Spontaneously fluctuating brain activity patterns that emerge at rest have been linked to the brain's health and cognition. Despite detailed descriptions of the spatio-temporal brain patterns, our understanding of their generative mechanism is still incomplete. Using a combination of computational modeling and dynamical systems analysis we provide a mechanistic description of the formation of a resting state manifold via the network connectivity. We demonstrate that the symmetry breaking by the connectivity creates a characteristic flow on the manifold, which produces the major data features across scales and imaging modalities. These include spontaneous high-amplitude co-activations, neuronal cascades, spectral cortical gradients, multistability, and characteristic functional connectivity dynamics. When aggregated across cortical hierarchies, these match the profiles from empirical data. The understanding of the brain's resting state manifold is fundamental for the construction of task-specific flows and manifolds used in theories of brain function. In addition, it shifts the focus from the single recordings towards the brain's capacity to generate certain dynamics characteristic of health and pathology.
- MeSH
- Adult MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Brain Mapping methods MeSH
- Models, Neurological * MeSH
- Brain * physiology diagnostic imaging MeSH
- Nerve Net physiology MeSH
- Rest * physiology MeSH
- Computer Simulation MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The aim of this work was to study the effect of deep brain stimulation of the subthalamic nucleus (STN-DBS) on the subnetwork of subcortical and cortical motor regions and on the whole brain connectivity using the functional connectivity analysis in Parkinson's disease (PD). The high-density source space EEG was acquired and analyzed in 43 PD subjects in DBS on and DBS off stimulation states (off medication) during a cognitive-motor task. Increased high gamma band (50-100 Hz) connectivity within subcortical regions and between subcortical and cortical motor regions was significantly associated with the Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III improvement after DBS. Whole brain neural correlates of cognitive performance were also detected in the high gamma (50-100 Hz) band. A whole brain multifrequency connectivity profile was found to classify optimal and suboptimal responders to DBS with a positive predictive value of 0.77, negative predictive value of 0.55, specificity of 0.73, and sensitivity of 0.60. Specific connectivity patterns related to PD, motor symptoms improvement after DBS, and therapy responsiveness predictive connectivity profiles were uncovered.
- MeSH
- Electroencephalography methods MeSH
- Deep Brain Stimulation * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Brain physiopathology diagnostic imaging MeSH
- Subthalamic Nucleus * physiopathology MeSH
- Parkinson Disease * therapy physiopathology MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
1. vydání ix, 229 stran : ilustrace ; 26 cm
Publikace, která se zaměřuje na různé komplikace diabetu. Určeno odborné veřejnosti.; Incidence diabetu raketově roste nejen v rozvinutých zemích. Pozdní komplikace diabetu a jejich důsledky představují jedno z největších zatížení medicíny celosvětově a přispívají k velmi vysoké morbiditě a mortalitě pacientů. Diabetologie je rychle se rozvíjející obor věnující se jak péči o diabetiky 1. typu s využitím nejmodernějších technologií k měření glukózy a k dodávkám inzulínu do organismu, tak i léčbě pacientů s diabetem 2. typu, u kterých za posledních 10 let přibylo několik lékových skupin. Kniha komplexně a kriticky popisuje a hodnotí nejnovější diagnostické a terapeutické postupy u jednotlivých komplikací diabetu – u diabetické retinopatie neopomíjí ani využití umělé inteligence ve screeningu a nejmodernější léčebných strategií včetně anti-VEGF terapie. Z hlediska diabetického onemocnění ledvin podrobně diskutuje přínos recentních léků, jako jsou SGLT-2 inhibitory a finerenon. Syndrom diabetické nohy a diabetické neuropatie jsou přehledně popsány s využitím nových poznatků ze světového konsenzu diabetické nohy. Důležitá část publikace je věnována i obezitě, v jejíž léčbě v posledních pěti letech došlo k neuvěřitelnému posunu, a srdečnímu selhání u pacientů s diabetem. V neposlední řadě je diskutována problematika prevence chronických komplikací diabetu s využitím moderních technologií, telemedicíny či zlepšení spánkové hygieny. Zmíněna je důležitost fyzické aktivity, která je často jak lékaři, tak pacienty opomíjena, je ovšem klíčová v prevenci těchto onemocnění. Moderně pojatá monografie využívá pro pochopení problematiky kromě textu řadu přehledných schémat a obrázků. Cílem autorů je srozumitelnou formou předat nejnovější vědecké poznatky a přiblížit jejich využití v běžné klinické praxi. Kniha je určena zejména pro lékaře z interních oborů, jako je diabetologie, nefrologie nebo kardiologie. Stejně tak může ale sloužit jako ucelený přehled pro praktické lékaře, pregraduální, ale i postgraduální studenty medicíny.
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- diabetologie
- NML Publication type
- kolektivní monografie
Background Stereotactic radiosurgery (SRS) and resection are treatment options for patients with facial nerve schwannomas without mass effect. Objective This article evaluates outcomes of patients treated with SRS versus resection + SRS. Method We retrospectively compared 43 patients treated with SRS to 12 patients treated with resection + SRS. The primary study outcome was unfavorable combined endpoint, defined as worsening or new clinical symptoms, and/or tumor radiological progression. SRS (38.81 ± 5.3) and resection + SRS (67.14 ± 11.8) groups had similar clinical follow-ups. Results At the time of SRS, the tumor volumes of SRS (mean ± standard error; 1.83 ± 0.35 mL) and resection + SRS (2.51 ± 0.75 mL) groups were similar. SRS (12.15 ± 0.08 Gy) and resection + SRS (12.16 ± 0.14 Gy) groups received similar radiation doses. SRS group (42/43, 98%) had better local tumor control than the resection + SRS group (10/12, 83%, p = 0.04). Most of SRS (32/43, 74%) and resection + SRS (10/12, 83%) group patients reached a favorable combined endpoint following SRS ( p = 0.52). Considering surgical associated side effects, only 2/10 patients of the resection + SRS group reached a favorable endpoint ( p < 0.001). Patients of SRS group, who are > 34 years old ( p = 0.02), have larger tumors (> 4 mL, 0.04), internal auditory canal (IAC) segment tumor involvement ( p = 0.01) were more likely to reach an unfavorable endpoint. Resection + SRS group patients did not show such a difference. Conclusion While resection is still needed for larger tumors, SRS offers better clinical and radiological outcomes compared to resection followed by SRS for facial schwannomas. Younger age, smaller tumors, and non-IAC situated tumors are factors that portend a favorable outcome.
- Publication type
- Journal Article MeSH
BACKGROUND AND OBJECTIVE: There are limited data on real-world outcomes for patients with advanced or metastatic urothelial cancer (mUC) since immune checkpoint inhibitors (ICIs) became available. Our objective was to analyze outcomes for patients with mUC since ICIs became available. METHODS: We performed a retrospective analysis of 131 patients with mUC attending the outpatient clinic of a single tertiary care center who received systemic therapy between June 2017 and July 2021 with follow-up up to December 2022. Summary and descriptive statistics were calculated for categorical and continuous variables. The Kaplan-Meier method was applied to calculate survival, and a Cox proportional-hazards model was used to explore associations between clinical variables and outcomes. KEY FINDINGS AND LIMITATIONS: The median patient age was 68 yr (range 35-90). The first systemic therapy administered was platinum-based in 79% of cases and ICI-based in 21%. Some 61% of the cohort received a second systemic treatment, with 75% of these an ICI. Median overall survival for the entire cohort was 24 mo (interquartile range 9-35). Patients on ICI therapy for ≥6 mo had median overall survival of 59 mo (95% confidence interval 39 mo-not reached). Metastatic sites on initiation of ICI therapy and C-reactive protein kinetics were prognostic in patients receiving ICIs. Limitations include the retrospective design and inherent selection bias. CONCLUSIONS AND CLINICAL IMPLICATIONS: More than 60% of patients with mUC received second-line treatment, and 75% of these received an ICI. Patients staying on immunotherapy for more than 6 mo have substantially better outcomes in comparison to patients with less time on immunotherapy and historical cohorts. PATIENT SUMMARY: We looked at the lines of therapy and outcomes for patients with advanced or metastatic cancer of the urinary tract, starting from when immunotherapy drugs called immune checkpoint inhibitors (ICIs) became available. We found that 60% of patients have received second-line therapy, which is a double the rate in comparison to historical groups of patients. Patients with long-term ICI therapy (>6 months) had significantly better outcomes, with a median survival of more than 3 years.
- MeSH
- Adult MeSH
- Immunotherapy * methods MeSH
- Immune Checkpoint Inhibitors * therapeutic use MeSH
- Carcinoma, Transitional Cell * drug therapy secondary pathology MeSH
- Practice Patterns, Physicians' statistics & numerical data MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Metastasis MeSH
- Survival Rate MeSH
- Urinary Bladder Neoplasms * drug therapy pathology MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Urologic Neoplasms drug therapy pathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Excess fluid in the interstitium can adversely affect the microcirculation. We studied how gradual dilution of the blood plasma by crystalloid fluid influences microcirculatory variables and capillary filtration in 20 patients undergoing surgery. METHODS: Video recordings of the sublingual mucosal were made on four occasions during the surgery and compared with quasi-measurements of the capillary filtration rate using retrospective volume kinetic data collected over 5-10-minute periods during 262 infusion experiments with crystalloid fluid. RESULTS: The number of crossings (vessel density) increased up to plasma dilution of 15-20 % whereafter it decreased. The proportion of the vessels that were perfused (PPV) decreased and reached a nadir of -15 % at a dilution of 20-30 %. Changes in the number of crossings and the PPV correlated (r = 0.62, P < 0.001) but the curve was displaced so that crossings showed no change when PPV had decreased by approximately 10 %. However, the PPV of vessels with a thickness of ≤25 μm increased or remained constant in the dilution range of up to 20 %. The volume kinetic analysis showed that the capillary filtration was greater than expected from proportionality with the volume expansion up to a plasma dilution of 15 %, the greatest difference (+89 %) being for plasma dilution up to 5 %. CONCLUSION: Plasma dilution of up to 15 % increased the vessel density, and the capillary filtration increased by more than suggested by the volume expansion. Dilution >15 % had a negative influence on these variables.
- MeSH
- Video Recording MeSH
- Time Factors MeSH
- Adult MeSH
- Hemodilution * MeSH
- Isotonic Solutions administration & dosage MeSH
- Capillary Permeability MeSH
- Capillaries physiopathology MeSH
- Kinetics MeSH
- Crystalloid Solutions * administration & dosage MeSH
- Middle Aged MeSH
- Humans MeSH
- Microcirculation * MeSH
- Regional Blood Flow MeSH
- Retrospective Studies MeSH
- Blood Flow Velocity MeSH
- Aged MeSH
- Mouth Mucosa blood supply MeSH
- Mouth Floor blood supply MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
CXCL12 and CXCR4 proteins and mRNAs were monitored in the dorsal root ganglia (DRGs) of lumbar (L4-L5) and cervical (C7-C8) spinal segments of naïve rats, rats subjected to sham operation, and those undergoing unilateral complete sciatic nerve transection (CSNT) on post-operation day 7 (POD7). Immunohistochemical, Western blot, and RT-PCR analyses revealed bilaterally increased levels of CXCR4 protein and mRNA in both lumbar and cervical DRG neurons after CSNT. Similarly, CXCL12 protein levels increased, and CXCL12 mRNA was upregulated primarily in lumbar DRGs ipsilateral to the nerve lesion. Intrathecal application of the CXCR4 inhibitor AMD3100 following CSNT reduced CXCL12 and CXCR4 protein levels in cervical DRG neurons, as well as the length of afferent axons regenerated distal to the ulnar nerve crush. Furthermore, treatment with the CXCR4 inhibitor decreased levels of activated Signal Transducer and Activator of Transcription 3 (STAT3), a critical transforming factor in the neuronal regeneration program. Administration of IL-6 increased CXCR4 levels, whereas the JAK2-dependent STAT3 phosphorylation inhibitor (AG490) conversely decreased CXCR4 levels. This indicates a link between the CXCL12/CXCR4 signaling axis and IL-6-induced activation of STAT3 in the sciatic nerve injury-induced pro-regenerative state of cervical DRG neurons. The role of CXCR4 signaling in the axon-promoting state of DRG neurons was confirmed through in vitro cultivation of primary sensory neurons in a medium supplemented with CXCL12, with or without AMD3100. The potential involvement of conditioned cervical DRG neurons in the induction of neuropathic pain is discussed.
- MeSH
- Benzylamines MeSH
- Chemokine CXCL12 * metabolism MeSH
- Cyclams pharmacology MeSH
- Heterocyclic Compounds pharmacology MeSH
- Interleukin-6 metabolism MeSH
- Rats MeSH
- Sciatic Neuropathy metabolism MeSH
- Sensory Receptor Cells * metabolism MeSH
- Sciatic Nerve * injuries metabolism MeSH
- Rats, Sprague-Dawley MeSH
- Receptors, CXCR4 * metabolism MeSH
- Nerve Regeneration * MeSH
- Signal Transduction * MeSH
- Ganglia, Spinal * metabolism MeSH
- STAT3 Transcription Factor * metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: Olfactory dysfunction (OD) is common and carries significant personal and societal burden. Accurate assessment is necessary for good clinical and research practice but is highly dependent on the assessment technique used. Current practice with regards to UK/international clinical assessment is unknown. We aimed to capture current clinical practice, with reference to contemporaneously available guidelines. We further aimed to compare UK to international practice. DESIGN: Anonymous online questionnaire with cross-sectional non-probability sampling. Subgroup analysis according to subspeciality training in rhinology ('rhinologists' and 'non-rhinologists') was performed, with geographical comparisons only made according to subgroup. PARTICIPANTS: ENT surgeons who assess olfaction. RESULTS: Responses were received from 465 clinicians (217 from UK and 17 countries total). Country-specific response rate varied, with the lowest rate being obtained from Japan (1.4%) and highest from Greece (72.5%). Most UK clinicians do not perform psychophysical smell testing during any of the presented clinical scenarios-though rhinologists did so more often than non-rhinologists. The most frequent barriers to testing related to service provision (e.g., time/funding limitations). Whilst there was variability in practice, in general, international respondents performed psychophysical testing more frequently than those from the UK. Approximately 3/4 of all respondents said they would like to receive training in psychophysical smell testing. Patient reported outcome measures were infrequently used in the UK/internationally. More UK respondents performed diagnostic MRI scanning than international respondents. CONCLUSIONS: To our knowledge, this is the most comprehensive UK-based, and only international survey of clinical practice in the assessment of OD. We present recommendations to improve practice, including increased education and funding for psychophysical smell testing. We hope this will promote accurate and reliable olfactory assessment, as is the accepted standard in other sensory systems.
Fast Photochemical Oxidation of Proteins (FPOP) is a promising technique for studying protein structure and dynamics. The quality of insight provided by FPOP depends on the reliability of the determination of the modification site. This study investigates the performance of two search engines, Mascot and PEAKS, for the data processing of FPOP analyses. Comparison of Mascot and PEAKS of the hemoglobin--haptoglobin Bruker timsTOF data set (PXD021621) revealed greater consistency in the Mascot identification of modified peptides, with around 26% of the IDs being mutual for all three replicates, compared to approximately 22% for PEAKS. The intersection between Mascot and PEAKS results revealed a limited number (31%) of shared modified peptides. Principal Component Analysis (PCA) using the peptide-spectrum match (PSM) score, site probability, and peptide intensity was applied to evaluate the results, and the analyses revealed distinct clusters of modified peptides. Mascot showed the ability to assess confident site determination, even with lower PSM scores. However, high PSM scores from PEAKS did not guarantee a reliable determination of the modification site. Fragmentation coverage of the modification position played a crucial role in Mascot assignments, while the AScore localizations from PEAKS often become ambiguous because the software employs MS/MS merging.
Acquiring pulmonary circulation parameters as a potential marker of cardiopulmonary function is not new. Methods to obtain these parameters have been developed over time, with the latest being first-pass perfusion sequences in cardiovascular magnetic resonance (CMR). Even though more data on these parameters has been recently published, different nomenclature and acquisition methods are used across studies; some works even reported conflicting data. The most commonly used circulation parameters obtained using CMR include pulmonary transit time (PTT) and pulmonary transit beats (PTB). PTT is the time needed for a contrast agent (typically gadolinium-based) to circulate from the right ventricle (RV) to the left ventricle (LV). PTB is the number of cardiac cycles the process takes. Some authors also include corrected heart rate (HR) versions along with standard PTT. Besides other methods, CMR offers an option to assess stress circulation parameters, but data are minimal. This review aims to summarize the up-to-date findings and provide an overview of the latest progress on this promising, dynamically evolving topic.
