Association of Blood Metabolomics Biomarkers with Brain Metabolites and Patient-Reported Outcomes as a New Approach in Individualized Diagnosis of Schizophrenia.

Given its polygenic nature, there is a need for a personalized approach to schizophrenia. The aim of the study was to select laboratory biomarkers from blood, brain imaging, and clinical assessment, with an emphasis on patients' self-report questionnaires. Metabolomics studies of serum samples from 51 patients and 45 healthy volunteers, based on the liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS), led to the identification of 3 biochemical indicators (cortisol, glutamate, lactate) of schizophrenia. These metabolites were sequentially correlated with laboratory tests results, imaging results, and clinical assessment outcomes, including patient self-report outcomes. The hierarchical cluster analysis on the principal components (HCPC) was performed to identify the most homogeneous clinical groups. Significant correlations were noted between blood lactates and 11 clinical and 10 neuroimaging parameters. The increase in lactate and cortisol were significantly associated with a decrease in immunological parameters, especially with the level of reactive lymphocytes. The strongest correlations with the level of blood lactate and cortisol were demonstrated by brain glutamate, N-acetylaspartate and the concentrations of glutamate and glutamine, creatine and phosphocreatine in the prefrontal cortex. Metabolomics studies and the search for associations with brain parameters and self-reported outcomes may provide new diagnostic evidence to specific schizophrenia phenotypes.

Transgelin-2 in Multiple Myeloma: A New Marker of Renal Impairment?

Transgelin is a 22-kDa protein involved in cytoskeletal organization and expressed in smooth muscle tissue. According to animal studies, it is a potential mediator of kidney injury and fibrosis, and moreover, its role in tumorigenesis is emerging in a variety of cancers. The study included 126 ambulatory patients with multiple myeloma (MM). Serum transgelin-2 concentrations were measured by enzyme-linked immunoassay. We evaluated associations between baseline transgelin and kidney function (serum creatinine, estimated glomerular filtration rate-eGFR, urinary markers of tubular injury: cystatin-C, neutrophil gelatinase associated lipocalin-NGAL monomer, cell cycle arrest biomarkers IGFBP-7 and TIMP-2) and markers of MM burden. Baseline serum transgelin was also evaluated as a predictor of kidney function after a follow-up of 27 months from the start of the study. Significant correlations were detected between serum transgelin-2 and serum creatinine (R = 0.29; p = 0.001) and eGFR (R = -0.25; p = 0.007). Transgelin significantly correlated with serum free light chains lambda (R = 0.18; p = 0.047) and serum periostin (R = -0.22; p = 0.013), after exclusion of smoldering MM patients. Patients with decreasing eGFR had higher transgelin levels (median 106.6 versus 83.9 ng/mL), although the difference was marginally significant (p = 0.05). However, baseline transgelin positively correlated with serum creatinine after the follow-up period (R = 0.37; p < 0.001) and negatively correlated with eGFR after the follow-up period (R = -0.33; p < 0.001). Moreover, higher baseline serum transgelin (beta = -0.11 ± 0.05; p = 0.032) significantly predicted lower eGFR values after the follow-up period, irrespective of baseline eGFR and follow-up duration. Our study shows for the first time that elevated serum transgelin is negatively associated with glomerular filtration in MM and predicts a decline in renal function over long-term follow-up.

Renal Impairment Detectors: IGFBP-7 and NGAL as Tubular Injury Markers in Multiple Myeloma Patients.

Background and Objectives: Urine insulin-like growth factor-binding protein 7 (IGFBP-7), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), and neutrophil gelatinase-associated lipocalin (NGAL) monomer are novel tubular kidney injury biomarkers. In multiple myeloma (MM), immunoglobulin free light chains (FLCs) play an integral role in renal impairment. This study aimed to investigate the correlation between new biomarkers and acclaimed parameters of renal failure, MM stage, and prognosis. Materials and Methods: The examined parameters included: urinary and serum cystatin-C, IGFBP-7, and TIMP-2, and urinary NGAL monomer in 124 enrolled patients. Results: Urinary and serum IGFBP-7 and urinary NGAL were higher among patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and positively correlated with urine light chains. Serum and urine IGFBP-7 and urine NGAL were greater among patients with a higher disease stage. In the whole study group, urinary concentrations of the studied markers were positively correlated with each other. In multiple linear regression, urinary IGFBP-7 and NGAL were associated with lower eGFR, independently of other urinary markers. Conclusions: Urinary IGFBP-7 and NGAL monomer may be useful markers of tubular renal damage in patients with MM. Biomarker-based diagnostics may contribute to earlier treatment that may improve renal outcomes and life expectancy in MM.

Neutrophil to lymphocyte ratio at the early phase of acute pancreatitis correlates with serum urokinase-type plasminogen activator receptor and interleukin 6 and predicts organ failure.

BACKGROUND: In early phase of acute pancreatitis (AP), systemic inflammatory response syndrome may lead to organ failure. The severe form of AP is associated with high mortality that may be prevented by timely diagnosis and treatment of the predicted severe cases. Serum interleukin 6 (IL-6) and urokinase-type plasminogen activator receptor (uPAR) have been proposed as accurate early markers of severe AP. The aim of the study was to assess whether widely available blood count indexes: neutrophil to lymphocyte (NLR), lymphocyte to monocyte (LMR) and platelet to lymphocyte ratios correlate with IL-6 and uPAR and may be utilized to predict organ complications at the early phase of AP. METHODS: The study included 95 adult patients with AP treated at the Surgical Ward Complex of Health Care Centers in Wadowice, Poland. Organ failure was diagnosed according to modi ed Marshall scoring system, as recommended by 2012 Atlanta classification. Blood samples for laboratory tests were collected on days 1, 2 and 3 following the onset of AP symptoms. RESULTS: Patients with organ failure presented significantly lower LMR on day 1 and significantly higher NLR on days 2 and 3. Strong positive correlations between NLR and IL-6 and moderate correlations between NLR and uPAR were observed throughout the study. Day 2 and 3 NLR values significantly predicted organ failure at the early phase of AP. CONCLUSIONS: Taking into account the wide availability of NLR, it may be considered as a surrogate of more expensive tests to help the early assessment of organ failure complicating AP.

From periphery immunity to central domain through clinical interview as a new insight on schizophrenia.

Identifying disease predictors through advanced statistical models enables the discovery of treatment targets for schizophrenia. In this study, a multifaceted clinical and laboratory analysis was conducted, incorporating magnetic resonance spectroscopy with immunology markers, psychiatric scores, and biochemical data, on a cohort of 45 patients diagnosed with schizophrenia and 51 healthy controls. The aim was to delineate predictive markers for diagnosing schizophrenia. A logistic regression model was used, as utilized to analyze the impact of multivariate variables on the prevalence of schizophrenia. Utilization of a stepwise algorithm yielded a final model, optimized using Akaike's information criterion and a logit link function, which incorporated eight predictors (White Blood Cells, Reactive Lymphocytes, Red Blood Cells, Glucose, Insulin, Beck Depression score, Brain Taurine, Creatine and Phosphocreatine concentration). No single factor can reliably differentiate between healthy patients and those with schizophrenia. Therefore, it is valuable to simultaneously consider the values of multiple factors and classify patients using a multivariate model.

SDS Electrophoresis on Gradient Polyacrylamide Gels as a Semiquantitative Tool for the Evaluation of Proteinuria.

Proteinuria is an important sign of kidney diseases. Different protein patterns in urine associated with glomerular, tubular and overload proteinuria may be differentiated using the immunochemical detection of indicator proteins or via urinary proteins electrophoresis. Our aim was to characterize sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) using commercially available 4-20% gradient gels as a method to detect and differentiate proteinuria. Our laboratory-based study used excess urine samples collected for routine diagnostic purposes from adult patients of a tertiary-care hospital, including patients with albumin/creatinine < 30 mg/g and patients with dipstick proteinuria. The limit of albumin detection was estimated to be 3 mg/L. In 93 samples with albumin/creatinine < 30 mg/g, an albumin fraction was detected in 87% of samples with a minimum albumin concentration of 2.11 mg/L. The separation of 300 urine samples of patients with proteinuria revealed distinct protein patterns differentiated using the molecular weights of the detected proteins: glomerular (albumin and higher molecular weights) and two types of tubular proteinuria ("upper" ≥20 kDa and "lower" with lower molecular weights). These patterns were associated with different values of the glomerular filtration rate (median 66, 71 and 31 mL/min/1.72 m2, respectively, p = 0.004) and different proportions of multiple myeloma and nephrological diagnoses. As confirmed using tandem mass spectrometry and western blot, the SDS-PAGE protein fractions contained indicator proteins including immunoglobulin G, transferrin (glomerular proteinuria), α1-microglobulin, retinol-binding protein, neutrophil gelatinase-associated lipocalin, cystatin C, and ß2-microglobulin (tubular), immunoglobulin light chain, myoglobin, and lysozyme (overflow). SDS-PAGE separation of urine proteins on commercially available 4-20% gradient gels is a reliable technique to diagnose proteinuria and differentiate between its main clinically relevant types.

Influence of Life Satisfaction on Self-Esteem Among Young Adults: The Mediating Role of Self-Presentation.

BACKGROUND: A comprehensive literature review suggests that self-esteem seems to be contingent on being satisfied in various domains of life. Although there are multiple studies that have addressed the direct relationship between both variables, there is still little known about the psychological mechanisms that underlie this association. Since self-presentation is an important process in young adulthood, the main goal of the present study was to consider self-promotion and self-deprecation as potential mediators between life satisfaction and self-esteem. PARTICIPANTS METHODS AND DATA COLLECTION: The study included 328 young adults aged between 18 and 35. Most of them were women (74.1%). The data were collected in Poland through an anonymous self-administered battery of questionnaires on the Internet platform. The participants completed the Satisfaction with Life Scale, the Rosenberg Self-Esteem Scale, and the Self-Presentation Style Questionnaire. RESULTS: A high and positive correlation coefficient was obtained between self-esteem and life satisfaction (r = 0.73; p < 0.001). The level of self-esteem correlated positively with the style of self-promotion (r = 0.46; p < 0.001) and negatively with the style of self-deprecation (r = -0.63; p < 0.001). Similarly, life satisfaction was positively associated with self-promotion (r = 0.37; p < 0.001) and negatively with self-depreciation (r = -0.42; p < 0.001). Moreover, both self-promotion (ß = 0.67; p < 0.001) and self-deprecation (ß = 0.58; p < 0.001) acted as mediators between life satisfaction and self-esteem. CONCLUSION: The present study increases our knowledge about the mediatory role of self-promotion and self-deprecation. An overall sense of satisfaction with one's own life can lead to higher self-esteem when young people are aware of their strengths and talents. Likewise, lower life satisfaction can elicit less positive self-esteem when people tend to undervalue their capabilities.

Is the Activity-Based Anorexia Model a Reliable Method of Presenting Peripheral Clinical Features of Anorexia Nervosa?

Anorexia nervosa (AN) causes the highest number of deaths among all psychiatric disorders. Reduction in food intake and hyperactivity/increased anxiety observed in AN are also the core features of the activity-based anorexia animal model (ABA). Our aim was to assess how the acute ABA protocol mimics common AN complications, including gonadal and cardiovascular dysfunctions, depending on gender, age, and initial body weight, to form a comprehensive description of ABA as a reliable research tool. Wheel running, body weight, and food intake of adolescent female and male rats were monitored. Electrocardiography, heart rate variability, systolic blood pressure, and magnetic resonance imaging (MRI) measurements were performed. Immediately after euthanasia, tissue fragments and blood were collected for further analysis. Uterine weight was 2 times lower in ABA female rats, and ovarian tissue exhibited a reduced number of antral follicles and decreased expression of estrogen and progesterone receptors. Cardiovascular measurements revealed autonomic decompensation with prolongation of QRS complex and QT interval. The ABA model is a reliable research tool for presenting the breakdown of adaptation mechanisms observed in severe AN. Cardiac and hormonal features of ABA with underlying altered neuroendocrine pathways create a valid phenotype of a human disease.

Synergistic ROS-Associated Antimicrobial Activity of Silver Nanoparticles and Gentamicin Against Staphylococcus epidermidis.

INTRODUCTION: Increasing bacteria resistance to antibiotics is a major problem of healthcare system. There is a need for solutions that broaden the spectrum of bactericidal agents improving the efficacy of commonly used antibiotics. One of the promising directions of search are silver nanoparticles (obtained by different methods and displaying diversified physical and chemical properties), and their combination with antibiotics. PURPOSE: In this study, we tested the role of reactive oxygen species in the mechanism of synergistic antibacterial activity of gentamicin and Tween-stabilized silver nanoparticles against gentamicin-resistant clinical strains of Staphylococcus epidermidis. METHODS: Synergistic bactericidal activity of gentamicin and silver nanoparticles stabilized with non-ionic detergent (Tween 80) was tested by the checkerboard titration method on microtiter plates. Detection of reactive oxygen species was based on the chemiluminescence of luminol. RESULTS: Hydrophilic non-ionic surface functionalization of silver nanoparticles enabled the existence of non-aggregated active nanoparticles in a complex bacterial culture medium. Tween-stabilized silver nanoparticles in combination with gentamicin exhibited bactericidal activity against multidrug-resistant biofilm forming clinical strains of Staphylococcus epidermidis. A synergistic effect significantly decreased the minimal inhibitory concentration of gentamicin (the antibiotic with numerous undesirable effects). Gentamicin significantly enhanced the generation of reactive oxygen species by silver nanoparticles. CONCLUSION: Generation of reactive oxygen species by Tween-coated metallic silver nanoparticles was significantly enhanced by gentamicin, confirming the hypothesis of oxidative-associated mechanism of the synergistic antibacterial effect of the gentamicin-silver nanoparticles complex.