Performance of a 70-mer oligonucleotide microarray for genotyping of Campylobacter jejuni

<p>Abstract</p> <p>Background</p> <p><it>Campylobacter jejuni </it>is widespread in the environment and is the major cause of bacterial gastroenteritis in humans. In the present study we use microarray-based comparative genomic hybridizations (CGH), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) to analyze closely related <it>C. jejuni </it>isolates from chicken and human infection.</p> <p>Results</p> <p>With the exception of one isolate, the microarray data clusters the isolates according to the five groups determined by PFGE. In contrast, MLST defines only three genotypes among the isolates, indicating a lower resolution. All methods show that there is no inherit difference between isolates infecting humans and chicken, suggesting a common underlying population of <it>C. jejuni</it>. We further identify regions that frequently differ between isolates, including both previously described and novel regions. Finally, we show that genes that belong to certain functional groups differ between isolates more often than expected by chance.</p> <p>Conclusion</p> <p>In this study we demonstrated the utility of 70-mer oligonucleotide microarrays for genotyping of <it>Campylobacter jejuni </it>isolates, with resolution outperforming MLST.</p

Interleukin-1 receptor antagonist haplotype associated with prostate cancer risk

IL1-RN is an important anti-inflammatory cytokine that modulate the inflammation response by binding to IL1 receptors, and as a consequence inhibits the action of proinflammatory cytokines IL1α and IL1β. In this study, we hypothesise that sequence variants in the IL1-RN gene are associated with prostate cancer risk. The study population, a population-based case–control study in Sweden, consisted of 1383 prostate cancer case patients and 779 control subjects. We first selected 18 sequence variants covering the IL1-RN gene and genotyped these single-nucleotide polymorphisms (SNPs) in 96 control subjects. Gene-specific haplotypes of IL1-RN were constructed and four haplotype-tagging single-nucleotide polymorphisms (htSNPs) were identified (rs878972, rs315934, rs3087263 and rs315951) that could uniquely describe >95% of the haplotypes. All study subjects were genotyped for the four htSNPs. No significant difference in genotype frequencies between cases and controls were observed for any of the four SNPs based on a multiplicative genetic model. Overall there was no significant difference in haplotype frequencies between cases and controls; however, the prevalence of the most common haplotype (ATGC) was significantly higher among cases (38.7%) compared to controls (33.5%) (haplotype-specific P=0.009). Evaluation of the prostate cancer risk associated with carrying the ‘ATGC' haplotype revealed that homozygous carriers were at significantly increased risk (odds ratio (OR)=1.6, 95% confidence interval (CI)=1.2–2.2), compared to noncarriers, while no significant association was found among subjects heterozygous for the haplotype (OR=1.0, 95% CI=0.8–1.2). Restricting analyses to advanced prostate cancer strengthened the association between the ‘ATGC' haplotype and disease risk (OR for homozygous carriers vs noncarriers 1.8, 95% CI=1.3–2.5). In conclusion, the results from this study support the hypothesis that inflammation has a role of in the development of prostate cancer, but further studies are needed to identify the causal variants in this region and to elucidate the biological mechanism for this association

Dolphin morbillivirus infection in different parts of the Mediterranean Sea

Morbillivirus were isolated from Mediterranean striped dolphins (Stenella coeruleoalba) dying along the coasts of Italy and Greece in 1991. They were antigenically identical to the morbilliviruses isolated from striped dolphins in Spain in 1990

Criteria-based audit on management of eclampsia patients at a tertiary hospital in Dar es Salaam, Tanzania

\ud Criteria-based audits have been used to improve clinical management in developed countries, but have only recently been introduced in the developing world. This study discusses the introduction of a criteria-based audit in a tertiary hospital in an African setting, assesses the quality of care among eclampsia patients and discusses possible interventions in order to improve the quality of care. We conducted a criteria based audit of 389 eclampsia patients admitted to Muhimbili National Hospital (MNH), Dar es Salaam Tanzania between April 14, 2006 and December 31, 2006. Cases were assessed using evidence-based criteria for appropriate care. Antepartum, intrapartum and postpartum eclampsia constituted 47%, 41% and 12% of the eclampsia cases respectively. Antepartum eclampsia was mostly (73%) preterm whereas the majority (71%) of postpartum eclampsia cases ware at term. The case fatality rate for eclampsia was 7.7%. Medical histories were incomplete, the majority (75%) of management plans were not reviewed by specialists in obstetrics, specialist doctors live far from the hospital and do not spend nights in hospital even when they are on duty, monitoring of patients on magnesium sulphate was inadequate, and important biochemical tests were not routinely done. Two thirds of the patient scheduled for caesarean section did not undergo surgery within agreed time. Potential areas for further improvement in quality of emergency care for eclampsia relate to standardizing management guidelines, greater involvement of specialists in the management of eclampsia and continued medical education on current management of eclampsia for junior staff.\u

The prognostic value of four interleukin-1 gene polymorphisms in caucasian women with breast cancer – a multicenter study

<p>Abstract</p> <p>Background</p> <p>The proinflammatory cytokine interleukin-1 (IL-1) is known to play an important role in the carcinogenesis of breast cancer. Although IL-1 gene polymorphisms were reported to be associated with increased risk of breast cancer, their influence on survival of Caucasian breast cancer patients remains to be shown.</p> <p>Methods</p> <p>We studied the influence of four common gene polymorphisms (<it>IL1A </it>-889C/T, <it>IL1B </it>-511C/T, <it>IL1B </it>+3953E1/E2, and <it>IL1RN </it>long/2) of the IL-1 family on survival in 262 Caucasian patients with breast cancer by univariate and multivariate survival analysis. The combined effect of the four gene polymorphisms on overall survival was studied by haplotype analysis.</p> <p>Results</p> <p>In the present study 38 cases of cancer related death and a median time of follow-up (range) of 55.3 (0.4–175.8) months was observed. <it>IL1RN </it>2/2 (homozygous mutant) gene polymorphism was associated with shortened disease free and overall survival in a univariate (p = 0.001 and p = 0.01, respectively) and multivariate analysis (p = 0.002, Odds Ratio [95% Confidence Interval] = 3.6 [1.6–8.0] and p = 0.05, Odds Ratio = 3.0 [1.1–9.3], respectively). Presence of the homozygous mutant genotype of the <it>IL1A </it>-889 and <it>IL1B </it>+3953 gene polymorphism was associated with overall survival in the univariate (p = 0.004 and p = 0.002, respectively), but not in the multivariate analysis. No association was observed between all possible haplotype combinations and overall survival.</p> <p>Conclusion</p> <p>Carriage of the mutant alleles of <it>IL1RN </it>was independently associated with shortened disease free and overall survival rates in Caucasian patients with breast cancer.</p

Quorum Sensing Regulation of the Two hcp Alleles in Vibrio cholerae O1 Strains

BACKGROUND: The type VI secretion system (T6SS) has emerged as a protein secretion system important to several gram-negative bacterial species. One of the common components of the system is Hcp, initially described as a hemolysin co-regulated protein in a serotype O17 strain of Vibrio cholerae. Homologs to V. cholerae hcp genes have been found in all characterized type VI secretion systems and they are present also in the serotype O1 strains of V. cholerae that are the cause of cholera diseases but seemed to have non-functional T6SS. METHODOLOGY/PRINCIPAL FINDINGS: The serotype O1 V. cholerae strain A1552 was shown to express detectable levels of Hcp as determined by immunoblot analyses using polyclonal anti-Hcp antiserum. We found that the expression of Hcp was growth phase dependent. The levels of Hcp in quorum sensing deficient mutants of V. cholerae were compared with the levels in wild type V. cholerae O1 strain A1552. The expression of Hcp was positively and negatively regulated by the quorum sensing regulators HapR and LuxO, respectively. In addition, we observed that expression of Hcp was dependent on the cAMP-CRP global transcriptional regulatory complex and required the RpoN sigma factor. CONCLUSION/SIGNIFICANCE: Our results show that serotype O1 strains of V. cholerae do express Hcp which is regarded as one of the important T6SS components and is one of the secreted substrates in non-O1 non-O139 V. cholerae isolates. We found that expression of Hcp was strictly regulated by the quorum sensing system in the V. cholerae O1 strain. In addition, the expression of Hcp required the alternative sigma factor RpoN and the cAMP-CRP global regulatory complex. Interestingly, the environmental isolates of V. cholerae O1 strains that showed higher levels of the HapR quorum sensing regulator in comparison with our laboratory standard serotype O1 strain A1552 where also expressing higher levels of Hcp

High ANC coverage and low skilled attendance in a rural Tanzanian district: a case for implementing a birth plan intervention

BACKGROUND: In Tanzania, more than 90% of all pregnant women attend antenatal care at least once and approximately 62% four times or more, yet less than five in ten receive skilled delivery care at available health units. We conducted a qualitative study in Ngorongoro district, Northern Tanzania, in order to gain an understanding of the health systems and socio-cultural factors underlying this divergent pattern of high use of antenatal services and low use of skilled delivery care. Specifically, the study examined beliefs and behaviors related to antenatal, labor, delivery and postnatal care among the Maasai and Watemi ethnic groups. The perspectives of health care providers and traditional birth attendants on childbirth and the factors determining where women deliver were also investigated. METHODS: Twelve key informant interviews and fifteen focus group discussions were held with Maasai and Watemi women, traditional birth attendants, health care providers, and community members. Principles of the grounded theory approach were used to elicit and assess the various perspectives of each group of participants interviewed. RESULTS: The Maasai and Watemi women's preferences for a home birth and lack of planning for delivery are reinforced by the failure of health care providers to consistently communicate the importance of skilled delivery and immediate post-partum care for all women during routine antenatal visits. Husbands typically serve as gatekeepers of women's reproductive health in the two groups - including decisions about where they will deliver- yet they are rarely encouraged to attend antenatal sessions. While husbands are encouraged to participate in programs to prevent maternal-to-child transmission of HIV, messages about the importance of skilled delivery care for all women are not given emphasis. CONCLUSIONS: Increasing coverage of skilled delivery care and achieving the full implementation of Tanzania's Focused Antenatal Care Package in Ngorongoro depends upon improved training and monitoring of health care providers, and greater family participation in antenatal care visits

Sense of coherence and diabetes: A prospective occupational cohort study

<p>Abstract</p> <p>Background</p> <p>Sense of coherence (SOC) is an individual characteristic related to a positive life orientation leading to effective coping. A weak SOC has been associated with indicators of general morbidity and mortality. However, the relationship between SOC and diabetes has not been studied in prospective design. The present study prospectively examined the relationship between a weak SOC and the incidence of diabetes.</p> <p>Methods</p> <p>The relationship between a weak SOC and the incidence of diabetes was investigated among 5827 Finnish male employees aged 18–65 at baseline (1986). SOC was measured by questionnaire survey at baseline. Data on prescription diabetes drugs from 1987 to 2004 were obtained from the Drug Imbursement Register held by the Social Insurance Institution.</p> <p>Results</p> <p>During the follow-up, 313 cases of diabetes were recorded. A weak SOC was associated with a 46% higher risk of diabetes in participants who had been =<50 years of age on entry into the study. This association was independent of age, education, marital status, psychological distress, self-rated health, smoking status, binge drinking and physical activity. No similar association was observed in older employees.</p> <p>Conclusion</p> <p>The results suggest that besides focusing on well-known risk factors for diabetes, strengthening SOC in employees of =<50 years of age can also play a role in attempts to tackle increasing rates of diabetes.</p

Catalytic living ring-opening metathesis polymerization

In living ring-opening metathesis polymerization (ROMP), a transition-metal–carbene complex polymerizes ring-strained olefins with very good control of the molecular weight of the resulting polymers. Because one molecule of the initiator is required for each polymer chain, however, this type of polymerization is expensive for widespread use. We have now designed a chain-transfer agent (CTA) capable of reducing the required amount of metal complex while still maintaining full control over the living polymerization process. This new method introduces a degenerative transfer process to ROMP. We demonstrate that substituted cyclohexene rings are good CTAs, and thereby preserve the ‘living’ character of the polymerization using catalytic quantities of the metal complex. The resulting polymers show characteristics of a living polymerization, namely narrow molecular-weight distribution, controlled molecular weights and block copolymer formation. This new technique provides access to well- defined polymers for industrial, biomedical and academic use at a fraction of the current costs and significantly reduced levels of residual ruthenium catalyst