A comprehensive evaluation of colonic mucosal isolates of Sutterella wadsworthensis from inflammatory bowel disease

Peer reviewedPublisher PD

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

The inflammatory microenvironment in colorectal neoplasia

Peer reviewedPublisher PD

Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain.

BACKGROUND: Chlamydia trachomatis is the most common cause of sexually transmitted infections globally and the leading cause of preventable blindness in the developing world. There are two biovariants of C. trachomatis: 'trachoma', causing ocular and genital tract infections, and the invasive 'lymphogranuloma venereum' strains. Recently, a new variant of the genital tract C. trachomatis emerged in Sweden. This variant escaped routine diagnostic tests because it carries a plasmid with a deletion. Failure to detect this strain has meant it has spread rapidly across the country provoking a worldwide alert. In addition to being a key diagnostic target, the plasmid has been linked to chlamydial virulence. Analysis of chlamydial plasmids and their cognate chromosomes was undertaken to provide insights into the evolutionary relationship between chromosome and plasmid. This is essential knowledge if the plasmid is to be continued to be relied on as a key diagnostic marker, and for an understanding of the evolution of Chlamydia trachomatis. RESULTS: The genomes of two new C. trachomatis strains were sequenced, together with plasmids from six C. trachomatis isolates, including the new variant strain from Sweden. The plasmid from the new Swedish variant has a 377 bp deletion in the first predicted coding sequence, abolishing the site used for PCR detection, resulting in negative diagnosis. In addition, the variant plasmid has a 44 bp duplication downstream of the deletion. The region containing the second predicted coding sequence is the most highly conserved region of the plasmids investigated. Phylogenetic analysis of the plasmids and chromosomes are fully congruent. Moreover this analysis also shows that ocular and genital strains diverged from a common C. trachomatis progenitor. CONCLUSION: The evolutionary pathways of the chlamydial genome and plasmid imply that inheritance of the plasmid is tightly linked with its cognate chromosome. These data suggest that the plasmid is not a highly mobile genetic element and does not transfer readily between isolates. Comparative analysis of the plasmid sequences has revealed the most conserved regions that should be used to design future plasmid based nucleic acid amplification tests, to avoid diagnostic failures

Effects on heart pumping function when using foam and gauze for negative pressure wound therapy of sternotomy wounds

<p>Abstract</p> <p>Background</p> <p>Negative pressure wound therapy (NPWT) has remarkable effects on the healing of poststernotomy mediastinitis. Foam is presently the material of choice for NPWT in this indication. There is now increasing interest in using gauze, as this has proven successful in the treatment of peripheral wounds. It is important to determine the effects of NPWT using gauze on heart pumping function before it can be used for deep sternotomy wounds. The aim was to examine the effects of NPWT when using gauze and foam on the heart pumping function during the treatment of a sternotomy wound.</p> <p>Methods</p> <p>Eight pigs underwent median sternotomy followed by NPWT at -40, -70, -120 and -160 mmHg, using foam or gauze. The heart frequency, cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, central venous pressure and left atrial pressure were recorded.</p> <p>Results</p> <p>Cardiac output was not affected by NPWT using gauze or foam. Heart frequency decreased during NPWT when using foam, but not gauze. Treatment with foam also lowered the central venous pressure and the left atrial pressure, while gauze had no such effects. Mean systemic arterial pressure, mean pulmonary artery pressure and systemic vascular resistance were not affected by NPWT. Similar haemodynamic effects were observed at all levels of negative pressure studied.</p> <p>Conclusions</p> <p>NPWT using foam results in decreased heart frequency and lower right and left atrial filling pressures. The use of gauze in NPWT did not affect the haemodynamic parameters studied. Gauze may thus provide an alternative to foam for NPWT of sternotomy wounds.</p

Trend and status of air quality at three different monitoring stations in the Klang Valley, Malaysia

Over the last decades, the development of the Klang Valley (Malaysia), as an urban commercial and industrial area, has elevated the risk of atmospheric pollutions. There are several significant sources of air pollutants which vary depending on the background of the location they originate from. The aim of this study is to determine the trend and status of air quality and their correlation with the meteorological factors at different air quality monitoring stations in the Klang Valley. The data of five major air pollutants (PM10, CO, SO2, O3, NO2) were recorded at the Alam Sekitar Sdn Bhd (ASMA) monitoring stations in the Klang Valley, namely Petaling Jaya (S1), Shah Alam (S2) and Gombak (S3). The data from these three stations were compared with the data recorded at Jerantut, Pahang (B), a background station established by the Malaysian Department of Environment. Results show that the concentrations of CO, NO2 and SO2 are higher at Petaling Jaya (S1) which is due to influence of heavy traffic. The concentrations of PM10 and O3, however, are predominantly related to regional tropical factors, such as the influence of biomass burning and of ultra violet radiation from sunlight. They can, though, also be influenced by local sources. There are relatively stronger inter-pollutant correlations at the stations of Gombak and Shah Alam, and the results also suggest that heavy traffic flow induces high concentrations of PM10, CO, NO2 and SO2 at the three sampling stations. Additionally, meteorological factors, particularly the ambient temperature and wind speed, may influence the concentration of PM10 in the atmosphere

Interleukin-1beta Promoter (−31T/C and −511C/T) Polymorphisms in Major Recurrent Depression

To elucidate a genetic predisposition to major depressive disorder, we investigated two polymorphisms (−31T/C and −511C/T) in the interleukin-1beta promoter region in patients who suffered from major recurrent depression. The aim of the current work was to compare alleles and genotype layout between patients with major recurrent depression and healthy people. We would like to indicate such combination of genotypes which corresponds with major recurrent depression. Correlations between genotypes for analyzed polymorphisms and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset were investigated as well. The study group consisted of 94 patients diagnosed with major recurrent depression. The control group included 206 healthy individuals. Both groups involved representatives of Caucasian population. Genotyping of polymorphisms was performed by using PCR-RFLP technique. A specific haplotype, composed of the C allele at −31 and the T allele at −511, has a tendency to have a statistically significant difference (p = 0.064) between patients and control group. Correspondence analysis revealed that genotype T/T at −31 and genotype C/C at −511 are associated with major recurrent depression. No association was found between genotypes for studied polymorphic sites and number of episodes, number of points in Hamilton Depression Rating Scale, and age of onset

Antibiotic resistance prediction for Mycobacterium tuberculosis from genome sequence data with Mykrobe [version 1; peer review: 2 approved, 1 approved with reservations]

Two billion people are infected with Mycobacterium tuberculosis, leading to 10 million new cases of active tuberculosis and 1.5 million deaths annually. Universal access to drug susceptibility testing (DST) has become a World Health Organization priority. We previously developed a software tool, Mykrobe predictor, which provided offline species identification and drug resistance predictions for M. tuberculosis from whole genome sequencing (WGS) data. Performance was insufficient to support the use of WGS as an alternative to conventional phenotype-based DST, due to mutation catalogue limitations. Here we present a new tool, Mykrobe, which provides the same functionality based on a new software implementation. Improvements include i) an updated mutation catalogue giving greater sensitivity to detect pyrazinamide resistance, ii) support for user-defined resistance catalogues, iii) improved identification of non-tuberculous mycobacterial species, and iv) an updated statistical model for Oxford Nanopore Technologies sequencing data. Mykrobe is released under MIT license at https://github.com/mykrobe-tools/mykrobe. We incorporate mutation catalogues from the CRyPTIC consortium et al. (2018) and from Walker et al. (2015), and make improvements based on performance on an initial set of 3206 and an independent set of 5845 M. tuberculosis Illumina sequences. To give estimates of error rates, we use a prospectively collected dataset of 4362 M. tuberculosis isolates. Using culture based DST as the reference, we estimate Mykrobe to be 100%, 95%, 82%, 99% sensitive and 99%, 100%, 99%, 99% specific for rifampicin, isoniazid, pyrazinamide and ethambutol resistance prediction respectively. We benchmark against four other tools on 10207 (=5845+4362) samples, and also show that Mykrobe gives concordant results with nanopore data. We measure the ability of Mykrobe-based DST to guide personalized therapeutic regimen design in the context of complex drug susceptibility profiles, showing 94% concordance of implied regimen with that driven by phenotypic DST, higher than all other benchmarked tools

Assessment of vitamin D intake among Libyan women - adaptation and validation of specific food frequency questionnaire

Vitamin D deficiency (VDD) has pandemic proportions worldwide. Numerous studies report on high prevalence of VDD in sunny regions like Near East and North Africa (NENA). Previous studies indicated that Libyan population was at risk of VDD. To contribute to the body of evidence, measurement of vitamin D status on children, adults, in Misurata region was conducted, and confirmed with validated dietary intake study. Serum 25(OH)D was analysed using electrochemiluminescence protein binding assay. Existing Food Frequency Questionnaires (FFQ) were adapted to Libyan Women Food Frequency Questionnaire (LW-FFQ). Repeated 24h dietary recalls and LW-FFQ were employed in vitamin D intake evaluation. LW-FFQ was validated using 24h dietary recall and vitamin D status as referent methods. The questionnaires included anthropometry and lifestyle information. Vitamin D status assessment revealed inadequate levels (25(OH)D lt 50nmol/l) in almost 80% of participants. Women (25-64y) were identified as the most vulnerable group with vitamin D inadequacy present in 82% (61.6% had 25(OH)D lt 25nmol/l, and 20.2% had 25-50nmol/l 25(OH)D). Average Vitamin D intake within the study sample (n=316) was 3.9 +/- 7.9 mu g/d, with 92% participants below both Institute of Medicine (IOM) (10 mu g/d) and European Food Safety Authority (15 mu g/d) recommendations. Measured vitamin D status, in 13% of this group, correlated significantly (p=0.015) with intake estimates. Based on self-report, consumption of vitamin D supplements does not exist among study participants. Additional lifestyle factors influencing vitamin D status were analysed. Only 2% of study participants spend approximately 11 min on the sun daily, 60.4% were obese, 23.1% were overweight and 71.2% reported low physical activity. These findings confirm previous reports on high prevalence of VDD in women across NENA, and in Libya. The situation calls for multi-sectoral actions and public health initiatives to address dietary and lifestyle habits