Electroencephalographic features of convulsive epilepsy in Africa: A multicentre study of prevalence, pattern and associated factors

Objective: We investigated the prevalence and pattern of electroencephalographic (EEG) features of epilepsy and the associated factors in Africans with active convulsive epilepsy (ACE). Methods: We characterized electroencephalographic features and determined associated factors in a sample of people with ACE in five African sites. Mixed-effects modified Poisson regression model was used to determine factors associated with abnormal EEGs. Results: Recordings were performed on 1426 people of whom 751 (53%) had abnormal EEGs, being an adjusted prevalence of 2.7 (95% confidence interval (95% CI), 2.5–2.9) per 1000. 52% of the abnormal EEG had focal features (75% with temporal lobe involvement). The frequency and pattern of changes differed with site. Abnormal EEGs were associated with adverse perinatal events (risk ratio (RR) = 1.19 (95% CI, 1.07–1.33)), cognitive impairments (RR = 1.50 (95% CI, 1.30–1.73)), use of anti-epileptic drugs (RR = 1.25 (95% CI, 1.05–1.49)), focal seizures (RR = 1.09 (95% CI, 1.00–1.19)) and seizure frequency (RR = 1.18 (95% CI, 1.10–1.26) for daily seizures; RR = 1.22 (95% CI, 1.10–1.35) for weekly seizures and RR = 1.15 (95% CI, 1.03–1.28) for monthly seizures)). Conclusions: EEG abnormalities are common in Africans with epilepsy and are associated with preventable risk factors. Significance: EEG is helpful in identifying focal epilepsy in Africa, where timing of focal aetiologies is problematic and there is a lack of neuroimaging services

Transcriptional activation of endothelial cells by TGFβ coincides with acute microvascular plasticity following focal spinal cord ischaemia/reperfusion injury

Microvascular dysfunction, loss of vascular support, ischaemia and sub-acute vascular instability in surviving blood vessels contribute to secondary injury following SCI (spinal cord injury). Neither the precise temporal profile of the cellular dynamics of spinal microvasculature nor the potential molecular effectors regulating this plasticity are well understood. TGFβ (transforming growth factor β) isoforms have been shown to be rapidly increased in response to SCI and CNS (central nervous system) ischaemia, but no data exist regarding their contribution to microvascular dysfunction following SCI. To examine these issues, in the present study we used a model of focal spinal cord ischaemia/reperfusion SCI to examine the cellular response(s) of affected microvessels from 30 min to 14 days post-ischaemia. Spinal endothelial cells were isolated from affected tissue and subjected to focused microarray analysis of TGFβ-responsive/related mRNAs 6 and 24 h post-SCI. Immunohistochemical analyses of histopathology show neuronal disruption/loss and astroglial regression from spinal microvessels by 3 h post-ischaemia, with complete dissolution of functional endfeet (loss of aquaporin-4) by 12 h post-ischaemia. Coincident with this microvascular plasticity, results from microarray analyses show 9 out of 22 TGFβ-responsive mRNAs significantly up-regulated by 6 h post-ischaemia. Of these, serpine 1/PAI-1 (plasminogen-activator inhibitor 1) demonstrated the greatest increase (>40-fold). Furthermore, uPA (urokinase-type plasminogen activator), another member of the PAS (plasminogen activator system), was also significantly increased (>7.5-fold). These results, along with other select up-regulated mRNAs, were confirmed biochemically or immunohistochemically. Taken together, these results implicate TGFβ as a potential molecular effector of the anatomical and functional plasticity of microvessels following SCI

Rapid effect of progesterone on transepithelial resistance of human fetal membranes: Evidence for non-genomic action

1. The factors that regulate human fetal membrane transport mechanisms are unknown. The aim of the present study was to investigate the effect of progesterone on transepithelial electrical resistance (R-TE) in the human amniochorion. 2. Fetal membranes from uncomplicated term pregnancies were obtained immediately after vaginal or Caesarean deliveries. Intact pieces were mounted as planar sheets separating an Ussing chamber. Progesterone (10(-4) to 10(-7) mol/L), mifepristone (10(-4) to 10(-8) mol/L) and combinations of progesterone plus mifepristone were applied to the chambers facing the fetal or maternal sides of the membrane. The R-TE was measured before and 1, 5, 10, 15, 20, 25, 30, 45 and 60 min after each solution was added (at 37 degrees C). The R-TE was calculated in Omega.cm(2), according to Ohm's law. 3. The mean (+/- SEM) basal value of R-TE before the application of any substance in all experiments was 29.1 +/- 0.4 Omega.cm(2). The net change in the R-TE (Delta R-TE) in relation to the basal value was calculated in each experiment. Progesterone, mifepristone and the combination of progesterone and mifepristone induced a rapid, surge-type increase in R-TE during the 1st min on both sides of the membrane. The combination of progesterone plus mifepristone exerted a synergistic action. The effect was stronger on the fetal side than on the maternal side for all substances tested (P < 0.05). The highest Delta R-TE during the 1st min on the fetal side was seen with the combination of progesterone plus mifepristone (4.0 +/- 0.3 Omega.cm(2)) and the lowest Delta R-TE occurred with mifepristone (1.5 +/- 0.1 Omega.cm(2)). 4. The present results demonstrated that the R-TE of human fetal membranes increases rapidly in response to progesterone. It is possible that changes in R-TE play a role in the control of membrane permeability during pregnancy

CpG methylation analysis of hpv16 in laser capture microdissected archival tissue and whole tissue sections from high grade anal squamous intraepithelial lesions: A potential disease biomarker

Incidence and mortality rates of anal cancer are increasing globally. More than 90% of anal squamous cell carcinomas (ASCC) are associated with human papillomavirus (HPV). Studies on HPV-related anogenital lesions have shown that patterns of methylation of viral and cellular DNA targets could potentially be developed as disease biomarkers. Lesion-specific DNA isolated from formalin-fixed paraffin-embedded (FFPE) tissues from existing or prospective patient cohorts may constitute a valuable resource for methylation analysis. However, low concentrations of DNA make these samples technically challenging to analyse using existing methods. We therefore set out to develop a sensitive and reproducible nested PCR-pyrosequencing based method to accurately quantify methylation at 10 CpG sites within the E2BS1, E2BS2,3,4 and Sp1 binding sites in the viral upstream regulatory region of HPV16 genome. Methylation analyses using primary and nested PCR-pyrosequencing on 52 FFPE tissue [26 paired whole tissue sections (WTS) and laser capture microdissected (LCM) tissues] from patients with anal squamous intraepithelial lesions was performed. Using nested PCR, methylation results were obtained for the E2BS1, E2BS2,3,4 and Sp1 binding sites in 86.4% of the WTS and 81.8% of the LCM samples. Methylation patterns were strongly correlated within median values of matched pairs of WTS and LCM sections, but overall methylation was higher in LCM samples at different CpG sites. High grade lesions showed low methylation levels in the E2BS1 and E2BS2 regions, with increased methylation detected in the E2BS,3,4/Sp1 regions, showing the highest methylation at CpG site 37. The method developed is highly sensitive in samples with low amounts of DNA and demonstrated to be suitable for archival samples. Our data shows a possible role of specific methylation in the HPV16 URR for detection of HSIL