Nasal lysine aspirin challenge in the diagnosis of aspirin - exacerbated respiratory disease

Background Aspirin-exacerbated respiratory disease is under-diagnosed and therefore effective and inexpensive therapy with aspirin desensitization is rarely performed. Methods We present an audit of 150 patients with difficult to treat nasal polyposis, 132 of whom also had asthma, 131 of whom underwent challenge with the only soluble form of aspirin, lysine aspirin (LAS), to confirm or exclude the diagnosis of aspirin-exacerbated respiratory disease (AERD). Results One hundred patients proved positive on nasal challenge, 31 who were negative went onto oral LAS challenge and a further 14 gave positive results, leaving 17 who were negative to a dose equivalent to over 375 mg of aspirin. Nineteen were not challenged because of contraindications. With the exception of one patient who developed facial angioedema and two patients with > 20% drop in FEV1 (following nasal plus oral challenge) no other severe adverse events occurred. No hospitalization was required for these three patients. Nasal inspiratory peak flow monitoring was less sensitive to obstruction caused by aspirin than was acoustic rhinometry – which should be employed when aspirin challenge is an outpatient procedure. Conclusions Provided patients are carefully chosen and monitored LAS challenge is suitable for ENT day case practice where respiratory physician help with asthma is available and should reduce the under-diagnosis of this condition

Exploring access to end of life care for ethnic minorities with end stage kidney disease through recruitment in action research

BACKGROUND: Variation in provision of palliative care in kidney services and practitioner concerns to provide equitable access led to the development of this study which focussed on the perspectives of South Asian patients and their care providers. As people with a South Asian background experience a higher risk of Type 2 Diabetes (T2DM) and end stage kidney failure (ESKF) compared to the majority population but wait longer for a transplant, there is a need for end of life care to be accessible for this group of patients. Furthermore because non English speakers and people at end of life are often excluded from research there is a dearth of research evidence with which to inform service improvement. This paper aims to explore issues relating to the process of recruitment of patients for a research project which contribute to our understanding of access to end of life care for ethnic minority patients in the kidney setting. METHODS: The study employed an action research methodology with interviews and focus groups to capture and reflect on the process of engaging with South Asian patients about end of life care. Researchers and kidney care clinicians on four NHS sites in the UK recruited South Asian patients with ESKF who were requiring end of life care to take part in individual interviews; and other clinicians who provided care to South Asian kidney patients at end of life to take part in focus groups exploring end of life care issues. In action research planning, action and evaluation are interlinked and data were analysed with emergent themes fed back to care providers through the research cycle. Reflections on the process of patient recruitment generated focus group discussions about access which were analysed thematically and reported here. RESULTS: Sixteen patients were recruited to interview and 45 different care providers took part in 14 focus groups across the sites. The process of recruiting patients to interview and subsequent focus group data highlighted some of the key issues concerning access to end of life care. These were: the identification of patients approaching end of life; and their awareness of end of life care; language barriers and informal carers' roles in mediating communication; and contrasting cultures in end of life kidney care. CONCLUSIONS: Reflection on the process of recruitment in this action research study provided insight into the complex scenario of end of life in kidney care. Some of the emerging issues such as the difficulty identifying patients are likely to be common across all patient groups, whilst others concerning language barriers and third party communication are more specific to ethnic minorities. A focus on South Asian ethnicity contributes to better understanding of patient perspectives and generic concepts as well as access to end of life kidney care for this group of patients in the UK. Action research was a useful methodology for achieving this and for informing future research to include informal carers and other ethnic groups.Peer reviewedFinal Published versio

An appropriate verbal probability lexicon for communicating surgical risks is unlikely to exist

Effective risk communication about medical procedures is critical to ethical shared decision-making. Here, we explore the potential for development of an evidence-based lexicon for verbal communication of surgical risk. We found that Ear, Nose and Throat (ENT) surgeons expressed a preference for communicating such risks using verbal probability expressions (VPEs; e.g., “high risk”). However, there was considerable heterogeneity in the expressions they reported using (Study 1). Study 2 compared ENT surgeons’ and laypeople’s (i.e., potential patients) interpretations of the ten most frequent VPEs listed in Study 1. While both groups displayed considerable variability in interpretations, lay participants demonstrated more, as well as providing systematically higher interpretations than those of surgeons. Study 3 found that lay participants were typically unable to provide unique VPEs to differentiate between the ranges of (low) probabilities required. Taken together, these results add to arguments that reliance on VPEs for surgical risk communication is ill-advised. Not only are there systematic interpretational differences between surgeons and potential patients, but the coarse granularity of VPEs raises severe challenges for developing an appropriate evidence-based lexicon for surgical risk communication. We caution against the use of VPEs in any risk context characterized by low, but very different, probabilities. (PsycInfo Database Record (c) 2022 APA, all rights reserved

Phylogeny and evolutionary history of glycogen synthase kinase 3/SHAGGY-like kinase genes in land plants

Background: GSK3 (glycogen synthase kinase 3) genes encode signal transduction proteins with roles in a variety of biological processes in eukaryotes. In contrast to the low copy numbers observed in animals, GSK3 genes have expanded into a multi-gene family in land plants (embryophytes), and have also evolved functions in diverse plant specific processes, including floral development in angiosperms. However, despite previous efforts, the phylogeny of land plant GSK3 genes is currently unclear. Here, we analyze genes from a representative sample of phylogenetically pivotal taxa, including basal angiosperms, gymnosperms, and monilophytes, to reconstruct the evolutionary history and functional diversification of the GSK3 gene family in land plants. Results: Maximum Likelihood phylogenetic analyses resolve a gene tree with four major gene duplication events that coincide with the emergence of novel land plant clades. The single GSK3 gene inherited from the ancestor of land plants was first duplicated along the ancestral branch to extant vascular plants, and three subsequent duplications produced three GSK3 loci in the ancestor of euphyllophytes, four in the ancestor of seed plants, and at least five in the ancestor of angiosperms. A single gene in the Amborella trichopoda genome may be the sole survivor of a sixth GSK3 locus that originated in the ancestor of extant angiosperms. Homologs of two Arabidopsis GSK3 genes with genetically confirmed roles in floral development, AtSK11 and AtSK12, exhibit floral preferential expression in several basal angiosperms, suggesting evolutionary conservation of their floral functions. Members of other gene lineages appear to have independently evolved roles in plant reproductive tissues in individual taxa. Conclusions: Our phylogenetic analyses provide the most detailed reconstruction of GSK3 gene evolution in land plants to date and offer new insights into the origins, relationships, and functions of family members. Notably, the diversity of this “green” branch of the gene family has increased in concert with the increasing morphological and physiological complexity of land plant life forms. Expression data for seed plants indicate that the functions of GSK3 genes have also diversified during evolutionary time

Evolving information systems: meeting the ever-changing environment

To meet the demands of organizations and their ever-changing environment, information systems are required which are able to evolve to the same extent as organizations do. Such a system has to support changes in all time-and application-dependent aspects. In this paper, requirements and a conceptual framework for evolving information systems are presented. This framework includes an architecture for such systems and a revision of the traditional notion of update. Based on this evolutionary notion of update (recording, correction and forgetting) a state transition-oriented model on three levels of abstraction (event level, recording level, correction level) is introduced. Examples are provided to illustrate the conceptual framework for evolving information systems

Evolutionary Analysis of the LAFL Genes Involved in the Land Plant Seed Maturation Program

Seeds are one of the most significant innovations in the land plant lineage, critical to the diversification and adaptation of plants to terrestrial environments. From perspective of seed evo-devo, the most crucial developmental stage in this innovation is seed maturation, which includes accumulation of storage reserves, acquisition of desiccation tolerance, and induction of dormancy. Based on previous studies of seed development in the model plant Arabidopsis thaliana, seed maturation is mainly controlled by the LAFL regulatory network, which includes LEAFY COTYLEDON1 (LEC1) and LEC1-LIKE (L1L) of the NF-YB gene family, and ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2 (LEAFY COTYLEDON2) of the B3-AFL gene family. In the present study, molecular evolution of these LAFL genes was analyzed, using representative species from across the major plant lineages. Additionally, to elucidate the molecular mechanisms of the seed maturation program, co-expression pattern analyses of LAFL genes were conducted across vascular plants. The results show that the origin of AFL gene family dates back to a common ancestor of bryophytes and vascular plants, while LEC1-type genes are only found in vascular plants. LAFL genes of vascular plants likely specify their co-expression in two different developmental phrases, spore and seed maturation, respectively, and expression patterns vary slightly across the major vascular plants lineages. All the information presented in this study will provide insights into the origin and diversification of seed plants.National Natural Science Foundation of China (NSFC) [91231105]SCI(E)ARTICLE

Pembentukan 8-OHdG Dari Zat Toksik Pemicu Radikal Bebas

This study was conducted to observethe profile of DNA Adduct (8-OHdG) formation as DNA damage indicators, by using calf thymus DNA incubated with toxic and carcinogenic compounds. The compounds which could trigger free radicals in this research were PAH(Benzo[a]Pyrene), TiO2, and CuCl2. Calf thymus DNA was incubated with Benzo[a]Pyrene and CuCl2 compounds under pH and temperature variations. The incubation of calf thymus DNA with TiO2-UV radiation (254 nm) wasused to induce the formation of reactive oxygen species (ROS) in the process of oxidative DNA damage. From this research, all of compounds have potency to trigger the formation of DNA Adduct (8-OHdG). The ratio of absorbance to assess the purity of DNA at 260 nm and 280 nm (λ260/ λ280 ) was measured at ~1.9. The shifted peaks at λmax were indicating changes on structures of DNA as a result of calf thymus DNA incubation with B[a]P and CuCl2. The highest level of 8-OHdG results in calf thymus DNA incubation with B[a]P and CuCl2 under pH 8.5 and incubation temperature at 60°C, was about 120.856 μg/L. Calf thymus DNA incubation with TiO2-UV radiation (254 nm) under pH 8.5 resulting 8-OHdG level at 57.025 μg/L

Mapping ecologically sensitive, significant and salient areas of Western Ghats: proposed protocols and methodology

The Western Ghats Ecology Expert Panel (WGEEP) of the Ministry of Environment and Forests, Government of India (GOI) has been asked to identify ecologically sensitive areas (ESAs) along the Western Ghats, and to suggest how to manage them. The concept of ESAs has been extensively discussed in the literature. Several ESAs have been set up in India over the last 22 years under the Environment Protection Act, 1986, and a GOI committee under the chairmanship of Pranob Sen has proposed certain criteria for identification of ESAs. However, WGEEP noted that we still lack a global consensus either on the criteria to define ESAs or on a workable methodology to identify them. Furthermore, there are no clear guidelines on the management regime that should prevail in ESAs, and the Pranob Sen Committee has not addressed this issue at all. Hence, WGEEP decided to undertake an exercise of defining ESAs and developing a workable methodology to assign levels of ecological significance/sensitivity as a first step towards putting ESAs on the map of the Western Ghats. This article provides a report on the outcome of a series of discussions and consultations held by WGEEP to build a consensus on defining and mapping ESAs. It hopes to provoke discussion and feedback from a wider section of experts, with the aim of finalizing a generic methodology for mapping ESAs in other ecologically sign ificant, biodiversity-rich areas within and outside the country. We hope to shortly prepare a companion paper that will address the equally vital management issues

The scientific basis of combination therapy for chronic hepatitis B functional cure

Functional cure of chronic hepatitis B (CHB) — or hepatitis B surface antigen (HBsAg) loss after 24 weeks off therapy — is now the goal of treatment, but is rarely achieved with current therapy. Understanding the hepatitis B virus (HBV) life cycle and immunological defects that lead to persistence can identify targets for novel therapy. Broadly, treatments fall into three categories: those that reduce viral replication, those that reduce antigen load and immunotherapies. Profound viral suppression alone does not achieve quantitative (q)HBsAg reduction or HBsAg loss. Combining nucleos(t)ide analogues and immunotherapy reduces qHBsAg levels and induces HBsAg loss in some patients, particularly those with low baseline qHBsAg levels. Even agents that are specifically designed to reduce viral antigen load might not be able to achieve sustained HBsAg loss when used alone. Thus, rationale exists for the use of combinations of all three therapy types. Monitoring during therapy is important not just to predict HBsAg loss but also to understand mechanisms of HBsAg loss using viral and immunological biomarkers, and in selected cases intrahepatic sampling. We consider various paths to functional cure of CHB and the need to individualize treatment of this heterogeneous infection until a therapeutic avenue for all patients with CHB is available