The impact of cross-border movement on South African towns on the Lesotho border

This article investigates the impact of cross-border movement from Lesotho to the eastern Free State towns of Ficksburg, Ladybrand and Wepener. The many Basotho who visit these towns have a tangible impact on economic activity and service provision. The findings include, among other things, the major economic benefits for the border towns and the impact on South Africa’s health and education services. Stakeholders attributed both the fast growth of informal settlements and the high rate of unemployment to the movement of Lesotho citizens, but this could not be verified. Policy recommendations include the need to facilitate the flow of people and to garner reliable information on which to base planning and decision-making

Capillary leakage in post-cardiac arrest survivors during therapeutic hypothermia - a prospective, randomised study

Background: Fluids are often given liberally after the return of spontaneous circulation. However, the optimal fluid regimen in survivors of cardiac arrest is unknown. Recent studies indicate an increased fluid requirement in post-cardiac arrest patients. During hypothermia, animal studies report extravasation in several organs, including the brain. We investigated two fluid strategies to determine whether the choice of fluid would influence fluid requirements, capillary leakage and oedema formation. Methods: 19 survivors with witnessed cardiac arrest of primary cardiac origin were allocated to either 7.2% hypertonic saline with 6% poly (O-2-hydroxyethyl) starch solution (HH) or standard fluid therapy (Ringer's Acetate and saline 9 mg/ml) (control). The patients were treated with the randomised fluid immediately after admission and continued for 24 hours of therapeutic hypothermia. Results: During the first 24 hours, the HH patients required significantly less i.v. fluid than the control patients (4750 ml versus 8010 ml, p = 0.019) with comparable use of vasopressors. Systemic vascular resistance was significantly reduced from 0 to 24 hours (p = 0.014), with no difference between the groups. Colloid osmotic pressure (COP) in serum and interstitial fluid (p < 0.001 and p = 0.014 respectively) decreased as a function of time in both groups, with a more pronounced reduction in interstitial COP in the crystalloid group. Magnetic resonance imaging of the brain did not reveal vasogenic oedema. Conclusions: Post-cardiac arrest patients have high fluid requirements during therapeutic hypothermia, probably due to increased extravasation. The use of HH reduced the fluid requirement significantly. However, the lack of brain oedema in both groups suggests no superior fluid regimen. Cardiac index was significantly improved in the group treated with crystalloids. Although we do not associate HH with the renal failures that developed, caution should be taken when using hypertonic starch solutions in these patients

Biomechanical factors in atherosclerosis: mechanisms and clinical implications†

Blood vessels are exposed to multiple mechanical forces that are exerted on the vessel wall (radial, circumferential and longitudinal forces) or on the endothelial surface (shear stress). The stresses and strains experienced by arteries influence the initiation of atherosclerotic lesions, which develop at regions of arteries that are exposed to complex blood flow. In addition, plaque progression and eventually plaque rupture is influenced by a complex interaction between biological and mechanical factors—mechanical forces regulate the cellular and molecular composition of plaques and, conversely, the composition of plaques determines their ability to withstand mechanical load. A deeper understanding of these interactions is essential for designing new therapeutic strategies to prevent lesion development and promote plaque stabilization. Moreover, integrating clinical imaging techniques with finite element modelling techniques allows for detailed examination of local morphological and biomechanical characteristics of atherosclerotic lesions that may be of help in prediction of future events. In this ESC Position Paper on biomechanical factors in atherosclerosis, we summarize the current ‘state of the art' on the interface between mechanical forces and atherosclerotic plaque biology and identify potential clinical applications and key questions for future researc

Contemporary South African Urbanization Dynamics

Abstract The paper provides an overview of urbanization patterns and trends in the current era in South Africa, focusing in particular on the key dynamics and driving forces underlying migration and urbanization. It considers overall demographic trends with regard to migration and urbanization, and points to some of the difficulties with data, and with the analysis of trends and patterns. The paper explores the changing rural context and dynamics, and some of the significant processes in this context: large-scale displacement of black people off farms, the impact of land reform, and conditions in the former homeland areas. Circular migration continues to be an important way in which households in rural areas survive, but some are unable to move, and are falling out of these networks. International migration—the consequence of both conditions in the home country and the draw of the South African economy— is another significant process fuelling mainly urban growth. The paper demonstrates the importance of cities in terms of economic growth and employment, and thus their attractiveness to migrants. Continuing migration to cities is of course a challenge fo

Sleep and Economic Status are Linked to Daily Life Stress in African-born Blacks Living in America.

To identify determinants of daily life stress in Africans in America, 156 African-born Blacks (Age: 40 ± 10 years (mean ± SD), range 22-65 years) who came to the United States as adults (age ≥ 18 years) were asked about stress, sleep, behavior and socioeconomic status. Daily life stress and sleep quality were assessed with the Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index (PSQI), respectively. High-stress was defined by the threshold of the upper quartile of population distribution of PSS (≥16) and low-stress as PSS \u3c 16. Poor sleep quality required PSQI \u3e 5. Low income was defined as groups, PSS were: 21 ± 4 versus 9 ± 4, p \u3c 0.001 and PSQI were: 6 ± 3 versus 4 ± 3, p \u3c 0.001, respectively. PSS and PSQI were correlated (r = 0.38, p \u3c 0.001). The odds of high-stress were higher among those with poor sleep quality (OR 5.11, 95% CI: 2.07, 12.62), low income (OR 5.03, 95% CI: 1.75, 14.47), and no health insurance (OR 3.01, 95% CI: 1.19, 8.56). Overall, in African-born Blacks living in America, daily life stress appears to be linked to poor quality sleep and exacerbated by low income and lack of health insurance

Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder

<p>Abstract</p> <p>Background</p> <p>Obsessive-compulsive disorder (OCD) is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome), suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients.</p> <p>Methods</p> <p>We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA).</p> <p>Results</p> <p>No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients.</p> <p>Conclusions</p> <p>Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD.</p

Future directions for therapeutic strategies in post-ischaemic vascularization: a position paper from European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology

Modulation of vessel growth holds great promise for treatment of cardiovascular disease. Strategies to promote vascularization can potentially restore function in ischaemic tissues. On the other hand, plaque neovascularization has been shown to associate with vulnerable plaque phenotypes and adverse events. The current lack of clinical success in regulating vascularization illustrates the complexity of the vascularization process, which involves a delicate balance between pro- and anti-angiogenic regulators and effectors. This is compounded by limitations in the models used to study vascularization that do not reflect the eventual clinical target population. Nevertheless, there is a large body of evidence that validate the importance of angiogenesis as a therapeutic concept. The overall aim of this Position Paper of the ESC Working Group of Atherosclerosis and Vascular biology is to provide guidance for the next steps to be taken from pre-clinical studies on vascularization towards clinical application. To this end, the current state of knowledge in terms of therapeutic strategies for targeting vascularization in post-ischaemic disease is reviewed and discussed. A consensus statement is provided on how to optimize vascularization studies for the identification of suitable targets, the use of animal models of disease, and the analysis of novel delivery methods

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation