Refractory periods and climate forcing in cholera dynamics

Outbreaks of many infectious diseases, including cholera, malaria and dengue, vary over characteristic periods longer than 1 year(1,2). Evidence that climate variability drives these interannual cycles has been highly controversial, chiefly because it is difficult to isolate the contribution of environmental forcing while taking into account nonlinear epidemiological dynamics generated by mechanisms such as host immunity(2-4). Here we show that a critical interplay of environmental forcing, specifically climate variability, and temporary immunity explains the interannual disease cycles present in a four-decade cholera time series from Matlab, Bangladesh. We reconstruct the transmission rate, the key epidemiological parameter affected by extrinsic forcing, over time for the predominant strain ( El Tor) with a nonlinear population model that permits a contributing effect of intrinsic immunity. Transmission shows clear interannual variability with a strong correspondence to climate patterns at long periods ( over 7 years, for monsoon rains and Brahmaputra river discharge) and at shorter periods ( under 7 years, for flood extent in Bangladesh, sea surface temperatures in the Bay of Bengal and the El Nino Southern Oscillation). The importance of the interplay between extrinsic and intrinsic factors in determining disease dynamics is illustrated during refractory periods, when population susceptibility levels are low as the result of immunity and the size of cholera outbreaks only weakly reflects climate forcing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62876/1/nature03820.pd

The sinus tarsi approach in displaced intra-articular calcaneal fractures: a systematic review

Purpose: Although open reduction and internal fixation is currently considered the gold standard in surgical treatment of displaced intra-articular calcaneal fractures, various different approaches exist including the limited lateral approach. The aim of this systematic review was to combine the results of studies using the sinus tarsi approach, which is the most frequently applied limited lateral approach. Method: A literature search in the electronic databases of the Cochrane Library and Pubmed Medline, between January 1st 2000 to December 1st 2010, was conducted to identify studies in which the sinus tarsi approach or a modified sinus tarsi approach was utilized for the treatment of displaced intra-articular calcaneal fractures. The methodological quality of the included studies was assessed using the Coleman methodology score. Results: A total of eight case series reporting on 256 patients with 271 calcaneal fractures was identified. Overall good to excellent outcome was reached in three-quarters of all patients. An average complication rate of minor wound complications of 4.1% was reported and major wound complications in 0.7%. The need for a secondary subtalar arthrodesis occurred at an average rate of 4.3%. The average Coleman methodology score was 56.8 (range 39-72) points. Conclusion: The results, i.e. functional outcome and complication rates, of the sinus tarsi approach compare similarly or favourably to the extended lateral approach. Therefore, in the process of tailoring the best treatment modality to the right patient and the right fracture type, the sinus tarsi approach might be a valuable asset

Soluble Fas might serve as a diagnostic tool for gastric adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Fas (Apo-1/CD95) and its specific ligand (FasL) are key elements in apoptosis. They have been studied in different malignancies but there are few published studies about the soluble forms of these markers (i.e. sFas/sFasL) in gastric cancer. We have compared the serum levels of sFas/sFasL in gastric adenocarcinoma patients and cases with pre-neoplastic lesions as potential markers for early diagnosis, and investigated their relation with clinicopathological characteristics.</p> <p>Methods</p> <p>Fifty-nine newly-diagnosed cases of gastric adenocarcinoma who had undergone gastrectomy, along with 62 endoscopically- and histologically-confirmed non-cancer individuals were enrolled in this study. sFas/sFasL serum levels were detected by Enzyme Linked Immunosurbent Assay.</p> <p>Results</p> <p>Mean serum sFas level was significantly higher in gastric cancer patients than in control group (305.97 ± 63.71 (pg/ml) vs. 92.98 ± 4.95 (pg/ml), P < 0.001); while the mean serum level of sFasL was lower in patients with gastric adenocarcinoma (0.138 ± 0.04 (pg/ml) vs. 0.150 ± 0.02 (pg/ml), P < 0.001). Mean serum levels of sFas/sFasL were significantly different in both intestinal/diffuse and cardiac/non-cardiac subtypes when compared to the control group (P < 0.001). There was an increase in the serum level of sFas from the first steps of pre-neoplastic lesions to gastric adenocarcinoma (P < 0.001). Patients who had no lymph node involvement (<it>N₀</it>) showed significantly higher serum levels of sFas compared to others (P = 0.044).</p> <p>Conclusions</p> <p>Production of sFas may play a critical role in the carcinogenesis of intestinal-type gastric cancer. sFas serum level may serve as a non-invasive tool for early diagnosis of gastric cancer.</p

Predictors of mortality among elderly people living in a south Indian urban community; a 10/66 Dementia Research Group prospective population-based cohort study

<p>Abstract</p> <p>Background</p> <p>Eighty percent of deaths occur in low and middle income countries (LMIC), where chronic diseases are the leading cause. Most of these deaths are of older people, but there is little information on the extent, pattern and predictors of their mortality. We studied these among people aged 65 years and over living in urban catchment areas in Chennai, south India.</p> <p>Methods</p> <p>In a prospective population cohort study, 1005 participants were followed-up after three years. Baseline assessment included sociodemographic and socioeconomic characteristics, health behaviours, physical, mental and cognitive disorders, disability and subjective global health.</p> <p>Results</p> <p>At follow-up, 257 (25.6%) were not traced. Baseline characteristics were similar to the 748 whose vital status was ascertained; 154 (20.6%) had died. The mortality rate was 92.5/1000 per annum for men and 51.0/1000 per annum for women. Adjusting for age and sex, mortality was associated with older age, male sex, having no friends, physical inactivity, smaller arm circumference, dementia, depression, poor self-rated health and disability. A parsimonious model included, in order of aetiologic force, male sex, smaller arm circumference, age, disability, and dementia. The total population attributable risk fraction was 0.90.</p> <p>Conclusion</p> <p>A balanced approach to prevention of chronic disease deaths requires some attention to proximal risk factors in older people. Smoking and obesity seem much less relevant than in younger people. Undernutrition is preventable. While dementia makes the largest contribution to disability and dependency, comorbidity is the rule, and more attention should be given to the chronic care needs of those affected, and their carers.</p

Blood lead, cadmium and mercury among children from urban, industrial and rural areas of Fez Boulemane Region (Morocco): Relevant factors and early renal effects

Objectives: To describe blood lead (Pb-B), cadmium (Cd-B) and mercury (Hg-B) levels in children living in urban, industrial and rural areas in Fez city (north of Morocco) and to identify the determinants and some renal effects of exposure. Material and Methods: The study was conducted from June 2007 to January 2008 in 209 school children (113 girls, 96 boys), aged 6-12 years, from urban, industrial and rural areas in Fez city. Interview and questionnaires data were obtained. Blood and urinary samples were analyzed. Results: The mean of blood lead levels (Pb-B) in our population was 55.53 μg/l (range: 7.5-231.1 μg/l). Children from the urban area had higher blood lead levels (BLLs) mean (82.36 μg/l) than children from industrial and rural areas (48.23 and 35.99 μg/l, respectively); with no significant difference between boys and girls. BLLs were associated with traffic intensity, passive smoking and infancy in the urban area. The mean of blood cadmium levels (BCLs) was 0.22 μg/l (range: 0.06-0.68 μg/l), with no difference between various areas. Rural boys had higher BCLs mean than rural girls, but no gender influence was noticed in the other areas. BCLs were associated with the number of cigarettes smoked at children's homes. The blood mercury levels (BMLs) mean was 0.49 μg/l (range: 0.01-5.31 μg/l). The BMLs mean was higher in urban and industrial areas than in the rural area with no gender-related difference. BMLs were associated with amalgam fillings and infancy in the urban area. About 8% of the children had BLLs ≥ 100 μg/l particularly in the urban area, microalbuminuria and a decrease in height were noticed in girls from the inner city of Fez and that can be related to high BLLs (89.45 μg/l). Conclusions: There is a need to control and regulate potential sources of contamination by these trace elements in children; particularly for lead

Bound Water at Protein-Protein Interfaces: Partners, Roles and Hydrophobic Bubbles as a Conserved Motif

Background There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region. Methodology A data set of 4741 water molecules abstracted from 179 high-resolution (≤ 2.30 Å) X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed Relevance was used to classify the general roles of the water molecules. Results The water molecules were found to be involved in: a) (bridging) interactions with both proteins (21%), b) favorable interactions with only one protein (53%), and c) no interactions with either protein (26%). This trend is shown to be independent of the crystallographic resolution. Interactions with residue backbones are consistent for all classes and account for 21.5% of all interactions. Interactions with polar residues are significantly more common for the first group and interactions with non-polar residues dominate the last group. Waters interacting with both proteins stabilize on average the proteins\u27 interaction (−0.46 kcal mol−1), but the overall average contribution of a single water to the protein-protein interaction energy is unfavorable (+0.03 kcal mol−1). Analysis of the waters without favorable interactions with either protein suggests that this is a conserved phenomenon: 42% of these waters have SASA ≤ 10 Å2 and are thus largely buried, and 69% of these are within predominantly hydrophobic environments or “hydrophobic bubbles”. Such water molecules may have an important biological purpose in mediating protein-protein interactions

Six RNA Viruses and Forty-One Hosts: Viral Small RNAs and Modulation of Small RNA Repertoires in Vertebrate and Invertebrate Systems

We have used multiplexed high-throughput sequencing to characterize changes in small RNA populations that occur during viral infection in animal cells. Small RNA-based mechanisms such as RNA interference (RNAi) have been shown in plant and invertebrate systems to play a key role in host responses to viral infection. Although homologs of the key RNAi effector pathways are present in mammalian cells, and can launch an RNAi-mediated degradation of experimentally targeted mRNAs, any role for such responses in mammalian host-virus interactions remains to be characterized. Six different viruses were examined in 41 experimentally susceptible and resistant host systems. We identified virus-derived small RNAs (vsRNAs) from all six viruses, with total abundance varying from “vanishingly rare” (less than 0.1% of cellular small RNA) to highly abundant (comparable to abundant micro-RNAs “miRNAs”). In addition to the appearance of vsRNAs during infection, we saw a number of specific changes in host miRNA profiles. For several infection models investigated in more detail, the RNAi and Interferon pathways modulated the abundance of vsRNAs. We also found evidence for populations of vsRNAs that exist as duplexed siRNAs with zero to three nucleotide 3′ overhangs. Using populations of cells carrying a Hepatitis C replicon, we observed strand-selective loading of siRNAs onto Argonaute complexes. These experiments define vsRNAs as one possible component of the interplay between animal viruses and their hosts