A Clinical and Epidemiological Investigation of the First Reported Human Infection With the Zoonotic Parasite Trypanosoma evansi in Southeast Asia

Background. Trypanosoma is a genus of unicellular parasitic flagellate protozoa. Trypanosoma brucei species and Trypanosoma cruzi are the major agents of human trypanosomiasis; other Trypanosoma species can cause human disease, but are rare. In March 2015, a 38-year-old woman presented to a healthcare facility in southern Vietnam with fever, headache, and arthralgia. Microscopic examination of blood revealed infection with Trypanosoma. Methods. Microscopic observation, polymerase chain reaction (PCR) amplification of blood samples, and serological testing were performed to identify the infecting species. The patient's blood was screened for the trypanocidal protein apolipoprotein L1 (APOL1), and a field investigation was performed to identify the zoonotic source. Results. PCR amplification and serological testing identified the infecting species as Trypanosoma evansi. Despite relapsing 6 weeks after completing amphotericin B therapy, the patient made a complete recovery after 5 weeks of suramin. The patient was found to have 2 wild-type APOL1 alleles and a normal serum APOL1 concentration. After responsive animal sampling in the presumed location of exposure, cattle and/or buffalo were determined to be the most likely source of the infection, with 14 of 30 (47%) animal blood samples testing PCR positive for T. evansi. Conclusions. We report the first laboratory-confirmed case of T. evansi in a previously healthy individual without APOL1 deficiency, potentially contracted via a wound while butchering raw beef, and successfully treated with suramin. A linked epidemiological investigation revealed widespread and previously unidentified burden of T. evansi in local cattle, highlighting the need for surveillance of this infection in animals and the possibility of further human cases

Identification of possible virulence marker from Campylobacter jejuni isolates

This is the final version of the article. Available from the publisher via the DOI in this record.A novel protein translocation system, the type-6 secretion system (T6SS), may play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni isolates from humans, chickens, and environmental sources in Vietnam, Thailand, Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human and chicken isolates from Vietnam.The work was partly supported by the UK Biotechnology and Biological Sciences Research Council, award BB/1024631/1 to R.T., D.S., and O.C.; by a Wellcome Trust Institutional Strategic Support Award (WT097835MF); and by a studentship awarded to J.H. Mr Harrison is a PhD student at the University of Exeter under the supervision of D.S. His research focuses on using bioinformatic methods to investigate the comparative genomics of emerging diseases and plant-associated microbes

Validation of a contemporary prostate cancer grading system using prostate cancer death as outcome

BACKGROUND: Gleason scoring (GS) has major deficiencies and a novel system of five grade groups (GS⩽6; 3+4; 4+3; 8; ⩾9) has been recently agreed and included in the WHO 2016 classification. Although verified in radical prostatectomies using PSA relapse for outcome, it has not been validated using prostate cancer death as an outcome in biopsy series. There is debate whether an ‘overall' or ‘worst' GS in biopsies series should be used. METHODS: Nine hundred and eighty-eight prostate cancer biopsy cases were identified between 1990 and 2003, and treated conservatively. Diagnosis and grade was assigned to each core as well as an overall grade. Follow-up for prostate cancer death was until 31 December 2012. A log-rank test assessed univariable differences between the five grade groups based on overall and worst grade seen, and using univariable and multivariable Cox proportional hazards. Regression was used to quantify differences in outcome. RESULTS: Using both ‘worst' and ‘overall' GS yielded highly significant results on univariate and multivariate analysis with overall GS slightly but insignificantly outperforming worst GS. There was a strong correlation with the five grade groups and prostate cancer death. CONCLUSIONS: This is the largest conservatively treated prostate cancer cohort with long-term follow-up and contemporary assessment of grade. It validates the formation of five grade groups and suggests that the ‘worst' grade is a valid prognostic measure

Multi-omic data integration elucidates Synechococcus adaptation mechanisms to fluctuations in light intensity and salinity

Synechococcus sp. PCC 7002 is a fast-growing cyanobacterium which flourishes in freshwater and marine environments, owing to its ability to tolerate high light intensity and a wide range of salinities. Harnessing the properties of cyanobacteria and understanding their metabolic efficiency has become an imperative goal in recent years owing to their potential to serve as biocatalysts for the production of renewable biofuels. To improve characterisation of metabolic networks, genome-scale models of metabolism can be integrated with multi-omic data to provide a more accurate representation of metabolic capability and refine phenotypic predictions. In this work, a heuristic pipeline is constructed for analysing a genome-scale metabolic model of Synechococcus sp. PCC 7002, which utilises flux balance analysis across multiple layers to observe flux response between conditions across four key pathways. Across various conditions, the detection of significant patterns and mechanisms to cope with fluctuations in light intensity and salinity provides insights into the maintenance of metabolic efficiency

Upper atmospheres and ionospheres of planets and satellites

The upper atmospheres of the planets and their satellites are more directly exposed to sunlight and solar wind particles than the surface or the deeper atmospheric layers. At the altitudes where the associated energy is deposited, the atmospheres may become ionized and are referred to as ionospheres. The details of the photon and particle interactions with the upper atmosphere depend strongly on whether the object has anintrinsic magnetic field that may channel the precipitating particles into the atmosphere or drive the atmospheric gas out to space. Important implications of these interactions include atmospheric loss over diverse timescales, photochemistry and the formation of aerosols, which affect the evolution, composition and remote sensing of the planets (satellites). The upper atmosphere connects the planet (satellite) bulk composition to the near-planet (-satellite) environment. Understanding the relevant physics and chemistry provides insight to the past and future conditions of these objects, which is critical for understanding their evolution. This chapter introduces the basic concepts of upper atmospheres and ionospheres in our solar system, and discusses aspects of their neutral and ion composition, wind dynamics and energy budget. This knowledge is key to putting in context the observations of upper atmospheres and haze on exoplanets, and to devise a theory that explains exoplanet demographics.Comment: Invited Revie

Surface Modifications by Field Induced Diffusion

By applying a voltage pulse to a scanning tunneling microscope tip the surface under the tip will be modified. We have in this paper taken a closer look at the model of electric field induced surface diffusion of adatoms including the van der Waals force as a contribution in formations of a mound on a surface. The dipole moment of an adatom is the sum of the surface induced dipole moment (which is constant) and the dipole moment due to electric field polarisation which depends on the strength and polarity of the electric field. The electric field is analytically modelled by a point charge over an infinite conducting flat surface. From this we calculate the force that cause adatoms to migrate. The calculated force is small for voltage used, typical 1 pN, but due to thermal vibration adatoms are hopping on the surface and even a small net force can be significant in the drift of adatoms. In this way we obtain a novel formula for a polarity dependent threshold voltage for mound formation on the surface for positive tip. Knowing the voltage of the pulse we then can calculate the radius of the formed mound. A threshold electric field for mound formation of about 2 V/nm is calculated. In addition, we found that van der Waals force is of importance for shorter distances and its contribution to the radial force on the adatoms has to be considered for distances smaller than 1.5 nm for commonly used voltages

Fully-Unintegrated Parton Distribution and Fragmentation Functions at Perturbative k_T

We define and study the properties of generalized beam functions (BFs) and fragmenting jet functions (FJFs), which are fully-unintegrated parton distribution functions (PDFs) and fragmentation functions (FFs) for perturbative k_T. We calculate at one loop the coefficients for matching them onto standard PDFs and FFs, correcting previous results for the BFs in the literature. Technical subtleties when measuring transverse momentum in dimensional regularization are clarified, and this enables us to renormalize in momentum space. Generalized BFs describe the distribution in the full four-momentum k_mu of a colliding parton taken out of an initial-state hadron, and therefore characterize the collinear initial-state radiation. We illustrate their importance through a factorization theorem for pp -> l^+ l^- + 0 jets, where the transverse momentum of the lepton pair is measured. Generalized FJFs are relevant for the analysis of semi-inclusive processes where the full momentum of a hadron, fragmenting from a jet with constrained invariant mass, is measured. Their significance is shown for the example of e^+ e^- -> dijet+h, where the perpendicular momentum of the fragmenting hadron with respect to the thrust axis is measured.Comment: Journal versio

Single-Cell Profiling Reveals the Origin of Phenotypic Variability in Adipogenesis

Phenotypic heterogeneity in a clonal cell population is a well-observed but poorly understood phenomenon. Here, a single-cell approach is employed to investigate non-mutative causes of phenotypic heterogeneity during the differentiation of 3T3-L1 cells into fat cells. Using coherent anti-Stokes Raman scattering microscopy and flow cytometry, adipogenic gene expression, insulin signaling, and glucose import are visualized simultaneously with lipid droplet accumulation in single cells. Expression of adipogenic genes PPARγ, C/EBPα, aP2, LP2 suggests a commitment to fat cell differentiation in all cells. However, the lack of lipid droplet in many differentiating cells suggests adipogenic gene expression is insufficient for lipid droplet formation. Instead, cell-to-cell variability in lipid droplet formation is dependent on the cascade responses of an insulin signaling pathway which includes insulin sensitivity, kinase activity, glucose import, expression of an insulin degradation enzyme, and insulin degradation rate. Increased and prolonged insulin stimulation promotes lipid droplet accumulation in all differentiating cells. Single-cell profiling reveals the kinetics of an insulin signaling cascade as the origin of phenotypic variability in drug-inducible adipogenesis

Assessing computer skills in Tanzanian medical students: an elective experience.

BACKGROUND: One estimate suggests that by 2010 more than 30% of a physician's time will be spent using information technology tools. The aim of this study is to assess the information and communication technologies (ICT) skills of medical students in Tanzania. We also report a pilot intervention of peer mentoring training in ICT by medical students from the UK tutoring students in Tanzania. DESIGN: Cross sectional study and pilot intervention study. PARTICIPANTS: Fourth year medical students (n = 92) attending Muhimbili University College of Health Sciences, Dar es Salaam, Tanzania. MAIN OUTCOME MEASURES: Self-reported assessment of competence on ICT-related topics and ability to perform specific ICT tasks. Further information related to frequency of computer use (hours per week), years of computer use, reasons for use and access to computers. Skills at specific tasks were reassessed for 12 students following 4 to 6 hours of peer mentoring training. RESULTS: The highest levels of competence in generic ICT areas were for email, Internet and file management. For other skills such as word processing most respondents reported low levels of competence. The abilities to perform specific ICT skills were low - less than 60% of the participants were able to perform the core specific skills assessed. A period of approximately 5 hours of peer mentoring training produced an approximate doubling of competence scores for these skills. CONCLUSION: Our study has found a low level of ability to use ICT facilities among medical students in a leading university in sub-Saharan Africa. A pilot scheme utilising UK elective students to tutor basic skills showed potential. Attention is required to develop interventions that can improve ICT skills, as well as computer access, in order to bridge the digital divide

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology