Socioeconomic and Environmental Risk Factors among Rheumatic Heart Disease Patients in Uganda

Background

Although low socioeconomic status, and environmental factors are known risk factors for rheumatic heart disease in other societies, risk factors for rheumatic heart disease remain less well described in Uganda.

Aims and Objective

The objective of this study was to investigate the role of socio-economic and environmental factors in the pathogenesis of rheumatic heart disease in Ugandan patients.

Methods

This was a case control study in which rheumatic heart disease cases and normal controls aged 5–60 years were recruited and investigated for socioeconomic and environmental risk factors such as income status, employment status, distance from the nearest health centre, number of people per house and space area per person.

Results

486 participants (243 cases and 243 controls) took part in the study. Average age was 32.37+/−14.6 years for cases and 35.75+/−12.6 years for controls. At univariate level, Cases tended to be more overcrowded than controls; 8.0+/−3.0 versus 6.0+/−3.0 persons per house. Controls were better spaced at 25.2 square feet versus 16.9 for cases. More controls than cases were employed; 45.3% versus 21.1%. Controls lived closer to health centers than the cases; 4.8+/−3.8 versus 3.3+/−12.9 kilometers. At multivariate level, the odds of rheumatic heart disease was 1.7 times higher for unemployment status (OR = 1.7, 95% CI = 1.05–8.19) and 1.3 times higher for overcrowding (OR = 1.35, 95% CI = 1.1–1.56). There was interaction between overcrowding and longer distance from the nearest health centre (OR = 1.20, 95% CI = 1.05–1.42).

Conclusion

The major findings of this study were that there was a trend towards increased risk of rheumatic heart disease in association with overcrowding and unemployment. There was interaction between overcrowding and distance from the nearest health center, suggesting that the effect of overcrowding on the risk of acquiring rheumatic heart disease increases with every kilometer increase from the nearest health center.     

A dual role of extracellular DNA during biofilm formation of Neisseria meningitidis

Major pathogenic clonal complexes (cc) of Neisseria meningitidis differ substantially in their point prevalence among healthy carriers. We show that frequently carried pathogenic cc (e.g. sequence type ST‐41/44 cc and ST‐32 cc) depend on extracellular DNA (eDNA) to initiate in vitro biofilm formation, whereas biofilm formation of cc with low point prevalence (ST‐8 cc and ST‐11 cc) was eDNA‐independent. For initial biofilm formation, a ST‐32 cc type strain, but not a ST‐11 type strain, utilized eDNA. The release of eDNA was mediated by lytic transglycosylase and cytoplasmic N‐acetylmuramyl‐l ‐alanine amidase genes. In late biofilms, outer membrane phospholipase A‐dependent autolysis, which was observed in most cc, but not in ST‐8 and ST‐11 strains, was required for shear force resistance of microcolonies. Taken together, N. meningitidis evolved two different biofilm formation strategies, an eDNA‐dependent one yielding shear force resistant microcolonies, and an eDNA‐independent one. Based on the experimental findings and previous epidemiological observations, we hypothesize that most meningococcal cc display a settler phenotype, which is eDNA‐dependent and results in a stable interaction with the host. On the contrary, spreaders (ST‐11 and ST‐8 cc) are unable to use eDNA for biofilm formation and might compensate for poor colonization properties by high transmission rates.     

Leishmania amazonensis Promastigotes Present Two Distinct Modes of Nucleus and Kinetoplast Segregation during Cell Cycle

Here, we show the morphological events associated with organelle segregation and their timing in the cell cycle of a reference strain of Leishmania (L.) amazonensis promastigotes, the main causative agent of Tegumentary leishmaniasis in the Americas. We show evidences that during the cell cycle, L. amazonensis promastigotes present two distinct modes of nucleus and kinetoplast segregation, which occur in different temporal order in different proportions of cells. We used DAPI-staining and EdU-labeling to monitor the segregation of DNA-containing organelles and DNA replication in wild-type parasites. The emergence of a new flagellum was observed using a specific monoclonal antibody. The results show that L. amazonensis cell cycle division is peculiar, with 65% of the dividing cells duplicating the kinetoplast before the nucleus, and the remaining 35% doing the opposite or duplicating both organelles concomitantly. In both cases, the new flagellum appeared during S to G2 phase in 1N1K cells and thus before the segregation of both DNA-containing organelles; however, we could not determine the exact timing of flagellar synthesis. Most of these results were confirmed by the synchronization of parasites using hydroxyurea. Altogether, our data show that during the cell cycle of L. amazonensis promastigotes, similarly to L. donovani, the segregation of nucleus and kinetoplast do not follow a specific order, especially when compared to other trypanosomatids, reinforcing the idea that this characteristic seems to be species-specific and may represent differences in cellular biology among members of the Leishmania genus.     

Quantile-based permutation thresholds for quantitative trait Loci hotspots

Quantitative trait loci (QTL) hotspots (genomic locations affecting many traits) are a common feature in genetical genomics studies and are biologically interesting since they may harbor critical regulators. Therefore, statistical procedures to assess the significance of hotspots are of key importance. One approach, randomly allocating observed QTL across the genomic locations separately by trait, implicitly assumes all traits are uncorrelated. Recently, an empirical test for QTL hotspots was proposed on the basis of the number of traits that exceed a predetermined LOD value, such as the standard permutation LOD threshold. The permutation null distribution of the maximum number of traits across all genomic locations preserves the correlation structure among the phenotypes, avoiding the detection of spurious hotspots due to nongenetic correlation induced by uncontrolled environmental factors and unmeasured variables. However, by considering only the number of traits above a threshold, without accounting for the magnitude of the LOD scores, relevant information is lost. In particular, biologically interesting hotspots composed of a moderate to small number of traits with strong LOD scores may be neglected as nonsignificant. In this article we propose a quantile-based permutation approach that simultaneously accounts for the number and the LOD scores of traits within the hotspots. By considering a sliding scale of mapping thresholds, our method can assess the statistical significance of both small and large hotspots. Although the proposed approach can be applied to any type of heritable high-volume "omic" data set, we restrict our attention to expression (e)QTL analysis. We assess and compare the performances of these three methods in simulations and we illustrate how our approach can effectively assess the significance of moderate and small hotspots with strong LOD scores in a yeast expression data set.     

Sequencing intractable DNA to close microbial genomes

Advancement in high throughput DNA sequencing technologies has supported a rapid proliferation of microbial genome sequencing projects, providing the genetic blueprint for in-depth studies. Oftentimes, difficult to sequence regions in microbial genomes are ruled "intractable" resulting in a growing number of genomes with sequence gaps deposited in databases. A procedure was developed to sequence such problematic regions in the "non-contiguous finished" Desulfovibrio desulfuricans ND132 genome (6 intractable gaps) and the Desulfovibrio africanus genome (1 intractable gap). The polynucleotides surrounding each gap formed GC rich secondary structures making the regions refractory to amplification and sequencing. Strand-displacing DNA polymerases used in concert with a novel ramped PCR extension cycle supported amplification and closure of all gap regions in both genomes. The developed procedures support accurate gene annotation, and provide a step-wise method that reduces the effort required for genome finishing.     

A model invalidation-based approach for elucidating biological signalling pathways,applied to the chemotaxis pathway in R. sphaeroides

Background  

Developing methods for understanding the connectivity of signalling pathways is a major challenge in biological research. For this purpose, mathematical models are routinely developed based on experimental observations, which also allow the prediction of the system behaviour under different experimental conditions. Often, however, the same experimental data can be represented by several competing network models.     

Worldwide genetic relationships among Francisella tularensis isolates determined by multiple-locus variable-number tandem repeat analysis

The intracellular bacterium Francisella tularensis is the causative agent of tularemia and poses a serious threat as an agent of bioterrorism. We have developed a highly effective molecular subtyping system from 25 variable-number tandem repeat (VNTR) loci. In our study, multiple-locus VNTR analysis (MLVA) was used to analyze genetic relationships and potential population structure within a global collection of 192 F. tularensis isolates, including representatives from each of the four subspecies. The VNTR loci displayed between 2 and 31 alleles with Nei's diversity values between 0.05 and 0.95. Neighbor-joining cluster analysis of VNTR data revealed 120 genotypes among the 192 F. tularensis isolates, including accurate subspecies identification. F. tularensis subsp. tularensis (type A) isolates showed great diversity at VNTR loci, while F. tularensis subsp. holarctica (type B) isolates showed much lower levels despite a much broader geographical prevalence. The resolution of two distinct clades within F. tularensis subsp. tularensis (designated A.I and A.II) revealed a previously unrecognized genetic division within this highly virulent subspecies. F. tularensis subsp. holarctica appears to have recently spread globally across continents from a single origin, while F. tularensis subsp. tularensis has a long and complex evolutionary history almost exclusively in North America. The sole non-North American type A isolates (Slovakian) were closely related to the SCHU S4 strain. Significant linkage disequilibrium was detected among VNTR loci of F. tularensis consistent with a clonal population structure. Overall, this work greatly augments the study of tularemia ecology and epidemiology, while providing a framework for future forensic analysis of F. tularensis isolates.     

A survey on Triatoma dimidiata in an urban area of the province of Heredia, Costa Rica

Triatoma dimidiata has been found in several cities and towns of those countries where the insect is a domestic or peridomestic pest. In Central America, urban infestations occur in the capitals of at least five countries. During 2001 and 2002 a survey was carried out in the county of San Rafael, Heredia province, located 15 km northwest of San José, capital of Costa Rica, in order to determine the degree of infestation by T. dimidiata in an entire city block. Six peridomestic colonies of the insect were detected in the backyards of eight households. The ecotopes occupied by the insects consisted of store rooms with old objects, wood piles or firewood, and chicken coops. A total of 1917 insects were found in the six foci, during two sampling periods, and a mean infection rate by Trypanosoma cruzi of 28.4% was found in 1718 insects examined. The largest colony found in one of the households yielded 872 insects that were thriving mainly at the expenses of two dogs. Opossums and adult insects were common visitors of the houses and it became evident that this marsupial is closely related to the peridomestic cycle of the Chagas disease agent. Lack of colonization of the insect inside the human dwellings is explained by the type of construction and good sanitary conditions of the houses, in contrast to the situation in most peridomiciliary areas. Stomach blood samples from the insects showed that the main hosts were, in order of decreasing frequency: rodents, dogs, fowl, humans, opossums, and cats. The fact that no indication of infection with Chagas disease could be detected in the human occupants of the infested houses, vis a vis the high infection rate in dogs, is discussed.     

Short-term responses of photosynthetic membrane lipids and photochemical efficiency in plants of <Emphasis Type="Italic">Phaseolus vulgaris</Emphasis> and <Emphasis Type="Italic">Vigna unguiculata</Emphasis> submitted to high irradiance

Primary leaves of young plants of common bean (Phaseolus vulgaris cv. Carioca and Negro Huasteco) and cowpea (Vigna unguiculata Walp cv. Epace 10) were exposed to high irradiance (HI) of 2 000 μmol m⁻² s⁻¹ for 10, 20, and 30 min. The initial fluorescence (F₀) was nearly constant in response to HI in each genotype except for Carioca. A distinct reduction of maximum fluorescence (F_m) was clearly observed in stressed genotypes of beans after 20 min followed by a slight recovery for the longer stress times. In common bean, the maximum quantum yield (F_v/F_m) was reduced slowly from 10 to 30 min of HI. In cowpea, only a slight reduction of F_v/F_m was observed at 20 min followed by recovery to normal values at 30 min. HI resulted in changes in the photochemical (q_P) and non-photochemical (q_N) quenching in both species, but to a different extent. In cowpea plants, more efficiency in the use of the absorbed energy under photoinhibitory conditions was related to increase in q_P and decrease in q_N. In addition, lipid peroxidation changed significantly in common bean genotypes with an evident increase after 20 min of HI. Hence the photosynthetic apparatus of cowpea was more tolerant to HI than that of common bean and the integrity of cowpea cell membranes was apparently maintained under HI.     

Für welche Pflanzenarten hat die Schweiz eine internationale Verantwortung?

Eggenberg S. and Landolt E. 2006. For which plant species does Switzerland have an international responsibility? Bot. Helv. 116: 119 – 133. Priorities in plant species conservation are often based on national Red Lists. In an international context, however, the Red List status (threat) of a species within a limited territory may be misleading because the local disappearance of a species may or may not have serious implications for its global persistence. A second important aspect to consider in species conservation is therefore the responsibility of a country for the species, i.e. the importance of the conservation of local populations for the persistence of the species worldwide. In this contribution, we assess the responsibility of Switzerland for its vascular flora using three biogeographical criteria: (1) the Swiss portion of the species range (high responsibility for species with a large fraction of the range in Switzerland), (2) the degree of endemism (high responsibility for species with a small total range) and (3) the degree of isolation (high responsibility for isolated outposts, which may contain a large part of a species’ genetic variation). The three criteria were derived for each species from global and European distribution maps, and were then combined to an overall index of responsibility. On this basis, 397 taxa for which Switzerland has an intermediate to high international responsibility were identified. These are almost 15% of the whole vascular flora of Switzerland. Of the 397 taxa, 75% are endemic species of the Alps, and 48% are threatened taxa within Switzerland. The Responsibility List can be used together with the Red List to set priorities in plant conservation or to identify areas of particular floristic value. Manuskript angenommen am 11. September 2006