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.

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.

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.

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.

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.

Immunological routine laboratory parameters at admission influence the improvement of positive symptoms in schizophrenia patients after pharmacological treatment.

Introduction: The standard care of schizophrenia patients is based on the assessment of their psychotic behavior, using interview-based, subjective scales that measure symptoms severity. We aimed at defining easily accessible and inexpensive blood-derived clinical diagnostic parameters that might serve as objective markers in the prediction of the effects of pharmacological treatment of schizophrenia patients. Methods: A total of 40 patients with schizophrenia diagnosis according to ICD 10 during psychotic decompensation were included in the study. Blood-based biochemical parameters, BMI and interview-based medical scales of symptom severity were determined - all at admission and after 12 weeks of standard pharmacological treatment. Results: The drops in scale values were correlated with clinical parameters. All scale changes after treatment were dependent on the value of the given scale at admission, with higher initial values leading to larger drops of the values after treatment. Models based on those correlations were significantly improved when immune and metabolism parameters were included. C4 complement and C-reactive protein (CRP) level at admission were predictive of changes in Positive and Negative Syndrome Scale (PANSS) subscales related to significant disruption of thought processes, reality testing and disorganization. The pharmacological treatment-driven changes in scales representing negative symptoms were correlated with markers of the patients' thyroid status and metabolism. Discussion: We show that objective markers can be obtained by testing immune and metabolic parameters from the patients' blood and may be added at a low cost to the standard care of schizophrenia patients in order to predict the outcome of pharmacological treatment.

The Association of the Oral Microbiota with the Effects of Acid Stress Induced by an Increase of Brain Lactate in Schizophrenia Patients.

The altered cerebral energy metabolism central to schizophrenia can be linked to lactate accumulation. Lactic acid is produced by gastrointestinal bacteria, among others, and readily crosses the blood-brain barrier, leading to the brain acidity. This study aimed to examine the association of the oral microbiota with the effects of acid stress induced by an increase of brain lactate in schizophrenia patients. The study included patients with a diagnosis of acute polyphasic psychotic disorder meeting criteria for schizophrenia at 3-month follow-up. Results: Individuals with a significantly higher total score on the Positive and Negative Syndrome Scale had statistically significantly lower lactate concentrations compared to those with a lower total score and higher brain lactate. We observed a positive correlation between Actinomyces and lactate levels in the anterior cingulate cap and a negative correlation between bacteria associated with lactate metabolism and some clinical assessment scales. Conclusions: Shifts in the oral microbiota in favour of lactate-utilising bacterial genera may represent a compensatory mechanism in response to increased lactate production in the brain. Assessment of neuronal function mediated by ALA-LAC-dependent NMDA regulatory mechanisms may, thus, support new therapies for schizophrenia, for which acidosis has become a differentiating feature of individuals with schizophrenia endophenotypes.

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.

Effect of a Short-Term Intervention with Lactobacillus salivarius Probiotic on Early Childhood Caries-An Open Label Randomized Controlled Trial.

ECC is a significant therapeutic and social problem and a global burden on public health. The aim of this clinical trial was to test whether a 2-week daily consumption of chewing tablets containing thermally inactivated L. salivarius reduces the 12-month caries increment compared to the control group. The investigation was a single-center, randomized, controlled open-label, blinded end-point evaluation trial in two parallel groups. At baseline, 140 generally healthy children between 3 and 6 years of age with or without ECC were randomly assigned to the probiotic test group (n = 70) or to the treatment as the usual control group (n = 70). The primary outcome measure was the 1-year increment in caries incidence and prevalence. Secondary endpoints assessed were the initial, cavitated and obvious dentinal caries increment as well as the measurement of dental plaque accumulation, as an indicator of the ECC risk. Data were collected through the clinical assessment of the children's caries (dmft and ICDAS II) and oral hygiene status (DI-S of OHI-S index). Caries incidence and prevalence were statistically significantly lower in the probiotic group versus the control group (p < 0.001 and p = 0.0075). The initial and final mean OHI-S scores in the probiotic group did not show any significant differences. In conclusion, the regular short-term intake of probiotics may reduce caries development. Our findings suggest that self-administered probiotic therapy may provide a good complement to increase the effectiveness of individual preventive home care in preschool children. This is the first clinical study evaluating the effect of a short-term probiotic intervention on reducing early childhood caries with 12 months of follow-up.

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.

The Assessment of Endovascular Therapies in Ischemic Stroke: Management, Problems and Future Approaches.

Ischemic stroke accounts for over 80% of all strokes and is one of the leading causes of mortality and permanent disability worldwide. Intravenous administration of recombinant tissue plasminogen activator (rt-PA) is an approved treatment strategy for acute ischemic stroke of large arteries within 4.5 h of onset, and mechanical thrombectomy can be used for large arteries occlusion up to 24 h after onset. Improving diagnostic work up for acute treatment, reducing onset-to-needle time and urgent radiological access angiographic CT images (angioCT) and Magnetic Resonance Imaging (MRI) are real problems for many healthcare systems, which limits the number of patients with good prognosis in real world compared to the results of randomized controlled trials. The applied endovascular procedures demonstrated high efficacy, but some cellular mechanisms, following reperfusion, are still unknown. Changes in the morphology and function of mitochondria associated with reperfusion and ischemia-reperfusion neuronal death are still understudied research fields. Moreover, future research is needed to elucidate the relationship between continuously refined imaging techniques and the variable structure or physical properties of the clot along with vascular permeability and the pleiotropism of ischemic reperfusion lesions in the penumbra, in order to define targeted preventive procedures promoting long-term health benefits.

Redefining the Cut-Off Ranges for TSH Based on the Clinical Picture, Results of Neuroimaging and Laboratory Tests in Unsupervised Cluster Analysis as Individualized Diagnosis of Early Schizophrenia.

Thyroid abnormalities, including mild forms of hypothyroidism and hyperthyroidism, are reported as risk factors for the development of a number of neuropsychiatric disorders, including schizophrenia. The diagnostic process still takes into account the extreme ranges of the accepted reference values for serum TSH since the concentration of free thyroxine in the serum does not change by definition. TSH mU/L cut-off values in psychiatric patients are currently clinically considered in the case of extremely high serum TSH levels (>4.0 mU/L). The results obtained in this study suggest that the clinically significant value has a lower TSH cut-off point with an upper limit of 2-2.5 mU/L. The criteria for the differential diagnosis of patients with schizophrenia, however, mainly take into account statutory reference ranges without a background related to the history of thyroid diseases in the family. The results indicate the need to lower the upper cut-off values for TSH among patients with early psychosis, which is related to the potential clinical significance of the obtained values both in the field of clinical evaluation and neuroimaging and laboratory evaluation parameters. The cut-off points obtained with the prior available knowledge coincided with the values established in the unsupervised clustering method, which further confirms the legitimacy of their use in the individualized diagnosis strategy of schizophrenia.

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.

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.

Relationship of metabolic parameters with the course of the first episode of psychosis - preliminary research. / Zwiazek parametrów metabolicznych z przebiegiem pierwszego epizodu psychozy ­ badania wstepne.

OBJECTIVES: Cardiometabolic syndromes are the most common causes of complications shortening life expectancy in patients treated for mental disorders, especially schizophrenia. However, how much cardiometabolic risk is related to lifestyle, side-effects of treatment or psychosis is not clear. The aim of this study was a prospective assessment of metabolic changes in young, initially somatically healthy patients diagnosed with the first acute episode of psychosis with no prior pharmacological treatment. METHODS: The study involved 15 young patients (average age of 19.95 ± 6.88 years). Analyses (laboratory and clinical) were performed at the time of admission and after 3 and 12 weeks and included morphology, lipid profile, glucose, inflammation markers, blood pressure (BP), and body mass index (BMI). The severity of clinical symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS), and the cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA). The duration of untreated psychosis (DUP) was also measured. RESULTS: There was a significant increase in BMI, dyslipidemia, inflammation, and systolic blood pressure after 12 weeks from the start of the treatment, while cortisol level decreased. A negative correlation was observed between PANSS-P (PANSS positivescale) measurements and total cholesterol, PANSS total and low-density lipoprotein, as well as DUPand MoCA. High-density lipoprotein (HDL) correlated positively with DUP, cortisol, monocytes, and white blood cells in the first week. CONCLUSIONS: The results of the study indicate a relationship between the development and treatment of the first acute episode of psychosis and the results of laboratory tests that are indicators of the development of metabolic stress in patients.

Improvement in clinical symptoms in patients with the first episode of psychosis is associated with a decrease in systemic nitric oxide availability. A pilot study. / Zwiazek poprawy objawów klinicznych u pacjentów z pierwszym epizodem psychozy i jej zwiazek ze spadkiem ogólnoustrojowej dostepnosci tlenku azotu. Badanie pilotazowe.

OBJECTIVES: The aim of the study was to assess the relationship between the improvement of the clinical condition of patients with the first episode of psychosis (FEP) and changes in - nitric oxide (NO) plasma concentration based on the level of its metabolites NO2- and NO3, as well as changes in lipid profile and biomarkers of systemic inflammation. METHODS: The study was carried out in agroup of 25 young patients with FEP (aged 14-35). Blood samples were collected in the 1st and 12th week after admission to the hospital to assess NO metabolites, lipid profile and inflammatory biomarkers. Demographic and clinical data were also analysed. RESULTS: In the study group, three months after admission to the hospital, an improvement in the clinical symptoms was observed, as evidenced by a decrease in the Positive and Negative Syndrome Scale (PANSS) scores. This improvement was associated with a decrease in the plasma nitrite concentration, a deterioration of the lipid profile and the activation of systemic inflammation. Interestingly, in the 1st week after the hospital admission, a longer duration of untreated psychosis (DUP) was associated with a lower NO2- plasma concentration, and a higher intensity of positive symptoms (PANSS Positive Symptoms Scale) was associated with higher CRP plasma level. CONCLUSIONS: Our results suggest that adverse metabolic response, systemic inflammation and a fall in systemic NO bioavailability represent early systemic manifestations of FEP that are not controlled by short-term anti-psychotic treatment and may pose cardiovascular risk.

Determinants of Schizophrenia Endophenotypes Based on Neuroimaging and Biochemical Parameters.

Despite extensive research, there is no convincing evidence of a reliable diagnostic biomarker for schizophrenia beyond clinical observation. Disorders of glutamatergic neurotransmission associated with N-methyl-D-aspartate (NMDA) receptor insufficiency, neuroinflammation, and redox dysregulation are the principal common mechanism linking changes in the periphery with the brain, ultimately contributing to the emergence of negative symptoms of schizophrenia that underlie differential diagnosis. The aim of the study was to evaluate the influence of these systems via peripheral and cerebral biochemical indices in relation to the patient's clinical condition. Using neuroimaging diagnostics, we were able to define endophenotypes of schizophrenia based on objective laboratory data that form the basis of a personalized approach to diagnosis and treatment. The two distinguished endophenotypes differed in terms of the quality of life, specific schizophrenia symptoms, and glutamatergic neurotransmission metabolites in the anterior cingulate gyrus. Our results, as well as further studies of the excitatory or inhibitory balance of microcircuits, relating the redox systems on the periphery with the distant regions of the brain might allow for predicting potential biomarkers of neuropsychiatric diseases, including schizophrenia. To the best of our knowledge, our study is the first to identify an objective molecular biomarker of schizophrenia outcome.

Phenolic Compounds of Reynoutria sp. as Modulators of Oral Cavity Lactoperoxidase System.

Lactoperoxidase (LPO) together with its (pseudo)halogenation cycle substrates, H2O2 and thiocyanate ions oxidized to hypothiocyanite ions, form one of the main systems involved in antimicrobial defense within the oral cavity. In bacterial diseases such as dental caries, lactoperoxidase is oxidized to a form known as Compound II, which is characterized by its inability to oxidize SCN-, resulting in a decreased generation of antimicrobial products. Reynoutria sp. rizome extracts, due to their high polyphenol content, have been tested as a source of compounds able to regenerate the antimicrobial activity of lactoperoxidase through converting the Compound II to the native LPO state. In the presented study, acetone extracts of R. japonica, R. sachalinensis, and R. x bohemica, together with their five fractions and four selected polyphenols dominating in the studied in extracts, were tested toward lactoperoxidase reactivating potential. For this purpose, IC50, EC50, and activation percentage were determined by Ellman's method. Furthermore, the rate constants for the conversion of Compound I-Compound II and Compound II-native-LPO in the presence of extracts, extracts fractions, and selected polyphenols were determined. Finally, the ability to enhance the antimicrobial properties of the lactoperoxidase system was tested against Streptococcus mutans. We proved that Reynoutria sp. rhizome is the source of lactoperoxidase peroxidation cycle substrates, which can act as activators and inhibitors of the antimicrobial properties of that system. The presented study shows that the reactivation of lactoperoxidase could become a potential therapeutic target in prevention and treatment support in some infectious oral diseases.

The Relationship between the Level of Anterior Cingulate Cortex Metabolites, Brain-Periphery Redox Imbalance, and the Clinical State of Patients with Schizophrenia and Personality Disorders.

Schizophrenia is a complex mental disorder whose course varies with periods of deterioration and symptomatic improvement without diagnosis and treatment specific for the disease. So far, it has not been possible to clearly define what kinds of functional and structural changes are responsible for the onset or recurrence of acute psychotic decompensation in the course of schizophrenia, and to what extent personality disorders may precede the appearance of the appropriate symptoms. The work combines magnetic resonance spectroscopy imaging with clinical evaluation and laboratory tests to determine the likely pathway of schizophrenia development by identifying peripheral cerebral biomarkers compared to personality disorders. The relationship between the level of metabolites in the brain, the clinical status of patients according to International Statistical Classification of Diseases and Related Health Problems, 10th Revision ICD-10, duration of untreated psychosis (DUP), and biochemical indices related to redox balance (malondialdehyde), the efficiency of antioxidant systems (FRAP), and bioenergetic metabolism of mitochondria, were investigated. There was a reduction in the level of brain N-acetyl-aspartate and glutamate in the anterior cingulate gyrus of patients with schisophrenia compared to the other groups that seems more to reflect a biological etiopathological factor of psychosis. Decreased activity of brain metabolites correlated with increased peripheral oxidative stress (increased malondialdehyde MDA) associated with decreased efficiency of antioxidant systems (FRAP) and the breakdown of clinical symptoms in patients with schizophrenia in the course of psychotic decompensation compared to other groups. The period of untreated psychosis correlated negatively with glucose value in the brain of people with schizophrenia, and positively with choline level. The demonstrated differences between two psychiatric units, such as schizophrenia and personality disorders in relation to healthy people, may be used to improve the diagnosis and prognosis of schizophrenia compared to other heterogenous psychopathology in the future. The collapse of clinical symptoms of patients with schizophrenia in the course of psychotic decompensation may be associated with the occurrence of specific schizotypes, the determination of which is possible by determining common relationships between changes in metabolic activity of particular brain structures and peripheral parameters, which may be an important biological etiopathological factor of psychosis. Markers of peripheral redox imbalance associated with disturbed bioenergy metabolism in the brain may provide specific biological factors of psychosis however, they need to be confirmed in further studies.