Failure of microvenous valves in small superficial veins is a key to the skin changes of venous insufficiency

ObjectiveTo determine the role of microvenous valves in the superficial venous system in the prevention of reflux and skin changes in the progression of venous insufficency.MethodsThe venous anatomy of 15 amputated lower limbs, eight free from clinical venous disease and seven with varicose veins and ulcers, was examined using retrograde venography corrosion casting. Prior to amputation, all limbs were scanned by duplex ultrasound to confirm the presence or absence of reflux in the great (GSV) and small saphenous veins or their tributaries. The resulting resin casts were photographed and mapped to show the position, orientation, and competency of valves in the superficial venous network. Casts were also examined by scanning electron microscopy.ResultsRetrograde venous filling was demonstrated in the “normal” limbs despite a competent GSV. Microvalves were identified down to the sixth generation of tributaries from the GSV. Only in regions where incompetence existed in microvalves out to the third (ie, the “boundary”) generation was the resin able to penetrate deeper into microvenous networks of the dermis. This was despite the presence of subsequent competent valves, which were able to be bypassed in the network. In limbs with varicose veins and venous ulcers, reflux into the small venous networks and capillary loops was more extensive with more dense networks and greater tortuousity.ConclusionsThis study demonstrates that valvular incompetence can occur independently in small superficial veins in the absence of reflux within the GSV and the major tributaries. We have shown that once there is incompetence of the third generation “boundary” microvalves, reflux can extend into the microvenous networks in the skin. These effects are markedly worse in the presence of GSV incompetence. We propose that degenerative changes with valve incompetence are required in both the larger proximal vessels and the small superficial veins, in particular at the “boundary” valve level, for the severe skin changes in venous insufficiency to occur.Clinical RelevanceThis study describes the presence of microvalves in the very small veins in the skin, which may be critical to whether skin changes occur in venous insufficiency. The concept may explain why some people with longstanding varicose veins do not develop venous ulcers. In addition, this article describes degenerative changes in the network of very small veins in the skin of the leg which may relate to appearances of reticular veins, corona phlebectatica, and venous flares. These degenerative changes occur without varicose veins but are much worse when they occur together

"I try and smile, I try and be cheery, I try not to be pushy. I try to say ‘I’m here for help’ but I leave feeling… worried’’: A qualitative study of perceptions of interactions with health professionals by community-based older adults with chronic pain

Background: Over 50% of community-dwelling older adults experience chronic pain, which threatens their quality of life. Of importance to their pain management is older people’s interaction with health professionals that, if unsatisfactory, may impair the outcome. Aims: To add to the limited research specific to older people living with chronic pain in the community, we explored how they perceive their experiences of interacting with health professionals, seeking factors that might optimise these interactions. Methods: Purposive sampling was used to recruit men and women .65 years with self-reported musculoskeletal chronic pain. Qualitative individual interviews and one group interview were undertaken with 23 participants. Data were transcribed verbatim and underwent Framework Analysis. Results: Three themes were identified. Seeking help illustrates issues around why older people in the community may or may not seek help for chronic pain, and highlights the potential involvement of social comparison. Importance of diagnosis illustrates the desire for professional validation of their condition and an aversion to vague explanations based on the person’s age. Being listened to and being heard illustrates the importance of empathic communication and understanding expectations, with due respect for the person’s age. Conclusions: In common with people of all ages, an effective partnership between an older person in pain and health professionals is essential if pain is to be reported, appropriately assessed and managed, because of the subjective nature of pain and its treatment responses. For older people with pain, perception about their age, by both parties in the partnership, is an additional factor that can unnecessarily interfere with the effectiveness of this partnership. Health professionals should engage with older adults to clarify their expectations about pain and its management, which may be influenced by perceptions about age; and to encourage expression of their concerns, which may also be affected by perceptions about age

Crop Updates 2005 - Katanning

This session covers twenty five papers from different authors KEYNOTE How Farmers Can Work Together for a More Sustainable and Profitable Business, Brian McAlpine Farmer, Nuffield Scholar GENERAL 2005 Seasonal Outlook, David Stephens and Nicola Telcik, Department of Agriculture Essentials for cereal leaf disease management, K. Jayasena, R. Loughman, G. Thomas, C. Beard, and B. Paynter, Department of Agriculture Benefits to the grower of grain licensing, Colin Mann, Grain Licensing Authority SOIL & NUTRIENTS The effect of higher nitrogen fertiliser prices on rotation and fertiliser strategies in cropping systems, Ross Kingwell, Department of Agriculture Effect of stubble burning and seasonality on microbial processes and nutrient cycling, Francis Hoyle, University of Western Australia Soil Biology and Crop Production in Western Australian Farming Systems, D.V. Murphy, N. Milton, M. Osman, F.C. Hoyle, L.K Abbott, W.R. Cookson and S. Darmawanto, University of Western Australia Nutrient Management to get optimal production, Bill Bowden, Department of Agriculture OTHER CROPS Which malting barley variety and why? Blakely Paynter, Department of Agriculture KASPA AND OTHER NEW PULSE VARIETIES, 1. New Pulse varieties and where they fit in, K. Regan, P. White, Department of Agriculture & CLIMA, K. Siddique, CLIMA, K. Adhikari, Department of Agriculture & CLIMA, M. Harries, CLIMA Kaspa in the WA Grain Belt 2003-2004, Ian Pritchard, Department of Agriculture New annual pastures for Mediterranean farming systems, Angelo Loi, Phil Nichols, Clinton Revell & David Ferris, Department of Agriculture Challenging herbicide resistant ryegrass, Bill Roy, Agricultural Consulting & Research Services Pty.Ltd WEED MANAGEMENT Ingest, incinerate or invert? The pro’s and con’s of 3 weed seed removal tactics, Sally Peltzer1, Dave Minkey1 and Michael Walsh2 Department of Agriculture 1 and Western Australian Herbicide Resistance lnitiative2 A good use guide for pre-emergent herbicides, Alexandra Douglas, Department of Agriculture OTHER USEFUL INFORMATION 17.Growing season outlook, Meredith Fairbanks, Ian Foster, Geraldine Pasqual, David Stephens, Nicola Telcik, David Tennant, Department of Agriculture 18. Status Of Department Of Agriculture Western Australia Crop Varieties 19. Seed Licensee Details 20. Gene technology for growers. What is it? How does it Work? Belinda Barr, Australian Centre for Plant Functional Genomics, Dr Heather Bray, Molecular Plant Breeding Cooperative Research Centre. 21. Agronomic package for EGA Eagle Rock, Steve Penny, Department of Agriculture 22. Nutrient timing and requirements for increased crop yields in the high rainfall cropping zone, Narelle Hill, Ron McTaggart, Dr. Wal Anderson and Ray Tugwell Department of Agriculture 23. Insect contamination of cereal grain at harvest, Svetlana Micic and Phil Michael, Department of Agriculture 24. Crop leftovers: what’s in stubble for sheep? Roy Butler and Keith Croker, Department of Agriculture 25. Mandelup – Narrow-leafed lupi

Genomewide Expression Analysis in Zebrafish mind bomb Alleles with Pancreas Defects of Different Severity Identifies Putative Notch Responsive Genes

10.1371/journal.pone.0001479PLoS ONE3

Identification of Pax6-Dependent Gene Regulatory Networks in the Mouse Lens

Lineage-specific DNA-binding transcription factors regulate development by activating and repressing particular set of genes required for the acquisition of a specific cell type. Pax6 is a paired domain and homeodomain-containing transcription factor essential for development of central nervous, olfactory and visual systems, as well as endocrine pancreas. Haploinsufficiency of Pax6 results in perturbed lens development and homeostasis. Loss-of-function of Pax6 is incompatible with lens lineage formation and results in abnormal telencephalic development. Using DNA microarrays, we have identified 559 genes expressed differentially between 1-day old mouse Pax6 heterozygous and wild type lenses. Of these, 178 (31.8%) were similarly increased and decreased in Pax6 homozygous embryonic telencephalon [Holm PC, Mader MT, Haubst N, Wizenmann A, Sigvardsson M, Götz M (2007) Loss- and gain-of-function analyses reveals targets of Pax6 in the developing mouse telencephalon. Mol Cell Neurosci 34: 99–119]. In contrast, 381 (68.2%) genes were differently regulated between the lens and embryonic telencephalon. Differential expression of nine genes implicated in lens development and homeostasis: Cspg2, Igfbp5, Mab21l2, Nrf2f, Olfm3, Spag5, Spock1, Spon1 and Tgfb2, was confirmed by quantitative RT-PCR, with five of these genes: Cspg2, Mab21l2, Olfm3, Spag5 and Tgfb2, identified as candidate direct Pax6 target genes by quantitative chromatin immunoprecipitation (qChIP). In Mab21l2 and Tgfb2 promoter regions, twelve putative individual Pax6-binding sites were tested by electrophoretic mobility shift assays (EMSAs) with recombinant Pax6 proteins. This led to the identification of two and three sites in the respective Mab21l2 and Tgfb2 promoter regions identified by qChIPs. Collectively, the present studies represent an integrative genome-wide approach to identify downstream networks controlled by Pax6 that control mouse lens and forebrain development

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms

Background: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results: We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA‐, AAA‐, and TAA‐associated SNPs and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10−5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10−3). Conclusions: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant