low-latency
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BACKGROUND: In adults, motion-onset visual evoked potentials (M-VEPs) with a dominant N2 peak represent a useful diagnostic tool. However, it is difficult to use this type of VEP in children because of the long maturation (up to 18 years) of M-VEPs, which is characterised by a gradual decrease in N2 peak latency and shape development. Moreover, in some children, M-VEPs are difficult to identify with standard stimuli. METHODS: We tested features of M-VEPs in 30 children (7-12 years) with the following set of standard stimuli used in our lab for examining adults ( https://web.lfhk.cuni.cz/elf ): low-contrast translation motion (TM) and expansion/contraction motion (ExCoM) in full field and in periphery (with central 20° masked). In 16 children, a high-contrast TM was also tested. RESULTS: With standard (low-contrast) stimuli, a common M-VEP to TM and to ExCoM was detected in 77 and 83 % of children, respectively. The M-VEPs to ExCoM in the periphery were detected in only 43 % of children. An abnormal dominant P1 peak was found in 9 % of VEPs to TM, 12 % of VEPs to full-field ExCoM and 14 % of VEPs to peripheral ExCoM. The M-VEPs to all low-contrast stimuli displayed large inter-individual latency variability (N2 peak latency differed for more than 100 ms). High contrast (more suitable for the non-mature magnocellular pathway) shortened M-VEP latencies and improved amplitudes. CONCLUSIONS: Our findings show that the maturation of motion perception in children is inter-individually variable, which limits the diagnostic use of M-VEPs.
- MeSH
- citlivost na kontrast fyziologie MeSH
- dítě MeSH
- lidé MeSH
- oči růst a vývoj MeSH
- senzorické prahy fyziologie MeSH
- vnímání pohybu fyziologie MeSH
- zrakové evokované potenciály fyziologie MeSH
- zrakové korové centrum fyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
More than one in three adult patients suffering from narcolepsy-cataplexy experience rapid eye movement (REM) behavior disorder (RBD), while RBD in childhood is extremely rare. We present the cases of two girls (aged 9 and 7 years old) with narcolepsy-cataplexy, in whom RBD was one of the first symptoms of the disease. The coincidence of RBD was seen by nocturnal video-polysomnography (v-PSG), and narcolepsy was diagnosed from short sleep latency and multiple sleep onset REMs (SOREMs) during a multiple sleep latency test (MSLT). Both girls were human leukocyte antigen (HLA)-DQB1 *0602 positive, and their cerebrospinal fluid (CSF) hypocretin level (Hcrt-1) was extremely low.
N-methyl-d-aspartate receptors (NMDARs) play a crucial role in spatial memory formation. In neuropharmacological studies their functioning strongly depends on testing conditions and the dosage of NMDAR antagonists. The aim of this study was to assess the immediate effects of NMDAR block by (+)MK-801 or memantine on short-term allothetic memory. Memory was tested in a working memory version of the Morris water maze test. In our version of the test, rats underwent one day of training with 8 trials, and then three experimental days when rats were injected intraperitoneally with low- 5 (MeL), high - 20 (MeH) mg/kg memantine, 0.1mg/kg MK-801 or 1ml/kg saline (SAL) 30min before testing, for three consecutive days. On each experimental day there was just one acquisition and one test trial, with an inter-trial interval of 5 or 15min. During training the hidden platform was relocated after each trial and during the experiment after each day. The follow-up effect was assessed on day 9. Intact rats improved their spatial memory across the one training day. With a 5min interval MeH rats had longer latency then all rats during retrieval. With a 15min interval the MeH rats presented worse working memory measured as retrieval minus acquisition trial for path than SAL and MeL and for latency than MeL rats. MK-801 rats had longer latency than SAL during retrieval. Thus, the high dose of memantine, contrary to low dose of MK-801 disrupts short-term memory independent on the time interval between acquisition and retrieval. This shows that short-term memory tested in a working memory version of water maze is sensitive to several parameters: i.e., NMDA receptor antagonist type, dosage and the time interval between learning and testing.
- MeSH
- antagonisté excitačních aminokyselin farmakologie MeSH
- bludiště - učení účinky léků MeSH
- časové faktory MeSH
- dizocilpinmaleát farmakologie MeSH
- krátkodobá paměť účinky léků MeSH
- memantin farmakologie MeSH
- potkani Long-Evans MeSH
- prostorová paměť účinky léků MeSH
- receptory N-methyl-D-aspartátu antagonisté a inhibitory MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Úvod: Jedním z hlavních trendů u chronické lymfocytární leukemie (CLL) se v posledních letech stalo hledání nových prognostických faktorů umožňujících zpřesnit prognózu, a předpovědět tak klinický průběh onemocnění již v době stanovení diagnózy s možností načasování a přizpůsobení intenzity léčby individuálnímu riziku nemocného. Pacienti a metody, cíle práce: Cílem naší práce bylo zhodnocení prognostického významu vybraných ukazatelů apoptózy a angiogeneze: byly měřeny sérové koncentrace tumor nekrotizujícího faktoru α (TNF‑α) a transformujícího růstového faktoru β‑1 (TGF‑β1) metodou ELISA a exprese receptoru typu II pro TGF‑β (TGFβRII) a receptoru typu 2 pro fibroblastový růstový faktor (FGFR2) průtokovou cytometrií na lymfocytech periferní krve u 75 neléčených pacientů s CLL (47 mužů a 28 žen, medián věku 65 let, rozmezí 38–82 let). Výsledky: Sérové koncentrace TNF‑α byly významně vyšší u nemocných s CLL v porovnání s kontrolní skupinou (p < 0,0001) a byly spojeny s nepříznivou prognózou: významně vyšší TNF‑α měli nemocní s vysokým rizikem dle Raie v porovnání s nemocnými s nízkým i středním rizikem (p = 0,0008, resp. p = 0,0097), nemocní s vysokou hodnotou sérového b2-mikroglobulinu (p = 0,045), masivní lymfadenopatií (p = 0,0083), nemutovanými geny pro variabilní části těžkých řetězců imunoglobulinů (p = 0,041) a nepříznivými cytogenetickými aberacemi (p = 0,0014). Nemocní s progresí CLL měli významně vyšší hodnoty TNF‑α než nemocní se stabilním průběhem (p = 0,0009) a období do zahájení léčby bylo významně kratší u pacientů s vyššími koncentracemi TNF‑α (p = 0,0049). Zvýšené koncentrace TGF‑β1 byly naopak spojeny s příznivou prognózou: významně vyšší TGF‑β1 byl zjištěn u nemocných s nízkým rizikem dle Raie v porovnání s vysokým rizikem (p = 0,011), u nemocných bez masivní lymfadenopatie (p = 0,041), s mutovanými IgVH geny (p = 0,012) a negativitou ZAP‑70 (zeta-asociovaný protein o 70 kilodaltonech) (p = 0,044). Nemocní s progredující chorobou měli významně nižší hodnoty TGF‑β1 než nemocní se stabilním onemocněním (p = 0,0014). Období do zahájení léčby bylo významně delší u nemocných s vyšším TGF‑β1 (p = 0,016). U nemocných s vysokým rizikem dle Raie v porovnání s nemocnými s nízkým rizikem byla zjištěna významně nižší exprese TGFβRII (p = 0,022). Prognostický význam exprese FGFR2 nebyl prokázán. Statisticky významnými a nezávislými prognostickými faktory pro celkové přežití byly zvýšené sérové koncentrace TNF‑α a masivní lymfadenopatie (p = 0,036, resp. p = 0,047). Závěr: Další výzkum TNF‑α a TGF‑β je cenný nejen z prognostického, ale také léčebného hlediska, neboť signální dráhy těchto cytokinů by se mohly stát terapeutickým cílem u nemocných s CLL.
Introduction: Search for new prognostic markers in order to improve prognostic accuracy and predict clinical outcome at the time of diagnosis has recently become one of the major trends in chronic lymphocytic leukemia (CLL). Patients and methods, aim of study: The aim of our study was assessment of selected markers of apoptosis and angiogenesis and their potential as new prognostic factors. We evaluated serum levels of tumor necrosis factor α (TNF‑α) and transforming growth factor β‑1 (TGF‑β1) using comercially available enzyme‑linked immunosorbent assay; furthemore, we quantified expression of type II receptor for transforming growth factor beta (TGFβRII) and type 2 receptor for fibroblast growth factor‑2 (FGFR2) on CLL cells using flow cytometry analysis in 75 previously untreated patients with CLL (47 males and 28 females, median age, 65 years, range 38–82) and healthy donors. Results: We found significantly elevated TNF‑α in patients with CLL compared to the control group (p < 0.0001); high expression of TNF‑α was associated with unfavourable prognosis: significantly higher concentrations were found in patients with Rai high‑risk group compared to low and intermediate-risk group (p = 0.0008 and p = 0.0097), with high serum β2-microglobulin (p = 0.045), massive lymphadenopathy (p = 0.0083), unmutated genes for variable region of immunoglobulin heavy chain (IgVH) (p = 0.041) and unfavourable cytogenetic aberrations (p = 0.0014). In addition, patients with progressive CLL had significantly higher TNF‑α than those with stable clinical course (p = 0.0009); time to treatment was significantly shorter in patients with higher TNF‑α (p = 0.0049). Higher TGF‑β1 concentrations were associated with favourable subgroups: with Rai low‑risk group compared to high‑risk group (p = 0.011), patients without massive lymphadenopathy (p = 0.041), patients with mutated IgVH (p = 0.012) and ZAP‑70 negativity (zeta‑associated protein of 70 kilodaltons) (p = 0.044). Patients with progressive CLL had significantly lower TGF‑β1 levels than those with stable course (p = 0.0014) and time to treatment was significantly longer in patients with higher TGF‑β1 (p = 0.016). Patients with Rai high‑risk group had significantly lower TGFβRII expression than those with low‑risk group (p = 0.022). The prognostic significance of FGFR2 was not found. Significant and independent prognostic factors for overall survival were high serum concentrations of TNF‑α and massive lymphadenopathy (p = 0.036, resp. p = 0.047). Conclusion: Based on our results, TNF‑α and TGF‑β1 possess prognostic significance in CLL; further research in this direction may also be important therapeutically, because these signal pathways could serve as possible treatment targets.
- Klíčová slova
- angiogeneze,
- MeSH
- apoptóza MeSH
- biochemická analýza krve MeSH
- časové faktory MeSH
- chronická lymfatická leukemie * genetika patologie MeSH
- dospělí MeSH
- ELISA MeSH
- exprese genu MeSH
- fibroblastový růstový faktor 2 MeSH
- laktátdehydrogenasy MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty MeSH
- mezibuněčné signální peptidy a proteiny MeSH
- NF-kappa B MeSH
- přežití MeSH
- prognóza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sérum * cytologie MeSH
- statistika jako téma MeSH
- stupeň závažnosti nemoci MeSH
- TNF-alfa * MeSH
- transformující růstový faktor beta * MeSH
- transformující růstový faktor beta1 MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
This review focuses on recent advances in HIV research and therapy that seek to eradicate persistent HIV in patients on suppressive therapy. RECENT FINDINGS: The source of persistent HIV in patients on suppressive therapy is debated. Recent studies of treatment intensification have produced varied results: no reduction in low-level plasma viremia indicating the source of persistent viremia is long-lived HIV-infected cells that release HIV when activated and increase in episomal HIV DNA indicating active replication persists in some infected individuals on suppressive therapy. In addition, clonal HIV sequences found in plasma from patients on long-term suppressive therapy are rarely found in CD4+ memory T cells. These results indicate that persistent viremia may arise from several different sources. Recent studies emphasize the complexity of HIV latency. Current strategies for HIV eradication focus on compounds that activate viral transcription in memory CD4+ T cells by many routes, including inhibiting histone deacetylation and activating nuclear factor kappa B. Several compounds and combinations of these compounds appear to induce the expression of integrated HIV in different latency models. SUMMARY: The eradication of HIV requires the elimination of persistent HIV during suppressive therapy. Recent studies have focused on the source of persistent viremia, mechanisms of intracellular HIV latency, and reactivation of latent HIV. It remains to be seen whether alternative treatment strategies may be required to eradicate HIV.
- MeSH
- aktivace viru MeSH
- CD4-pozitivní T-lymfocyty virologie MeSH
- financování organizované MeSH
- HIV infekce farmakoterapie imunologie virologie MeSH
- HIV séropozitivita farmakoterapie virologie MeSH
- HIV fyziologie genetika účinky léků MeSH
- latence viru fyziologie účinky léků MeSH
- látky proti HIV farmakologie terapeutické užití MeSH
- lidé MeSH
- replikace viru fyziologie účinky léků MeSH
- RNA virová krev účinky léků MeSH
- T-lymfocyty - podskupiny virologie MeSH
- viremie farmakoterapie virologie MeSH
- vysoce aktivní antiretrovirová terapie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
This review article summarises the research on the motion-onset visual evoked potentials (VEPs) and important motion stimulus parameters which have been clarified. For activation of the visual motion processing system and evocation of the motion-onset specific N2 peak (with latency of 160-200ms) from the extra-striate temporo-occipital and/or parietal cortex, the following stimulus parameters can be recently recommended: low luminance (
Methylphenidate is a stimulant used to treat attention deficit and hyperactivity disorder (ADHD). In the last decade, illicit use of methylphenidate has increased among healthy young adults, who consume the drug under the assumption that it will improve cognitive performance. However, the studies that aimed to assess the methylphenidate effects on memory are not consistent. Here, we tested whether the effect of methylphenidate on a spatial memory task can be explained as a motivational and/or a reward effect. We tested the effects of acute and chronic i.p. administration of 0.3, 1 or 3 mg/kg of methylphenidate on motivation, learning and memory by using the 8-arm radial maze task. Adult male Wistar rats learned that 3 of the 8 arms of the maze were consistently baited with 1, 3, or 6 sucrose pellets, and the number of entries and reentries into reinforced and non-reinforced arms of the maze were scored. Neither acute nor chronic (20 days) methylphenidate treatment affected the number of entries in the non-baited arms. However, chronic, but not acute, 1-3 mg/kg methylphenidate increased the number of reentries in the higher reward arms, which suggests a motivational/rewarding effect rather than a working memory deficit. In agreement with this hypothesis, the methylphenidate treatment also decreased the approach latency to the higher reward arms, increased the approach latency to the low reward arm, and increased the time spent in the high, but not low, reward arm. These findings suggest that methylphenidate may act more as a motivational enhancer rather than a cognitive enhancer in healthy people.
- MeSH
- hyperkinetická porucha * farmakoterapie MeSH
- krysa rodu rattus MeSH
- methylfenidát * farmakologie terapeutické užití MeSH
- motivace MeSH
- odměna MeSH
- potkani Wistar MeSH
- stimulanty centrálního nervového systému * farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Effort-based decision-making is particularly relevant to psychiatric conditions where motivation deficits are prominent features. Despite its clinical significance, the neurochemical mechanisms of this cognitive process remain unclarified. This study explores the impact of serotonin synthesis inhibition (PCPA) and modulation of serotonin release and 5-HT1A receptor agonism (8-OH-DPAT) on effort-based decision-making in rats. Adult male rats were trained in a modified T-maze task where they could obtain a high reward for climbing a mesh barrier or a low reward for no extra effort. Following training, rats received either acute 8-OH-DPAT treatment or subchronic PCPA treatment and were tested on their choices between high- and low-effort arms. The goal-arm choices and goal-arm entrance latencies were recorded. Next, homovanillic acid and 5-hydroxyindoleacetic acid, metabolites of dopamine and serotonin, respectively, were quantified in the rats' prefrontal cortex, striatum, and hippocampus. 8-OH-DPAT significantly increased low-effort, low-reward choices and increased goal-arm latency. In contrast, PCPA treatment did not affect these measures. Both PCPA and 8-OH-DPAT significantly decreased 5-hydroxyindoleacetic acid levels in the prefrontal cortex and the hippocampus. 8-OH-DPAT treatment was also associated with decreased homovanillic acid levels in the hippocampus. Our findings suggest that the overall reduction of serotonin levels alone does not affect effort-based decision-making and highlights the possible role of the hippocampus and the 5-HT1A receptor in this cognitive process.
- MeSH
- 8-hydroxy-2-(di-N-propylamino)tetralin * farmakologie MeSH
- agonisté serotoninového receptoru 5-HT1 farmakologie MeSH
- bludiště - učení účinky léků fyziologie MeSH
- chování zvířat účinky léků MeSH
- krysa rodu rattus MeSH
- odměna MeSH
- potkani Sprague-Dawley MeSH
- rozhodování * fyziologie účinky léků MeSH
- serotonin * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Deep brain stimulation (DBS) of the globus pallidus interna is an effective tool for the treatment of dystonia with possible distant effects reaching beyond the basal ganglia network. AIM: We analyzed the cortical silent period (CoSP) to test inhibitory circuits at the cortical level, and the cutaneous silent period (CuSP) and the H-reflex to test inhibitory circuits at the spinal level. METHODS: The upper limb muscles of 16 patients (9F, aged 54±(SD)16years) with generalized (N=9) and cervical (N=7) dystonia treated with DBS bilaterally were examined by the CoSP, CuSP and H-reflex in two states with random order: (i) in DBS ON and (ii) in DBS OFF condition two hours later, and compared with healthy controls. RESULTS: While the CuSP and H-Reflex did not differ between groups and remained unaffected by DBS, the CoSP was influenced significantly in dystonia. The CoSP onset latency was shortened (p<0.05 corrected) and the CoSP duration prolonged (p<0.01 corrected) in ON versus OFF condition. This effect was especially larger in generalized or phasic type of dystonia. Compared to healthy controls, the CoSP latency and duration became shorter in patients during the OFF condition only. CONCLUSION: The pallidal DBS did not affect the spinal inhibitory circuitry in dystonia. However, the abnormally low cortical inhibition was normalized after DBS possibly offering more efficient suppression of aberrant dystonic movements.
- MeSH
- dospělí MeSH
- dystonie terapie MeSH
- globus pallidus fyziologie MeSH
- H-reflex fyziologie MeSH
- hluboká mozková stimulace metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mícha patofyziologie MeSH
- mladý dospělý MeSH
- motorické evokované potenciály fyziologie MeSH
- mozková kůra patofyziologie MeSH
- nervový útlum fyziologie MeSH
- senioři MeSH
- šířící se kortikální deprese fyziologie MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Objektivní metoda vyšetření sluchu, založená na principu měření střednědobýchevokovaných potenciálů je nová a svým způsobem revoluční. Předkládáme základní principy a možnosti techniky Steady State Evoked Potentials (SSEP), neboli ustálené evokované potenciály (UEP).Snímané potenciály patří mezi odpovědi středních latencí (Middle Latency Response - MLR) a jsoucharakterizovány frekvenční shodou s podnětem. Stimulem je kontinuální, amplitudově a frekvenčně modulovaný zvukový podnět a mezi podnětem a odpovědí je stálý fázový posun. Programovávýbava umožňuje rekonstrukci tónového audiogramu na základě statistického zpracování naměřených dat. Tento fakt je zejména v dětské audiologii velmi významný.
The purpose of this publication is to evaluate a new technology using Steady - State Evoked Potentials (SSEPs) for determining frequency - specific hearing impairment in infants and children. The authors describe the basic principles of this technique and possibilities of the methodology. The potentials are within the range of the middle latency response (MLR) and are characterised by the frequency dependence of the stimulus and evoked potential. The stimulus is amplitude and frequency modulated and is continuous. The computer equipment calculates a frequency specific objective audiogram, and is particularly useful for pediatric audiology. The techni- que evaluates tresholds between 125 - 8000 Hz at intesities of -10 - 130 dB. Early experience shows SSEP is very useful for testing very young and difficult to test individuals with hearing impairment. This method is also extremly useful in paediatric assessments for cochlear implantation due to detection of responses at low intensities. In summary this technique may allow earlier rehabilitation or cochlear implantation.