Risk Factors of Streptococcus suis Infection in Vietnam. A Case-Control Study

Background: Streptococcus suis infection, an emerging zoonosis, is an increasing public health problem across South East Asia and the most common cause of acute bacterial meningitis in adults in Vietnam. Little is known of the risk factors underlying the disease. Methods and Findings: A case-control study with appropriate hospital and matched community controls for each patient was conducted between May 2006 and June 2009. Potential risk factors were assessed using a standardized questionnaire and investigation of throat and rectal S. suis carriage in cases, controls and their pigs, using real-time PCR and culture of swab samples. We recruited 101 cases of S. suis meningitis, 303 hospital controls and 300 community controls. By multivariate analysis, risk factors identified for S. suis infection as compared to either control group included eating "high risk" dishes, including such dishes as undercooked pig blood and pig intestine (OR1 = 2.22; 95% CI = [1.15-4.28] and OR2 = 4.44; 95% CI = [2.15-9.15]), occupations related to pigs (OR1 = 3.84; 95% CI = [1.32-11.11] and OR2 = 5.52; 95% CI = [1.49-20.39]), and exposures to pigs or pork in the presence of skin injuries (OR1 = 7.48; 95% CI = [1.97-28.44] and OR2 = 15.96; 95% CI = [2.97-85.72]). S. suis specific DNA was detected in rectal and throat swabs of 6 patients and was cultured from 2 rectal samples, but was not detected in such samples of 1522 healthy individuals or patients without S. suis infection. Conclusions: This case control study, the largest prospective epidemiological assessment of this disease, has identified the most important risk factors associated with S. suis bacterial meningitis to be eating 'high risk' dishes popular in parts of Asia, occupational exposure to pigs and pig products, and preparation of pork in the presence of skin lesions. These risk factors can be addressed in public health campaigns aimed at preventing S. suis infectio

Evidence That Mutation Is Universally Biased towards AT in Bacteria

Mutation is the engine that drives evolution and adaptation forward in that it generates the variation on which natural selection acts. Mutation is a random process that nevertheless occurs according to certain biases. Elucidating mutational biases and the way they vary across species and within genomes is crucial to understanding evolution and adaptation. Here we demonstrate that clonal pathogens that evolve under severely relaxed selection are uniquely suitable for studying mutational biases in bacteria. We estimate mutational patterns using sequence datasets from five such clonal pathogens belonging to four diverse bacterial clades that span most of the range of genomic nucleotide content. We demonstrate that across different types of sites and in all four clades mutation is consistently biased towards AT. This is true even in clades that have high genomic GC content. In all studied cases the mutational bias towards AT is primarily due to the high rate of C/G to T/A transitions. These results suggest that bacterial mutational biases are far less variable than previously thought. They further demonstrate that variation in nucleotide content cannot stem entirely from variation in mutational biases and that natural selection and/or a natural selection-like process such as biased gene conversion strongly affect nucleotide content

Lobe-Specific Calcium Binding in Calmodulin Regulates Endothelial Nitric Oxide Synthase Activation

BACKGROUND: Human endothelial nitric oxide synthase (eNOS) requires calcium-bound calmodulin (CaM) for electron transfer but the detailed mechanism remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using a series of CaM mutants with E to Q substitution at the four calcium-binding sites, we found that single mutation at any calcium-binding site (B1Q, B2Q, B3Q and B4Q) resulted in ∼2-3 fold increase in the CaM concentration necessary for half-maximal activation (EC50) of citrulline formation, indicating that each calcium-binding site of CaM contributed to the association between CaM and eNOS. Citrulline formation and cytochrome c reduction assays revealed that in comparison with nNOS or iNOS, eNOS was less stringent in the requirement of calcium binding to each of four calcium-binding sites. However, lobe-specific disruption with double mutations in calcium-binding sites either at N- (B12Q) or at C-terminal (B34Q) lobes greatly diminished both eNOS oxygenase and reductase activities. Gel mobility shift assay and flavin fluorescence measurement indicated that N- and C-lobes of CaM played distinct roles in regulating eNOS catalysis; the C-terminal EF-hands in its calcium-bound form was responsible for the binding of canonical CaM-binding domain, while N-terminal EF-hands in its calcium-bound form controlled the movement of FMN domain. Limited proteolysis studies further demonstrated that B12Q and B34Q induced different conformational change in eNOS. CONCLUSIONS: Our results clearly demonstrate that CaM controls eNOS electron transfer primarily through its lobe-specific calcium binding

Supporting adolescent emotional health in schools: a mixed methods study of student and staff views in England

<p>Abstract</p> <p>Background</p> <p>Schools have been identified as an important place in which to support adolescent emotional health, although evidence as to which interventions are effective remains limited. Relatively little is known about student and staff views regarding current school-based emotional health provision and what they would like to see in the future, and this is what this study explored.</p> <p>Methods</p> <p>A random sample of 296 English secondary schools were surveyed to quantify current level of emotional health provision. Qualitative student focus groups (27 groups, 154 students aged 12-14) and staff interviews (12 interviews, 15 individuals) were conducted in eight schools, purposively sampled from the survey respondents to ensure a range of emotional health activity, free school meal eligibility and location. Data were analysed thematically, following a constant comparison approach.</p> <p>Results</p> <p>Emergent themes were grouped into three areas in which participants felt schools did or could intervene: emotional health in the curriculum, support for those in distress, and the physical and psychosocial environment. Little time was spent teaching about emotional health in the curriculum, and most staff and students wanted more. Opportunities to explore emotions in other curriculum subjects were valued. All schools provided some support for students experiencing emotional distress, but the type and quality varied a great deal. Students wanted an increase in school-based help sources that were confidential, available to all and sympathetic, and were concerned that accessing support should not lead to stigma. Finally, staff and students emphasised the need to consider the whole school environment in order to address sources of distress such as bullying and teacher-student relationships, but also to increase activities that enhanced emotional health.</p> <p>Conclusion</p> <p>Staff and students identified several ways in which schools can improve their support of adolescent emotional health, both within and outside the curriculum. However, such changes should be introduced as part of a wider consideration of how the whole school environment can be more supportive of students' emotional health. Clearer guidance at policy level, more rigorous evaluation of current interventions, and greater dissemination of good practice is necessary to ensure adolescents' emotional health needs are addressed effectively within schools.</p

Guiding Principles for Chronic Total Occlusion Percutaneous Coronary Intervention.

Outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have improved because of advancements in equipment and techniques. With global collaboration and knowledge sharing, we have identified 7 common principles that are widely accepted as best practices for CTO-PCI.  1. Ischemic symptom improvement is the primary indication for CTO-PCI.  2. Dual coronary angiography and in-depth and structured review of the angiogram (and, if available, coronary computed tomography angiography) are key for planning and safely performing CTO-PCI.  3. Use of a microcatheter is essential for optimal guidewire manipulation and exchanges.  4. Antegrade wiring, antegrade dissection and reentry, and the retrograde approach are all complementary and necessary crossing strategies. Antegrade wiring is the most common initial technique, whereas retrograde and antegrade dissection and reentry are often required for more complex CTOs.  5. If the initially selected crossing strategy fails, efficient change to an alternative crossing technique increases the likelihood of eventual PCI success, shortens procedure time, and lowers radiation and contrast use.  6. Specific CTO-PCI expertise and volume and the availability of specialized equipment will increase the likelihood of crossing success and facilitate prevention and management of complications, such as perforation.  7. Meticulous attention to lesion preparation and stenting technique, often requiring intracoronary imaging, is required to ensure optimum stent expansion and minimize the risk of short- and long-term adverse events. These principles have been widely adopted by experienced CTO-PCI operators and centers currently achieving high success and acceptable complication rates. Outcomes are less optimal at less experienced centers, highlighting the need for broader adoption of the aforementioned 7 guiding principles along with the development of additional simple and safe CTO crossing and revascularization strategies through ongoing research, education, and training

Reconciling the stratigraphy and depositional history of the Lycian orogen-top basins, SW Anatolia

Terrestrial fossil records from the SWAnatolian basins are crucial both for regional correlations and palaeoenvironmental reconstructions. By reassessing biostratigraphic constraints and incorporating new fossil data, we calibrated and reconstructed the late Neogene andQuaternary palaeoenvironments within a regional palaeogeographical framework. The culmination of the Taurides inSWAnatolia was followed by a regional crustal extension from the late Tortonian onwards that created a broad array of NE-trending orogen-top basins with synchronic associations of alluvial fan, fluvial and lacustrine deposits. The terrestrial basins are superimposed on the upper Burdigalian marine units with a c. 7 myr of hiatus that corresponds to a shift from regional shortening to extension. The initial infill of these basins is documented by a transition from marginal alluvial fans and axial fluvial systems into central shallow-perennial lakes coinciding with a climatic shift from warm/humid to arid conditions. The basal alluvial fan deposits abound in fossil macro-mammals of an early Turolian (MN11–12; late Tortonian) age. The Pliocene epoch in the region was punctuated by subhumid/humid conditions resulting in a rise of local base levels and expansion of lakes as evidenced by marsh-swamp deposits containing diverse fossilmammal assemblages indicating late Ruscinian (lateMN15; late Zanclean) ageWe are grateful for the support of the international bilateral project between The Scientific and Technological Research Council of Turkey (TUBITAK) and The Russian Scientific Foundation (RFBR) with grant a number of 111Y192. M.C.A. is grateful to the Turkish Academy of Sciences (TUBA) for a GEBIP (Young Scientist Award) grant. T.K. and S.M. are grateful to the Ege University Scientific Research Center for the TTM/002/2016 and TTM/001/2016 projects. M.C.A., H.A., S.M. and M.B. have obtained Martin and Temmick Fellowships at Naturalis Biodiversity Center (Leiden). F.A.D. is supported by a Mehmet Akif Ersoy University Scientific Research Grant. T.A.N. is supported by an Alexander-von-Humboldt Scholarship. L.H.O. received support from TUBITAK under the 2221 program for visiting scientists

Thermal decomposition of Bayer precipitates formed at varying temperatures

Bayer hydrotalcites prepared using the seawater neutralisation (SWN) process of Bayer liquors are characterised using X-ray diffraction and thermal analysis techniques. The Bayer hydrotalcites are synthesised at four different temperatures (0, 25, 55, 75 °C) to determine the effect on the thermal stability of the hydrotalcite structure, and to identify other precipitates that form at these temperatures. The interlayer distance increased with increasing synthesis temperature, up to 55 °C, and then decreased by 0.14 Å for Bayer hydrotalcites prepared at 75 °C. The three mineralogical phases identified in this investigation are; 1) Bayer hydrotalcite, 2), calcium carbonate species, and 3) hydromagnesite. The DTG curve can be separated into four decomposition steps; 1) the removal of adsorbed water and free interlayer water in hydrotalcite (30 – 230 °C), 2) the dehydroxylation of hydrotalcite and the decarbonation of hydrotalcite (250 – 400 °C), 3) the decarbonation of hydromagnesite (400 – 550 °C), and 4) the decarbonation of aragonite (550 – 650 °C)

Mechanism of genetic exchange in American trypanosomes.

The kinetoplastid Protozoa are responsible for devastating diseases. In the Americas, Trypanosoma cruzi is the agent of Chagas' disease--a widespread disease transmissible from animals to humans (zoonosis)--which is transmitted by exposure to infected faeces of blood-sucking triatomine bugs. The presence of genetic exchange in T. cruzi and in Leishmania is much debated. Here, by producing hybrid clones, we show that T. cruzi has an extant capacity for genetic exchange. The mechanism is unusual and distinct from that proposed for the African trypanosome, Trypanosoma brucei. Two biological clones of T. cruzi were transfected to carry different drug-resistance markers, and were passaged together through the entire life cycle. Six double-drug-resistant progeny clones, recovered from the mammalian stage of the life cycle, show fusion of parental genotypes, loss of alleles, homologous recombination, and uniparental inheritance of kinetoplast maxicircle DNA. There are strong genetic parallels between these experimental hybrids and the genotypes among natural isolates of T. cruzi. In this instance, aneuploidy through nuclear hybridization results in recombination across far greater genetic distances than mendelian genetic exchange. This mechanism also parallels genome duplication