Silent circulation of arboviruses in Cameroon

Objectives: To investigate the silent circulation and transmission of arthropod-borne viruses (arboviruses) in the Fako Division of Cameroon.Design: This survey was conducted based on clinical observations and laboratory diagnosis; field collections of mosquitoes.Setting: This study was conducted in the Fako Division of South West Cameroon.Subjects: One hundred and two sera were obtained from febrile patients (with negative laboratory findings for malaria and typhoid fever) at clinics in the Fako Division, and diurnal anthropophilic mosquitoes (4,764) collected.Interventions: Virus isolation was attempted from these, and sera were screened for antibodies against 18 African arboviruses by haemagglutination inhibition (HI) and complement fixation (CF) tests.Results: No virus was isolated. Fifty three of 79 (67.1%) sera reacted with one or more viral antigens. Twenty nine sera (36.7%) reacted with members of the genus Alphavirus, with Chikungunya (CHIKV) and O’nyong-nyong (ONNV) viruses as the most frequent (34.2%). Forty six sera (58.2%) reacted with members of the genus Flavivirus: 24 (30.4%)were cross-reactive, but 11.4% reacted monotypically with Zika, 5.1% with yellow fever virus (YFV), 5.1% with dengue virus-2 (DENV-2), 2.5% with DENV-1 and 1.3% with Wesselsbron virus, respectively. The plaque reduction neutralisation test used to specify the agent that elicited the response could not resolve 33.3% of the cross reactions between CHIKV and ONNV. Neutralising antibody titres against ONNV and CHIKV were very high indicating probable re-infection.Conclusion: Our results indicate previously undetected circulation of arboviruses in Cameroon, and suggest that they are important, overlooked public health problems

Malpais spring virus is a new species in the genus vesiculovirus

BACKGROUND: Malpais Spring virus (MSPV) is a mosquito-borne rhabdovirus that infects a variety of wild and feral ungulates in New Mexico, including horses and deer. Although, initial serologic tests and electron microscopy at the time of isolation nearly 25 years ago provided evidence that MSPV is a novel virus, possibly related to vesiculoviruses, the virus still has not been approved as a new species. FINDINGS: Use of the illumina platform allowed us to obtain the complete genome of MSPV. Analysis of the complete 11019 nt genome sequence of the prototype 85-488NM strain of MSPV indicates that it encodes the five common rhabdovirus structural proteins (N, P, M, G and L) with alternative ORFs (> 180 nt) in the N, M and G genes, including a 249 nt ORF in the G gene predicted to encode a 9.26 kDa highly basic transmembrane protein. Although antigenically very distant, phylogenetic analysis of the L gene indicates that MSPV is most closely related to Jurona virus, also isolated from mosquitoes in Brazil, as well as a number of other vesiculoviruses. CONCLUSIONS: In sum, our analysis indicates MSPV should be classified as a member of the genus Vesiculovirus, family Rhabdoviridae. The complete genome sequence of MSPV will be helpful in the development of a reverse genetics system to study the unique aspects of this vesiculovirus in vivo and in vitro, and will assist development of specific diagnostic tests to study the epidemiology of MSPV infection

The impact of a bariatric rehabilitation service on weight loss and psychological adjustment - study protocol

Bariatric surgery is currently the most effective form of obesity management for those whose BMI is greater than 40 (or 35 with co morbidities). A minority of patients, however, either do not show the desired loss of excess weight or show weight regain by follow up. Research highlights some of the reasons for this variability, most of which centres on the absence of any psychological support with patients describing how although surgery fixes their body, psychological issues relating to dietary control, self esteem, coping and emotional eating remain neglected.The present study aims to evaluate the impact of a health psychology led bariatric rehabilitation service (BRS) on patient health outcomes. The bariatric rehabilitation service will provide information, support and mentoring pre and post surgery and will address psychological issues such as dietary control, self esteem, coping and emotional eating. The package reflects the rehabilitation services now common place for patients post heart attack and stroke which have been shown to improve patient health outcomes

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81

Recent breast cancer trends among Asian/Pacific Islander, Hispanic, and African-American women in the US: changes by tumor subtype

Abstract available at publisher's website

Long-Lasting Inhibitory Effects of Fetal Liver Mesenchymal Stem Cells on T-Lymphocyte Proliferation

Human bone marrow mesenchymal stem cells (BM-MSC) are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK) cells, Dendritic Cells (DC), and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC) to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb), cyclins A and D1, as well as up-regulating p27kip1expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4low/CD8low T subset that had decreased secretion of IFN-γ, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection

Field pathogenomics reveals the emergence of a diverse wheat yellow rust population

BACKGROUND: Emerging and re-emerging pathogens imperil public health and global food security. Responding to these threats requires improved surveillance and diagnostic systems. Despite their potential, genomic tools have not been readily applied to emerging or re-emerging plant pathogens such as the wheat yellow (stripe) rust pathogen Puccinia striiformis f. sp. tritici (PST). This is due largely to the obligate parasitic nature of PST, as culturing PST isolates for DNA extraction remains slow and tedious. RESULTS: To counteract the limitations associated with culturing PST, we developed and applied a field pathogenomics approach by transcriptome sequencing infected wheat leaves collected from the field in 2013. This enabled us to rapidly gain insights into this emerging pathogen population. We found that the PST population across the United Kingdom (UK) underwent a major shift in recent years. Population genetic structure analyses revealed four distinct lineages that correlated to the phenotypic groups determined through traditional pathology-based virulence assays. Furthermore, the genetic diversity between members of a single population cluster for all 2013 PST field samples was much higher than that displayed by historical UK isolates, revealing a more diverse population of PST. CONCLUSIONS: Our field pathogenomics approach uncovered a dramatic shift in the PST population in the UK, likely due to a recent introduction of a diverse set of exotic PST lineages. The methodology described herein accelerates genetic analysis of pathogen populations and circumvents the difficulties associated with obligate plant pathogens. In principle, this strategy can be widely applied to a variety of plant pathogens

Mechanosensing is critical for axon growth in the developing brain.

During nervous system development, neurons extend axons along well-defined pathways. The current understanding of axon pathfinding is based mainly on chemical signaling. However, growing neurons interact not only chemically but also mechanically with their environment. Here we identify mechanical signals as important regulators of axon pathfinding. In vitro, substrate stiffness determined growth patterns of Xenopus retinal ganglion cell axons. In vivo atomic force microscopy revealed a noticeable pattern of stiffness gradients in the embryonic brain. Retinal ganglion cell axons grew toward softer tissue, which was reproduced in vitro in the absence of chemical gradients. To test the importance of mechanical signals for axon growth in vivo, we altered brain stiffness, blocked mechanotransduction pharmacologically and knocked down the mechanosensitive ion channel piezo1. All treatments resulted in aberrant axonal growth and pathfinding errors, suggesting that local tissue stiffness, read out by mechanosensitive ion channels, is critically involved in instructing neuronal growth in vivo.This work was supported by the German National Academic Foundation (scholarship to D.E.K.), Wellcome Trust and Cambridge Trusts (scholarships to A.J.T.), Winston Churchill Foundation of the United States (scholarship to S.K.F.), Herchel Smith Foundation (Research Studentship to S.K.F.), CNPq 307333/2013-2 (L.d.F.C.), NAP-PRP-USP and FAPESP 11/50761-2 (L.d.F.C.), UK EPSRC BT grant (J.G.), Wellcome Trust WT085314 and the European Research Council 322817 grants (C.E.H.); an Alexander von Humboldt Foundation Feodor Lynen Fellowship (K.F.), UK BBSRC grant BB/M021394/1 (K.F.), the Human Frontier Science Program Young Investigator Grant RGY0074/2013 (K.F.), the UK Medical Research Council Career Development Award G1100312/1 (K.F.) and the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number R21HD080585 (K.F.).This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/nn.439

Homocysteinylated Albumin Promotes Increased Monocyte-Endothelial Cell Adhesion and Up-Regulation of MCP1, Hsp60 and ADAM17

RATIONALE:The cardiovascular risk factor homocysteine is mainly bound to proteins in human plasma, and it has been hypothesized that homocysteinylated proteins are important mediators of the toxic effects of hyperhomocysteinemia. It has been recently demonstrated that homocysteinylated proteins are elevated in hemodialysis patients, a high cardiovascular risk population, and that homocysteinylated albumin shows altered properties. OBJECTIVE:Aim of this work was to investigate the effects of homocysteinylated albumin - the circulating form of this amino acid, utilized at the concentration present in uremia - on monocyte adhesion to a human endothelial cell culture monolayer and the relevant molecular changes induced at both cell levels. METHODS AND RESULTS:Treated endothelial cells showed a significant increase in monocyte adhesion. Endothelial cells showed after treatment a significant, specific and time-dependent increase in ICAM1 and VCAM1. Expression profiling and real time PCR, as well as protein analysis, showed an increase in the expression of genes encoding for chemokines/cytokines regulating the adhesion process and mediators of vascular remodeling (ADAM17, MCP1, and Hsp60). The mature form of ADAM17 was also increased as well as Tnf-α released in the cell medium. At monocyte level, treatment induced up-regulation of ICAM1, MCP1 and its receptor CCR2. CONCLUSIONS:Treatment with homocysteinylated albumin specifically increases monocyte adhesion to endothelial cells through up-regulation of effectors involved in vascular remodeling

The impact of psychological support on weight loss post weight loss surgery: a randomised control trial

Background The purpose of the present study is to evaluate the impact of a health psychology-led bariatric rehabilitation service (BRS) on patient weight loss following bariatric surgery at 1 year. Methods A single-site open-randomised parallel group control trial based at St. Richard’s Hospital in Chichester in the UK. Patients (n=162) were recruited immediately prior to Roux-en-Y gastric bypass and randomly allocated to receive either treatment as usual (n=80) or the BRS (n=82). The BRS involved three 50-min one-to-one sessions with a health psychologist and provided information, support and mentoring pre and post surgery addressing psychological issues such as dietary control, self esteem, coping and emotional eating. Weight loss was assessed at 1 year. The key outcome variable was BMI and change in BMI. Results Follow-up weight was available for 145 patients. Intention-to-treat analysis (n=162) using last measured weights showed that mean change in BMI by 1 year post surgery was −16.49. There was no significant difference between the two groups (control group=−16.37, 95 % CI= 15.15–17.57; intervention=−16.6, 95 % CI=15.42–17.81; ηp 2=0.001). Similarly, explanatory analysis (n=145) showed a mean change inBMI of −17.17. The difference between the two groups was not significant (control group=−16.9, 95 % CI=15.78–18.18; intervention=−17.35, 95 % CI=18.5– 16.16; ηp 2=0.001). Conclusions Psychological support pre and post bariatric surgery had no impact on weight loss as measured by BMI and change in BMI by 1 year. It is argued that psychological support should be targeted to patients who start to demonstrate weight regain at a later stage