Equilibrium correlations in a model for multidimensional epistasis

We investigate a statistical model for multidimensional epistasis. The genotype is devided into subsequences, and within each subsequence mutations which occur in a prescribed order are beneficial. The bit-string model used to represent the genotype, may be cast in the form of a ferromagnetic Ising model with a staggered field. We describe the actual correlations between mutations at different sites, within an equilibrium population at a given tolerance, which we define to be the temperature of the statistical ensemble.     

Effect of preventive supplementation with zinc and other micronutrients on non-malarial morbidity in tanzanian pre-school children: a randomized trial

Background

The efficacy of preventive zinc supplementation against diarrhea and respiratory illness may depend on simultaneous supplementation with other micronutrients. We aimed to assess the effect of supplementation with zinc and multiple micronutrients on diarrhea and other causes of non-malarial morbidity.

Methods and Findings

Rural Tanzanian children (n = 612) aged 6–60 months and with height-for-age z-score < –1.5 SD were randomized to daily supplementation with zinc (10 mg) alone, multi-nutrients without zinc, multi-nutrients with zinc, or placebo. Children were followed for an average of 45 weeks. During follow-up, we recorded morbidity episodes. We found no evidence that concurrent supplementation with multi-nutrients influenced the magnitude of the effect of zinc on rates of diarrhea, respiratory illness, fever without localizing signs, or other illness (guardian-reported illness with symptoms involving skin, ears, eyes and abscesses, but excluding trauma or burns). Zinc supplementation reduced the hazard rate of diarrhea by 24% (4%–40%). By contrast, multi-nutrients seemed to increase this rate (HR; 95% CI: 1.19; 0.94–1.50), particularly in children with asymptomatic Giardia infection at baseline (2.03; 1.24–3.32). Zinc also protected against episodes of fever without localizing signs (0.75; 0.57–0.96), but we found no evidence that it reduced the overall number of clinic visits.

Conclusions

We found no evidence that the efficacy of zinc supplements in reducing diarrhea rates is enhanced by concurrent supplementation with other micronutrients. By reducing rates of fever without localizing signs, supplementation with zinc may reduce inappropriate drug use with anti-malarial medications and antibiotics.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00623857","term_id":"NCT00623857"}}NCT00623857     

Determining Toxoplasma high-risk autologous and allogeneic hematopoietic stem cell transplantation patients by systematic pre-transplant PCR screening of stem cell originated buffy coat

The diagnosis of Toxoplasma infection or disease in hematopoietic stem cell transplantation (HSCT) patients is achieved mainly by PCR screening; however screening did not find wide field of use in practice due to costly expenditures of PCR. This study aimed to determine patients at high risk of Toxoplasma infection or disease before transplantation by stem cell originated buffy coat PCR and subsequently to screen them. Buffy coats collected from 12 autologous and 18 allogeneic HSCT patients' donors were investigated by PCR before transplantation. After transplantation, blood and sera collected at fixed time intervals were screened by two PCR methods and serological assays. Screening results first time assessed a toxoplasmosis incidence level as 25% in autologous HSCT patients and increased incidence level in allogeneic HSCT patients to 22%. Importantly, buffy coat PCR was first time performed before transplantation, to determine the risk of toxoplasmosis. Buffy coat PCR results showed that four patients were at high risk of toxoplasmosis before transplantation. After transplantation, these patients experienced toxoplasmosis. In conclusion, for the determination of patients at risk of toxoplasmosis, clinicians should consider buffy coat PCR in combination with serology before transplantation. After transplantation, PCR screening can be initiated in high risk patients upon clinical suspicion.     

Toxic Metals in Breast Milk Samples from Ankara, Turkey: Assessment of Lead, Cadmium, Nickel, and Arsenic Levels

Toxic metals are one of the significant groups of chemical contaminants that humans are exposed to by oral, inhalation, and dermal routes. Exposure to these chemicals begins with intrauterine life and continues during lactation period at the first years of life. Breastfeeding has a much more special place than other nutrition options for infants. However, when possibility of contaminant transfer by breast milk is considered, its safety and quality is essential. Regarding infant and mother health and limited number of information on this field in Turkey, measuring contamination levels in breast milk is important. Therefore, in the present study, lead (Pb), cadmium (Cd), nickel (Ni), and arsenic (As) levels were measured by atomic absorption spectrometry in 64 breast milk samples obtained from mothers from Ankara, Turkey. Pb and Ni levels in breast milk samples were found to be 391.45?±?269.01?μg/l and 43.94?±?33.82?μg/l (mean ± SD), respectively. Cd was found only in one of 64 samples, and the level was 4.62?μg/l. As level was below the limit of quantification (LOQ, 7.6?μg/l) in all samples. These findings will accurately direct strategies and solutions of protection against contaminants in order to reduce their levels in biological fluids.     

Metabolic network alignment in large scale by network compression

Metabolic network alignment is a system scale comparative analysis that discovers important similarities and differences across different metabolisms and organisms. Although the problem of aligning metabolic networks has been considered in the past, the computational complexity of the existing solutions has so far limited their use to moderately sized networks. In this paper, we address the problem of aligning two metabolic networks, particularly when both of them are too large to be dealt with using existing methods. We develop a generic framework that can significantly improve the scale of the networks that can be aligned in practical time. Our framework has three major phases, namely the compression phase, the alignment phase and the refinement phase. For the first phase, we develop an algorithm which transforms the given networks to a compressed domain where they are summarized using fewer nodes, termed supernodes, and interactions. In the second phase, we carry out the alignment in the compressed domain using an existing network alignment method as our base algorithm. This alignment results in supernode mappings in the compressed domain, each of which are smaller instances of network alignment problem. In the third phase, we solve each of the instances using the base alignment algorithm to refine the alignment results. We provide a user defined parameter to control the number of compression levels which generally determines the tradeoff between the quality of the alignment versus how fast the algorithm runs. Our experiments on the networks from KEGG pathway database demonstrate that the compression method we propose reduces the sizes of metabolic networks by almost half at each compression level which provides an expected speedup of more than an order of magnitude. We also observe that the alignments obtained by only one level of compression capture the original alignment results with high accuracy. Together, these suggest that our framework results in alignments that are comparable to existing algorithms and can do this with practical resource utilization for large scale networks that existing algorithms could not handle. As an example of our method's performance in practice, the alignment of organism-wide metabolic networks of human (1615 reactions) and mouse (1600 reactions) was performed under three minutes by only using a single level of compression.     

Effects of alpha tocopherol and ascorbic acid on Helicobacter pylori colonization and the severity of gastric inflammation

Background and Aim: We aimed to evaluate the changes in histopathologic features, concentrations of vitamins C and E in gastric mucosa, and total antioxidant capacity of the body after ingestion of ascorbic acid and alpha tocopherol in patients with Helicobacter pylori. Material and Method: Patients with H. pylori‐positive nonulcer dyspepsia were included in this study. Tissue samples were taken from the lesser and greater curvature in both prepyloric antrum and corpus for histopathologic examination and measurement of vitamins C and E concentrations. Blood samples were obtained for measurement of the total antioxidant capacity of the body. The patients were given vitamin C 500 mg BID and vitamin E 200 IU BID for 4 weeks orally. At the end of the 4th week, the initial procedures were repeated. Histopathologic examination of the tissue samples were carried out by two pathologists. Results: The mean vitamins C and E concentrations in gastric mucosa at the 4th week were higher than those at the beginning (p = .000 and p = .006, respectively). Mean total antioxidant capacity of the body at the beginning and that at the 4th week were similar (p = .689). H. pylori intensity in the antrum at the beginning was higher than that at the 4th week for both pathologists (p = .007 and p = .039). Neutrophilic activity in the antrum at the beginning was higher than that at the 4th week for both pathologists (p = .000 and p = .025). Neutrophilic activity in the corpus at the beginning was higher than that at the 4th week for pathologist 1 (p = .033), and they were similar for pathologist 2 (p = .763). Conclusion: The findings that H. pylori intensity and neutrophilic activity decrease through increasing gastric ascorbic acid and alpha tocopherol concentrations suggest that supplementation with vitamins C and E increases the eradication rates via impairing the microenvironment created by the bacteria and facilitating the diffusion of antibiotics into gastric mucosa.     

Investigation of anti-Toxoplasma gondii antibodies in cats of the Ankara region of Turkey Using the Sabin-Feldman dye test and an indirect fluorescent antibody test

Blood samples from 99 cats from the Ankara province of Turkey were examined for the presence of anti-Toxoplasma gondii antibody with the use of both the Sabin-Feldman dye test (DT) and an indirect fluorescent antibody test (IFAT). Forty of the 99 sera (40.3%) were positive for antibodies against T. gondii with the DT, whereas the IFAT assay detected antibodies in 34 (34.3%). The study also evaluated 3 factors for their potential association with the presence of T. gondii antibody: age (<1 yr, 1-2 yr, and >2 yr), gender (female vs. male), and outdoor access (stray, owned with outdoor access, or indoor only). The DT detected antibodies in 3 cats under 1 yr of age, 22 cats between 1 and 2 yr, and 15 cats older than 2 yr, whereas the IFAT found 1, 18, and 15 cats positive for antibodies, respectively, in each of these categories. Of 61 female cats, 27 (44.2%) were positive by the DT; and of 38 male cats, 13 (34%) were positive by the DT. For the IFAT, 24 female cats (39.3%) and 10 male cats (26.3%) were positive. The percent seropositivity in indoor cats was 30.8% by the DT and 23.1% by the IFAT. In stray cats, the percent seropositivity was 52.8% by the DT and 41.7% by the IFAT. Antibody presence was significantly associated with age, but not with outdoor access.     

Using hydroxymethylphenoxy derivates with the SPOT technology to generate peptides with authentic C-termini

The SPOT technology can fulfill most requirements for highly parallel, multiple peptide synthesis of soluble peptides within the upper microgram range. Here, we report on an improved method using hydroxymethylphenoxyacetic acid (HMPA) for 19 amino acids and 4-(4-hydroxymethyl-3-methoxyphenoxy)-butyric acid (HMPB) for proline as acidic labile linkers in SPOT synthesis. Using this approach we could reduce side-chain reactions normally occurring during conventional alkaline peptide cleavage from cellulose membranes. All synthesis steps were adapted to fully-automated SPOT synthesis and therefore represent a time- and cost-saving procedure. Furthermore, the improved cleavage and washing steps resulted in peptides with authentic C-termini in a purity range of 60–95%. Our improved method is ideal for synthesizing many thousand different peptides subsequently used directly for different biological assays requiring authentic C-termini, such as CD8 T-cell epitope screening, vaccine immunization, or tumor imaging.     

The use of wild edible plants in western and central Anatolia (Turkey)

In this study, 121 wild edible plants used as food in Anatolia were surveyed to determine the plant parts used and their detailed preparation methods. The results of this study show that the plants may be boiled, fried in fat, and eaten raw or as rolled vegetables. They may also be consumed as pickles, fruits, sweets and spices, and drunk as cold and hot drinks. Thirty species (8 genera) were identified as belonging to the Lamiaceae family, 15 species (15 genera) belong to the Asteraceae family, 13 species (5 genera) belong to the Rosaceae family, 8 species (7 genera) belong to the Brassicaceae family, 6 species (3 genera) belong to the Orchidaceae family and 5 species (5 genera) belong to the Apiaceae family. The genera represented by the highest number of species in the study are as follows:Sideritis L. is represented by 13 species, Origanum L. by 7 species,Rubus L. by 5 species,Thymus L. by 4 species andRumex L. by 4 species.     

Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study

Introduction

We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care.

Methods

The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models.

Results

Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries.

Conclusion

In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.