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.

Coagulation abnormalities in a prospective cohort of 50 patients with PMM2-congenital disorder of glycosylation.

BACKGROUND: Given the lack of reliable data on the prevalence of bleeding abnormalities and thrombotic episodes in PMM2-CDG patients, and whether coagulation abnormalities change over time, we prospectively collected and reviewed natural history data. Patients with PMM2-CDG often have abnormal coagulation studies due to glycosylation abnormalities but the frequency of complications resulting from these has not been prospectively studied. METHODS: We studied fifty individuals enrolled in the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) natural history study with molecularly confirmed diagnosis of PMM2-CDG. We collected data on prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), platelets, factor IX activity (FIX), factor XI activity (FXI), protein C activity (PC), protein S activity (PS) and antithrombin activity (AT). RESULTS: Prothrombotic and antithrombotic factor activities were frequently abnormal in PMM2-CDG patients, including AT, PC, PT, INR, and FXI. AT deficiency was the most common abnormality in 83.3% of patients. AT activity was below 50% in 62.5% of all patients (normal range 80-130%). Interestingly, 16% of the cohort experienced symptoms of spontaneous bleeding and 10% had thrombosis. Stroke-like episodes (SLE) were reported in 18% of patients in our cohort. Based on the linear growth models, on average, patients did not show significant change in AT (n = 48; t(23.8) = 1.75, p = 0.09), FIX (n = 36; t(61) = 1.60, p = 0.12), FXI (n = 39; t(22.8) = 1.88, p = 0.07), PS (n = 25; t(28.8) = 1.08, p = 0.29), PC (n = 38; t(68) = 1.61, p = 0.11), INR (n = 44; t(184) = -1.06, p = 0.29), or PT (n = 43; t(192) = -0.69, p = 0.49) over time. AT activity positively correlated with FIX activity. PS activity was significantly lower in males. CONCLUSION: Based on our natural history data and previous literature, we conclude that caution should be exercised when the AT levels are lower than 65%, as most thrombotic events occur in patients with AT below this level. All five, male PMM2-CDG patients in our cohort who developed thrombosis had abnormal AT levels, ranging between 19% and 63%. Thrombosis was associated with infection in all cases. We did not find significant change in AT levels over time. Several PMM2-CDG patients had an increased bleeding tendency. More long-term follow-up is necessary on coagulation abnormalities and the associated clinical symptoms to provide guidelines for therapy, patient management, and appropriate counseling. SYNOPSIS: Most PMM2-CDG patients display chronic coagulation abnormalities without significant improvement, associated with a frequency of 16% clinical bleeding abnormalities, and 10% thrombotic episodes in patients with severe antithrombin deficiency.

Safety Assessment of the Modified Lactoperoxidase System-In Vitro Studies on Human Gingival Fibroblasts.

One strategy in caries prevention is to inhibit the formation of cariogenic biofilms. Attempts are being made to develop oral hygiene products enriched with various antimicrobial agents. One of them is lactoperoxidase-an enzyme that can oxidise (pseudo)halide ions to reactive products with antimicrobial activity. Currently, commercially available products utilise thiocyanate as a substrate; however, several alternatives that are oxidised to products with greater antimicrobial potential have been found. In this study, toxicity against human gingival fibroblasts of the lactoperoxidase system was evaluated using four different (pseudo)halide substrate systems-thiocyanate, iodide, selenocyanate, and a mixture of thiocyanate and iodide. For this purpose, cells were treated with the systems and then apoptosis, cell cycle, intracellular glutathione concentration, and mitochondrial superoxide production were assessed. The results showed that each system, after generating 250 µM of the product, inhibited cell divisions, increased apoptosis, and increased the percentage of dead cells. It was concluded that the mechanism of the observed phenomena was not related to increased superoxide production or the depletion of glutathione concentration. These findings emphasised the need for the further in vitro and in vivo toxicity investigation of the modified lactoperoxidase system to assess its safety and the possibility of use in oral hygiene products.

Modified Lactoperoxidase System as a Promising Anticaries Agent: In Vitro Studies on Streptococcus mutans Biofilms.

The lactoperoxidase (LPO) system shows promise in the prevention of dental caries, a common chronic disease. This system has antimicrobial properties and is part of the non-specific antimicrobial immune system. Understanding the efficacy of the LPO system in the fight against biofilms could provide information on alternative strategies for the prevention and treatment of caries. In this study, the enzymatic system was modified using four different (pseudo)halide substrates (thiocyanate, thiocyanate-iodide mixture, selenocyanate, and iodide). The study evaluated the metabolic effects of applying such modifications to Streptococcus mutans; in particular: (1) biofilm formation, (2) synthesis of insoluble polysaccharides, (3) lactate synthesis, (4) glucose and sucrose consumption, (5) intracellular NAD+ and NADH concentrations, and (6) transmembrane glucose transport efficiency (PTS activity). The results showed that the LPO-iodide system had the strongest inhibitory effect on biofilm growth and lactate synthesis (complete inhibition). This was associated with an increase in the NAD+/NADH ratio and an inhibition of glucose PTS activity. The LPO-selenocyanate system showed a moderate inhibitory effect on biofilm biomass growth and lactate synthesis. The other systems showed relatively small inhibition of lactate synthesis and glucose PTS but no effect on the growth of biofilm biomass. This study provides a basis for further research on the use of alternative substrates with the LPO system, particularly the LPO-iodide system, in the prevention and control of biofilm-related diseases.

Benefits and Meaning of Lipids Profile in Relation to Oxidative Balance and Brain Morphology in Schizophrenia.

Schizophrenia is characterized by complex metabolic dysregulations and their consequences. Until now, numerous theories have explained its pathogenesis, using a spectrum of available technologies. We focused our interest on lipid profile-periphery high-density cholesterol level and lipoproteins in the human brain and compared magnetic resonance imaging (MRI) scans of patients with schizophrenia and the healthy group. Detailed analysis of biochemical parameters was performed using magnetic resonance spectroscopy. Our study aimed to reveal correlations between periphery high-density lipoproteins levels and lipoproteins in the brain, depicted in MRI scans, and parameters of peripheral oxidative stress expressed as paraoxonase. Patients with schizophrenia have decreased levels of high-density lipoproteins, low paraoxonase activity, and slightly raised sodium in the blood. Positive significant correlations between serum high-density cholesterol and anterior cingulate cortex, unique brain area for schizophrenia pathophysiology, MR spectroscopy signals, and diffusion have been revealed. To our knowledge, this is the first study to describe the effect of an anterior cingulate disorder on high-density cholesterol levels on the development of schizophrenia.

Patient-reported outcomes and quality of life in PMM2-CDG.

Patient-reported outcomes (PROs) measure important aspects of disease burden, however they have received limited attention in the care of patients with Congenital Disorders of Glycosylation (CDG). We evaluated the PROs and correlation between clinical disease severity scoring and reported quality of life (QoL) in a PMM2-CDG patient cohort. Twenty-five patients with diagnosis of PMM2-CDG were enrolled as part of the Frontiers in Congenital Disorders of Glycosylation Consortium (FCDGC) natural history study. Patient- Reported Outcomes Measurement Information System (PROMIS) was completed by caregivers to assess health-related QoL. Clinical disease severity was scored by medical providers using the Nijmegen Progression CDG Rating Scale (NPCRS). The domains such as physical activity, strength impact, upper extremity, physical mobility, and a satisfaction in social roles (peer relationships) were found to be the most affected in the PMM2-CDG population compared to US general population. We found a strong correlation between NPCRS 1 (current functional ability) and three out of ten PROMIS subscales. NPCRS 2 (laboratory and organ function) and NPCRS 3 (neurological involvement) did not correlate with PROMIS. Mental health domains, such as anxiety, were positively correlated with depressive symptoms (r = 0.76, p = 0.004), fatigue (r = 0.67, p = 0.04). Surprisingly, patients with severely affected physical mobility showed low anxiety scores according to PROMIS (inverse correlation, r = -0.74, p = 0.005). Additionally, there was a positive correlation between upper extremity and physical mobility (r = 0.75, p = 002). Here, we found that PROMIS is an informative additional tool to measure CDG disease burden, which could be used as clinical trial outcome measures. The addition of PROMIS to clinical follow-up could help improve the quality of care for PMM2-CDG by facilitating a holistic approach for clinical decision-making. SYNOPSIS: We recommend PROMIS as an informative tool to measure disease burden in PMM2-CDG in addition to traditional CDG disease severity scores.

Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications.

OBJECTIVE: Epalrestat, an aldose reductase inhibitor increases phosphomannomutase (PMM) enzyme activity in a PMM2-congenital disorders of glycosylation (CDG) worm model. Epalrestat also decreases sorbitol level in diabetic neuropathy. We evaluated the genetic, biochemical, and clinical characteristics, including the Nijmegen Progression CDG Rating Scale (NPCRS), urine polyol levels and fibroblast glycoproteomics in patients with PMM2-CDG. METHODS: We performed PMM enzyme measurements, multiplexed proteomics, and glycoproteomics in PMM2-deficient fibroblasts before and after epalrestat treatment. Safety and efficacy of 0.8 mg/kg/day oral epalrestat were studied in a child with PMM2-CDG for 12 months. RESULTS: PMM enzyme activity increased post-epalrestat treatment. Compared with controls, 24% of glycopeptides had reduced abundance in PMM2-deficient fibroblasts, 46% of which improved upon treatment. Total protein N-glycosylation improved upon epalrestat treatment bringing overall glycosylation toward the control fibroblasts' glycosylation profile. Sorbitol levels were increased in the urine of 74% of patients with PMM2-CDG and correlated with the presence of peripheral neuropathy, and CDG severity rating scale. In the child with PMM2-CDG on epalrestat treatment, ataxia scores improved together with significant growth improvement. Urinary sorbitol levels nearly normalized in 3 months and blood transferrin glycosylation normalized in 6 months. INTERPRETATION: Epalrestat improved PMM enzyme activity, N-glycosylation, and glycosylation biomarkers in vitro. Leveraging cellular glycoproteome assessment, we provided a systems-level view of treatment efficacy and discovered potential novel biosignatures of therapy response. Epalrestat was well-tolerated and led to significant clinical improvements in the first pediatric patient with PMM2-CDG treated with epalrestat. We also propose urinary sorbitol as a novel biomarker for disease severity and treatment response in future clinical trials in PMM2-CDG. ANN NEUROL 20219999:n/a-n/a.

Biological Therapies in the Treatment of Cancer-Update and New Directions.

Biological therapies have changed the face of oncology by targeting cancerous cells while reducing the effect on normal tissue. This publication focuses mainly on new therapies that have contributed to the advances in treatment of certain malignancies. Immunotherapy, which has repeatedly proven to be a breakthrough therapy in melanoma, as well as B-ALL therapy with CAR T cells, are of great merit in this progress. These therapies are currently being developed by modifying bispecific antibodies and CAR T cells to improve their efficiency and bioavailability. Work on improving the therapy with oncolytic viruses is also progressing, and efforts are being made to improve the immunogenicity and stability of cancer vaccines. Combining various biological therapies, immunotherapy with oncolytic viruses or cancer vaccines is gaining importance in cancer therapy. New therapeutic targets are intensively sought among neoantigens, which are not immunocompromised, or antigens associated with tumor stroma cells. An example is fibroblast activation protein α (FAPα), the overexpression of which is observed in the case of tumor progression. Universal therapeutic targets are also sought, such as the neurotrophic receptor tyrosine kinase (NTRK) gene fusion, a key genetic driver present in many types of cancer. This review also raises the problem of the tumor microenvironment. Stromal cells can protect tumor cells from chemotherapy and contribute to relapse and progression. This publication also addresses the problem of cancer stem cells resistance to treatment and presents attempts to avoid this phenomenon. This review focuses on the most important strategies used to improve the selectivity of biological therapies.

The role of oxidative stress in the cooperation of parthenolide and etoposide in HL-60 cells.

BACKGROUND: The aim of this study was to determine the effect of sesquiterpene lactone parthenolide on the cytotoxic and pro-oxidative effects of etoposide in HL-60 cells. METHODS: Cytotoxic effects were determined by incubation of HL-60 cells with various concentrations of examined compounds and combinations thereof, which were then stained with propidium iodide and analyzed using a flow cytometer. To determine the role of oxidative stress in the action of the compounds, co-incubation with N-acetyl-l-cysteine (NAC) and parthenolide and/or etoposide was used and the level of reduced glutathione (GSH) was detected. RESULTS: Parthenolide significantly enhanced the cytotoxic and pro-apoptotic effects of etoposide. However, in most cases of the combinations of parthenolide and etoposide, their effect was antagonistic, as confirmed by an analysis using the CalcuSyn program. The examined compounds significantly reduced the level of GSH in HL-60 cells. Combination of etoposide at a concentration of 1.2 µM and parthenolide also significantly reduced GSH level. However, in the case of a combination of etoposide at a concentration of 2.5 µM with parthenolide, a significant increase in the level of GSH was obtained compared to compounds acting alone. This last observation seems to confirm the antagonism between the compounds tested. CONCLUSIONS: Parthenolide did not limit the cytotoxic effect of etoposide in HL-60 cells even in the case of antagonistic interaction. If parthenolide does increase GSH levels in combination with etoposide in the normal hematopoietic cells, it could protect them against the pro-oxidative effects of this anti-cancer drug.

The Significance of Lactoperoxidase System in Oral Health: Application and Efficacy in Oral Hygiene Products.

Lactoperoxidase (LPO) present in saliva are an important element of the nonspecific immune response involved in maintaining oral health. The main role of this enzyme is to oxidize salivary thiocyanate ions (SCN-) in the presence of hydrogen peroxide (H2O2) to products that exhibit antimicrobial activity. LPO derived from bovine milk has found an application in food, cosmetics, and medical industries due to its structural and functional similarity to the human enzyme. Oral hygiene products enriched with the LPO system constitute an alternative to the classic fluoride caries prophylaxis. This review describes the physiological role of human salivary lactoperoxidase and compares the results of clinical trials and in vitro studies of LPO alone and complex dentifrices enriched with bovine LPO. The role of reactivators and inhibitors of LPO is discussed together with the possibility of using nanoparticles to increase the stabilization and activity of this enzyme.

Relative homogeneity of oral bacterial oral in Crohn's disease compared to ulcerative colitis and its connections with antioxidant defense - preliminary report.

INTRODUCTION: Interactions between oral microbiota and systemic diseases have been suggested. We aimed to examine the composition of oral microbiota with reference to antioxidative defense and its correlation with clinical state in Crohn's disease (CD) in comparison to ulcerative colitis (UC). MATERIALS AND METHODS: Smears were taken from the buccal and tongue mucosa of patients with CD, UC and controls, and cultured with classical microbiology methods. Bacterial colonies were identified using matrix-assisted laser desorption/ionization (MALDI) with a time-of-flight analyzer (TOF). Blood morphology and C-reactive protein (CRP) were analyzed in the hospital laboratory. Antioxidative defense potential (FRAP) was determined using spectrophotometry in saliva and serum. RESULTS: Oral microbiota in CD patients were characterized by lower diversity in terms of the isolated bacteria species compared to UC and this correlated with reduced FRAP in the oral cavity and intensified systemic inflammation. Oral microbiota composition in CD did not depend on the applied treatment. In CD patients, a negative correlation was observed between the FRAP value in saliva and serum and the CRP value in serum. Individual differences in the composition of oral microbiota suggest that different bacteria species may be involved in the induction of oxidative stress associated with a weakening of antioxidative defense in the oral cavity, manifested by ongoing systemic inflammation. CONCLUSIONS: Analysis of both the state of the microbiota and antioxidative defense of the oral cavity, as well as their referencing to systemic inflammation may potentially prove helpful in routine diagnostic applications and in aiding a better understanding of CD and UC pathogenesis associated with oral microbiota.

Correlation of Paraoxonase-1 with the Severity of Crohn's Disease.

Diagnostics of Crohn's disease (CD) requires noninvasive biomarkers facilitating early detection and differentiation of the disease. Therefore, in this study, we aimed to determine the relationship between paraoxonase-1 (PON-1), the severity of CD, oxidative stress, and inflammation in CD. The CD activity index was based on the current classification. Plasma PON-1 was measured in 47 patients with CD, and in 23 control volunteers. Using quantitative variables such as receiver operating characteristics (ROC) (area under the curve (AUC)), the diagnostic utility of PON-1 in differentiating the severity of CD was assessed. Circulating PON-1 was found to be decreased in the CD group compared to the control group (269.89 vs. 402.56 U/L, respectively), and it correlated well with the disease activity. PON-1 correlated positively with hemoglobin (Hb) (r = 0.539, p < 0.001), hematocrit (Ht) (r = 0.48, p < 0.001), total cholesterol (TC) (r = 0.343, p < 0.001), high density lipoprotein (HDL) (r = 0.536, p < 0.001), low density lipoprotein (LDL) (r = 0.54, p < 0.001), and triglyceride (TG) (r = 0.561, p < 0.001) and correlated negatively with white blood cell count (WBC) (r = -0.262, p = 0.029), platelet count (PLT) (r = -0.326, p = 0.006), C-reactive protein (CRP) (r = -0.61, p < 0.001), and malondialdehyde (MDA) (r = -0.924, p < 0.001). PON-1 as a marker for CD differentiation possessed a sensitivity and specificity of 93.62% and 91.30%, respectively. CD was found to be associated with the decrease in the levels of PON-1, which correlates well with activity of the disease and reflects the intensification of inflammation, as well as intensified lipid peroxidation. High sensitivity and specificity of PON-1 determines its selection as a good screening test for CD severity.

Evaluation of plasma concentrations of selected antioxidant parameters in patients with active Crohn's disease.

Oxidative stress (OxS) has been implicated in the pathogenesis of Crohn's disease (CD). The aim of this study was to examine whether nonenzymatic antioxidants are associated with active CD, by using the FRAP and GSH assay in plasma. Additionally, we measured bilirubin and albumin levels as two individual components of the plasma antioxidant system. A total of 55 patients with established CD, 30 with active CD and 25 with inactive disease, and 25 healthy individuals were prospectively enrolled in this study. We evaluated CD activity index, BMI and blood morphology, platelet count, serum CRP level, and bochemical parameters of OxS: ferric reducing ability of plasma (FRAP), reduced glutathione (GSH) in plasma and bilirubin and albumin levels in serum. Plasma FRAP and GSH concentrations were decreased in both CD groups compared to controls and negatively correlated with CDAI values (FRAP: r = -0.572, p = 0.003; GSH: r = -0.761, p = 0.001), CRP and platelet count. Bilirubin and albumin levels were lower in the serum of active CD patients than inactive CD patients and controls and negatively correlated with the CD activity index (r = -0328, p = 0.036, r = -0.518, p = 0.002) and CRP (r = -0.433, p = 0.002). e decreased FRAP and GSH levels in plasma and bilirubin and albumin levels in serum of patients with active CD compared to inactive CD and controls underlines the importance of OxS in the pathophysiology and activity of CD.

A study on ß-defensin-2 and histatin-5 as a diagnostic marker of early childhood caries progression.

BACKGROUND: Recently, a continuous growth of interest has been observed in antimicrobial peptides (AMPs) in the light of an alarming increase in resistance of bacteria and fungi against antibiotics. AMPs are used as biomarkers in diagnosis and monitoring of oral cavity pathologies. Therefore, the determination of specific protein profiles in children diagnosed with early childhood caries (ECC) might be a basis for effective screening tests and specialized examinations which may enable progression of disease. METHODS: The objective of the studies was to determine the role of histatin-5 and ß-defensing-2 as a diagnostic marker of early childhood caries progression. In this work, results of concentration determination of two salivary proteins (histatin-5 and ß-defensin-2) were presented. In addition, bacterial profiles from dental plaque in various stages of ECC and control were marked. The assessment of alteration in the concentration of these two proteins in a study group of children with various stages of ECC and a control group consisting of children with no symptoms was performed by enzyme-linked immunosorbent assays. RESULTS: The statistical analysis showed a significant increase in the concentration of histatin-5 and ß-defensin-2 in the study group compared to the control group and correlated with the progression of the disease. CONCLUSIONS: The confirmation of concentration changes in these proteins during the progression of dental caries may discover valuable disease progression biomarkers.

Effect of histatin-5 and lysozyme on the ability of Streptococcus mutans to form biofilms in in vitro conditions.

INTRODUCTION: The mechanisms of adhesion to solid surfaces enable S. mutans to colonize oral cavities and form biofilms, which play an important role in caries development. Additional properties enabling the survival of S. mutans in the oral cavity include its ability to survive in acidic environments and specific interactions with other microorganisms inhabiting this ecosystem. AIM OF THE STUDY: The aim of this study was to determine the antibacterial activity of saliva histatin-5 (peptide) and lysozyme (protein) against S. mutans and L. rhamnosus, as representatives of physiological flora. MATERIALS AND METHODS: The study involved strains of physiological (L. rhamnosus) and cariogenic (S. mutans) flora isolated from one patient with diagnosed early caries of the deciduous teeth. RESULTS: It was proved that the presence of probiotic L. rhamnosus bacteria in the environment had a negative impact on the ability of S. mutans to produce biofilm. Moreover, the antibacterial activity of histatin-5 was confirmed, and it inhibited S. mutans growth at concentrations of 27.2 µg/ml and 54.4 µg/ml, both individually and in a mixture with lysozyme (in a total concentration of 54.4 µg/ml). CONCLUSIONS: The data obtained constitute a promising result due to their potential future application in the prevention and early diagnosis of caries.

Inhibition of myeloperoxidase activity have impact on the formation of DNA double-strand breaks induced by etoposide in HL-60 cell line.

Many studies have shown the role of myeloperoxidase (MPO) in leukemogenic activity of etoposide. The aim of our study was to determine whether inhibition of MPO activity has influence on the formation of double-stranded DNA breaks (DSBs) that may contribute to the characteristic of leukemia translocations. Studies were carried out on HL-60 cell line, which were preincubated with the MPO inhibitor 4-aminobenzoic acid hydrazide (ABAH), or antioxidant N-acetyl-L-cysteine (NAC), followed by incubation at different concentrations of etoposide (1-10 mM) for 4 hours. Cytotoxicity was investigated using propidium iodide staining. Marker of DSBs, a phosphorylated form of histone 2AX (gH2AX) was detected using immunocytochemical methods. Cells were analyzed by flow cytometry. ABAH significantly reduced the cytotoxicity and the gH2AX level induced by lower concentrations of etoposide (1 and 1.5 mM) and did not modify the action of higher concentration (10 mM) of this cytostatic drug. NAC exerted similar impact as ABAH on the level of gH2AX induced by etoposide. The results of this study suggest that MPO contributes to increase of the DSBs level induced by low concentrations of etoposide in myeloid cells.

The usefulness of biotyping in the determination of selected pathogenicity determinants in Streptococcus mutans.

BACKGROUND: Streptococcus mutans is known to be a primary etiological factor of dental caries, a widespread and growing disease in Polish children. Recognition of novel features determining the pathogenicity of this pathogen may contribute to understanding the mechanisms of bacterial infections.The goal of the study was to determine the activity of prephenate dehydrogenase (PHD) and to illuminate the role of the enzyme in S. mutans pathogenicity. The strains were biotyped based on STREPTOtest 24 biochemical identification tests and the usefulness of biotyping in the determination of S. mutans pathogenicity determinants was examined. RESULTS: Out of ninety strains isolated from children with deciduous teeth fifty three were classified as S. mutans species. PDH activity was higher (21.69 U/mg on average) in the experimental group compared to the control group (5.74 U/mg on average) (P <0.001). Moreover, it was demonstrated that biotype I, established basing on the biochemical characterization of the strain, was predominant (58.5%) in oral cavity streptococcosis. Its dominance was determined by higher PDH activity compared to biotypes II and III (P = 0.0019). CONCLUSIONS: The usefulness of biotyping in the determination of Streptococcus mutans pathogenicity determinants was demonstrated. The obtained results allow for better differentiation of S. mutans species and thus may contribute to recognition of pathogenic bacteria transmission mechanisms and facilitate treatment.

The dual effect of curcumin on etoposide action in leukemic and healthy bone marrow cells of rats with acute myeloid leukemia.

The effect of curcumin, a promising anticancer agent, on the action of certain cytostatic drugs, including etoposide, is not well understood. This paper examines the effect of curcumin on etoposide action in leukemic and normal bone marrow cells in vivo conditions. The experimental model used was Brown Norway rats with a transplantable acute promyelocytic leukemia. Leukemia was induced by intravenous injection of BNML (Brown Norway Myeloid Leukemia) cells. Curcumin was administered by oral gavage (200 mg/kg) for 23 consecutive days and etoposide was used intraperitoneally (50 mg/kg) for the last three days of the experiment. Control leukemic and healthy rats received the solvent for the tested compounds only. Curcumin significantly reduced the number of leukemic promyelocytes in the bone marrow of BNML rats in comparison to the leukemic control. Treatment with curcumin plus etoposide led to a decrease in the number of promyelocytes to the normal values occurring in healthy individuals. In contrast, the percentage of the normal precursors of granulocytes (p <0.001) and erythrocytes (p <0.001) increased significantly in comparison to the group treated with only etoposide. The results of the study indicate that curcumin may protect healthy myeloid cells against the cytotoxic effect of etoposide and potentiate the antileukemic action of this anticancer drug.

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.

Risk factors for weight gain in patients with first-episode psychosis. / Czynniki ryzyka przyrostu masy ciala u pacjentów z pierwszym epizodem psychozy.

OBJECTIVES: Assessment of the association between weight gain in patients with first-episode psychosis (FEP) and biopsychosocial and sociological factors. METHODS: 25 subjects with FEP aged 14-35 examined in week 1 (P1) and after three months of hospitalization (P3) were enrolled in the study. Within 3 months all patients were diagnosed with schizophrenia. The study used: a socio-demographic survey, Positive and Negative Syndrome Scale (PANSS), State-Trait Anxiety Inventory (STAI), Coping Inventory for Stressful Situations (CISS), Questionnaire Eating Behaviors (QEB), and routine biochemical test findings. For some variables, the differences (variable_D) between the values at P1 and P3 were calculated. RESULTS: Statistically significant correlations were shown between body weight_P1, _P3, _D, and healthy diet index_P1, _P3, severity of psychotic symptoms measured by the PANSS_P1 and _D, the CISS focused on emotions and task_P1, _P3 and _D, mother's body weight in youth and now, father's body weight in youth and now, and the number of the patient's siblings. In the linear regression analysis, body weight_P1 and the CISS focused on emotions_P1 turned out to be significant predictors of body weight_P3. CONCLUSIONS: Multifactorial influence of weight gain in FEP in schizophrenia was observed. Countermeasures against weight gain should refer not only to the diet, but also to the way the eating habits are related to psychopathology associated with psychosis and to the emotional functioning of the patient.