Emergence of a globally dominant IncHI1 plasmid type associated with multiple drug resistant typhoid.

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), remains a serious global health concern. Since their emergence in the mid-1970s multi-drug resistant (MDR) S. Typhi now dominate drug sensitive equivalents in many regions. MDR in S. Typhi is almost exclusively conferred by self-transmissible IncHI1 plasmids carrying a suite of antimicrobial resistance genes. We identified over 300 single nucleotide polymorphisms (SNPs) within conserved regions of the IncHI1 plasmid, and genotyped both plasmid and chromosomal SNPs in over 450 S. Typhi dating back to 1958. Prior to 1995, a variety of IncHI1 plasmid types were detected in distinct S. Typhi haplotypes. Highly similar plasmids were detected in co-circulating S. Typhi haplotypes, indicative of plasmid transfer. In contrast, from 1995 onwards, 98% of MDR S. Typhi were plasmid sequence type 6 (PST6) and S. Typhi haplotype H58, indicating recent global spread of a dominant MDR clone. To investigate whether PST6 conferred a selective advantage compared to other IncHI1 plasmids, we used a phenotyping array to compare the impact of IncHI1 PST6 and PST1 plasmids in a common S. Typhi host. The PST6 plasmid conferred the ability to grow in high salt medium (4.7% NaCl), which we demonstrate is due to the presence in PST6 of the Tn6062 transposon encoding BetU

In ricordo di Paolo Sylos Labini

Background: Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. Methods/Findings: The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged 93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1–2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. Conclusions: This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved

Sanitation and Hygiene-Specific Risk Factors for Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study, 2007-2011: Case-Control Study.

Background: Diarrheal disease is the second leading cause of disease in children less than 5 y of age. Poor water, sanitation, and hygiene conditions are the primary routes of exposure and infection. Sanitation and hygiene interventions are estimated to generate a 36% and 48% reduction in diarrheal risk in young children, respectively. Little is known about whether the number of households sharing a sanitation facility affects a child's risk of diarrhea. The objective of this study was to describe sanitation and hygiene access across the Global Enteric Multicenter Study (GEMS) sites in Africa and South Asia and to assess sanitation and hygiene exposures, including shared sanitation access, as risk factors for moderate-to-severe diarrhea (MSD) in children less than 5 y of age. Methods/Findings: The GEMS matched case-control study was conducted between December 1, 2007, and March 3, 2011, at seven sites in Basse, The Gambia; Nyanza Province, Kenya; Bamako, Mali; Manhiça, Mozambique; Mirzapur, Bangladesh; Kolkata, India; and Karachi, Pakistan. Data was collected for 8,592 case children aged 93%) had access to a sanitation facility, while 70% of households in rural Kenya had access to a facility. Practicing open defecation was a risk factor for MSD in children <5 y old in Kenya. Sharing sanitation facilities with 1–2 or ≥3 other households was a statistically significant risk factor for MSD in Kenya, Mali, Mozambique, and Pakistan. Among those with a designated handwashing area near the home, soap or ash were more frequently observed at control households and were significantly protective against MSD in Mozambique and India. Conclusions: This study suggests that sharing a sanitation facility with just one to two other households can increase the risk of MSD in young children, compared to using a private facility. Interventions aimed at increasing access to private household sanitation facilities may reduce the burden of MSD in children. These findings support the current World Health Organization/ United Nations Children's Emergency Fund (UNICEF) system that categorizes shared sanitation as unimproved

Number of days required to measure sedentary time and physical activity using accelerometery in rheumatoid arthritis: a reliability study

This study aimed to determine the minimum number of days required to reliably estimate free-living sedentary time, light-intensity physical activity (LPA) and moderate-intensity physical activity (MPA) using accelerometer data in people with Rheumatoid Arthritis (RA), according to Disease Activity Score-28-C-reactive protein (DAS-28-CRP). Secondary analysis of two existing RA cohorts with controlled (cohort 1) and active (cohort 2) disease was undertaken. People with RA were classified as being in remission (DAS-28-CRP &lt; 2.4, n = 9), or with low (DAS-28-CRP ≥ 2.4—≤ 3.2, n = 15), moderate (DAS-28-CRP &gt; 3.2—≤ 5.1, n = 41) or high (DAS-28-CRP &gt; 5.1, n = 16) disease activity. Participants wore an ActiGraph accelerometer on their right hip for 7 days during waking hours. Validated RA-specific cut-points were applied to accelerometer data to estimate free-living sedentary time, LPA and MPA (%/day). Single-day intraclass correlation coefficients (ICC) were calculated and used in the Spearman Brown prophecy formula to determine the number of monitoring days required to achieve measurement reliability (ICC ≥ 0.80) for each group. The remission group required ≥ 4 monitoring days to achieve an ICC ≥ 0.80 for sedentary time and LPA, with low, moderate and high disease activity groups requiring ≥ 3 monitoring days to reliably estimate these behaviours. The monitoring days required for MPA were more variable across disease activity groups (remission =  ≥ 3 days; low =  ≥ 2 days; moderate =  ≥ 3 days; high =  ≥ 5 days). We conclude at least 4 monitoring days will reliably estimate sedentary time and LPA in RA, across the whole spectrum of disease activity. However, to reliably estimate behaviours across the movement continuum (sedentary time, LPA, MPA), at least 5 monitoring days are required

Mouse DRG Cell Line with Properties of Nociceptors

In vitro cell lines from DRG neurons aid drug discovery because they can be used for early stage, high-throughput screens for drugs targeting pain pathways, with minimal dependence on animals. We have established a conditionally immortal DRG cell line from the Immortomouse. Using immunocytochemistry, RT-PCR and calcium microfluorimetry, we demonstrate that the cell line MED17.11 expresses markers of cells committed to the sensory neuron lineage. Within a few hours under differentiating conditions, MED17.11 cells extend processes and following seven days of differentiation, express markers of more mature DRG neurons, such as NaV1.7 and Piezo2. However, at least at this time-point, the nociceptive marker NaV1.8 is not expressed, but the cells respond to compounds known to excite nociceptors, including the TRPV1 agonist capsaicin, the purinergic receptor agonist ATP and the voltage gated sodium channel agonist, veratridine. Robust calcium transients are observed in the presence of the inflammatory mediators bradykinin, histamine and norepinephrine. MED17.11 cells have the potential to replace or reduce the use of primary DRG culture in sensory, pain and developmental research by providing a simple model to study acute nociception, neurite outgrowth and the developmental specification of DRG neurons

Randomized Trial of Community Treatment With Azithromycin and Ivermectin Mass Drug Administration for Control of Scabies and Impetigo.

BACKGROUND: Scabies is a public health problem in many countries, with impetigo and its complications important consequences. Ivermectin based mass drug administration (MDA) reduces the prevalence of scabies and, to a lesser extent, impetigo. We studied the impact of co-administering azithromycin on the prevalence of impetigo and antimicrobial resistance. METHODS: Six communities were randomized to receive either ivermectin-based MDA or ivermectin-based MDA co-administered with azithromycin. We measured scabies and impetigo prevalence at baseline and 12 months. We collected impetigo lesions swabs at baseline, 3 and 12 months to detect antimicrobial resistance. RESULTS: At baseline, scabies and impetigo prevalences were 11.8% and 10.1% in the ivermectin-only arm and 9.2% and 12.1% in the combined treatment arm. At 12 months, the prevalences had fallen to 1.0% and 2.5% in the ivermectin-only arm and 0.7% and 3.3% in the combined treatment arm. The proportion of impetigo lesions containing Staphylococcus aureus detected did not change (80% at baseline vs 86% at 12 months; no significant difference between arms) but the proportion containing pyogenic streptococci fell significantly (63% vs 23%, P < .01). At 3 months, 53% (8/15) of S. aureus isolates were macrolide-resistant in the combined treatment arm, but no resistant strains (0/13) were detected at 12 months. CONCLUSIONS: Co-administration of azithromycin with ivermectin led to similar decreases in scabies and impetigo prevalence compared to ivermectin alone. The proportion of impetigo lesions containing pyogenic streptococci declined following MDA. There was a transient increase in the proportion of macrolide-resistant S. aureus strains following azithromycin MDA. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov (NCT02775617)

Current practice and surgical outcomes of neoadjuvant chemotherapy for early breast cancer : UK NeST study

Funding Information: This work was funded by a grant from the Association of Breast SurgeryPeer reviewedPublisher PD

One-Step Preservation of Phosphoproteins and Tissue Morphology at Room Temperature for Diagnostic and Research Specimens

BACKGROUND: There is an urgent need to measure phosphorylated cell signaling proteins in cancer tissue for the individualization of molecular targeted kinase inhibitor therapy. However, phosphoproteins fluctuate rapidly following tissue procurement. Snap-freezing preserves phosphoproteins, but is unavailable in most clinics and compromises diagnostic morphology. Formalin fixation preserves tissue histomorphology, but penetrates tissue slowly, and is unsuitable for stabilizing phosphoproteins. We originated and evaluated a novel one-step biomarker and histology preservative (BHP) chemistry that stabilizes signaling protein phosphorylation and retains formalin-like tissue histomorphology with equivalent immunohistochemistry in a single paraffin block. RESULTS: Total protein yield extracted from BHP-fixed, routine paraffin-embedded mouse liver was 100% compared to snap-frozen tissue. The abundance of 14 phosphorylated proteins was found to be stable over extended fixation times in BHP fixed paraffin embedded human colon mucosa. Compared to matched snap-frozen tissue, 8 phosphoproteins were equally preserved in mouse liver, while AMPKβ1 Ser108 was slightly elevated after BHP fixation. More than 25 tissues from mouse, cat and human specimens were evaluated for preservation of histomorphology. Selected tissues were evaluated in a multi-site, independent pathology review. Tissue fixed with BHP showed equivalent preservation of cytoplasmic and membrane cytomorphology, with significantly better nuclear chromatin preservation by BHP compared to formalin. Immunohistochemical staining of 13 non-phosphorylated proteins, including estrogen receptor alpha, progesterone receptor, Ki-67 and Her2, was equal to or stronger in BHP compared to formalin. BHP demonstrated significantly improved immunohistochemical detection of phosphorylated proteins ERK Thr202/Tyr204, GSK3-α/β Ser21/Ser9, p38-MAPK Thr180/Tyr182, eIF4G Ser1108 and Acetyl-CoA Carboxylase Ser79. CONCLUSION: In a single paraffin block BHP preserved the phosphorylation state of several signaling proteins at a level comparable to snap-freezing, while maintaining the full diagnostic immunohistochemical and histomorphologic detail of formalin fixation. This new tissue fixative has the potential to greatly facilitate personalized medicine, biobanking, and phospho-proteomic research

Crop Updates 2006 - Lupins and Pulses

This session covers sixty six papers from different authors: 2005 LUPIN AND PULSE INDUSTRY HIGHLIGHTS 1. Lupin Peter White, Department of Agriculture 2. Pulses Mark Seymour, Department of Agriculture 3. Monthly rainfall at experimental sites in 2005 4. Acknowledgements Amelia McLarty EDITOR 5. Contributors 6. Background Peter White, Department of Agriculture 2005 REGIONAL ROUNDUP 7. Northern agricultural region Wayne Parker, Department of Agriculture 8. Central agricultural region Ian Pritchard and Bob French, Department of Agriculture 9. Great southern and lakes Rodger Beermier, Department of Agriculture 10. South east region Mark Seymour, Department of Agriculture LUPIN AND PULSE PRODUCTION AGRONOMY AND GENETIC IMPROVEMENT 11. Lupin Peter White, Department of Agriculture 12. Narrow-leafed lupin breeding Bevan Buirchell, Department of Agriculture 13. Progress in the development of pearl lupin (Lupinus mutabilis) for Australian agriculture, Mark Sweetingham1,2, Jon Clements1, Geoff Thomas2, Roger Jones1, Sofia Sipsas1, John Quealy2, Leigh Smith1 and Gordon Francis1 1CLIMA, The University of Western Australia 2Department of Agriculture 14. Molecular genetic markers and lupin breeding, Huaan Yang, Jeffrey Boersma, Bevan Buirchell, Department of Agriculture 15. Construction of a genetic linkage map using MFLP, and identification of molecular markers linked to domestication genes in narrow-leafed lupin (Lupinus augustiflolius L) Jeffrey Boersma1,2, Margaret Pallotta3, Bevan Buirchell1, Chengdao Li1, Krishnapillai Sivasithamparam2 and Huaan Yang1 1Department of Agriculture, 2The University of Western Australia, 3Australian Centre for Plant Functional Genomics, South Australia 16. The first gene-based map of narrow-leafed lupin – location of domestication genes and conserved synteny with Medicago truncatula, M. Nelson1, H. Phan2, S. Ellwood2, P. Moolhuijzen3, M. Bellgard3, J. Hane2, A. Williams2, J. Fos‑Nyarko4, B. Wolko5, M. Książkiewicz5, M. Cakir4, M. Jones4, M. Scobie4, C. O’Lone1, S.J. Barker1, R. Oliver2, and W. Cowling1 1School of Plant Biology, The University of Western Australia, 2Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University, 3Centre for Bioinformatics and Biological Computing, Murdoch University, 4School of Biological Sciences and Biotechnology, SABC, Murdoch University,5Institute of Plant Genetics, Polish Academy of Sciences, Poznań, Poland 17. How does lupin optimum density change row spacing? Bob French and Laurie Maiolo, Department of Agriculture 18. Wide row spacing and seeding rate of lupins with conventional and precision seeding machines Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 19. Influence of row spacing and plant density on lupin competition with annual ryegrass, Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 20. Effect of timing and speed of inter-row cultivation on lupins, Martin Harries, Jo Walker and Steve Cosh, Department of Agriculture 21. The interaction of atrazine herbicide rate and row spacing on lupin seedling survival, Martin Harries and Jo Walker Department of Agriculture 22. The banding of herbicides on lupin row crops, Martin Harries, Jo Walker and Murray Blyth, Department of Agriculture 23. Large plot testing of herbicide tolerance of new lupin lines, Wayne Parker, Department of Agriculture 24. Effect of seed source and simazine rate of seedling emergence and growth, Peter White and Greg Shea, Department of Agriculture 25. The effect of lupin row spacing and seeding rate on a following wheat crop, Martin Harries, Jo Walker and Dirranie Kirby, Department of Agriculture 26. Response of crop lupin species to row spacing, Leigh Smith1, Kedar Adhikari1, Jon Clements2 and Patrizia Guantini3, 1Department of Agriculture, 2CLIMA, The University of Western Australia, 3University of Florence, Italy 27. Response of Lupinus mutabilis to lime application and over watering, Peter White, Leigh Smith and Mark Sweetingham, Department of Agriculture 28. Impact of anthracnose on yield of Andromeda lupins, Geoff Thomas, Kedar Adhikari and Katie Bell, Department of Agriculture 29. Survey of lupin root health (in major production areas), Geoff Thomas, Ken Adcock, Katie Bell, Ciara Beard and Anne Smith, Department of Agriculture 30. Development of a generic forecasting and decision support system for diseases in the Western Australian wheatbelt, Tim Maling1, Art Diggle1,2, Debbie Thackray1, Kadambot Siddique1 and Roger Jones1,2 1CLIMA, The University of Western Australia, 2Department of Agriculture 31.Tanjil mutants highly tolerant to metribuzin, Ping Si1, Mark Sweetingham1,2, Bevan Buirchell1,2 and Huaan Yang l,2 1CLIMA, The University of Western Australia, 2Department of Agriculture 32. Precipitation pH vs. yield and functional properties of lupin protein isolate, Vijay Jayasena1, Hui Jun Chih1 and Ken Dods2 1Curtin University of Technology, 2Chemistry Centre 33. Lupin protein isolation with the use of salts, Vijay Jayasena1, Florence Kartawinata1,Ranil Coorey1 and Ken Dods2 1Curtin University of Technology, 2Chemistry Centre 34. Field pea, Mark Seymour, Department of Agriculture 35. Breeding highlights Kerry Regan1,2, Tanveer Khan1,2, Stuart Morgan1 and Phillip Chambers1 1Department of Agriculture, 2CLIMA, The University of Western Australia 36. Variety evaluation, Kerry Regan1,2, Tanveer Khan1,2, Jenny Garlinge1 and Rod Hunter1 1Department of Agriculture, 2CLIMA, The University of Western Australia 37. Days to flowering of field pea varieties throughout WA Mark Seymour1, Ian Pritchard1, Rodger Beermier1, Pam Burgess1 and Dr Eric Armstrong2 Department of Agriculture, 2NSW Department of Primary Industries, Wagga Wagga 38. Semi-leafless field peas yield more, with less ryegrass seed set, in narrow rows, Glen Riethmuller, Department of Agriculture 39. Swathing, stripping and other innovative ways to harvest field peas, Mark Seymour, Ian Pritchard, Rodger Beermier and Pam Burgess, Department of Agriculture 40. Pulse demonstrations, Ian Pritchard, Wayne Parker, Greg Shea, Department of Agriculture 41. Field pea extension – focus on field peas 2005, Ian Pritchard, Department of Agriculture 42. Field pea blackspot disease in 2005: Prediction versus reality, Moin Salam, Jean Galloway, Pip Payne, Bill MacLeod and Art Diggle, Department of Agriculture 43. Pea seed-borne mosaic virus in pulses: Screening for seed quality defects and virus resistance, Rohan Prince, Brenda Coutts and Roger Jones, Department of Agriculture, and CLIMA, The University of Western Australia 44. Yield losses from sowing field peas infected with pea seed-borne mosaic virus, Rohan Prince, Brenda Coutts and Roger Jones, Department of Agriculture, and CLIMA, The University of Western Australia 45. Desi chickpea, Wayne Parker, Department of Agriculture 46. Breeding highlights, Tanveer Khan 1,2, Pooran Gaur3, Kadambot Siddique2, Heather Clarke2, Stuart Morgan1and Alan Harris1, 1Department of Agriculture2CLIMA, The University of Western Australia, 3International Crop Research Institute for Semi Arid Tropics (ICRISAT), India 47. National chickpea improvement program, Kerry Regan1, Ted Knights2 and Kristy Hobson3,1Department of Agriculture, 2Agriculture New South Wales 3Department of Primary Industries, Victoria 48. Chickpea breeding lines in CVT exhibit excellent ascochyta blight resistance, Tanveer Khan1,2, Alan Harris1, Stuart Morgan1 and Kerry Regan1,2, 1Department of Agriculture, 2CLIMA, The University of Western Australia 49. Variety evaluation, Kerry Regan1,2, Tanveer Khan1,2, Jenny Garlinge2 and Rod Hunter2, 1CLIMA, The University of Western Australia 2Department of Agriculture 50. Desi chickpeas for the wheatbelt, Wayne Parker and Ian Pritchard, Department of Agriculture 51. Large scale demonstration of new chickpea varieties, Wayne Parker, MurrayBlyth, Steve Cosh, Dirranie Kirby and Chris Matthews, Department of Agriculture 52. Ascochyta management with new chickpeas, Martin Harries, Bill MacLeod, Murray Blyth and Jo Walker, Department of Agriculture 53. Management of ascochyta blight in improved chickpea varieties, Bill MacLeod1, Colin Hanbury2, Pip Payne1, Martin Harries1, Murray Blyth1, Tanveer Khan1,2, Kadambot Siddique2, 1Department of Agriculture, 2CLIMA, The University of Western Australia 54. Botrytis grey mould of chickpea, Bill MacLeod, Department of Agriculture 55. Kabuli chickpea, Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 56. New ascochyta blight resistant, high quality kabuli chickpea varieties, Kerry Regan1,2, Kadambot Siddique2, Tim Pope2 and Mike Baker1, 1Department of Agriculture, 2CLIMA, The University of Western Australia 57. Crop production and disease management of Almaz and Nafice, Kerry Regan and Bill MacLeod, Department of Agriculture, and CLIMA, The University of Western Australia 58. Faba bean,Mark Seymour, Department of Agriculture 59. Germplasm evaluation – faba bean, Mark Seymour1, Tim Pope2, Peter White1, Martin Harries1, Murray Blyth1, Rodger Beermier1, Pam Burgess1 and Leanne Young1,1Department of Agriculture, 2CLIMA, The University of Western Australia 60. Factors affecting seed coat colour of faba bean during storage, Syed Muhammad Nasar-Abbas1, Julie Plummer1, Kadambot Siddique2, Peter White 3, D. Harris4 and Ken Dods4.1The University of Western Australia, 2CLIMA, The University of Western Australia, 3Department of Agriculture, 4Chemistry Centre 61. Lentil,Kerry Regan, Department of Agriculture, and CLIMA, The University of Western Australia 62. Variety and germplasm evaluation, Kerry Regan1,2, Tim Pope2, Leanne Young1, Phill Chambers1, Alan Harris1, Wayne Parker1 and Michael Materne3, 1Department of Agriculture 2CLIMA, The University of Western Australia, 3Department of Primary Industries, Victoria Pulse species 63. Land suitability for production of different crop species in Western Australia, Peter White, Dennis van Gool, and Mike Baker, Department of Agriculture 64. Genomic synteny in legumes: Application to crop breeding, Huyen Phan1, Simon Ellwood1, J. Hane1, Angela Williams1, R. Ford2, S. Thomas3 and Richard Oliver1,1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University 2BioMarka, School of Agriculture and Food Systems, ILFR, University of Melbourne 3NSW Department of Primary Industries 65. ALOSCA – Development of a dry flow legume seed inoculant, Rory Coffey and Chris Poole, ALOSCA Technologies Pty Ltd 66. Genetic dissection of resistance to fungal necrotrophs in Medicago truncatula, Simon Ellwood1, Theo Pfaff1, Judith Lichtenzveig12, Lars Kamphuis1, Nola D\u27Souza1, Angela Williams1, Emma Groves1, Karam Singh2 and Richard Oliver1 1Australian Centre of Necrotrophic Plant Pathogens, Murdoch University, 2CSIRO Plant Industry APPENDIX I: LIST OF COMMON ACRONYM