Sequence analysis of the cupin gene family in Synechocystis PCC6803

The recently described cupin superfamily of proteins includes the germin and germinlike proteins, of which the cereal oxalate oxidase is the best characterized. This superfamily also includes seed storage proteins, in addition to several microbial enzymes and proteins with unknown function. All these proteins are characterized by the conservation of two central motifs, usually containing two or three histidine residues presumed to be involved with metal binding in the catalytic active site. The present study on the coding regions of Synechocystis PCC6803 identifies a previously unknown group of 12 related cupins, each containing the characteristic two-motif signature. This group comprises 11 single-domain proteins, ranging in length from 104 to 289 residues, and includes two phosphomannose isomerases and two epimerases involved in cell wall synthesis, a member of the pirin group of nuclear proteins, a possible transcriptional regulator, and a close relative-of a cytochrome c551 from Rhodococcus. Additionally, there is a duplicated, two-domain protein that has close similarity to an oxalate decarboxylase from the fungus Collybia velutipes and that is a putative progenitor of the storage proteins of land plants

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

Use of Cone Beam Computed Tomography in Endodontics

Cone Beam Computed Tomography (CBCT) is a diagnostic imaging modality that provides high-quality, accurate three-dimensional (3D) representations of the osseous elements of the maxillofacial skeleton. CBCT systems are available that provide small field of view images at low dose with sufficient spatial resolution for applications in endodontic diagnosis, treatment guidance, and posttreatment evaluation. This article provides a literature review and pictorial demonstration of CBCT as an imaging adjunct for endodontics

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

Cognitive-behavioural therapy (CBT) for renal fatigue (BReF) : a feasibility randomised-controlled trial of CBT for the management of fatigue in haemodialysis (HD) patients

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/INTRODUCTION: Fatigue is one of the most common and disabling symptoms in end-stage kidney disease, particularly among in-centre haemodialysis patients. This two-arm parallel group feasibility randomised controlled trial will determine whether a fully powered efficacy trial is achievable by examining the feasibility of recruitment, acceptability and potential benefits of a cognitive-behavioural therapy (CBT)-based intervention for fatigue among in-centre haemodialysis patients. METHODS: We aim to recruit 40 adult patients undergoing in-centre haemodialysis at secondary care outpatient dialysis units, who meet clinical levels of fatigue. Patients will be randomised individually (using a 1:1 ratio) to either a 4-6 weeks' CBT-based intervention (intervention arm) or to a waiting-list control (control arm). The primary feasibility outcomes include descriptive data on numbers within each recruiting centre meeting eligibility criteria, rates of recruitment, numbers retained postrandomisation and treatment adherence. To assess the potential benefits of the cognitive-behavioural therapy for renal fatigue intervention, secondary self-report outcomes include measures of fatigue severity (Chalder Fatigue Questionnaire), fatigue-related functional impairment (Work and Social Adjustment Scale), sleep quality (Pittsburgh Sleep Quality Index), depression (Patient Health Questionnaire-9) and anxiety (Generalised Anxiety Disorder-7). Changes in fatigue perceptions (Brief Illness Perception Questionnaire), cognitive and behavioural responses to fatigue (Cognitive and Behavioural Responses to Symptoms Questionnaire), sleep hygiene behaviours (Sleep Hygiene Index) and physical activity (International Physical Activity Questionnaire-short form) will also be explored. These self-report measures will be collected at baseline and 3 months postrandomisation. Nested qualitative interviews will be conducted postintervention to explore the acceptability of the intervention and identify any areas in need of improvement. The statistician and assessor will be blinded to treatment allocation. ETHICS AND DISSEMINATION: A National Health Service (NHS) Research Ethics Committee approved the study. Any amendments to the protocol will be submitted to the NHS Committee and study sponsor. TRIAL REGISTRATION NUMBER: ISRCTN91238019;Pre-results.Peer reviewe

Is loss of sense of smell a diagnostic marker in COVID-19: A Systematic Review and Meta-analysis

Aims: To systematically review the currently available evidence investigating the association between olfactory dysfunction (OD) and the novel coronavirus (COVID-19). To analyse the prevalence of OD in patients who have tested positive on polymerase chain reaction (PCR) for COVID-19. To perform a meta-analysis of patients presenting with olfactory dysfunction, during the pandemic, and to investigate the positive predictive value for a COVID-19-positive result in this population. To assess whether olfactory dysfunction could be used as a diagnostic marker for COVID-19 positivity and aid public health approaches in tackling the current outbreak. Methods: We systematically searched MedLine (PubMed), Embase, Health Management Information Consortium (HMIC), Medrxiv, the Cochrane Library, the Cochrane COVID-19 Study Register, NIHR Dissemination centre, Clinical Evidence, National Health Service Evidence and the National Institute of Clinical Excellence to identify the current published evidence which associates coronaviridae or similar RNA viruses with anosmia. The initial search identified 157 articles. A total of 145 papers were excluded following application of our exclusion criteria. The 12 remaining articles that presented evidence on the association between COVID-19 and olfactory dysfunction were critically analysed. Results: Olfactory dysfunction has been shown to be the strongest predictor of COVID-19 positivity when compared to other symptoms in logistic regression analysis. In patients who had tested positive for COVID-19, there was a prevalence of 62% of OD. In populations of patients who are currently reporting OD, there is a positive predictive value of 61% for a positive COVID-19 result. Conclusion: Our review has shown that there is already significant evidence which demonstrates an association between OD and the novel coronavirus—COVID-19. It is unclear if this finding is unique to this coronavirus as individual viral phenotypes rarely present in such concentrated large numbers. We have demonstrated that OD is comparatively more predictive for COVID-19 positivity compared to other associated symptoms. We recommend that people who develop OD during the pandemic should be self-isolate and this guidance should be adopted internationally to prevent transmission

Efficacy of Sofosbuvir, Velpatasvir, and GS-9857 in Patients With Hepatitis C Virus Genotype 2, 3, 4, or 6 Infections in an Open-Label, Phase 2 Trial

© 2016 AGA Institute Background & Aims Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. Methods We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6–12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). Results After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%–97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28 of 30; 95% CI, 78%–99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%–100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%–100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events. Conclusions In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961

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