Interictal EEG and ictal scalp EEG propagation are highly predictive of surgical outcome in mesial temporal lobe epilepsy

PURPOSE: Surgical outcome in patients with mesial temporal lobe sclerosis (MTS) is worse than that in patients with temporal lobe activity (TLE) with tumors. Previous studies of the ictal EEG focused on ictal EEG onset in scalp EEG or ictal EEG propagation in invasive recordings. Ictal EEG propagation with scalp electrodes has not been reported. METHODS: Ictal scalp EEG propagation patterns were studied in 347 seizures of 58 patients with MTS or nonlesional TLE. Interictal epileptiform discharges (IEDs) and the presence of unilateral mesial temporal lobe atrophy in magnetic resonance imaging (MRI) also were studied in these 58 patients. Forty-nine patients were operated on (minimal follow-up of 1 year). RESULTS: Postoperatively, seizure-free outcome was seen in (a) 82.8% of patients with regionalized EEG seizure without contralateral propagation, but in only 45.5% of patients with contralateral propagation (p = 0.007); (b) 84.6% of patients with 100% IED lateralized to one temporal lobe, but in only 52.2% with <100% unitemporal IED (p = 0.015); (c) 88.9% with 100% unitemporal IED and regionalized ictal EEG combined, 73.7% with one of both variables, and only 33.3% with <100% ipsitemporal IED combined with contralateral ictal EEG propagation (p = 0.007). CONCLUSIONS: Switch of lateralization or bitemporal asynchrony in the ictal scalp EEG and bitemporal IED are most probably an index of bitemporal epileptogenicity in MTS and are associated with a worse outcome.     

Suppression of hypoxia-inducible factor-1α contributes to the antiangiogenic activity of red propolis polyphenols in human endothelial cells

Polyphenol-enriched fractions from natural sources have been proposed to interfere with angiogenesis in pathological conditions. We recently reported that red propolis polyphenols (RPP) exert antiangiogenic activity. However, molecular mechanisms of this activity remain unclear. Here, we aimed at characterizing molecular mechanisms to explain the impact of RPP on endothelial cells' (EC) physiology. We used in vitro and ex and in vivo models to test the hypothesis that RPP inhibit angiogenesis by affecting hypoxia-inducible factor-1α (HIF1α) stabilization in EC. RPP (10 mg/L) affected angiogenesis by reducing migration and sprouting of EC, attenuated the formation of new blood vessels, and decreased the differentiation of embryonic stem cells into CD31-positive cells. Moreover, RPP (10 mg/L) inhibited hypoxia- or dimethyloxallylglycine-induced mRNA and protein expression of the crucial angiogenesis promoter vascular endothelial growth factor (VEGF) in a time-dependent manner. Under hypoxic conditions, RPP at 10 mg/L, supplied for 1-4 h, decreased HIF1α protein accumulation, which in turn attenuated VEGF gene expression. In addition, RPP reduced the HIF1α protein half-life from ~58 min to 38 min under hypoxic conditions. The reduced HIF1α protein half-life was associated with an increase in the von Hippel-Lindau (pVHL)-dependent proteasomal degradation of HIF1α. RPP (10 mg/L, 4 h) downregulated Cdc42 protein expression. This caused a corresponding increase in pVHL protein levels and a subsequent degradation of HIF1α. In summary, we have elucidated the underlying mechanism for the antiangiogenic action of RPP, which attenuates HIF1α protein accumulation and signaling.     

Methods of early detection： would clinical breastexamination and breast ultrasonography be a good alternative to mammography？

Breast cancer is one of the leading causes of cancer deaths among women[1].In the past 40 years,breast cancer incidence has doubled or even tripled in developed countries such as South Korea and Japan; whereas it is about 20% to 30% in China and India in the past decade[2-4]. An increasing incidence rate of 3%     

The sources of the nigrotectal pathway

The nigrotectal pathway plays a role in the generation of saccade related responses by cells in the deep layers of the superior colliculus. By using a retrograde horseradish peroxidase technique that homogeneously fills neurons, the present experiments demonstrate that the source of the nigrotectal projection to the intermediate gray layer of the grey squirrel (Sciurus carolinensis) is a heterogeneous population of neurons whose somas and dendrites are concentrated in the rostral pole of pars reticulata. This region of pars reticulata receives projections from the posterior caudate, which in turn is a target of both the pulvinar and visual cortex. In addition, these experiments reveal the presence of a second, distinct set of neurons projecting to the midbrain tectum that are located in pars lateralis of the substantia nigra. These neurons can be distinguished from those in pars reticulata by their homogeneity and by their prominent basal dendrites. Furthermore, pars lateralis of the squirrel substantia nigra is, on cytoarchitectonic and immunocytochemical grounds, a distinct subdivision that does not receive projections from the posterior caudate. We conclude that both pars reticulata and lateralis are sources of the nigrotectal pathway. In addition, our results suggest, on connectional grounds, that the rostral pole of pars reticulata may be specialized to subserve the visual guidance of orienting movements.     

Dual Inhibition of Human Rhinovirus 2A and 3C Proteases by Homophthalimides

The 2A and 3C proteases encoded by human rhinoviruses (HRVs) are attractive targets for antiviral drug development due to their important roles in viral replication. Homophthalimides were originally identified as inhibitors of rhinovirus 3C protease through our screening effort. Previous studies have indicated that the antiviral activity of certain homophthalimides exceeded their in vitro inhibitory activity against the viral 3C protease, suggesting that an additional mechanism might be involved. Reported here is the identification of homophthalimides as potent inhibitors for another rhinovirus protease, designated 2A. Several homophthalimides exhibit time-dependent inhibition of the 2A protease in the low-micromolar range, and enzyme-inhibitor complexes were identified by mass spectrometry. Compound LY343814, one of the most potent inhibitors against HRV14 2A protease, had an antiviral 50% inhibitory concentration of 4.2 μM in the cell-based assay. Our data reveal that homophthalimides are not only 3C but also 2A protease inhibitors in vitro, implying that the antiviral activity associated with these compounds might result from inactivation of both 2A and 3C proteases in vivo. Since the processing of the viral polyprotein is hierarchical, dual inhibition of the two enzymes may result in cooperative inhibition of viral replication. On the basis of the current understanding of their enzyme inhibitory mechanism, homophthalimides, as a group of novel nonpeptidic antirhinovirus agents, merit further structure-action relationship studies.     

Adenosine stress cardiac magnetic resonance imaging for the assessment of ischemic heart disease

Aims  This prospective study was designed to determine the diagnostic value of adenosine stress cardiac magnetic resonance imaging (CMRI) in patients referred to elective coronary angiography. Methods and results  Myocardial perfusion measurements at rest and adenosine stress were performed in 141 patients (105 men, 36 women, mean age 63.4 years) at 1.5 T with a Turbo Flash sequence. Stress-induced perfusion deficits were correlated to angiographic stenoses ≥75%. The overall sensitivity for CMRI depicting coronary artery disease (CAD) with relevant stenoses was 90.4%, the specificity was 77.4%, the positive predictive value was 85.9%, the negative predictive value was 84.2% and the accuracy 85.2%. Subgroup analysis was performed for 3-vessel disease (n = 44, sensitivity 92.3%, specificity 75.0%), 2-vessel disease (n = 43, sensitivity 92.6%, specificity 92.9%), 1-vessel disease (n = 27, sensitivity 93.1%, specificity 71.4%) and patients without CAD (n = 27, specificity 70.4%) as well as for patients with prior myocardial infarction (n = 44, sensitivity 92.9%, specificity 86.7%), prior coronary artery bypass surgery (n = 21, sensitivity 88.2%, specificity 66.7%), prior coronary interventions (n = 88, sensitivity 91.9%, specificity 75.0%), or diabetics (n = 27, sensitivity 90.5%, specificity 83.3%). Conclusion  Our study shows that stress perfusion CMRI can accurately predict relevant CAD and contributes to the identification of hemodynamic relevant stenoses in patients scheduled for coronary angiography. C. Doesch and A. Seeger have equally contributed to this publication.     

Relationship between family functioning and health-related quality of life among methadone maintenance patients: a Bayesian approach

Quality of Life Research - To examine the relationship of family functioning on health-related quality of life (HRQoL) among methadone maintenance patients using the Bayesian approach. A...     

Swallowing outcomes after radiotherapy for laryngeal carcinoma

OBJECTIVE: To describe swallowing physiology and functional outcomes at select intervals after definitive radiotherapy for laryngeal carcinoma. We also examined associations among patient, tumor, and treatment characteristics and swallowing outcomes. DESIGN: Retrospective review. SETTING: The University of Texas M. D. Anderson Cancer Center, Houston. PATIENTS: This study cohort included 40 patients who underwent definitive radiotherapy for laryngeal carcinoma (from February 2001 to June 2004). MAIN OUTCOME MEASURES: Modified barium swallow (MBS) studies were performed for 32 patients at 3 test intervals following irradiation: less than 6 months, 6 to 11 months, and 12 or more months. We recorded the presence or absence of aspiration (sensate or silent), 5 pharyngeal phase disorders, and 2 structural abnormalities. We also recorded pretreatment dysphagia complaints, feeding tube dependency, T classification, disease site, mucositis grade, and radiotherapy schedule with or without chemotherapy. RESULTS: Eighty-four percent of patients (27 of 32) referred for MBS studies after undergoing radiotherapy aspirated; 44% (12 of 27) did so silently. Silent aspiration was more prevalent during MBS studies conducted 1 or more years after radiotherapy. Pharyngeal phase disorders were observed more frequently than structural abnormalities (P < .01). Most patients required a feeding tube (78% [31 of 40]); however, 52% of the tubes (16) were eventually removed. We found no significant association between the occurrence of aspiration and disease site, T classification, treatment regimen, or pretreatment variables (P > .05). Pretreatment and posttreatment levels of feeding tube dependency were significantly associated (P = .03). Patient-reported dysphagia before treatment did not predict posttreatment swallowing outcomes (P > .05). CONCLUSIONS: Dysphagia is a common outcome after laryngeal preservation with radiotherapy. Contrary to expectations, few parameters that we measured were significantly associated with swallowing outcomes in our study.     

Staying vigilant during recurrent sleep restriction: dose-response effects of time-in-bed and benefits of daytime napping

Study ObjectivesWe characterized vigilance deterioration with increasing time-on-task (ToT) during recurrent sleep restriction of different extents on simulated weekdays and recovery sleep on weekends, and tested the effectiveness of afternoon napping in ameliorating ToT-related deficits.MethodsIn the Need for Sleep studies, 194 adolescents (age = 15–19 years) underwent two baseline nights of 9-h time-in-bed (TIB), followed by two cycles of weekday manipulation nights and weekend recovery nights (9-h TIB). They were allocated 9 h, 8 h, 6.5 h, or 5 h of TIB for nocturnal sleep on weekdays. Three additional groups with 5 h or 6.5 h TIB were given an afternoon nap opportunity (5 h + 1 h, 5 h + 1.5 h, and 6.5 h + 1.5 h). ToT effects were quantified by performance change from the first 2 min to the last 2 min in a 10-min Psychomotor Vigilance Task administered daily.ResultsThe 9 h and the 8 h groups showed comparable ToT effects that remained at baseline levels throughout the protocol. ToT-related deficits were greater among the 5 h and the 6.5 h groups, increased prominently in the second week of sleep restriction despite partial recuperation during the intervening recovery period and diverged between these two groups from the fifth sleep-restricted night. Daytime napping attenuated ToT effects when nocturnal sleep restriction was severe (i.e. 5-h TIB/night), and held steady at baseline levels for a milder dose of nocturnal sleep restriction when total TIB across 24 h was within the age-specific recommended sleep duration (i.e. 6.5 h + 1.5 h).ConclusionsReducing TIB beyond the recommended duration significantly increases ToT-associated vigilance impairment, particularly during recurrent periods of sleep restriction. Daytime napping is effective in ameliorating such decrement.Clinical Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT02838095","term_id":"NCT02838095"}}NCT02838095, {"type":"clinical-trial","attrs":{"text":"NCT03333512","term_id":"NCT03333512"}}NCT03333512, and {"type":"clinical-trial","attrs":{"text":"NCT04044885","term_id":"NCT04044885"}}NCT04044885.