Burden of podoconiosis in poor rural communities in Guliso woreda, western Ethiopia

Background. Podoconiosis is an environmental lymphoedema affecting people living and working barefoot on irritant red clay soil. Podoconiosis is relatively well described in southern Ethiopia, but remains neglected in other parts of the Ethiopian highlands. This study aimed to assess the burden of podoconiosis in rural communities in western Ethiopia. Methodology/Principal Findings. A cross-sectional study was conducted in Gulliso woreda (district), west Ethiopia. A household survey in the 26 rural kebeles (villages) of this district was conducted to identify podoconiosis patients and to measure disease prevalence. A more detailed study was done in six randomly selected kebeles to describe clinical features of the disease, patients’ experiences of foot hygiene, and shoe wearing practice. 1,935 cases of podoconiosis were registered, giving a prevalence of 2.8%. The prevalence was higher in those aged 15 – 64 years (5.2%) and in females than males (prevalence ratio 2.6:1). 90.3% of patients were in the 15 – 64 year age group. In the detailed study, 335 cases were interviewed and their feet assessed. The majority of patients were farmers, uneducated, and poor. Two-third of patients developed the disease before the age of thirty. Almost all patients (97.0%) had experienced adenolymphangitis (ALA - red, hot legs, swollen and painful groin) at least once during the previous year. Patients experienced an average of 5.5 ALA episodes annually, each of average 4.4 days, thus 24 working days were lost annually. The incidence of ALA in podoconiosis patients was higher than that reported for filariasis in other countries. Shoe wearing was limited mainly due to financial problems. Conclusions. We have documented high podoconiosis prevalence, frequent adenolymphangitis and high disease-related morbidity in west Ethiopia. Interventions must be developed to prevent, treat and control podoconiosis, one of the core neglected tropical diseases in Ethiopia

Cellular senescence and aging: the role of B-MYB

Cellular senescence is a stable cell cycle arrest, caused by insults, such as: telomere erosion, oncogene activation, irradiation, DNA damage, oxidative stress, and viral infection. Extrinsic stimuli such as cell culture stress can also trigger this growth arrest. Senescence is thought to have evolved as an example of antagonistic pleiotropy, as it acts as a tumor suppressor mechanism during the reproductive age, but can promote organismal aging by disrupting tissue renewal, repair, and regeneration later in life. The mechanisms underlying the senescence growth arrest are broadly considered to involve p16(INK4A) -pRB and p53-p21(CIP1/WAF1/SDI1) tumor suppressor pathways; but it is not known what makes the senescence arrest stable and what the critical downstream targets are, as they are likely to be key to the establishment and maintenance of the senescent state. MYB-related protein B (B-MYB/MYBL2), a member of the myeloblastosis family of transcription factors, has recently emerged as a potential candidate for regulating entry into senescence. Here, we review the evidence which indicates that loss of B-MYB expression has an important role in causing senescence growth arrest. We discuss how B-MYB acts, as the gatekeeper, to coordinate transit through the cell cycle, in conjunction with the multivulval class B (MuvB) complex and FOXM1 transcription factors. We also evaluate the evidence connecting B-MYB to the mTOR nutrient signaling pathway and suggest that inhibition of this pathway leading to an extension of healthspan may involve activation of B-MYB

Individual correlates of podoconiosis in areas of varying endemicity: a case-control study

BACKGROUND Podoconiosis is a non-filarial form of elephantiasis resulting in lymphedema of the lower legs. Previous studies have suggested that podoconiosis arises from the interplay of individual and environmental factors. Here, our aim was to understand the individual-level correlates of podoconiosis by comparing 460 podoconiosis-affected individuals and 707 unaffected controls. METHODS/PRINCIPAL FINDINGS This was a case-control study carried out in six kebeles (the lowest governmental administrative unit) in northern Ethiopia. Each kebele was classified into one of three endemicity levels: 'low' (prevalence 5%). A total of 142 (30.7%) households had two or more cases of podoconiosis. Compared to controls, the majority of the cases, especially women, were less educated (OR = 1.7, 95% CI = 1.3 to 2.2), were unmarried (OR = 3.4, 95% CI = 2.6-4.6) and had lower income (t = -4.4, p<0.0001). On average, cases started wearing shoes ten years later than controls. Among cases, age of first wearing shoes was positively correlated with age of onset of podoconiosis (r = 0.6, t = 12.5, p<0.0001). Among all study participants average duration of shoe wearing was less than 30 years. Between both cases and controls, people in 'high' and 'medium' endemicity kebeles were less likely than people in 'low' endemicity areas to 'ever' have owned shoes (OR = 0.5, 95% CI = 0.4-0.7). CONCLUSIONS Late use of shoes, usually after the onset of podoconiosis, and inequalities in education, income and marriage were found among cases, particularly among females. There were clustering of cases within households, thus interventions against podoconiosis will benefit from household-targeted case tracing. Most importantly, we identified a secular increase in shoe-wearing over recent years, which may give opportunities to promote shoe-wearing without increasing stigma among those at high risk of podoconiosis

A late Holocene onset of Aboriginal burning in southeastern Australia

The extent to which Aboriginal Australians used fire to modify their environment has been debated for decades and is generally based on charcoal and pollen records rather than landscape responses to land-use change. Here we investigate the sensitivity of in-situ–produced 10Be, an isotope commonly used in geomorphological contexts, to anthropogenic perturbations in the southeastern Australian Tablelands. Comparing 10Be-derived erosion rates from fluvial sediment (8.7 ± 0.9 mm k.y.–1; 1 standard error, SE; n = 11) and rock outcrops (5.3 ± 1.4 mm k.y.–1; 1 SE; n = 6) confirms that landscape lowering rates integrating over 104–105 yr are consistent with rates previously derived from studies integrating over 104 to >107 yr. We then model an expected 10Be inventory in fluvial sediment if background erosion rates were perturbed by a low-intensity, high-frequency Aboriginal burning regime. When we run the model using the average erosion rate derived from 10Be in fluvial sediment (8.7 mm k.y.–1), measured and modeled 10Be concentrations overlap between ca. 3 ka and 1 ka. Our modeling is consistent with intensified Aboriginal use of fire in the late Holocene, a time when Aboriginal population growth is widely recognized

Molecular cloning and characterization of B-cadherin, a novel chick cadherin.

Calcium-dependent cell-cell adhesion is mediated in large part by a set of homologous integral membrane glycoproteins termed cadherins. In this report, antibodies to conserved domains in previously described cadherins have been used to isolate cDNAs encoding a novel chick cadherin. The deduced primary structure of this novel molecule, assigned the name B-cadherin, contains 726 amino acid residues which include five extracellular domains characteristic of this class of adhesion molecules, a single putative transmembrane spanning region, and a cytoplasmic tail. In each domain, B-cadherin shares extensive homologies with other cadherins, but is more closely related to E-cadherin, P-cadherin, and L-CAM than to N-cadherin. It is expressed in a wide variety of chick tissues at embryonic day 13. In particular, immunohistochemical staining and in situ hybridization localize B-cadherin protein and mRNA to the epithelial lining of the choroid plexus and to cells in specific layers of the optic tectum in chick brain. Levels of the protein and RNA transcript change dramatically as development proceeds in chick brain. These results suggest that B-cadherin has important functions in neurogenesis, in at least some epithelia, and in embryogenesis

Exercise epigenetics and the foetal origins of disease

Exercise epigenetics is a nascent area of research with vast health implications (e.g., from the treatment of obesity-related diseases to beneficially decoupling epigenetic and chronological age). Evidence is accumulating [1] that exercise can acutely modify the epigenome (e.g., via DNA methylation) for short-term regulatory purposes (e.g., mRNA expression). More speculatively perhaps, maternal exercise during the pre and post–partum period could cause epigenetic changes in offspring. It is generally believed that there are benefits of regular moderate exercise during pregnancy [2]. The phenotypic benefits of maternal exercise notwithstanding, exercise can be viewed as a type of organismal stressor [1]. There are a myriad of ways in which environmental perturbations can affect foetal development. For example gestational stress could alter the epigenome and subsequent physical development. We suggest that maternal exercise -- like most gestational stressors -- will have a dose-response relationship on an offspring’s epigenome (i.e., negative effects at high doses), akin to the phenomenon of hormesis. Interestingly there is no research investigating the epigenetic effects of maternal exercise in humans. This editorial is a call for research on the subject

Avatar: A Time- and Space-Efficient Self-Stabilizing Overlay Network

Overlay networks present an interesting challenge for fault-tolerant computing. Many overlay networks operate in dynamic environments (e.g. the Internet), where faults are frequent and widespread, and the number of processes in a system may be quite large. Recently, self-stabilizing overlay networks have been presented as a method for managing this complexity. \emph{Self-stabilizing overlay networks} promise that, starting from any weakly-connected configuration, a correct overlay network will eventually be built. To date, this guarantee has come at a cost: nodes may either have high degree during the algorithm's execution, or the algorithm may take a long time to reach a legal configuration. In this paper, we present the first self-stabilizing overlay network algorithm that does not incur this penalty. Specifically, we (i) present a new locally-checkable overlay network based upon a binary search tree, and (ii) provide a randomized algorithm for self-stabilization that terminates in an expected polylogarithmic number of rounds \emph{and} increases a node's degree by only a polylogarithmic factor in expectation

Spatial distribution of podoconiosis in relation to environmental factors in Ethiopia: a historical review

BACKGROUND An up-to-date and reliable map of podoconiosis is needed to design geographically targeted and cost-effective intervention in Ethiopia. Identifying the ecological correlates of the distribution of podoconiosis is the first step for distribution and risk maps. The objective of this study was to investigate the spatial distribution and ecological correlates of podoconiosis using historical and contemporary survey data. METHODS Data on the observed prevalence of podoconiosis were abstracted from published and unpublished literature into a standardized database, according to strict inclusion and exclusion criteria. In total, 10 studies conducted between 1969 and 2012 were included, and data were available for 401,674 individuals older than 15 years of age from 229 locations. A range of high resolution environmental factors were investigated to determine their association with podoconiosis prevalence, using logistic regression. RESULTS The prevalence of podoconiosis in Ethiopia was estimated at 3.4% (95% CI 3.3%-3.4%) with marked regional variation. We identified significant associations between mean annual Land Surface Temperature (LST), mean annual precipitation, topography of the land and fine soil texture and high prevalence of podoconiosis. The derived maps indicate both widespread occurrence of podoconiosis and a marked variability in prevalence of podoconiosis, with prevalence typically highest at altitudes >1500 m above sea level (masl), with >1500 mm annual rainfall and mean annual LST of 19-21°C. No (or very little) podoconiosis occurred at altitudes 24°C. CONCLUSION Podoconiosis remains a public health problem in Ethiopia over considerable areas of the country, but exhibits marked geographical variation associated in part with key environmental factors. This is work in progress and the results presented here will be refined in future work