Vaclav Capek

Importance: Average gray matter volume (GMV) loss in early psychosis may conceal clinically relevant differences in brain change. Objective: To identify longitudinal GMV-change patterns, their cross-site correspondence, and clinical associations. Design, Setting, and Participants: Prospective cohort with T1-weighted MRI acquired during 2011–2026 at 2 Czech sites; median follow-up, approximately 13 months. Participants were 222 patients with first-episode schizophrenia-spectrum psychosis and 178 healthy controls frequency-matched by site and baseline age. Exposure: First-episode psychosis vs healthy control status. Main Outcomes and Measures: Diagnosis-blind clustering by site of image-quality-corrected, subsequently annualized GMV change across 333 cortical parcels; longitudinal voxel-based morphometry (VBM); Global Assessment of Functioning and consensus 5-factor Positive and Negative Syndrome Scale negative-symptom scores. Results: Among 400 participants (mean [SD] age, 28.2 [7.5] years), 208 (52.0%) were male. Each site independently yielded 3 clusters: C1 (near-stable GMV), C2 (pronounced decrease), and C3 (increase). Cross-site centroid correlations across 333 parcels were strong for C2 and C3 (Spearman ρ = 0.865 and 0.861); C1 correlation was weak (ρ = 0.138), as expected for near-zero profiles with little regional variation. C2/C3 correspondence supported pooling matched site-specific clusters for post hoc analyses. Pooled clusters contained 77 patients and 125 controls in C1, 66 patients and 16 controls in C2, and 79 patients and 37 controls in C3. Suffixes −P and −HC identify patient and control subgroups. To situate patient changes relative to controls, post hoc VBM revealed an unanticipated gradient of increasingly pronounced GMV reduction across C1-HC → C1-P → C2-P, prominently involving association cortex, and bilateral ventral temporal GMV increase in C3-P (familywise error–corrected P < .05). The opposite contrast along this ordering showed periventricular changes consistent with progressively greater ventricular enlargement. C2-P had the lowest mean follow-up functioning and highest mean negative-symptom severity (adjusted omnibus P = .005 and .02); clinical changes from baseline did not differ significantly among patient groups. Conclusions and Relevance: Early GMV change in psychosis was not uniform but comprised two contrasting directions: a clinically relevant, control-anchored pattern of increasingly pronounced GMV loss involving default mode regions and a distinct, directionally opposing ventral temporal increase. Key Points: Question: What patterns of cortical gray matter volume change emerge over approximately 1 year after first-episode schizophrenia-spectrum psychosis? Findings: In this 2-site cohort of 222 patients and 178 controls, nearly two-thirds of patients lay along a gradient from near-stability in controls to widespread volume decrease, whereas one-third showed an opposing ventral temporal increase. Follow-up functioning and negative symptoms differed significantly among patient groups, with the least favorable scores in those showing the greatest decrease. Meaning: Directions of within-person brain change may capture clinically relevant heterogeneity obscured by average volume loss.

Background: In primary ciliary dyskinesia (PCD) there is no single diagnostic test. Different predictive tools have been proposed to guide referral of high-risk patients for further diagnostic workup. We aimed to test clinical index (CI) on a large unselected cohort and compare its characteristics with other widely used tools—PICADAR and NA-CDCF. Methods: CI, PICADAR, and NA-CDCF scores were calculated in 1401 patients with suspected PCD referred to our center. Their predictive characteristics were analyzed using receiver operating characteristics (ROC) curves and compared to each other. Nasal nitric oxide (nNO) was measured in 569 patients older than 3 years. Results: PCD was diagnosed in 67 (4.8%) patients. CI, PICADAR, and NA-CDCF scores were higher in PCD than in nonPCD group (all p < 0.001). The area under the ROC curve (AUC) for CI was larger than for NA-CDCF (p = 0.005); AUC_PICADAR and AUC_NA-CDCF did not differ (p = 0.093). An overlap in signs and symptoms among tools was identified. PICADAR could not be assessed in 86 (6.1%) patients without chronic wet cough. For CI laterality or congenital heart defects assessment was not necessary. nNO further improved predictive power of all three tools. Conclusion: CI is a feasible predictive tool for PCD that may outperform PICADAR and NA-CFCD.

At the end of the mammalian intra-uterine foetal development, a rapid switch from glycolytic to oxidative metabolism must proceed. Using microarray techniques, qPCR, enzyme activities and coenzyme Q content measurements, we describe perinatal mitochondrial metabolism acceleration in rat liver and skeletal muscle during the perinatal period and correlate the results with those in humans. Out of 1546 mitochondrial genes, we found significant changes in expression in 1119 and 827 genes in rat liver and skeletal muscle, respectively. The most remarkable expression shift occurred in the rat liver at least two days before birth. Coenzyme Q-based evaluation in both the rat model and human tissues showed the same trend: the total CoQ content is low prenatally, significantly increasing after birth in both the liver and skeletal muscle. We propose that an important regulator of rat coenzyme Q biosynthesis might be COQ8A, an atypical kinase involved in the biosynthesis of coenzyme Q. Our microarray data, a total of 16,557 RefSeq (Entrez) genes, have been deposited in NCBI’s Gene Expression Omnibus and are freely available to the broad scientific community. Our microarray data could serve as a suitable background for finding key factors regulating mitochondrial metabolism and the preparation of the foetus for the transition to extra-uterine conditions.

The treatment of children with posterior fossa brain tumours (PFBT) impacts their long term functional and imaging outcomes. This study aimed to evaluate academic achievement correlated with long-term sequelae after different PFBT treatment modalities. The study cohort consisted of 110 survivors (median age at diagnosis 10.1 years and median time of follow up 13.2 years) who completed hearing questionnaires, neurological assessment and MRI of the brain ≥5 years after the end of treatment. There were three treatment groups. A cisplatin group which underwent cisplatin chemotherapy, radiotherapy and surgery (medulloblastoma N = 40), a radiotherapy group which underwent radiotherapy and surgery (astrocytoma/ependymoma N = 30), and a surgery group (astrocytoma N = 40). Academic achievement was correlated to the age at diagnosis, ototoxicity, Karnofsky score (KS), and MRI findings (Fazekas Score (FS)- treatment related parenchymal changes). For a modelled age at diagnosis of five years, the cisplatin group had lower academic achievements compared to the radiotherapy (p = 0.028) and surgery (p = 0.014) groups. Academic achievements evaluated at a modelled age of 10 years at diagnosis did not significantly differ among the treatment groups. The cisplatin group exhibited a higher occurrence of ototoxicity than the radiotherapy (p<0.019) and surgery groups (p<0.001); however, there was no correlation between ototoxicity and academic achievements (p = 0.722) in older age at diagnosis. The radiotherapy group exhibited lower KS than the surgery group (p<0.001). KS significantly influenced academic achievements in all groups (p<0.000). The cisplatin group exhibited higher FS than the surgery group (p<0.001) while FS did not correlate with academic achievement (p = 0.399). Older age is a protective factor for academic achievements irrespective of a treatment modality.

Mannose‐binding lectin (MBL) is an important component of the innate immunity, and it is responsible not only for opsonization of micro‐organisms, but also for efferocytosis. The aim of this study was to investigate whether MBL concentrations and lectin complement pathway activity are altered in non‐pregnant women with previous adverse pregnancy outcomes. Patients were divided into four groups on the basis of their history of pregnancy complications, including control patients who had uncomplicated pregnancies and term deliveries (control, n = 33), and three groups of patients with a history of pregnancy complications, including preterm labour (n = 29), recurrent miscarriage (n = 19) or unexplained intrauterine foetal death (IUFD; n = 17). All women enrolled in the study had an interval of three to six months following their previous pregnancy, and they agreed to have a blood sample taken. We found significantly higher MBL concentrations and functional activity of the lectin complement pathway in healthy controls who had previous uneventful term pregnancies (1341 ng/mL; activity 100% (IQR: 62%‐100%)), compared to women with the history of IUFD (684 ng/mL, P = .008; activity 8.5% (IQR: 0%‐97.8%), P = .011), recurrent miscarriage (524 ng/mL, P = .022; activity 44% (IQR: 4%‐83%), P = .011) or preterm labour (799 ng/mL, P = .022; activity 62.5% (IQR: 0%‐83%), P = .003). Our results suggest that inadequate function of the complement lectin pathway is associated with a higher risk of preterm labour, recurrent miscarriage and unexplained intrauterine foetal death.

Although numerous activity trackers have been validated in healthy populations, validation is lacking in chronic heart failure patients who normally walk at a slower pace, making it difficult for researchers and clinicians to implement activity monitors during physical activity interventions. Six consumer-level activity monitors were validated in a 3-day field study in patients with chronic heart failure and healthy individuals under free living conditions. Furthermore, the same devices were evaluated in a lab-based study during treadmill walking at speeds of 2.4, 3.0, 3.6, and 4.2 km·h^-1. Concordance correlation coefficients (CCC) were used to evaluate the agreement between the activity monitors and the criterion, and mean absolute percentage errors (MAPE) were calculated to assess differences between each device and the criterion (MAPE -1, all activity monitors showed substantial to almost perfect correlations (CCC ≥0.95) with the criterion and MAPE in the range 1%-3%. However, at slower speeds of 3.0 and 2.4 km·h^-1, the accuracy of all devices substantially deteriorated: their correlation with the criterion decreased below 90% and their MAPE increased to 4–8% and 10–45%, respectively. Even though none of the tested activity monitors fall within arbitrary thresholds for validity, most of them perform reasonably well enough to be useful tools that clinicians can use to simply motivate chronic heart failure patients to walk more.

Background: Public spaces are usually designed with respect to various patient populations, but not Parkinson's disease. The objective of this study was to explore what type of easily applicable visual cueing might be used in public spaces and some interiors to improve gait in people with Parkinson's disease.Methods: Thirty‐two patients with freezing of gait walked an 8‐meter track on 6 different floor patterns in single‐ and dual‐task conditions in random sequence. The reference pattern was a virtual large transverse chessboard, and the other patterns differed either in size (small floor stones), orientation (diagonal), nature (real paving), regularity (irregular), or no pattern. Time, number of steps, velocity, step length, cadence, and dual‐task effect were calculated. The number and total duration of freezing episodes were analyzed.Results: Virtual, large, transverse floor stones improve time (P = 0.0101), velocity (P = 0.0029), number of steps (P = 0.0291), and step length (P = 0.0254) in Parkinson's disease patients compared with walking on no pattern. Virtual floor stones were superior in time and velocity to the real ones. Transverse floor stones were better than diagonal, whereas regular pattern stones were superior to irregular in some gait parameters. Subjectively, the reference pattern was preferred to the irregular one and to no pattern. No direct effect on freezing of gait was observed.Conclusions: Parkinson's disease patients may benefit from floor patterns incorporating transverse oriented large rectangular visual cues. Because public space can be regulated with respect to people with medical conditions, the relevant legislative documents should be extended to allow for parkinsonian gait disorder. © 2019 International Parkinson and Movement Disorder Society

The recognition of active inflammation in the central nervous system (CNS) in the absence of infectious agents is challenging. The present study aimed to determine the diagnostic relevance of five selected chemo/cytokines in the recognition of CNS inflammation and in the context of traditional cerebrospinal fluid (CSF) biomarkers (white blood cell [WBC] counts, oligoclonal bands, protein levels, CSF/serum albumin ratios) and clinical diagnoses. C-C and C-X-C motif ligands (CCL2, CXCL8, 10 and 13) and interleukin (IL) 6 levels in the CSF and serum from 37 control and 87 symptomatic children with ten different (mostly noninfectious) inflammatory CNS disorders (16 of which had follow-up samples after recovery) were determined using Luminex multiple bead technology and software. Nonparametric tests were used; p < 0.05 was considered statistically significant. Receiver operating characteristic curves were constructed to analyze controls and 1) all symptomatic samples or 2) symptomatic samples without CSF pleocytosis. Compared with the control CSF samples, levels of all investigated chemo/cytokines were increased in symptomatic CSF samples, and only IL-6 remained elevated in recovery samples (p ≤ 0.001). CSF CXCL-13 levels (> 10.9 pg/mL) were the best individual discriminatory criterion to differentiate neuroinflammation (specificity/sensitivity: 97/72% and 97/61% for samples without pleocytosis), followed by CSF WBC counts (specificity/sensitivity: 97/62%). The clinical utility of the remaining CSF chemo/cytokine levels was determined in descending order of sensitivities corresponding to thresholds that ensured 97% specificity for neuroinflammation in samples without pleocytosis (pg/mL; sensitivity %): IL-6 (3.8; 34), CXCL8 (32; 26), CXCL10 (317; 24) and CCL2 (387; 10). Different diagnosis-related patterns of CSF chemo/cytokines were observed. The increased CSF level of CXCL13 was the marker with the greatest predictive utility for the general recognition of neuroinflammation among all of the individually investigated biomarkers. The potential clinical utility of chemo/cytokines in the differential diagnosis of neuroinflammatory diseases was identified.