Medical Research Council of South Africa.

Objective-Comparison of gene expression in stable versus unstable atherosclerotic plaque may be confounded by interpatient variability. The aim of this study was to identify differences in gene expression between stable and unstable segments of plaque obtained from the same patient. Methods and Results-Human carotid endarterectomy specimens were segmented and macroscopically classified using a morphological classification system. Two analytical methods, an intraplaque and an interplaque analysis, revealed 170 and 1916 differentially expressed genes, respectively using Affymetrix gene chip analysis. A total of 115 genes were identified from both analyses. The differential expression of 27 genes was also confirmed using quantitative-polymerase chain reaction on a larger panel of samples. Eighteen of these genes have not been associated previously with plaque instability, including the metalloproteinase, ADAMDEC1 (Ϸ37-fold), retinoic acid receptor responder-1 (Ϸ5-fold), and cysteine protease legumain (Ϸ3-fold). Matrix metalloproteinase-9 (MMP-9), cathepsin B, and a novel gene, legumain, a potential activator of MMPs and cathepsins, were also confirmed at the protein level. Key Words: atherosclerosis Ⅲ gene expression Ⅲ stroke Ⅲ affymetrix Ⅲ MMP-9 Ⅲ legumain Ⅲ plaque instability A therosclerosis is a chronic inflammatory disease that remains a major cause of morbidity in the Western world. The composition and vulnerability of the atherosclerotic plaque are considered to be important factors in the development of arterial thrombus and embolic complications. 1 However, the precise mechanisms by which plaque ruptures remain to be determined 2,3 Gene expression techniques such as microarrays and representational difference analysis are powerful tools that can be used to probe the complexities underlying atherosclerotic plaque initiation and progression. 4 -6 These techniques have already been used to show altered gene expression between normal and diseased arteries, 6,7 between different stages in disease progression 8,9 and differential expression in samples of atherosclerotic plaque classified according to patient symptomatology. 10 However, there are drawbacks to these types of comparisons. The differences in the cellular composition and morphology between plaque and normal arterial wall may lead to differences in gene expression that simply reflect this variation. In addition, the high degree of variability in plaque composition and gene expression in different patients may confound comparative analysis in studies that use pooled samples. [11][12][13] Features of unstable plaque such as surface ulceration and rupture occur in both symptomless and symptomatic patients, 14 and this can also confound studies that classify samples according to patient symptomatology. Conclusions-TheThe aim of this study was to use a whole transcriptome analysis to characterize the gene expression signature of unstable regions of carotid endarterectomy (CEA) specimens using a stable region of the same specimen as an internal control. ...

Background Maternal and neonatal mortality is high in Africa, but few large, prospective studies have been done to investigate the risk factors associated with these poor maternal and neonatal outcomes. Methods A 7-day, international, prospective, observational cohort study was done in patients having caesarean delivery in 183 hospitals across 22 countries in Africa. The inclusion criteria were all consecutive patients (aged ≥18 years) admitted to participating centres having elective and non-elective caesarean delivery during the 7-day study cohort period. To ensure a representative sample, each hospital had to provide data for 90% of the eligible patients during the recruitment week. The primary outcome was in-hospital maternal mortality and complications, which were assessed by local investigators. The study was registered on the South African National Health Research Database, number KZ_2015RP7_22, and on ClinicalTrials.gov, number NCT03044899. Findings Between February, 2016, and May, 2016, 3792 patients were recruited from hospitals across Africa. 3685 were included in the postoperative complications analysis (107 missing data) and 3684 were included in the maternal mortality analysis (108 missing data). These hospitals had a combined number of specialist surgeons, obstetricians, and anaesthetists totalling 0•7 per 100 000 population (IQR 0•2-2•0). Maternal mortality was 20 (0•5%) of 3684 patients (95% CI 0•3-0•8). Complications occurred in 633 (17•4%) of 3636 mothers (16•2-18•6), which were predominantly severe intraoperative and postoperative bleeding (136 [3•8%] of 3612 mothers). Maternal mortality was independently associated with a preoperative presentation of placenta praevia, placental abruption, ruptured uterus, antepartum haemorrhage (odds ratio 4•47 [95% CI 1•46-13•65]), and perioperative severe obstetric haemorrhage (5•87 [1•99-17•34]) or anaesthesia complications (11•47 (1•20-109•20]). Neonatal mortality was 153 (4•4%) of 3506 infants (95% CI 3•7-5•0). Interpretation Maternal mortality after caesarean delivery in Africa is 50 times higher than that of high-income countries and is driven by peripartum haemorrhage and anaesthesia complications. Neonatal mortality is double the global average. Early identification and appropriate management of mothers at risk of peripartum haemorrhage might improve maternal and neonatal outcomes in Africa.

Patients with mutations in FOXC2 and GJC2 have reduced venous valve number and leaflet length. Experiments in mice by Lyons et al. show that Foxc2-Calcineurin-Nfatc1, and Gja4, Gjc2, Gja1 regulate valve-forming cell organization. Foxc2, Calcineurin-Nfatc1, and blood flow regulate leaflet growth/maturation.