Greater methylation of the IL-6 promoter region is associated with decreased integrity of the corpus callosum in schizophrenia.

BACKGROUND: Schizophrenia is associated with chronic subclinical inflammation and decreased integrity of the corpus callosum (CC). Our previous study showed associations between peripheral IL-6 levels and the integrity of the CC. Epigenetic studies show associations between methylation of the genes related to immunological processes and integrity of the CC. AIM: To investigate correlations between methylation status of IL-6 promotor and peripheral IL-6 levels and the integrity of the CC in schizophrenia. MATERIAL AND METHODS: The participants were 29 chronic schizophrenia patients (SCH) and 29 controls. Decreased integrity of the CC was understood as increased mean diffusivity (MD) and/or decreased fractional anisotropy (FA) in diffusion tensor imaging. Peripheral IL-6 concentrations were measured in serum samples and IL-6 promoter methylation status of 6 CpG sites was analyzed in peripheral leukocytes by pyrosequencing. RESULTS: Moderate positive correlations were found between CpG1 methylation and the MD of proximal regions of the CC (CCR1-CCR3) and between CpGmean and MD of CCR1 in SCH. Weaker positive correlations were found for CpGmean with CCR2 and CCR3 and negative correlations were found for CpG1 and FA of CCR3 in SCH. Multivariate regression showed that methylation of CpG1, type of antipsychotic treatment, and their interaction were significant independent predictors of MD of CCR1 in SCH. Methylation of CpG2 was negatively correlated with serum IL-6 in SCH. CONCLUSIONS: The methylation level of the IL-6 promotor region in peripheral leukocytes is associated with the integrity of the CC in schizophrenia and this association may depend on the type of antipsychotic treatment. Further studies are necessary to explain the mechanisms of the observed associations.

Evaluating the effectiveness of a mobile app-based self-guided psychological interventions to reduce relapse in substance use disorder: protocol for a randomized controlled trial.

Background: Substance Use Disorder (SUD) persists as a significant public health challenge worldwide, with an estimated prevalence of approximately 10-15% across the global populace. This condition is characterized by a notably high risk of lapses and relapses, even subsequent to treatment interventions. Mobile health interventions, owing to their widespread accessibility, emerge as a promising approach to diminish the risk of relapse post-treatment and to broaden the scope of care, especially in regions with a scarcity of trained medical professionals. Method: This study is designed to assess the effectiveness of mobile interventions in mitigating cravings and preventing lapses among individuals diagnosed with SUD. Employing a two-armed, randomized controlled trial framework, the study will evaluate a self-administered psychological intervention delivered through a mobile application, Nalogometr 2.0. Over a period of three months, participants will engage with intervention modules that primarily incorporate mindfulness techniques and Cognitive Behavioral Therapy (CBT) principles. Ecological Momentary Assessment (EMA) will be utilized to gather longitudinal data on a range of variables that are indicative of craving intensity and the risk of lapse. In addition to this, a monthly-administered battery of questionnaires will be employed to gauge the severity of substance dependence, as well as to measure levels of anxiety, depression, and overall life satisfaction. Results: Results will be submitted for publication in peer-reviewed journals. Clinical trial registration: https://clinicaltrials.gov/, identifier [NCT05730504].

High-sensitivity cardiac troponin T in detecting obstructive coronary artery disease in hemodialysis patients listed for kidney transplantation.

BACKGROUND: Cardiovascular diseases are the leading cause of morbidity and mortality in patients with end-stage renal disease. AIMS: This study aimed to assess the prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) in identifying patients with obstructive coronary artery disease (CAD) among patients on hemodialysis listed for kidney transplantation. METHODS: The study prospectively enrolled consecutive adult hemodialysis patients listed for kidney transplantation. They underwent laboratory tests and a standardized set of imaging and functional tests, including coronary angiography, according to patient characteristics. RESULTS: The study included 100 consecutive patients (72 men)at a median age of 56.5 years. Ultimately, 48% of the patients were diagnosed with obstructive CAD. Age and plasma hs-cTnT levels predicted the diagnosis of obstructive CAD (OR, 1.13; 95% CI, 1.08-1.20; P < 0.001 and OR, 1.03; 95% CI, 1.01-1.05; P = 0.001, respectively). The calculated cut-off value for age was 53 years, which showed sensitivity of 87.5% and specificity of 76.9% for obstructive CAD diagnosis. The calculated value for hs-cTnT was 0.067 ng/ml, which showed sensitivity of 61.4% and specificity of 82.2% for the detection of obstructive CAD. In patients aged >52 years, 79.2% were diagnosed with obstructive CAD. However, in the group of patients ≤52 years and with hs-cTnT >0.069 ng/ml, the incidence of obstructive CAD was significantly higher than in the group with hs-cTnT level ≤0.069 ng/ml. CONCLUSIONS: Baseline hs-cTnT level is a useful prognostic biomarker in the diagnosis of obstructive CAD in hemodialysis patients listed for kidney transplantation.

Concomitant inhibition of the thioredoxin system and nonhomologous DNA repair potently sensitizes Philadelphia-positive lymphoid leukemia to tyrosine kinase inhibitors.

Breakpoint cluster region-Abelson (BCR::ABL1) gene fusion is an essential oncogene in both chronic myeloid leukemia (CML) and Philadelphia-positive (Ph+) B-cell acute lymphoblastic leukemia (B-ALL). While tyrosine kinase inhibitors (TKIs) are effective in up to 95% of CML patients, 50% of Ph+ B-ALL cases do not respond to treatment or relapse. This calls for new therapeutic approaches for Ph+ B-ALL. Previous studies have shown that inhibitors of the thioredoxin (TXN) system exert antileukemic activity against B-ALL cells, particularly in combination with other drugs. Here, we present that peroxiredoxin-1 (PRDX1), one of the enzymes of the TXN system, is upregulated in Ph+ lymphoid as compared to Ph+ myeloid cells. PRDX1 knockout negatively affects the viability of Ph+ B-ALL cells and sensitizes them to TKIs. Analysis of global gene expression changes in imatinib-treated, PRDX1-deficient cells revealed that the nonhomologous end-joining (NHEJ) DNA repair is a novel vulnerability of Ph+ B-ALL cells. Accordingly, PRDX1-deficient Ph+ B-ALL cells were susceptible to NHEJ inhibitors. Finally, we demonstrated the potent efficacy of a novel combination of TKIs, TXN inhibitors, and NHEJ inhibitors against Ph+ B-ALL cell lines and primary cells, which can be further investigated as a potential therapeutic approach for the treatment of Ph+ B-ALL.

Increased perception of the experience dimension of the animal mind reduces instrumental violence against animals.

In this study, we investigated whether the perception of animal experience capacities, enabling individuals to recognize animals as moral patients, decreases instrumental violence against animals. Additionally, we aimed to distinguish this effect from the influence of perceptions of agency capacities, referred to as anthropomorphization. To achieve this, we conducted an online experimental study (N = 471, 54% women). Participants performed a manipulation task that increased their perception of the experience dimension of the animal mind and completed online questionnaires as part of a manipulation check to measure acceptance and intentions of instrumental violence against animals. Regression and mediation analyses revealed that increasing perception of the experience dimension of animal mind decreases instrumental violence against animals, particularly intentions to commit such violence, and this effect is unique and distinct from the effect of perception of the agency dimension, i.e., anthropomorphization. The key capacities in lowering violence were homeostatic emotions (pain, fear, hunger, and thirst) which indicate suffering that humans would want animals to avoid. However, when people perceive homeostatic emotions, increased perception of more complex capacities (anger, joy, pleasure, personality) and anthropomorphization do not result in an additional reduction in violence. We interpret these results to mean that people limit violence by using perception of animal experience capacities as pre-violation justification. These findings expand our knowledge about the functions of perception of experience capacities and demonstrate that people diminish animal experience capacities not only to rationalize violence but also as pre-violation justification to facilitate instrumental violence against animals.

Quality of life and depression in patients with amyotrophic lateral sclerosis - does the country of origin matter?

BACKGROUND: Given the inevitable relentless progressing nature of amyotrophic lateral sclerosis (ALS), it is essential to identify factors influencing patients' wellbeing. The study aimed to prospectively assess factors influencing the quality of life (QoL) and depression in ALS patients compared to healthy controls (HCs) from Poland, Germany and Sweden and their relationship to socio-demographic and clinical factors. METHODS: 314 ALS patients (120 from Poland, 140 from Germany, 54 from Sweden) and 311 age-, sex- and education-level-matched HCs underwent standardized interviews for quality of life, depression, functional status and pain. RESULTS: Patients from all three countries showed similar levels of functional impairment (ALSFRS-R). Overall, ALS patients assessed their quality of life as lower compared to HCs (p < 0.001 for the anamnestic comparative self-assessment (ACSA), p = 0.002 for the Schedule for the evaluation of the subjective quality of life - SEIQoL- direct weighting (SEIQoL-DW). Also, the German and Swedish patients, but not the Polish, reported higher depression levels than the corresponding HCs (p < 0.001). Analysis of ALS groups revealed that functional impairment was related to a lower quality of life (ACSA) and higher depression levels among German ALS patients. Longer time since diagnosis predicted lower depression and (in male subjects) higher quality of life. CONCLUSIONS: ALS patients assess their quality of life and mood lower than healthy individuals within the studied countries. The relationships between clinical and demographic factors are moderated by country of provenance, which bears implications for the design and interpretation of scientific and clinical studies, which should reflect the complexity and heterogeneity of mechanisms determining QoL.

Executive Functions and Psychopathology Dimensions in Deficit and Non-Deficit Schizophrenia.

This study: (a) compared executive functions between deficit (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), controlling premorbid IQ and level of education; (b) compared executive functions in DS and NDS patients, controlling premorbid IQ and psychopathological symptoms; and (c) estimated relationships between clinical factors, psychopathological symptoms, and executive functions using structural equation modelling. Participants were 29 DS patients, 44 NDS patients, and 39 HC. Executive functions were measured with the Mazes Subtest, Spatial Span Subtest, Letter Number Span Test, Color Trail Test, and Berg Card Sorting Test. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. Compared to HC, both clinical groups performed poorer on cognitive flexibility, DS patients on verbal working memory, and NDS patients on planning. DS and NDS patients did not differ in executive functions, except planning, after controlling premorbid IQ and negative psychopathological symptoms. In DS patients, exacerbation had an effect on verbal working memory and cognitive planning; in NDS patients, positive symptoms had an effect on cognitive flexibility. Both DS and NDS patients presented deficits, affecting the former to a greater extent. Nonetheless, clinical variables appeared to significantly affect these deficits.

Cognitive Dysfunctions Measured with the MCCB in Deficit and Non-Deficit Schizophrenia.

This study compared cognitive domains between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), analyzing relationships between psychopathological dimensions and cognitive domains. A total of 29 DS patients, 45 NDS patients, and 39 HC subjects participated. Cognitive domains were measured using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Battery. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale. Clinical groups performed poorer than HC groups in regards to speed of processing, attention/vigilance, working memory, verbal and visual learning and memory, reasoning and problem solving, and social cognition. DS patients scored poorer than NDS patients in terms of all cognitive domains and the overall score, except for reasoning and problem solving. Positive, negative, disorganization, and resistance symptoms were related to cognitive functions only in NDS patients. Our findings suggest that the MCCB battery is sensitive to detecting cognitive dysfunctions in both deficit and non-deficit schizophrenia.

Religiosity in patients with amyotrophic lateral sclerosis, a cross-country comparison.

PURPOSE: Amyotrophic lateral sclerosis (ALS) is a progressive motor impairment leading to early death. Religiousness is one of the factors potentially alleviating the psychological burden of patients. However, its role might vary according to cultural context. Our study aimed to analyze religiosity, and its clinical, psychological and socio-demographic correlates in ALS patients and controls, comparing two European countries with different cultural backgrounds. METHODS: 268 Polish and German ALS patients, including 18 with locked-in syndrome (LIS) and 198 healthy controls (HC) were interviewed about religiousness, quality of life (Qol), depression, functional status and pain. A follow-up was conducted on 71 patients. RESULTS: Polish subjects had a significantly higher level of public, private and general religiosity than the German sample. Importantly, we found no difference in total and public religiousness between ALS patients and HC within either population. Only the private religiousness was significantly higher in German patients compared to controls. In the same sample, private religiousness correlated with functional impairment due to disease progression. In ALS groups and LIS patients, religiousness did not correlate with any disease-associated factors: disease duration, pain, Qol or depression. Follow-up comparisons in the ALS group revealed worsening functional status, increased depression and no significant change in religiosity. CONCLUSIONS: Religiosity was linked to the cultural background rather than ALS. Generally, it did not correlate with clinical, psychological and socio-demographic parameters and was stable throughout disease progression. The only exception was the relationship between the functional decline and private religiosity among German patients.

Complement Activation Products in Patients with Chronic Schizophrenia.

Evidence suggests a role of the immune system in the pathogenesis of a number of mental conditions, including schizophrenia (SCH). In terms of physiology, aside from its crucial protective function, the complement cascade (CC) is a critical element of the regeneration processes, including neurogenesis. Few studies have attempted to define the function of the CC components in SCH. To shed more light on this topic, we compared the levels of complement activation products (CAP) (C3a, C5a and C5b-9) in the peripheral blood of 62 patients with chronic SCH and disease duration of ≥ 10 years with 25 healthy controls matched for age, sex, BMI and smoking status. Concentrations of all the investigated CAP were elevated in SCH patients. However, after controlling for potential confounding factors, significant correlations were observed between SCH and C3a (M = 724.98 ng/mL) and C5a (M = 6.06 ng/mL) levels. In addition, multivariate logistic regression showed that C3a and C5b-9 were significant predictors of SCH. There were no significant correlations between any CAP and SCH symptom severity or general psychopathology in SCH patients. However, two significant links emerged between C3a and C5b-9 and global functioning. Increased levels of both complement activation products in the patient group as compared to healthy controls raise questions concerning the role of the CC in the etiology of SCH and further demonstrate dysregulation of the immune system in SCH patients.

Serum Inflammatory Markers and Integrity of the Superior Longitudinal Fasciculus and the Inferior Longitudinal Fasciculus in Schizophrenia, from Prodromal Stages to Chronic Psychosis-A Cross-Sectional Study.

Chronic subclinical inflammation is believed to be an important factor in the pathogenesis of schizophrenia. Meta-analyses confirm the presence of increased levels of peripheral inflammatory markers (IM) in schizophrenia and its prodromal stages. Peripheral cytokines may affect the brain microstructure through chronic activation of microglia. Disruptions in the integrity of the superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF) are commonly seen in patients with schizophrenia spectrum disorders. We therefore attempted to verify in a cross-sectional study whether there is a correlation between levels of peripheral IM and the integrity of these brain regions in healthy controls, from prodromal states and first episode psychosis to long-term schizophrenia. The integrity of white matter was measured using diffusion tensor imaging. Despite a broad analysis of six IM (CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ), we did not find any correlations with the integrity of the SLF or ILF in any of the analyzed groups (after correction for multiple comparisons). In conclusion, our study does not support the existence of a link between disrupted levels of peripheral IM and reduced integrity of ILF and SLF in schizophrenia spectrum disorders. However, prospective studies are needed to verify this over a long period of time.

Role of DTI-MRI parameters in diagnosis of ALS: useful biomarkers for daily practice? Tertiary centre experience and literature review.

INTRODUCTION: Despite the rapid development of neuroimaging techniques, the diagnosis of amyotrophic lateral sclerosis (ALS) remains a significant challenge. Magnetic resonance imaging (MRI) is important for ruling out ALS mimickers, while Diffusion Tensor Imaging (DTI) is a useful tool for the identification of cortical tract damage. The aim of this study was to identify the optimal set of DTI parameters to support the diagnosis of ALS that could be applied to everyday MRI and be used as a disease biomarker in daily practice. MATERIAL AND METHODS: Forty-seven ALS patients and 55 age- and gender-matched healthy individuals underwent MRI using a 1.5-Tesla scanner including a DTI sequence with 30 spatial directions and a b-value 0/1,000 s/mm2. Two independent researchers measured the DTI parameters: fractional anisotropy (FA), TRACE and apparent diffusion coefficient (ADC) using freehand regions of interest (ROIs) placed along both corticospinal tracts (CSTs), starting at the level of the internal capsule and ending at the medulla. RESULTS: Statistical significance was only achieved for fractional anisotropy (FA) (ALS vs controls, p < 0.001). The highest sensitivity was found in the brainstem (cerebral peduncles, pons and pyramids) where it ranged from 72.3% to 80.9%, whereas the highest specificity was observed at the level of the internal capsule (94.6%). The combined highest sensitivity and specificity was obtained in the pons (72.3% and 72.7%, respectively). Classifier based positive predictive values for Youden index cut-off scores varied between 60.7% and 69.4%. CONCLUSIONS: Fractional anisotropy (FA) measured at the level of the brainstem was shown to be the single most relevant parameter in differentiating patients with ALS from healthy subjects. This has the potential to become an ALS-specific biomarker for patient identification in daily practice.

Serum Inflammatory Markers and Their Associations with the Integrity of the Cingulum Bundle in Schizophrenia, from Prodromal Stages to Chronic Psychosis.

Peripheral cytokines may affect the brain through chronic activation of microglia and, as a result, can potentially lead to decreased integrity of white matter of cingulum bundle (CB). Therefore, the aim of the study was to analyze the relationships between peripheral inflammatory markers and the integrity of the CB in various states: from healthy controls, through prodromal states and first-episode psychosis, to long-term schizophrenia. The integrity of the CB was measured using diffusion tensor imaging. We analyzed six parameters: CRP, IL-6, IL-8, IL-10, TNF-α, and IFN-γ. We found that levels of IL-6 and IFN-γ differed significantly between groups. Initial analysis showed some correlations between the inflammatory markers and CB integrity, in particular a correlation with IL-6 that was present in several groups. However, none of the analyzed parameters were associated with the integrity of the CB after correction for multiple comparisons. Conclusions: Our results supported our hypothesis that there are increased levels of inflammatory markers in psychotic disorders, but did not allow to confirm our hypothesis that there is a link between increased peripheral inflammatory markers and decreased integrity of the CB. However, we found some interesting trend levels that need to be verified in larger studies.

Are you confident enough to act? Individual differences in action control are associated with post-decisional metacognitive bias.

The art of making good choices and being consistent in executing them is essential for having a successful and fulfilling life. Individual differences in action control are believed to have a crucial impact on how we make choices and whether we put them in action. Action-oriented people are more decisive, flexible and likely to implement their intentions in the face of adversity. In contrast, state-oriented people often struggle to commit to their choices and end up second-guessing themselves. Here, we employ a model-based computational approach to study the underlying cognitive differences between action and state-oriented people in simple binary-choice decision tasks. In Experiment 1 we show that there is little-to-no evidence that the two groups differ in terms of decision-related parameters and strong evidence for differences in metacognitive bias. Action-oriented people exhibit greater confidence in the correctness of their choices as well as slightly elevated judgement sensitivity, although no differences in performance are present. In Experiment 2 we replicate this effect and show that the confidence gap generalizes to value-based decisions, widens as a function of difficulty and is independent of deliberation interval. Furthermore, allowing more time for confidence deliberation indicated that state-oriented people focus more strongly on external features of choice. We propose that a positive confidence bias, coupled with appropriate metacognitive sensitivity, might be crucial for the successful realization of intentions in many real-life situations. More generally, our study provides an example of how modelling latent cognitive processes can bring meaningful insight into the study of individual differences.

The Relationship between Cognitive Functions and Psychopathological Symptoms in First Episode Psychosis and Chronic Schizophrenia.

Impairments in cognitive functions are one of the main features of schizophrenia. A variety of factors can influence the extent of cognitive deficits. In our study, we examined the severity of cognitive deficits at different stages of the disease and the relationship between psychopathological symptoms and cognitive functions. We recruited 32 patients with first-episode psychosis (FEP), 70 with chronic schizophrenia (CS), and 39 healthy controls (HC). Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functions were measured with the MATRICS Cognitive Consensus Battery (MCCB). Cognitive deficits were present in both FEP and CS participants. CS individuals had lower overall scores and poorer working memory; however, clinical variables appeared to play a significant role in these scores. In FEP, disorganization correlated negatively with verbal and visual learning and memory, social cognition, and overall score; negative symptoms negatively correlated with social cognition. In CS participants, disorganization correlated negatively with speed of processing, reasoning, problem solving, and overall score; negative symptoms were negatively correlated with speed of processing, visual learning, memory, and overall score; positive symptoms were negatively correlated with reasoning and problem solving. Our findings indicate that psychopathological symptoms have a significant impact on cognitive functions in FEP and CS patients.

Naturalistic use of psychedelics is related to emotional reactivity and self-consciousness: The mediating role of ego-dissolution and mystical experiences.

BACKGROUND: Psychedelics are able to acutely alter emotional reactivity and self-consciousness. However, whether the regular naturalistic use of psychedelics can be linked to more persistent trait-level changes in these domains remains an open question. AIM: To test the hypotheses that (1) using psychedelics is related to higher positive and lower negative emotional reactivity; and (2) an adaptive pattern of self-consciousness, including diminished public self-consciousness and rumination, and increased reflection and self-awareness; and (3) these relations are mediated by the intensity of past ego-dissolution and mystical experiences. METHOD: An online survey including questions about the history of psychoactive substance use; questionnaires measuring trait levels of emotional reactivity and self-consciousness; questionnaires for retrospective assessment of ego-dissolution and mystical experiences. Data collected from 2516 participants (1661 psychedelics users) were analyzed using robust linear regression and mediation analysis. RESULTS: A higher number of lifetime uses of psychedelics predicted greater positive and lower negative emotional reactivity; also, in the domain of self-consciousness, it predicted greater reflection and internal state awareness, and reduced rumination tendency and public self-consciousness. Finally, the intensity of past mystical and ego-dissolution experiences mediated almost all the observed relationships between the lifetime number of psychedelics uses and psychological variables. CONCLUSIONS: Lifetime psychedelics use predicts an adaptive pattern of trait-level emotional reactivity and self-consciousness. Ego-dissolution and mystical experiences are essential in understanding the long-lasting psychological effects of psychedelics use. Our findings might potentially explain previous observations of increased well-being in psychedelics users.

Relationship between White Matter Alterations and Pathophysiological Symptoms in Patients with Ultra-High Risk of Psychosis, First-Episode, and Chronic Schizophrenia.

Some symptoms of schizophrenia might be present before full-blown psychosis, so white matter changes must be studied both in individuals with emerging psychosis and chronic schizophrenia. A total of 86 patients­12 ultra-high risk of psychosis (UHR), 20 first episode psychosis (FEP), 54 chronic schizophrenia (CS), and 33 healthy controls (HC)­underwent psychiatric examination and diffusion tensor imaging (DTI) in a 3-Tesla MRI scanner. We assessed fractional anisotropy (FA) and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILS). We found that CS patients had lower FA than FEP patients (p = 0.025) and HC (p = 0.088), and higher MD than HC (p = 0.037) in the right SLF. In the CS group, we found positive correlations of MD in both right ILF (rho = 0.39, p < 0.05) and SLF (rho = 0.43, p < 0.01) with disorganization symptoms, as well as negative correlation of FA in the right ILF with disorganization symptoms (rho = −0.43, p < 0.05). Among UHR individuals, we found significant negative correlations between MD in the left ILF and negative (r = −0.74, p < 0.05) and general symptoms (r = −0.77, p < 0.05). However promising, these findings should be treated as preliminary, and further research must verify whether they can be treated as potential biomarkers of psychosis.

A Novel Doppler TRPG/AcT Index Improves Echocardiographic Diagnosis of Pulmonary Hypertension after Pulmonary Embolism.

BACKGROUND: We hypothesized that a Doppler index, the ratio of tricuspid regurgitation peak gradient (TRPG) to pulmonary ejection acceleration time (AcT), improves the assessment of the echocardiographic probability of pulmonary hypertension in the identification of CTEPH and chronic thromboembolic pulmonary disease (CTED) in symptomatic patients after PE. Doppler echocardiography is recommended as the initial imaging tool for the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE). METHODS: We analyzed the data from 845 consecutive PE (468 women; 61 ± 18 years) survivors who completed at least 6 months of anticoagulation therapy. Here, 555 patients (325 women; 66 ± 16 years) reporting functional impairment (FI) underwent transthoracic echocardiography. We included 506 patients (297 women; age 63.4 ± 16.6 years) in whom both AcT and TRPG were available into the current study. The presence of a minimum of intermediate echocardiographic probability of PH necessitated the diagnosis of CTEPH. RESULTS: Echocardiography revealed a high echocardiographic probability of PH in 69 (13.6%) and intermediate echocardiographic probability in 109 (21.5%) patients. CTEPH was diagnosed in 35 (6.9%) patients and CTED in 22 (4.3%) patients. TRPG/AcT was significantly higher in the combined CTEPH + CTED group than in those with other causes of FI (0.412 (0.100-2.197) vs. 0.208 (0.026-0.115), p < 0.001), and the area under the receiver operating characteristic curve of the TRPG/AcT for CTEPH + CTED was 0.804 (95% confidence interval (CI): 0.731-0.876). Importantly, multiple logistic regression showed that TRPG/AcT is a significant predictor of CTEPH + CTED after considering echocardiographic probability (odds ratio = 1.51, 95% CI: 1.25-1.91, p < 0.001). Conditional inference trees analysis revealed that TRPG/AcT > 0.595 identified patients with CTEPH or CTED with a positive predictive value of 78.6% and negative predictive value of 92.7%. CONCLUSIONS: A Doppler index TRPG/AcT improves the assessment of symptomatic PE survivors. TRPG/AcT > 0.6 indicates a high probability of CTEPH or CTED, whereas TRPG/AcT < 0.6 allows for the safe exclusion of CTEPH + CTED in patients with a low echocardiographic probability of PH.

Serum inflammatory markers and their associations with white matter integrity of the corpus callosum in schizophrenia patients and healthy controls.

Schizophrenia is associated with disrupted integrity of white matter microstructure of a variety of brain regions, especially the corpus callosum (CC). Chronic subclinical inflammation is considered to be one of the factors involved in the pathogenesis of this disease, and increased levels of peripheral inflammatory markers are often observed in schizophrenia patients. Therefore, we decided to investigate whether the integrity of the corpus callosum is correlated with levels of these markers. A total of 50 patients with stable chronic schizophrenia (SCH) and 30 controls (CON) were enrolled in the study. All participants underwent psychiatric evaluation, neuroimaging, and blood sampling including the measurement of serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL - 10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and C-reactive protein (CRP). Additional potentially related factors, such as age, gender, BMI, smoking, disease duration, and treatment were included in the analysis. Significantly higher IL-6 and IFN-γ levels were observed in SCH compared to CON. In SCH, IFN-γ was positively correlated with mean diffusivity of region 2 of the CC. In CON, IL-6 was inversely correlated with fractional anisotropy of region 1 of the CC. These results support the potential influence of peripheral inflammatory markers on the integrity of the CC in schizophrenia, but require verification in longitudinal studies.

Cognitive impairments in Polish children and adolescents with perinatal HIV infection. / Zaburzenia poznawcze u dzieci i mlodziezy z wrodzonym zakazeniem HIV w Polsce.

OBJECTIVES: The aim of the study was to assess the presence of cognitive impairments in children and adolescents with vertically transmitted HIV infection and to determine possible relationships with clinical and socio-demographic variables. METHODS: Fifty children with perinatal HIV infection aged 6-18 years were included in the experimental group (PHIV+). Two sex- and age-matched groups were recruited as reference groups: (1) a PHEU group that included 24 healthy children perinatally HIV-exposed but uninfected, and (2) an HIV-nA group that included 43 healthy children of uninfected parents. CANTAB Research Suite was used to assess cognitive functioning. RESULTS: In comparison with the HIV-nA group, the PHIV+ group scored worse in movement execution, shifting and flexibility of attention, reversal learning and working memory. In comparison with the PHEU group, the PHIV+ group had significantly longer planning time in the memory task. The analysis of results for the 12-18 year-old age group revealed deterioration of cognitive functions in all tests of the PHIV+ children in comparison with the HIV-nA group. A higher logarithm of viral load at the start of the ARV treatment was associated with worse results in the use of feedback, shifting of attention, cognitive flexibility and worse information processing. CONCLUSIONS: Results of the research indicate deterioration of executive functioning in the PHIV+ group associated with longer duration of HIV neuroinfection and severity of infection before treatment.