging were performed on 41 patients with MG and 45 race-, sex-, age-, and education-matched healthy controls (HCs). The results suggest that MG is accompanied by cognitive decline, as indicated by global cognitive function, visual-spatial function, language, memory, abnormalities in regional brain functional activity, and neurometabolite alterations (including GABA, NAA, and Cho) in the medial prefrontal cortex (MPFC) and left thalamus. Cognitive impairment in patients with MG may be related to abnormal regional brain functional activity and changes in neurometabolites, and regional brain functional activity may be modulated by specific neurometabolites. [ABSTRACT FROM AUTHOR]

Background: Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. Methods: We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. Discussion: Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990). [ABSTRACT FROM AUTHOR]

Introduction. To investigate the effects of acupuncture on endogenous metabolites in the liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) mice-based metabolomics. Methods. Proton nuclear magnetic resonance (1H-NMR) metabolomics combined with multivariate statistical analysis and univariate analysis were used to analyze the changes of endogenous metabolites in the liver of mice in each group and to provide new clinical ideas for acupuncture in the treatment of glycolipid metabolism disorders caused by T2DM and NAFLD. Results. After 4 weeks of continuous treatment, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), and triglyceride (TG) decreased significantly in mice in the acupuncture treatment group (ATG), and the content of liver glycogen increased significantly. Based on 1H-NMR metabolomic analysis, a total of 47 metabolites were identified in the liver of T2DM with NAFLD mice, of which eight metabolites: UDP-N-acetylglucosamine, adenosine, glutamate, isoleucine, ATP, 3-hydroxybutyric acid, NADP+, and leucine were significantly altered by acupuncture treatment. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it is found that acupuncture has an intervention effect on five metabolic pathways, mainly involving amino acid metabolism, energy metabolism, and oxidative stress. Conclusion. Our study shows that acupuncture can regulate the liver metabolism mode of T2DM in NAFLD mice. It can reduce blood glucose and lipid accumulation in the liver, and these findings provide a new idea and theoretical basis for acupuncture in the treatment of diseases related to glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

Objective: To evaluate near‐infrared (NIR) spectroscopy in differentiating between benign and malignant bladder pathologies ex vivo immediately after resection, including the grade and stage of malignancy. Patients and Methods: A total of 355 spectra were measured on 71 bladder specimens from patients undergoing transurethral resection of bladder tumour (TURBT) between April and August 2022. Scan time was 5 s, undertaken using a portable NIR spectrometer within 10 min from excision. Specimens were then sent for routine histopathological correlation. Machine learning models were applied to the spectral dataset to construct diagnostic algorithms; these were then tested for their ability to predict the histological diagnosis of each sample using its NIR spectrum. Results: A two‐group algorithm comparing low‐ vs high‐grade urothelial cancer demonstrated 97% sensitivity, 99% specificity, and the area under the receiver operating characteristic curve (AUC) was 0.997. A three‐group algorithm predicting stages Ta vs T1 vs T2 achieved 97% sensitivity, 92% specificity, and the AUC was 0.996. Conclusions: This first study evaluating the diagnostic potential of NIR spectroscopy in urothelial cancer shows that it can be accurately used to assess tissue in an ex vivo setting immediately after TURBT. This offers point‐of‐care assessment of bladder pathology, with potential to influence the extent of resection, reducing both the need for re‐resection where invasive disease may be suspected, and also the potential for complications where extent of diagnostic resection can be limited. Further studies utilising fibre‐optic probes offer the potential for in vivo assessment. [ABSTRACT FROM AUTHOR]

The current study investigates the thermophysical properties, including density, dynamic viscosity, and kinematic viscosity, of a zwitterionic surfactant, namely 3-(N,N–dimethylmyristylammonio)propane sulfonate (DMPS), in aqueous solutions both with and without electrolytes (specifically halide ions), within the temperature range of 293 to 333 K with 5 K gap. For the pure zwitterionic surfactant, a decreasing trend was observed in dynamic viscosity, density, and kinematic viscosity with rising temperature. However, in the presence of halide ions (salt), an increase in their concentration led to rising values of thermophysical properties. Nonetheless, akin to the pure surfactant, a declining trend was noted with rising temperature with electrolytes (halide ions). The efficacy of halide ions followed order: F– ˂ Cl– ˂ Br–. Additionally, the activation energy of the surfactant (DMPS) was assessed both with and without halide ions (electrolytes). Analysis through Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance spectroscopy (1H NMR) confirmed physical interactions between the surfactant DMPS and halide ions in the solutions. No evidence of chemical reactions or complex formations was observed during this interaction. [ABSTRACT FROM AUTHOR]

Objective This study aimed to assess the diagnostic performance of99m Tc-sestamibi SPECT/CT and18 F-choline PET/CT in detecting hyperfunctioning parathyroid glands in patients undergoing surgery for primary hyperparathyroidism (PHPT). Methods A retrospective analysis was conducted on patients who underwent PHPT-related surgery between April 2019 and May 2022. The study focused on patients undergoing either99m Tc-sestamibi SPECT/CT (81 patients) or18 F-choline PET/CT (33 patients) scans before surgery to pinpoint hyperfunctioning parathyroid gland(s). In the majority of patients,18 F-choline PET/CT was performed after negative or inconclusive findings on99m Tc-sestamibi SPECT/CT. Pathohistological reports were utilized as the reference standard for evaluating the accuracy of the imaging findings. Results The study encompassed 83 patients (70 females, 84.3%) with an average age of 57.2 years (24–80 years). The pathohistological analysis identified a total of 98 glands. In a per-lesion analysis, the detection rate of99m Tc-sestamibi SPECT/CT was 57% (95% CI 45.3–68.1), while the detection rate of18 F-choline PET/CT was 90.3% (95% CI 74.3–98.0). Conclusion The results of our study showed the significant usefulness of18 F-choline PET/CT in patients with negative or inconclusive results of99m Tc-sestamibi SPECT/CT in accurately locating hyperfunctioning parathyroid glands in PHPT patients. [ABSTRACT FROM AUTHOR]

This letter published in the Journal of Neurology discusses the diagnosis of tumefactive demyelinating lesions, which are large lesions in the central nervous system. These lesions can be associated with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein (MOG) associated disorders (MOGAD), as well as with viral infections, vasculitis, and systemic autoimmune diseases. The letter presents a case study of a young female patient with vision loss and left sensorimotor hemisyndrome due to these lesions. The patient was eventually diagnosed with MS and received treatment. The article discusses the use of advanced MRI techniques in diagnosing these lesions and highlights the unusual imaging pattern. [Extracted from the article]

We aimed to investigate the association between renal dysfunction at discharge and long-term survival in acute type A aortic dissection (ATAAD) patients following surgery. From 2000 to 2021, 784 patients underwent aortic repair for an ATAAD. Patients were stratified based on creatinine (Cr) level at discharge alive or dead: normal Cr (n = 582) and elevated Cr defined as >1.3 mg/dL for males and >1.0 mg/dL for females or on dialysis at discharge (n = 202). Preoperatively, both groups had similar rates of comorbidities except for the elevated-Cr group which had more diabetes, chronic obstructive pulmonary disease, and chronic and acute renal insufficiency. Both groups had similar open ATAAD repair procedures. Postoperative outcomes in the elevated-Cr group were significantly worse, including six times higher operative mortality (20% versus 3.4%, P < 0.0001). The landmark long-term survival after discharge alive was significantly worse in the elevated-Cr group than the normal-Cr group (10-y survival: 48% versus 69%, P = 0.0009). The elevated Cr on dialysis at discharge group had significantly worse five-year survival (40%) than the elevated Cr not on dialysis at discharge group (80%, P = 0.02) and the normal-Cr group (87%, P < 0.0001). Additionally, the elevated Cr not on dialysis had a worse five-year survival than the normal-Cr group (80% versus 87%, P = 0.02). Elevated Cr at discharge on dialysis was a significant risk factor for late mortality (hazard ratio = 4.22, 95% confidence interval: [2.07, 8.61], P < 0.0001). Renal dysfunction at discharge was associated with significantly decreased short-term and long-term survival following open ATAAD repair. Surgeons should aggressively prevent renal dysfunction, especially new-onset dialysis, at discharge as it is correlated with significantly worse short-term and long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: The favorable health-promoting adaptations to exercise result from cumulative responses to individual bouts of physical activity. Older adults often exhibit anabolic resistance; a phenomenon whereby the anabolic responses to exercise and nutrition are attenuated in skeletal muscle. The mechanisms contributing to age-related anabolic resistance are emerging, but our understanding of how chronological age influences responsiveness to exercise is incomplete. The objective was to determine the effects of healthy aging on peripheral blood metabolomic response to a single bout of resistance exercise and whether any metabolites in circulation are predictive of anabolic response in skeletal muscle. Methods: Thirty young (20–35 years) and 49 older (65–85 years) men and women were studied in a cross-sectional manner. Participants completed a single bout of resistance exercise consisting of eight sets of 10 repetitions of unilateral knee extension at 70% of one-repetition maximum. Blood samples were collected before exercise, immediately post exercise, and 30-, 90-, and 180-minutes into recovery. Proton nuclear magnetic resonance spectroscopy was used to profile circulating metabolites at all timepoints. Serial muscle biopsies were collected for measuring muscle protein synthesis rates. Results: Our analysis revealed that one bout of resistance exercise elicits significant changes in 26 of 33 measured plasma metabolites, reflecting alterations in several biological processes. Furthermore, 12 metabolites demonstrated significant interactions between exercise and age, including organic acids, amino acids, ketones, and keto-acids, which exhibited distinct responses to exercise in young and older adults. Pre-exercise histidine and sarcosine were negatively associated with muscle protein synthesis, as was the pre/post-exercise fold change in plasma histidine. Conclusions: This study demonstrates that while many exercise-responsive metabolites change similarly in young and older adults, several demonstrate age-dependent changes even in the absence of evidence of sarcopenia or frailty. Trial registration: Clinical trial registry: ClinicalTrials.gov NCT03350906. [ABSTRACT FROM AUTHOR]

Carnosine is an endogenous di-peptide (β-alanine -L- histidine) involved in maintaining tissue homeostasis. It is most abundant in skeletal muscle where its concentration has been determined in biopsy samples using tandem mass spectrometry (MS-MS). Carnosine levels can also be assessed in intact leg muscles by proton magnetic resonance spectroscopy (1H-MRS) or in blood and urine samples using mass spectrometry. Nevertheless, it remains uncertain how carnosine levels from these distinct compartments are correlated with each other when measured in the same individual. Furthermore, it is unclear which measurement modality might be most suitable for large-scale clinical studies. Hence, in 31 healthy volunteers, we assessed carnosine levels in skeletal muscle, via 1H-MRS, and in erythrocytes and urine by MS-MS. While muscle carnosine levels were higher in males (C2 peak, p = 0.010; C4 peak, p = 0.018), there was no sex-associated difference in urinary (p = 0.433) or erythrocyte (p = 0.858) levels. In a linear regression model adjusted for age, sex, race, and diet, there was a positive association between erythrocyte and urinary carnosine. However, no association was observed between 1H-MRS and erythrocytes or urinary measures. In the relationship between muscle versus urinary and erythrocyte measures, females had a positive association, while males did not show any association. We also found that 1H-MRS measures were highly sensitive to location of measurement. Thus, it is uncertain whether 1H-MRS can accurately and reliably predict endogenous carnosine levels. In contrast, urinary and erythrocyte carnosine measures may be stable and in greater synchrony, and given financial and logistical concerns, may be a feasible alternative for large-scale clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to compare the fecal metabolome in post pull-through HD with and without HAEC patients and healthy young children using nuclear magnetic resonance (NMR) spectroscopy. Methods: Fresh fecal samples were collected from children under 5 years of age in both post-pull-through HD patients and healthy Thai children. A total of 20 fecal samples were then analyzed using NMR spectroscopy. Results: Thirty-four metabolites identified among HD and healthy children younger than 5 years were compared. HD samples demonstrated a significant decrease in acetoin, phenylacetylglutamine, and N-acetylornithine (corrected p value = 0.01, 0.04, and 0.004, respectively). Succinate and xylose significantly decreased in HD with HAEC group compared to HD without HAEC group (corrected p value = 0.04 and 0.02, respectively). Moreover, glutamine and glutamate metabolism, and alanine, aspartate, and glutamate metabolism were the significant pathways involved, with pathway impact 0.42 and 0.50, respectively (corrected p value = 0.02 and 0.04, respectively). Conclusion: Differences in class, quantity, and metabolism of protein and other metabolites in young children with HD after pull-through operation were identified. Most of the associated metabolic pathways were correlated with the amino acids metabolism, which is required to maintain intestinal integrity and function. [ABSTRACT FROM AUTHOR]

Importance: Aspirin may reduce severity of metabolic dysfunction–associated steatotic liver disease (MASLD) and lower the incidence of end-stage liver disease and hepatocellular carcinoma, in patients with MASLD. However, the effect of aspirin on MASLD is unknown. Objective: To test whether low-dose aspirin reduces liver fat content, compared with placebo, in adults with MASLD. Design, Setting, and Participants: This 6-month, phase 2, randomized, double-blind, placebo-controlled clinical trial was conducted at a single hospital in Boston, Massachusetts. Participants were aged 18 to 70 years with established MASLD without cirrhosis. Enrollment occurred between August 20, 2019, and July 19, 2022, with final follow-up on February 23, 2023. Interventions: Participants were randomized (1:1) to receive either once-daily aspirin, 81 mg (n = 40) or identical placebo pills (n = 40) for 6 months. Main Outcomes and Measures: The primary end point was mean absolute change in hepatic fat content, measured by proton magnetic resonance spectroscopy (MRS) at 6-month follow-up. The 4 key secondary outcomes included mean percentage change in hepatic fat content by MRS, the proportion achieving at least 30% reduction in hepatic fat, and the mean absolute and relative reductions in hepatic fat content, measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). Analyses adjusted for the baseline value of the corresponding outcome. Minimal clinically important differences for study outcomes were not prespecified. Results: Among 80 randomized participants (mean age, 48 years; 44 [55%] women; mean hepatic fat content, 35% [indicating moderate steatosis]), 71 (89%) completed 6-month follow-up. The mean absolute change in hepatic fat content by MRS was −6.6% with aspirin vs 3.6% with placebo (difference, −10.2% [95% CI, −27.7% to −2.6%]; P =.009). Compared with placebo, aspirin treatment significantly reduced relative hepatic fat content (−8.8 vs 30.0 percentage points; mean difference, −38.8 percentage points [95% CI, −66.7 to −10.8]; P =.007), increased the proportion of patients with 30% or greater relative reduction in hepatic fat (42.5% vs 12.5%; mean difference, 30.0% [95% CI, 11.6% to 48.4%]; P =.006), reduced absolute hepatic fat content by MRI-PDFF (−2.7% vs 0.9%; mean difference, −3.7% [95% CI, −6.1% to −1.2%]; P =.004]), and reduced relative hepatic fat content by MRI-PDFF (−11.7 vs 15.7 percentage points; mean difference, −27.3 percentage points [95% CI, −45.2 to −9.4]; P =.003). Thirteen participants (32.5%) in each group experienced an adverse event, most commonly upper respiratory tract infections (10.0% in each group) or arthralgias (5.0% for aspirin vs 7.5% for placebo). One participant randomized to aspirin (2.5%) experienced drug-related heartburn. Conclusions and Relevance: In this preliminary randomized clinical trial of patients with MASLD, 6 months of daily low-dose aspirin significantly reduced hepatic fat quantity compared with placebo. Further study in a larger sample size is necessary to confirm these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT04031729 Key Points: Question: In patients with metabolic dysfunction–associated steatotic liver disease (MASLD), does 81 mg of aspirin daily reduce the quantity of hepatic fat at 6-month follow-up compared with placebo? Findings: In this phase 2 randomized clinical trial of 80 individuals with MASLD, daily aspirin reduced the quantity of hepatic fat at 6-month follow-up compared with placebo (mean difference, −10.2%). Meaning: In a preliminary randomized clinical trial of adults with MASLD, 6 months of daily low-dose aspirin significantly reduced liver fat content compared with placebo, but findings are preliminary and require confirmation in a larger population. This randomized clinical trial compares use of low-dose aspirin vs placebo in reducing hepatic fat among adult patients with metabolic dysfunction–associated steatotic liver disease (MASLD) without cirrhosis. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication after Percutaneous Coronary Intervention (PCI) for ST segment elevation myocardial infarction (STEMI) and is associated with poor outcomes. AKI is diagnosed by the dynamic change of serum Cr, but it could not predict AKI. This study aimed to evaluate a biomarker array that may fulfill this shortage. Setting: Cardiology Department, Tanta University Hospital. Design: Prospective interventional study included 280 acute STEMI patients who underwent emergency PCI. Serial samples of blood and urine were obtained at the time of admission to the hospital (T0) and PCI unit (T1) and at 12 h and 72 h (T12 and T72) after coronary revascularization to estimate levels of serum Cr, creatine phosphokinase, and heart-type fatty acid-binding protein (H-FABP) and calculation of neutrophil/lymphocyte ratio (NLR) and urinary liver-type FABP (L-FABP). AKI was diagnosed according to the recommendations of the European Renal Best Practice as the times of increased serum Cr concerning baseline level. 85 patients developed AKI. Regression analyses defined a high NLR ratio in the T0 sample as the most significant predictor for early AKI diagnosed at T1 time, while high NLR and serum H-FABP levels in T1 samples as the significant predictors for AKI defined at T12 time. However, high urinary L-FABP levels in T12 samples and high NLR are significant predictors for AKI at T72 time. Combined estimations of serum H-FABP and urinary L-FABP with the calculation of NLR could predict the oncoming AKI and discriminate its pathogenesis. The study protocol was approved by the Local Ethical Committee at Tanta Faculty of Medicine by approval number: 35327/3/22. For blindness purposes, the authors will be blinded about the laboratory results till the end of 72 h after revascularization and the clinical pathologist will be blinded about the indication for the requested investigations. [ABSTRACT FROM AUTHOR]

Purpose: MELAS syndrome is a genetic disorder caused by mitochondrial DNA mutations. We previously described that MELAS patients had increased CSF glutamate and decreased CSF glutamine levels and that oral glutamine supplementation restores these values. Proton magnetic resonance spectroscopy (1H-MRS) allows the in vivo evaluation of brain metabolism. We aimed to compare 1H-MRS of MELAS patients with controls, the 1H-MRS after glutamine supplementation in the MELAS group, and investigate the association between 1H-MRS and CSF lactate, glutamate, and glutamine levels. Methods: We conducted an observational case–control study and an open-label, single-cohort study with single-voxel MRS (TE 144/35 ms). We assessed the brain metabolism changes in the prefrontal (PFC) and parieto-occipital) cortex (POC) after oral glutamine supplementation in MELAS patients. MR spectra were analyzed with jMRUI software. Results: Nine patients with MELAS syndrome (35.8 ± 3.2 years) and nine sex- and age-matched controls were recruited. Lactate/creatine levels were increased in MELAS patients in both PFC and POC (0.40 ± 0.05 vs. 0, p < 0.001; 0.32 ± 0.03 vs. 0, p < 0.001, respectively). No differences were observed between groups in glutamate and glutamine (Glx/creatine), either in PFC (p = 0.930) or POC (p = 0.310). No differences were observed after glutamine supplementation. A positive correlation was found between CSF lactate and lactate/creatine only in POC (0.85, p = 0.003). Conclusion: No significant metabolite changes were observed in the brains of MELAS patients after glutamine supplementation. While we found a positive correlation between lactate levels in CSF and 1H-MRS in MELAS patients, we could not monitor treatment response over short periods with this tool. Trial registration: ClinicalTrials.gov Identifier: NCT04948138; initial release 24/06/2021; first patient enrolled on 1/07/2021. https://clinicaltrials.gov/ct2/show/NCT04948138 [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is characterized by depressed mood or loss of interest or pleasure. Generally, women are twice as likely as men to have depression. Taurine, a type of amino acid, plays critical roles in neuronal generation, differentiation, arborization, and formation of synaptic connections. Importantly, it enhances proliferation and synaptogenesis in the hippocampus. When injected into animals, taurine has an antidepressant effect. However, there is no in vivo evidence to show an association between taurine concentration in the human brain and the development of MDD. Forty-one unmedicated young women with MDD (ages 18–29) and 43 healthy control participants matched for gender and age were recruited in South Korea. Taurine concentration was measured in the hippocampus, anterior cingulate cortex, and occipital cortex of the MDD and healthy control groups using proton magnetic resonance spectroscopy at 7T. Analysis of covariance was used to examine differences in taurine concentration, adjusting for age as a covariate. Taurine concentration in the hippocampus was lower (F 1,75 = 5.729, p =.019, Δη2 = 0.073) for the MDD group (mean [SEM] = 0.91 [0.06] mM) than for the healthy control group (1.13 [0.06] mM). There was no significant difference in taurine concentration in the anterior cingulate cortex or occipital cortex between the two groups. This study demonstrates that a lower level of taurine concentration in the hippocampus may be a novel characteristic of MDD. [ABSTRACT FROM AUTHOR]

Background: Anesthetic agents, particularly intravenous anesthetics, may affect immune function and tumorigenic factors. We herein investigated whether the anti‐inflammatory effects of anesthetic agents are attributed to their antioxidant properties. The antioxidant and anti‐inflammatory effects of remimazolam, a new anesthetic, remain unclear. We hypothesized that remimazolam exerts anti‐inflammatory effects due to its antioxidant properties, which may affect the postoperative inflammatory response. This retrospective clinical study examined this hypothesis using laboratory and clinical approaches. Methods: The antioxidant effects of remimazolam and dexmedetomidine were assessed by electron spin resonance (ESR) spectroscopy, and postoperative inflammatory responses were compared in 143 patients who underwent transcatheter aortic valve replacement at Kindai University Hospital between April 2021 and December 2022. The primary endpoint was the presence or absence of the antioxidant effects of the anesthetics themselves using ESR. Results: Remimazolam at clinical concentrations exerted antioxidant effects, whereas dexmedetomidine did not. Increases in C‐reactive protein (CRP) levels on POD3 from preoperative values were significantly smaller in the remimazolam group than in the dexmedetomidine group (1.33 ± 1.29 vs. 2.17 ± 1.84, p =.014). Conclusions: Remimazolam exerted stronger anti‐inflammatory effects than dexmedetomidine, and these effects were enhanced by its antioxidant properties, which may have affected postoperative CRP production. [ABSTRACT FROM AUTHOR]

The purpose of this article is to provide a study of the hydroxylation reaction optimization of epoxidized soybean oil using a mathematical model based on surface response methodology. The variables were selected based on previous studies of the reaction. The three most influential factors are the time, the methanol ratio, and the catalyst ratio. Potentiometric characterization of the hydroxyl index allowed the influence of these factors and their interactions to be measured. It was possible to quantify these influences using multivariate regression. The results show that the three selected factors influenced the reaction yield positively; however, there were some interactions, such as an interaction between time and methanol and the interaction between time and catalyst, which had a negligible influence. The coefficients of the formulas used to construct the mathematical model were obtained from the influence values. The model was able to predict the optimum variable levels for an acceptable reaction yield efficiently and accurately. These levels were: time 244.4 min; methanol:oil ratio 1:4, and catalyst percentage 15.34%. The characterization of the hydroxylated oil product was carried out using Fourier‐transform infrared (FTIR) spectroscopy proton nuclear magnetic resonance (1H‐NMR) and carbon‐13 nuclear magnetic resonance (13C‐NMR) spectroscopy. [ABSTRACT FROM AUTHOR]

Background The effect of continuous myocardial perfusion (CMP) on the surgical results of acute type A aortic dissection (ATAAD) remains unclear. Methods From January 2017 to March 2022, 141 patients who underwent ATAAD (90.8%) or intramural hematoma (9.2%) surgery were reviewed. Fifty-one patients (36.2%) received proximal-first aortic reconstruction and CMP during distal anastomosis. Ninety patients (63.8%) underwent distal-first aortic reconstruction and were placed in traditional cold blood cardioplegic arrest (CA; 4°C, 4:1 blood-to-Plegisol) throughout the procedure. The preoperative presentations and intraoperative details were balanced using inverse probability of treatment weighting (IPTW). Their postoperative morbidity and mortality were analyzed. Results The median age was 60 years. The incidence of arch reconstruction in the unweighted data was higher in the CMP compared with the CA group (74.5 vs 52.2%, p = 0.017) but was balanced after IPTW (62.4 vs 58.9%, p = 0.932, standardized mean difference = 0.073). The median cardiac ischemic time was lower in the CMP group (60.0 vs 130.9 minutes, p < 0.001), but cerebral perfusion time and cardiopulmonary bypass time were similar. The CMP group did not demonstrate any benefit in the reduction of the postoperative maximum creatine kinase-MB ratio (4.4 vs 5.1% in CA, p = 0.437) or postoperative low cardiac output (36.6 vs 24.8%, p = 0.237). Surgical mortality was comparable between groups (15.5% in CMP vs 7.5% in the CA group, p = 0.265). Conclusion Application of CMP during distal anastomosis in ATAAD surgery, irrespective of the extent of aortic reconstruction, reduced myocardial ischemic time but did not improve cardiac outcome or mortality. [ABSTRACT FROM AUTHOR]

Primary angle-closure glaucoma (PACG) is a globally prevalent, irreversible eye disease leading to blindness. Previous neuroimaging studies demonstrated that PACG patients were associated with gray matter function changes. However, whether the white matter(WM) function changes in PACG patients remains unknown. The purpose of the study is to investigate WM function changes in the PACG patients. Methods: In total, 40 PACG patients and 40 well-matched HCs participated in our study and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. We compared between-group differences between PACG patients and HC in the WM function using amplitude of low-frequency fluctuations (ALFF). In addition, the SVM method was applied to the construction of the PACG classification model. Results: Compared with the HC group, ALFF was attenuated in right posterior thalamic radiation (include optic radiation), splenium of corpus callosum, and left tapetum in the PACG group, the results are statistically significant (GRF correction, voxel-level P < 0.001, cluster-level P < 0.05). Furthermore, the SVM classification had an accuracy of 80.0% and an area under the curve (AUC) of 0.86 for distinguishing patients with PACG from HC. Conclusion: The findings of our study uncover abnormal WM functional alterations in PACG patients and mainly involves vision-related regions. These findings provide new insights into widespread brain damage in PACG from an alternative WM functional perspective. [ABSTRACT FROM AUTHOR]

Broadband short-wave near-infrared (NIR) phosphor-converted light-emitting diodes (pc-LEDs) have been attracting keen interest for miniature NIR spectroscopy, while still lacking sufficient novel broadband NIR-emitting phosphors. Herein, we report a novel MgNb2O6:Cr3+ polycrystalline phosphor with a broad NIR emission band centered at 970 nm and a large full-width at half-maximum of approximately 155 nm under excitation of bluish-green light at around 515 nm. The optimized phosphor MgNb2O6:1%Cr3+ features a high internal quantum efficiency (IQE) of ∼85.5% and a moderate external QE of 25.2%. The fluorescence properties determined by two distorted hexa-coordination octahedral sites (i.e. [MgO6] and [NbO6]), low crystal field strength (Dq/B ∼ 1.65), and Cr3+-doping concentration were systematically investigated for comprehensive understanding of photophysical mechanisms. Besides, this broadband NIR phosphor MgNb2O6:Cr3+ exhibits a moderate thermal quenching of 21.4%@373 K for pc-LED application. An NIR pc-LED self-built by combining the optimal phosphor with a commercial cyan of ∼515 nm exhibits an NIR output power increase from 3.19 to 11.38 mW as the drive current is varied from 40 to 220 mA. With the help of this prototype pc-LED device, multiple applications were successfully performed to clearly recognize blood vessel distributions in the human finger, penetrate a plastic cap, and distinguish multi-color text. Undoubtedly, further development of such broadband short-wave NIR-emitting phosphors will make novel pc-LED devices for significant applications in biomedical imaging, nondestructive safety detection, intelligent identification, etc. [ABSTRACT FROM AUTHOR]

The objective of this study was the optimization of the extraction process and the qualitative and quantitative determination of the bioactive metabolites: 12-O-methylcarnosic acid (12MCA), carnosic acid (CA), carnosol (CS), 7-O-methyl-epi-rosmanol (7MER) and rosmanol (RO) in infusions, decoctions, turbulent flow extracts, tinctures and oleolites from three Salvia species: Salvia officinalis L. (common sage, SO), Salvia fruticosa Mill. (Greek sage, SF) and Salvia rosmarinus Spenn (syn Rosmarinus officinalis L.) (rosemary, SR), using Quantitative Proton Nuclear Magnetic Resonance Spectroscopy (1H-qNMR). Regarding the aqueous extracts, decoctions appeared to be richer sources of the studied metabolites than infusions among the three plants. For SR, the turbulent flow extraction under heating was the most efficient one. The optimum time for the preparation of decoctions was found to be 5 min for SF and SO and 15 min for SR. It is noteworthy that SR tinctures were not stable in time due to decomposition of the abietane-type diterpenes CA and CS because of the polar solvent used for their preparation. Contrary to this finding, the oleolites of SR appeared to be very stable. Olive oil as a solvent for extraction was very protective for the contained abietane-type diterpenes. A preliminary stability study on the effect of the storage time of the SF on the abietane-type diterpenes content showed that the total quantity of abietanes decreased by 16.51% and 40.79% after 12 and 36 months, respectively. The results of this investigation also demonstrated that 1H-qNMR is very useful for the analysis of sensitive metabolites, like abietane-type diterpenes, that can be influenced by solvents used in chromatographic analysis. [ABSTRACT FROM AUTHOR]

Extensive evidence supports the claim that the serum neurofilament light chain (sNfL) can be used as a biomarker to monitor disease severity in patients with spinocerebellar ataxia type 3 (SCA3). However, little is known about the associations between sNfL levels and neurochemical alterations in SCA3 patients. In this study, we performed a cross-sectional study to analyze the association between sNfL and brain metabolic changes in SCA3 patients. The severity of ataxia was assessed by using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). The sNfL levels and brain metabolic changes, represented by N-acetyl aspartate (NAA)/creatine (Cr) and choline complex (Cho)/Cr ratios, were measured by a single-molecule array and proton magnetic resonance spectroscopy, respectively. In this cohort, we observed consistently elevated sNfL levels and reduced brain metabolites in the cerebellar hemispheres, dentate nucleus, and cerebellar vermis. However, this correlation was further validated in the cerebellar cortex after analysis using pairwise comparisons and a Bonferroni correction. Taken together, our results further confirmed that sNfL levels were increased in SCA3 patients and were negatively correlated with metabolic changes in the cerebellar cortex. Our data also support the idea that sNfL levels are a promising potential complementary biomarker for patients with SCA3. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a metabolically heterogeneous disease, and although the concept of heterogeneous cancer metabolism is known, its precise role in human breast cancer is yet to be fully elucidated. Methods: We investigated in an explorative approach a cohort of 42 primary mamma carcinoma patients with positron emission tomography/magnetic resonance imaging (PET/MR) prior to surgery, followed by histopathology and molecular diagnosis. From a subset of patients, which showed high metabolic heterogeneity based on tracer uptake and pathology classification, tumour centre and periphery specimen tissue samples were further investigated by a targeted breast cancer gene expression panel and quantitative metabolomics by nuclear magnetic resonance (NMR) spectroscopy. All data were analysed in a combinatory approach. Results: [18F]FDG (2‐deoxy‐2‐[fluorine‐18]fluoro‐d‐glucose) tracer uptake confirmed dominance of glucose metabolism in the breast tumour centre, with lower levels in the periphery. Additionally, we observed differences in lipid and proliferation related genes between luminal A and B subtypes in the centre and periphery. Tumour periphery showed elevated acetate levels and enrichment in lipid metabolic pathways genes especially in luminal B. Furthermore, serine was increased in the periphery and higher expression of thymidylate synthase (TYMS) indicated one‐carbon metabolism increased in tumour periphery. The overall metabolic activity based on [18F]FDG uptake of luminal B subtype was higher than that of luminal A and the difference between the periphery and centre increased with tumour grade. Conclusion: Our analysis indicates variations in metabolism among different breast cancer subtypes and sampling locations which details the heterogeneity of the breast tumours. Correlation analysis of [18F]FDG tracer uptake, transcriptome and tumour metabolites like acetate and serine facilitate the search for new candidates for metabolic tracers and permit distinguishing luminal A and B. This knowledge may help to differentiate subtypes preclinically or to provide patients guide for neoadjuvant therapy and optimised surgical protocols based on individual tumour metabolism. [ABSTRACT FROM AUTHOR]

Introduction: In general, two characteristics are ever present in NMR-based metabolomics studies: (1) they are assays aiming to classify the samples in different groups, and (2) the number of samples is smaller than the feature (chemical shift) number. It is also common to observe imbalanced datasets due to the sampling method and/or inclusion criteria. These situations can cause overfitting. However, appropriate feature selection and classification methods can be useful to solve this issue. Objectives: Investigate the performance of metabolomics models built from the association between feature selectors, the absence of feature selection, and classification algorithms, as well as use the best performance model as an NMR-based metabolomic method for prostate cancer diagnosis. Methods: We evaluated the performance of NMR-based metabolomics models for prostate cancer diagnosis using seven feature selectors and five classification formalisms. We also obtained metabolomics models without feature selection. In this study, thirty-eight volunteers with a positive diagnosis of prostate cancer and twenty-three healthy volunteers were enrolled. Results: Thirty-eight models obtained were evaluated using AUROC, accuracy, sensitivity, specificity, and kappa's index values. The best result was obtained when Genetic Algorithm was used with Linear Discriminant Analysis with 0.92 sensitivity, 0.83 specificity, and 0.88 accuracy. Conclusion: The results show that the pick of a proper feature selection method and classification model, and a resampling method can avoid overfitting in a small metabolomic dataset. Furthermore, this approach would decrease the number of biopsies and optimize patient follow-up. 1H NMR-based metabolomics promises to be a non-invasive tool in prostate cancer diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the age-dependent effects of methylphenidate (MPH) on brain metabolites including choline (Cho), N-acetyl aspartate (NAA) and creatine (Cr) levels in the dorsolateral prefrontal cortex (DLPFC), striatum, cerebellum, and anterior cingulate cortex (ACC) regions of the brain in adult patients with attention deficit hyperactivity disorder (ADHD). Patients and Methods: The study was included 60 patients with ADHD between the ages of 18 and 60 years. The patients were grouped with respect to their ages as follows: 18– 24 years, 25– 30 years, and 31 and over years. Levels of NAA, Cr and Cho in DLPFC, ACC, cerebellum and striatum were measured with magnetic resonance spectroscopy (MRS). Subjects were then given 10 mg of oral MPH and the same metabolite levels were measured 30 minutes apart. Results: Twelve (20%) of the cases were female and 48 (80%) were male. The age distribution of the cases is as follows: 15 subjects between the ages of 18– 24, 26 subjects between the ages of 25– 30 and 19 subjects over the age of 30. NAA levels were higher after MPH in the DLPFC of the 18– 24 age group (p = 0.016) and in the cerebellum of the 25– 30 age group (p = 0.041). No increase in Cho and Cr levels was observed after treatment compared to before (p > 0.05). Conclusion: It is thought that treatment of MPH can be effective on metabolites in different brain regions and this effect can vary upon age adult ADHD patients. After MPH treatment, both the 18– 24 age group (in the DLPFC) and the 25– 30 age group (in the cerebellum) was detected significantly higher NAA levels compared to pre-treatment levels. This increase in NAA levels suggested that pharmacotherapy, especially at early ages, may be effective on neuronal damage. [ABSTRACT FROM AUTHOR]

Background Neonatal hypoxic-ischemic brain injury (HIBI) results from disruptions to blood supply and oxygen in the perinatal brain. The goal of this study was to measure brain sterol metabolites and plasma oxysterols after injury in a neonatal HIBI mouse model to assess for potential therapeutic targets in the brain biochemistry as well as potential circulating diagnostic biomarkers. Methods Postnatal day 9 CD1-IGS mouse pups were randomized to HIBI induced by carotid artery ligation followed by 30 minutes at 8% oxygen or to sham surgery and normoxia. Brain tissue was collected for sterol analysis by liquid chromatography with tandem mass spectrometry (LC–MS/MS). Plasma was collected for oxysterol analysis by LC–MS/MS. Results There were minimal changes in brain sterol concentrations in the first 72 hours after HIBI. In severely injured brains, there was a significant increase in desmosterol, 7-DHC, 8-DHC, and cholesterol 24 hours after injury in the ipsilateral tissue. Lanosterol, 24-dehydrolathosterol, and 14-dehydrozymostenol decreased in plasma 24 hours after injury. Severe neonatal HIBI was associated with increased cholesterol and sterol precursors in the cortex at 24 hours after injury. Conclusions Differences in plasma oxysterols were seen at 24 hours but were not present at 30 minutes after injury, suggesting that these sterol intermediates would be of little value as early diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Background: Sellar and suprasellar regions are complex areas of the brain, where different varieties of lesions can occur in this confined space. When evaluating sellar and suprasellar lesions prior to surgery, diffusion weighted MRI and MR spectroscopy are regarded as crucial diagnostic tools that supplement conventional MRI. Aim of the Study: The aim of the recent study was to evaluate the role of the DWI and Single-Voxel 1H MRS Metabolites in characterization of Sellar and Suprasellar masses. Methods: A prospective study has been conducted on 30 patients with various sellar and suprasellar masses consulted from Neurosurgery and Neurology Departments to the MRI unit over a period of 6 months between June 2023 and Nov 2023.They were examined with long-echo single voxel 1H -MRS and DWI by 1.5 Tesla clinical imaging machine. Examinations were guided by cMRI. We confirmed our diagnosis pathologically after surgical management. Results: Sellar and suprasellar tumors exhibited variable values for diffusion and the mean ADC value was for macroadenoma is (0.72±0.25)x10-3 mm2/sec, craniopharyngeoma is (1.8±0.1)x10-3 mm2/sec, glioma is (1.38±0.5)x10-3 mm2/sec, germinoma (0.80±0.2)x10-3 mm2/sec and for meningioma is (0.94±0.16)x10-3 mm2/sec. Pituitary macroadenoma were typically characterized by Cr peak, moderate elevation of Cho peak and significant reduction of NAA,. Craniopharyngiomas were classically distinguished by notable reduction of all metabolites .Rise of Cho peak and decrease of NAA and Cr peaks typically characterize Gliomas. The most distinguishing metabolite of meningioma is Alanine. Conclusions: Diffusion-weighted MRI and MR Spectroscopy can contribute to presurgical assessment and discrimination between various sellar, suprasellar masses. [ABSTRACT FROM AUTHOR]

Purpose: To assess relationships between ocular biometric parameters in dependence of age and sex in children and adolescents. Methods: In the Ural Children Eye Study, a school‐based cohort study, 4933 children underwent an ophthalmological and general examination. Results: Complete biometric measurements were available for 4406 (89.3%) children. Cycloplegic refractive error (mean: −0.87 ± 1.73 diopters (D); median: −0.38 D; range: −19.75 D to +11.25 D) increased (multivariable analysis; r2 = 0.73) with shorter axial length (β: −0.99; non‐standardized regression coefficient B: −1.64; 95% CI: −1.68, −1.59) and lower corneal refractive power (β: −0.55; B: −0.67; 95% CI: −0.70, −0.64), in addition to higher cylindrical refractive error (β: 0.10; B: 0.34; 95% CI: 0.27, 0.41), thinner lens (β: −0.11; −0.85; 95% CI: −1.02, −0.69) and male sex (β: 0.15; B: 0.50; 95% CI: 0.42, 0.57). In univariate analysis, decrease in refractive error with older age was more significant (β: −0.38 vs. β: −0.25) and steeper (B: −0.22 (95% CI: −0.24, −0.20) vs. B: −0.13 (95% CI: −0.15, −0.11)) in girls than boys, particularly for an age of 11+ years. Axial length increased with older age (steeper for age <11 years) (B: 0.22 (95% CI: 0.18, 0.25) vs. 0.07 (95% CI: 0.05, 0.09)). In multivariable analysis, axial length increased with lower refractive error (β: −0.77; B: −0.42; 95% CI: −0.43, −0.40) and lower corneal refractive power (β: −0.54; B: −0.39; 95% CI: −0.41, −0.38), in addition to older age (β: 0.04; B: 0.02; 95% CI: 0.01, 0.03), male sex (β: 0.13; B: 0.23; 95% CI: 0.21, 0.32), higher cylindrical refractive error (β: 0.05; B: 0.09; 95% CI: 0.05, 0.14) and thinner lens (β: −0.14; B: −0.62; 95% CI: −0.72, −0.51). The axial length/corneal curvature (AL/CR) ratio increased until the age of 14 years (β: 0.34; B: 0.017; 95% CI: 0.016, 0.019; p < 0001), and then became independent of age. The AL/CR ratio increased (r2 = 0.78) mostly with higher corneal refractive power (β: 0.25; B: 0.02; 95% CI: 0.02, 0.02; p < 0.001), lower refractive error (β: −0.75; B: −0.05; 95% CI: −0.05, −0.05; p < 0.001), thinner lens thickness (β: −01.6; B: −0.09; 95% CI: −0.10, −0.08; p < 0.001) and older age (β: 0.16; B: 0.006; 95% CI: 0.005, 0.007; p < 0.001). Conclusions: In this multiethnic group of school children in Russia, the age‐related increase in myopic refractive error was more significant and steeper in girls, particularly for the age group of 11+ years. Determinants of higher myopic refractive error were longer axial length, higher corneal refractive power, lower cylindrical refractive error, thicker lens and female sex. [ABSTRACT FROM AUTHOR]

Around 30 % of schizophrenia patients do not respond sufficiently to conventional antipsychotic treatment. Glutamate and γ-aminobutyric acid (GABA) may be implicated in treatment resistant (TR) patients. Some data indicate that TR patients show increased glutamate levels compared to responders, but findings are inconclusive and limited in the early disease stage. Furthermore, the two neurotransmitters have rarely been assessed in conjunction. We therefore aimed to investigate the role of GABA+ and glutamate in first episode TR patients and explore whether these neurometabolites could be potential predictive markers for TR schizophrenia. We used proton magnetic resonance spectroscopy (MRS) to assess glutamate + glutamine (Glx) and GABA including macromolecules (GABA+) in the anterior cingulate cortex (ACC) of 58 first episode psychosis patients. At six months follow-up treatment response was determined and in a subgroup of 33 patients a follow-up MRS scan was acquired. Glx and GABA+ levels were not significantly different between TR patients and responders at baseline and the levels did not change at six months follow-up. The groups differed in voxel fractions, which could have influenced our results even though we corrected for these differences. Our findings do not provide evidence that ACC Glx or GABA+ levels are potential biomarkers for TR in first episode psychosis. Future research needs to take in to account voxel fractions and report potential differences. Comparison with previous literature suggests that illness duration, clozapine responsiveness and medication effects may partly explain the heterogeneous results on Glx and GABA+ levels in TR. [ABSTRACT FROM AUTHOR]

Objective: We investigated the different life styles among the diet structures and exercise patterns of 100 patients with refractory gout and 79 healthy volunteers; of these, we selected 39 patients and 20 healthy volunteers for serum proton magnetic resonance (1H-NMR) metabolic network detection. We determined the potential biomarkers of refractory gout and attempted to explore the relation between potential biomarkers and diet structures and exercise patterns. Methods: The study employed a questionnaire survey to analyze diet structures and exercise patterns from 100 patients of refractory gout and 79 healthy volunteers. At the same time, using 1H-NMR metabolic technology to analyze the metabolites present in the serum samples obtained from 39 patients of refractory gout (group B) and 20 healthy subjects (group A). Employing MestReNova (Version 8.0.1) to analyze the metabolites maps, collecting the NMR results, further importing into SIMCA-P+ 14.0 software (Umetrics, Sweden) for principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) statistical analysis. Combining patterns recognition and multivariate statistics, potential biomarkers were searched. Other experimental data, including creatinine and adiponectin, were counted by the SPSS21.0. The measurement data were expressed by X ± S and t test. The counting data were expressed in percent and performed by X2 test. Results: Our results revealed that patients with gout tended to be obese, and there were differences in their lifestyle with exercise, sleep, and smoking, as well as in their preference for fructose drinks, alcohol, and total and structural distribution of meat, milk, eggs, and so on when compared with the healthy volunteers. Importantly, we found the adiponectin in the gout group was lower as compared to the healthy group. Further, metabolomics in combination with KEGG analysis revealed that the biosynthesis of aminoacyl tRNA, biosynthesis of valine, leucine, and isoleucine, metabolism of alanine, aspartic, and glutamate, metabolism of glycine, serine, and threonine, phenylalanine, glycolysis/gluconeogenesis, ketone body synthesis and degradation, metabolism of d‐glutamine, citric acid cycle (TCA cycle), triglyceride metabolism, and others could be used as specific biomarkers of this disease. Conclusion: Recurrent refractory gout and formation of tophus may be related to the diet structures and lifestyles between the patients and the healthy people, and their abnormal metabolic network may be related to the disorder of mitochondrial energy metabolism, which further results in abnormal metabolism of glucose, lipids, amino acids, and deposition of uric acid in joints, peripheral connective tissue, and kidney, inducing an inflammatory response. [ABSTRACT FROM AUTHOR]

Long term intake of antituberculosis drugs will lead to severe adverse reactions that will ultimately deteriorate a patient's health and well‐being. With that, the ternary inclusion complex was explored, whereby β‐cyclodextrin (β‐CD) was chosen as the supramolecular host carrier to accommodate two kinds of first line antituberculosis guest drug molecules simultaneously, namely isoniazid (INH) and ethambutol (ETB) which would provide many therapeutic benefits. The inclusion complex of β‐CD/INH/ETB was prepared using solvent evaporation method. Fourier transform infrared spectroscopy (FT‐IR), proton nuclear magnetic resonance spectroscopy (1H‐NMR), and 2‐dimensional nuclear Overhauser effect spectroscopy (2D‐NOESY) NMR were used to investigate the functional groups and structure of the complex. Scanning electron microscopy (SEM) and X‐ray diffraction (XRD) were employed to study the surface morphology and crystallinity changes during complex formation. Thermogravimetric analysis (TGA) was performed to investigate the thermal properties of the complex. FT‐IR and both types of NMR results had revealed the successful penetration of both the drug molecules into the β‐CD cavity. SEM images and XRD spectra had shown a drastic change in surface structure and reduction in crystallinity during complex formation, which had indicated successful formation of a new compound. TGA had proven that the complex had significantly greater thermal stability as compared to the pure components. Molecular dynamics (MD) and molecular docking simulations were also performed to understand the molecular interaction between β‐CD, INH, and ETB. Through precise calculations of interaction and binding energies, β‐CD/INH/ETB was found to be a more stable inclusion complex compared to the binary β‐CD/INH and β‐CD/ETB complexes. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance spectroscopy (1H-MRS) has shown inconsistent alterations in brain metabolites of adults with autism spectrum disorder (ASD). We investigated brain metabolites in the medial prefrontal cortex and amygdala of 24 drug-naive adults with ASD and no intellectual disability and 24 non-ASD control subjects, using 3 T 1H-MRS. Adults with ASD showed no significant differences from control in glutamate, glutamate plus glutamine, N-acetylaspartate, glycerophosphorylcholine plus phosphorylcholine, creatine plus phosphocreatine, or myo-inositol in either region. However, ASD subjects did show significant correlations of localized brain metabolites with autistic traits, empathy deficits, and personality traits using the Autism-Spectrum Quotient, Questionnaire of Cognitive and Affective Empathy, Interpersonal Reactivity Index, and NEO Personality Inventory-Revised. These findings should be taken as preliminary or exploratory. [ABSTRACT FROM AUTHOR]

Drug binding to plasma proteins influences processes such as liberation, adsorption, disposition, metabolism, and elimination of drugs, which are thus one of the key steps of a new drug development. As a result, the characterization of drug–protein interactions is an essential part of these time‐ and money‐consuming processes. It is important to determine not only the binding strength and the stoichiometry of interaction, but also the binding site of a drug on a protein molecule, because two drugs with the same binding site can mutually affect free drug concentration. Capillary electrophoresis‐frontal analysis with mobility shift affinity capillary electrophoresis is one of the most used affinity capillary electrophoresis methods for the characterization of these interactions. In this study, a well‐known sensitivity problem of most capillary electrophoresis‐frontal analyses using ultraviolet detection is solved by its combination with contactless conductivity detection, which provided sixfold lower limits of quantitation and detection. Binding parameters of the human serum albumin‐salicylic acid model affinity pair were evaluated by this newly developed approach and by the classical approach with ultraviolet detection primarily used for their mutual comparison. The results of both approaches agreed well and are also in agreement with literature data obtained using different techniques. [ABSTRACT FROM AUTHOR]