Qualitative evaluation of a rapid rollout of home blood pressure monitoring in pregnancy during Covid-19

In March 2020, the World Health Organisation named the severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2), which causes corona virus disease 2019 (COVID -19), as a pandemic. Pregnant women were considered at increased risk of developing severe COVID-19 after viral infection. In response maternity services reduced face-to-face consultations with high-risk pregnant women by supplying blood pressure monitors for supported self-monitoring. This paper explores the experiences of patients and clinicians of the rapid roll-out of supported self-monitoring programme in Scotland during the first and second wave of the COVID-19 pandemic. We conducted semi-structured telephone interviews with high-risk women and healthcare professionals who were using supported self-monitoring of blood pressure (BP) In four case studies during the COVID-19 pandemic. 20 women, 15 midwives and 4 obstetricians took part in the interviews. Interviews with healthcare professionals showed that while implementation occurred at pace and at scale across the National Health Service (NHS) in Scotland, implementation differed locally, resulting in mixed experiences. Study Participants observed several barriers and facilitators to implementation. Women value the simplicity of use and convenience of the digital communications platforms while health professionals were more interested in their impact on reducing workload for both women and health professionals largely found self-monitoring acceptable, with only a few exceptions. These results show that rapid change can occur in the NHS at a national level when there is a shared motivation. While self-monitoring is acceptable to most women, decisions regarding self-monitoring should be made jointly and on an individual basis

Computational identification of ubiquitylation sites from protein sequences

<p>Abstract</p> <p>Background</p> <p>Ubiquitylation plays an important role in regulating protein functions. Recently, experimental methods were developed toward effective identification of ubiquitylation sites. To efficiently explore more undiscovered ubiquitylation sites, this study aims to develop an accurate sequence-based prediction method to identify promising ubiquitylation sites.</p> <p>Results</p> <p>We established an ubiquitylation dataset consisting of 157 ubiquitylation sites and 3676 putative non-ubiquitylation sites extracted from 105 proteins in the UbiProt database. This study first evaluates promising sequence-based features and classifiers for the prediction of ubiquitylation sites by assessing three kinds of features (amino acid identity, evolutionary information, and physicochemical property) and three classifiers (support vector machine, <it>k</it>-nearest neighbor, and NaïveBayes). Results show that the set of used 531 physicochemical properties and support vector machine (SVM) are the best kind of features and classifier respectively that their combination has a prediction accuracy of 72.19% using leave-one-out cross-validation.</p> <p>Consequently, an informative physicochemical property mining algorithm (IPMA) is proposed to select an informative subset of 531 physicochemical properties. A prediction system UbiPred was implemented by using an SVM with the feature set of 31 informative physicochemical properties selected by IPMA, which can improve the accuracy from 72.19% to 84.44%. To further analyze the informative physicochemical properties, a decision tree method C5.0 was used to acquire if-then rule-based knowledge of predicting ubiquitylation sites. UbiPred can screen promising ubiquitylation sites from putative non-ubiquitylation sites using prediction scores. By applying UbiPred, 23 promising ubiquitylation sites were identified from an independent dataset of 3424 putative non-ubiquitylation sites, which were also validated by using the obtained prediction rules.</p> <p>Conclusion</p> <p>We have proposed an algorithm IPMA for mining informative physicochemical properties from protein sequences to build an SVM-based prediction system UbiPred. UbiPred can predict ubiquitylation sites accompanied with a prediction score each to help biologists in identifying promising sites for experimental verification. UbiPred has been implemented as a web server and is available at <url>http://iclab.life.nctu.edu.tw/ubipred</url>.</p

Tumour expression of leptin is associated with chemotherapy resistance and therapy-independent prognosis in gastro-oesophageal adenocarcinomas

Background: Cytotoxic chemotherapy remains the main systemic therapy for gastro-oesophageal adenocarcinoma, but resistance to chemotherapy is common, resulting in ineffective and often toxic treatment for patients. Predictive biomarkers for chemotherapy response would increase the probability of successful therapy, but none are currently recommended for clinical use. We used global gene expression profiling of tumour biopsies to identify novel predictive biomarkers for cytotoxic chemotherapy. Methods: Tumour biopsies from patients (n=14) with TNM stage IB–IV gastro-oesophageal adenocarcinomas receiving platinum-based combination chemotherapy were used as a discovery cohort and profiled with Affymetrix ST1.0 Exon Genechips. An independent cohort of patients (n=154) treated with surgery with or without neoadjuvant platinum combination chemotherapy and gastric adenocarcinoma cell lines (n=22) were used for qualification of gene expression profiling results by immunohistochemistry. A cisplatin-resistant gastric cancer cell line, AGS Cis5, and the oesophageal adenocarcinoma cell line, OE33, were used for in vitro validation investigations. Results: We identified 520 genes with differential expression (Mann–Whitney U, P<0.020) between radiological responding and nonresponding patients. Gene enrichment analysis (DAVID v6.7) was used on this list of 520 genes to identify pathways associated with response and identified the adipocytokine signalling pathway, with higher leptin mRNA associated with lack of radiological response (P=0.011). Similarly, in the independent cohort (n=154), higher leptin protein expression by immunohistochemistry in the tumour cells was associated with lack of histopathological response (P=0.007). Higher leptin protein expression by immunohistochemistry was also associated with improved survival in the absence of neoadjuvant chemotherapy, and patients with low leptin protein-expressing tumours had improved survival when treated by neoadjuvant chemotherapy (P for interaction=0.038). In the gastric adenocarcinoma cell lines, higher leptin protein expression was associated with resistance to cisplatin (P=0.008), but not to oxaliplatin (P=0.988) or 5fluorouracil (P=0.636). The leptin receptor antagonist SHLA increased the sensitivity of AGS Cis5 and OE33 cell lines to cisplatin. Conclusions: In gastro-oesophageal adenocarcinomas, tumour leptin expression is associated with chemoresistance but a better therapy-independent prognosis. Tumour leptin expression determined by immunohistochemistry has potential utility as a predictive marker of resistance to cytotoxic chemotherapy, and a prognostic marker independent of therapy in gastro-oesophageal adenocarcinoma. Leptin antagonists have been developed for clinical use and leptin and its associated pathways may also provide much needed novel therapeutic targets for gastro-oesophageal adenocarcinoma

Biofield Therapies: Helpful or Full of Hype? A Best Evidence Synthesis

Biofield therapies (such as Reiki, therapeutic touch, and healing touch) are complementary medicine modalities that remain controversial and are utilized by a significant number of patients, with little information regarding their efficacy. This systematic review examines 66 clinical studies with a variety of biofield therapies in different patient populations. We conducted a quality assessment as well as a best evidence synthesis approach to examine evidence for biofield therapies in relevant outcomes for different clinical populations. Studies overall are of medium quality, and generally meet minimum standards for validity of inferences. Biofield therapies show strong evidence for reducing pain intensity in pain populations, and moderate evidence for reducing pain intensity hospitalized and cancer populations. There is moderate evidence for decreasing negative behavioral symptoms in dementia and moderate evidence for decreasing anxiety for hospitalized populations. There is equivocal evidence for biofield therapies' effects on fatigue and quality of life for cancer patients, as well as for comprehensive pain outcomes and affect in pain patients, and for decreasing anxiety in cardiovascular patients. There is a need for further high-quality studies in this area. Implications and future research directions are discussed

AHR2 Mutant Reveals Functional Diversity of Aryl Hydrocarbon Receptors in Zebrafish

The aryl hydrocarbon receptor (AHR) is well known for mediating the toxic effects of TCDD and has been a subject of intense research for over 30 years. Current investigations continue to uncover its endogenous and regulatory roles in a wide variety of cellular and molecular signaling processes. A zebrafish line with a mutation in ahr2 (ahr2hu3335), encoding the AHR paralogue responsible for mediating TCDD toxicity in zebrafish, was developed via Targeting Induced Local Lesions IN Genomes (TILLING) and predicted to express a non-functional AHR2 protein. We characterized AHR activity in the mutant line using TCDD and leflunomide as toxicological probes to investigate function, ligand binding and CYP1A induction patterns of paralogues AHR2, AHR1A and AHR1B. By evaluating TCDD-induced developmental toxicity, mRNA expression changes and CYP1A protein in the AHR2 mutant line, we determined that ahr2hu3335 zebrafish are functionally null. In silico modeling predicted differential binding of TCDD and leflunomide to the AHR paralogues. AHR1A is considered a non-functional pseudogene as it does not bind TCCD or mediate in vivo TCDD toxicity. Homology modeling, however, predicted a ligand binding conformation of AHR1A with leflunomide. AHR1A-dependent CYP1A immunohistochemical expression in the liver provided in vivo confirmation of the in silico docking studies. The ahr2hu3335 functional knockout line expands the experimental power of zebrafish to unravel the role of the AHR during development, as well as highlights potential activity of the other AHR paralogues in ligand-specific toxicological responses

Patient safety culture in care homes for older people: a scoping review

Background: In recent years, there has been an increasing focus on the role of safety culture in preventing incidents such as medication errors and falls. However, research and developments in safety culture has predominantly taken place in hospital settings, with relatively less attention given to establishing a safety culture in care homes. Despite safety culture being accepted as an important quality indicator across all health and social care settings, the understanding of culture within social care settings remains far less developed than within hospitals. It is therefore important that the existing evidence base is gathered and reviewed in order to understand safety culture in care homes. Methods: A scoping review was undertaken to describe the availability of evidence related to care homes’ patient safety culture, what these studies focused on, and identify any knowledge gaps within the existing literature. Included papers were each reviewed by two authors for eligibility and to draw out information relevant to the scoping review. Results: Twenty-four empirical papers and one literature review were included within the scoping review. The collective evidence demonstrated that safety culture research is largely based in the USA, within Nursing Homes rather than Residential Home settings. Moreover, the scoping review revealed that empirical evidence has predominantly used quantitative measures, and therefore the deeper levels of culture have not been captured in the evidence base. Conclusions: Safety culture in care homes is a topic that has not been extensively researched. The review highlights a number of key gaps in the evidence base, which future research into safety culture in care home should attempt to address

Restriction of trophic factors and nutrients induces PARKIN expression

Parkinson’s disease (PD) is the most frequent neurodegenerative movement disorder and manifests at old age. While many details of its pathogenesis remain to be elucidated, in particular the protein and mitochondrial quality control during stress responses have been implicated in monogenic PD variants. Especially the mitochondrial kinase PINK1 and the ubiquitin ligase PARKIN are known to cooperate in autophagy after mitochondrial damage. As autophagy is also induced by loss of trophic signaling and PINK1 gene expression is modulated after deprivation of cytokines, we analyzed to what extent trophic signals and starvation stress regulate PINK1 and PARKIN expression. Time course experiments with serum deprivation and nutrient starvation of human SH-SY5Y neuroblastoma cells and primary mouse neurons demonstrated phasic induction of PINK1 transcript up to twofold and PARKIN transcript levels up to sixfold. The corresponding threefold starvation induction of PARKIN protein was limited by its translocation to lysosomes. Analysis of primary mouse cells from PINK1-knockout mice indicated that PARKIN induction and lysosomal translocation occurred independent of PINK1. Suppression of the PI3K-Akt-mTOR signaling by pharmacological agents modulated PARKIN expression accordingly. In conclusion, this expression survey demonstrates that PARKIN and PINK1 are coregulated during starvation and suggest a role of both PD genes in response to trophic signals and starvation stress

The influence of organizational culture and climate on entrepreneurial intentions among research scientists

Over the past decades, universities have increasingly become involved in entrepreneurial activities. Despite efforts to embrace their ‘third mission’, universities still demonstrate great heterogeneity in terms of their involvement in academic entrepreneurship. This papers adopts an institutional perspective to understand how organizational characteristics affect research scientists’ entrepreneurial intentions. Specifically, we study the impact of university culture and climate on entrepreneurial intentions, including intentions to spin off a company, to engage in patenting or licensing and to interact with industry through contract research or consulting. Using a sample of 437 research scientists from Swedish and German universities, our results reveal that the extent to which universities articulate entrepreneurship as a fundamental element of their mission fosters research scientists’ intentions to engage in spin-off creation and intellectual property rights, but not industry-science interaction. Furthermore, the presence of university role models positively affects research scientists’ propensity to engage in entrepreneurial activities, both directly and indirectly through entrepreneurial self-efficacy. Finally, research scientists working at universities which explicitly reward people for ‘third mission’ related output show higher levels of spin-off and patenting or licensing intentions. This study has implications for both academics and practitioners, including university managers and policy makers

Discovery of the First Insect Nidovirus, a Missing Evolutionary Link in the Emergence of the Largest RNA Virus Genomes

Nidoviruses with large genomes (26.3–31.7 kb; ‘large nidoviruses’), including Coronaviridae and Roniviridae, are the most complex positive-sense single-stranded RNA (ssRNA+) viruses. Based on genome size, they are far separated from all other ssRNA+ viruses (below 19.6 kb), including the distantly related Arteriviridae (12.7–15.7 kb; ‘small nidoviruses’). Exceptionally for ssRNA+ viruses, large nidoviruses encode a 3′-5′exoribonuclease (ExoN) that was implicated in controlling RNA replication fidelity. Its acquisition may have given rise to the ancestor of large nidoviruses, a hypothesis for which we here provide evolutionary support using comparative genomics involving the newly discovered first insect-borne nidovirus. This Nam Dinh virus (NDiV), named after a Vietnamese province, was isolated from mosquitoes and is yet to be linked to any pathology. The genome of this enveloped 60–80 nm virus is 20,192 nt and has a nidovirus-like polycistronic organization including two large, partially overlapping open reading frames (ORF) 1a and 1b followed by several smaller 3′-proximal ORFs. Peptide sequencing assigned three virion proteins to ORFs 2a, 2b, and 3, which are expressed from two 3′-coterminal subgenomic RNAs. The NDiV ORF1a/ORF1b frameshifting signal and various replicative proteins were tentatively mapped to canonical positions in the nidovirus genome. They include six nidovirus-wide conserved replicase domains, as well as the ExoN and 2′-O-methyltransferase that are specific to large nidoviruses. NDiV ORF1b also encodes a putative N7-methyltransferase, identified in a subset of large nidoviruses, but not the uridylate-specific endonuclease that – in deviation from the current paradigm - is present exclusively in the currently known vertebrate nidoviruses. Rooted phylogenetic inference by Bayesian and Maximum Likelihood methods indicates that NDiV clusters with roniviruses and that its branch diverged from large nidoviruses early after they split from small nidoviruses. Together these characteristics identify NDiV as the prototype of a new nidovirus family and a missing link in the transition from small to large nidoviruses