Borrelia recurrentis employs a novel multifunctional surface protein with anti-complement, anti-opsonic and invasive potential to escape innate immunity

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever

Prioritising public health: a qualitative study of decision making to reduce health inequalities

<p>Abstract</p> <p>Background</p> <p>The public health system in England is currently facing dramatic change. Renewed attention has recently been paid to the best approaches for tackling the health inequalities which remain entrenched within British society and across the globe. In order to consider the opportunities and challenges facing the new public health system in England, we explored the current experiences of those involved in decision making to reduce health inequalities, taking cardiovascular disease (CVD) as a case study.</p> <p>Methods</p> <p>We conducted an in-depth qualitative study employing 40 semi-structured interviews and three focus group discussions. Participants were public health policy makers and planners in CVD in the UK, including: Primary Care Trust and Local Authority staff (in various roles); General Practice commissioners; public health academics; consultant cardiologists; national guideline managers; members of guideline development groups, civil servants; and CVD third sector staff.</p> <p>Results</p> <p>The short term target- and outcome-led culture of the NHS and the drive to achieve "more for less", combined with the need to address public demand for acute services often lead to investment in "downstream" public health intervention, rather than the "upstream" approaches that are most effective at reducing inequalities. Despite most public health decision makers wishing to redress this imbalance, they felt constrained due to difficulties in partnership working and the over-riding influence of other stakeholders in decision making processes. The proposed public health reforms in England present an opportunity for public health to move away from the medical paradigm of the NHS. However, they also reveal a reluctance of central government to contribute to shifting social norms.</p> <p>Conclusions</p> <p>It is vital that the effectiveness and cost effectiveness of all new and existing policies and services affecting public health are measured in terms of their impact on the social determinants of health and health inequalities. Researchers have a vital role to play in providing the complex evidence required to compare different models of prevention and service delivery. Those working in public health must develop leadership to raise the profile of health inequalities as an issue that merits attention, resources and workforce capacity; and advocate for central government to play a key role in shifting social norms.</p

Giant pulmonary artery aneurysm in a patient with vasoreactive pulmonary hypertension: a case report

<p>Abstract</p> <p>Background</p> <p>Pulmonary artery aneurysms are a rare condition, frequently associated with pulmonary hypertension. However, the evolution and treatment of this pathology is still not clear.</p> <p>Case Presentation</p> <p>The authors report a case of a 65-year old patient with pulmonary artery aneurysm associated with pulmonary arterial hypertension. Due to a positive vasoreactivity test, treatment with calcium channel blockers was started with near normalization of the right cardiac pressures. Nevertheless, after 20 months of treatment, the pulmonary artery aneurysm size remained unchanged with an associated severe pulmonary regurgitation and causing extrinsic compression of the main left coronary artery. Surgical correction was successfully performed.</p> <p>Conclusions</p> <p>This is the first case report of a pulmonary artery aneurysm described to be associated with vasoreactive pulmonary hypertension in a living patient. Although medical therapy for pulmonary hypertension was started, surgical correction of the aneurysm was executed in order to prevent its future complications.</p

Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

Biodiversity of Borrelia burgdorferi Strains in Tissues of Lyme Disease Patients

Plant and animal biodiversity are essential to ecosystem health and can provide benefits to humans ranging from aesthetics to maintaining air quality. Although the importance of biodiversity to ecology and conservation biology is obvious, such measures have not been applied to strains of an invasive bacterium found in human tissues during infection. In this study, we compared the strain biodiversity of Borrelia burgdorferi found in tick populations with that found in skin, blood, synovial fluid or cerebrospinal fluid of Lyme disease patients. The biodiversity of B. burgdorferi strains is significantly greater in tick populations than in the skin of patients with erythema migrans. In turn, strains from skin are significantly more diverse than strains at any of the disseminated sites. The cerebrospinal fluid of patients with neurologic Lyme disease harbored the least pathogen biodiversity. These results suggest that human tissues act as niches that can allow entry to or maintain only a subset of the total pathogen population. These data help to explain prior clinical observations on the natural history of B. burgdorferi infection and raise several questions that may help to direct future research to better understand the pathogenesis of this infection

Physicians Report Barriers to Deliver Best Practice Care for Asplenic Patients: A Cross-Sectional Survey

Background: Current management of asplenic patients is not in compliance with best practice standards, such as defined by the British Committee for Standards in Haematology. To improve quality of care, factors inhibiting best practice care delivery need to be identified first. With this study, we aimed to identify and quantify physicians' barriers to adhere to best practice management of asplenic patients in the Netherlands. Methods and Principal Findings: A cross-sectional survey, preceded by multiple focus group discussions, was performed among Dutch physicians responsible for prevention of infections in asplenic patients, including specialists ( of Internal medicine and Surgery) and general practitioners (GPs). Forty seven GPs and seventy three hospital specialists returned the questionnaire, yielding response rates of 47% and 36,5% respectively. Physicians reported several barriers to deliver best practice. For both GPs and specialists, the most frequently listed barriers were: poor patient knowledge (> 80% of hospital specialists and GPs) and lack of clarity about which physician is responsible for the management of asplenic patients (50% of Internists, 46% of Surgeons, 55% of GPs). Both GPs and hospital specialists expressed to experience a lack of mutual trust: specialists were uncertain whether the GP would follow their advice given on patient discharge (33-59%), whereas half of GPs was not convinced that specialists' discharge letters contained the correct recommendations. Almost all physicians (> 90%) indicated that availability of a national guideline would improve adherence to best practice, especially if accessible online. Conclusion: This study showed that, in accordance with reports on international performance, care delivery for asplenic patients in the Netherlands is suboptimal. We identified and quantified perceived barriers by physicians that prevent adherence to post-splenectomy guidelines for the first time. Better transmural collaboration and better informed patients are likely to improve the quality of care of the asplenic patient population. A national, online-available guideline is urgently require

Sharp bounds and normalization of Wiener-type indices

10.1371/journal.pone.0078448PLoS ONE811-POLN

Towards Predictive Computational Models of Oncolytic Virus Therapy: Basis for Experimental Validation and Model Selection

Oncolytic viruses are viruses that specifically infect cancer cells and kill them, while leaving healthy cells largely intact. Their ability to spread through the tumor makes them an attractive therapy approach. While promising results have been observed in clinical trials, solid success remains elusive since we lack understanding of the basic principles that govern the dynamical interactions between the virus and the cancer. In this respect, computational models can help experimental research at optimizing treatment regimes. Although preliminary mathematical work has been performed, this suffers from the fact that individual models are largely arbitrary and based on biologically uncertain assumptions. Here, we present a general framework to study the dynamics of oncolytic viruses that is independent of uncertain and arbitrary mathematical formulations. We find two categories of dynamics, depending on the assumptions about spatial constraints that govern that spread of the virus from cell to cell. If infected cells are mixed among uninfected cells, there exists a viral replication rate threshold beyond which tumor control is the only outcome. On the other hand, if infected cells are clustered together (e.g. in a solid tumor), then we observe more complicated dynamics in which the outcome of therapy might go either way, depending on the initial number of cells and viruses. We fit our models to previously published experimental data and discuss aspects of model validation, selection, and experimental design. This framework can be used as a basis for model selection and validation in the context of future, more detailed experimental studies. It can further serve as the basis for future, more complex models that take into account other clinically relevant factors such as immune responses

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente