Leishmania-Specific Surface Antigens Show Sub-Genus Sequence Variation and Immune Recognition

Single-celled Leishmania parasites, transmitted by sand flies, infect humans and other mammals in many tropical and sub-tropical regions, giving rise to a spectrum of diseases called the leishmaniases. Species of parasite within the Leishmania genus can be divided into two groups (referred to as sub-genera) that are separated by up to 100 million years of evolution yet are highly related at the genome level. Our research is focused on identifying gene differences between these sub-genera that may identify proteins that impact on the transmission and pathogenicity of different Leishmania species. Here we report the presence of a highly-variant genomic locus (OHL) that was previously described as absent in parasites of the L. (Viannia) subgenus (on the basis of lack of key genes) but is present and well-characterised (as the LmcDNA16 locus) in all members of the alternative subgenus, L. (Leishmania). We demonstrate that the proteins encoded within the LmcDNA16 and OHL loci are similar in their structure and surface localisation in mammalian-infective amastigotes, despite significant differences in their DNA sequences. Most importantly, we demonstrate that the OHL locus proteins, like the HASP proteins from the LmcDNA16 locus, contain highly variable amino acid repeats that are antigenic in man and may therefore contribute to future vaccine development

Beetroot supplementation improves the physiological responses to incline walking

The final publication is available at Springer via http://dx.doi.org/10.1007/s00421-018-3843-xPurpose: We investigated the effects of an acute 24-h nitrate-rich beetroot juice supplement (BR) on the energy cost, exercise efficiency and blood pressure responses to intermittent walking at different gradients. Methods: In a double-blind, cross-over design, eight participants were provided with a total of 350 ml of nitrate-rich (~20.5 mmol nitrate) BR or placebo (PLA) across 24-h before completing intermittent walking at 3 km/h on treadmill at gradients of 1%, 5%, 10%, 15% and 20%. Results: Resting mean arterial pressure (MAP) was ~4.1% lower after BR (93 vs. 89 mmHg; P = 0.001), as well as during exercise (102 vs. 99 mmHg; P = 0.011) and recovery (97 vs. 94 mmHg; P = 0.001). Exercising (1227 vs. 1129 ml/min P < 0.001) and end-stage (1404 vs. 1249 ml/min; P = 0.002) oxygen uptake (O2) was lower in BR compared to PLA, which was accompanied by an average reduction in phase II ̇O2 amplitude (1067 vs. 940 ml/min; P = 0.025). Similarly, recovery O2 (509 vs. 458 ml/min; P = 0.001) was lower in BR. Whole-blood potassium concentration increased from pre-post exercise in PLA (4.1 ± 0.3 vs. 4.5 ± 0.3 mmol/L; P = 0.013) but not BR (4.1 ± 0.31 vs. 4.3 ± 0.2 mmol/L; P = 0.188). Conclusions: Energy cost of exercise, recovery of O2, MAP and blood markers were ameliorated after BR. Previously reported mechanisms explain these findings, which are more noticeable during less efficient walking at steep gradients (15-20%). These findings have practical implications for hill-walkers

The epidemiology of enterococci

The enterococci are emerging as a significant cause of nosocomial infections, accounting for approximately 10 % of hospital acquired infections. They are found as normal inhabitants of the human gastrointestinal tract, but may also colonize the oropharynx, vagina, perineal region and soft tissue wounds of asymtomatic patients. Until recently, evidence indicated that most enterococcal infections arose from patients' own endogenous flora. Recent studies, however, suggest that exogeneous acquisition may occur and that person-to-person spread, probably on the hands of medical personnel, may be a significant mode of transmission of resistant enterococci within the hospital. The use of broad-spectrum antibiotics, especially cephalosporins, is another major factor in the increasing incidence of enterococcal infections. These findings suggest that barrier precautions, as applied with other resistant nosocomial pathogens, along with more judicial use of antibiotics may be beneficial in preventing nosocomial spread of resistant enterococci.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47899/1/10096_2005_Article_BF01963631.pd

Ischemic heart disease in the emergency room: state of the art, innovation and research.

Ischemic heart disease in the emergency room: state of the art, innovation and research

Opinion paper on utility of point-of-care biomarkers in the emergency department pathways decision making

Abstract Overcrowding of the emergency department (ED) is rapidly becoming a global challenge and a major source of concern for emergency physicians. The evaluation of cardiac biomarkers is critical for confirming diagnoses and expediting treatment decisions to reduce overcrowding, however, physicians currently face the dilemma of choosing between slow and accurate central-based laboratory tests, or faster but imprecise assays. With improvements in technology, point-of-care testing (POCT) systems facilitate the efficient and high-throughput evaluation of biomarkers, such as troponin (cTn), brain natriuretic peptide (BNP) and neutrophil gelatinase-associated lipocalin (NGAL). In this context, POCT may help ED physicians to confirm a diagnosis of conditions, such as acute coronary syndrome, heart failure or kidney damage. Compared with classic laboratory methods, the use of cTn, BNP, and NGAL POCT has shown comparable sensitivity, specificity and failure rate, but with the potential to provide prompt and accurate diagnosis, shorten hospital stay, and alleviate the burden on the ED. Despite this potential, the full advantages of rapid delivery results will only be reached if POCT is implemented within hospital standardized procedures and ED staff receive appropriate training

Evaluating the clonal hierarchy in light-chain multiple myeloma: implications against the myeloma stem cell hypothesis

An exclusive production of light chains can be found in ~15% of myeloma cases, and in these light-chain multiple myeloma (LC-MM) cases, the phenotype remains unchanged throughout subsequent progression and relapse. Once established, it suggests that this phenotype is maintained by the ‘feeder cell’ that re-populates the tumor bulk as disease re-emerges<br/