JURNAL AGROTEKNOLOGI
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Risk factors for mobility decline in community-dwelling older adults: a systematic literature review
No full textMobility is essential to maintaining independence for older adults. This systematic review aimed to summarize evidence about self-reported risk factors for self-reported mobility decline; and to provide an overview of published prognostic models for self-reported mobility decline among community-dwelling older adults. Databases were searched from inception to June 2, 2020. Studies were screened by two independent reviewers who extracted data and assessed study quality. Sixty-one studies (45,187 participants) were included, providing information on 107 risk factors. High-quality evidence and moderate/large effect sizes for the association with mobility decline were found for older age beyond 75 years, the presence of widespread pain, and mobility modifications. Moderate–high quality evidence and small effect sizes were found for a further 21 factors. Three model development studies demonstrated acceptable model performance, limited by high risk of bias. These findings should be considered in intervention development, and in developing a prediction instrument for practical application
Evaluation of loading strategies to improve tumor uptake of gemcitabine in a murine orthotopic bladder cancer model using ultrasound and microbubbles
No full textIn this study we compared three different microbubble-based approaches to the delivery of a widely used chemotherapy drug, gemcitabine: (i) co-administration of gemcitabine and microbubbles (Gem+MB); (ii) conjugates of microbubbles and gemcitabine-loaded liposomes (GemlipoMB); and (iii) microbubbles with gemcitabine directly bound to their surfaces (GembioMB). Both in vitro and in vivo investigations were carried out, respectively, in the RT112 bladder cancer cell line and in a murine orthotopic muscle-invasive bladder cancer model. The in vitro (in vivo) ultrasound exposure conditions were a 1 (1.1) MHz centre frequency, 0.07 (1.0) MPa peak negative pressure, 3000 (20,000) cycles and 100 (0.5) Hz pulse repetition frequency. Ultrasound exposure produced no significant increase in drug uptake either in vitro or in vivo compared with the drug-only control for co-administered gemcitabine and microbubbles. In vivo, GemlipoMB prolonged the plasma circulation time of gemcitabine, but only GembioMB produced a statistically significant increase in cleaved caspase 3 expression in the tumor, indicative of gemcitabine-induced apoptosis
Changes to management of hypertension in pregnancy, and attitudes to self-management: An online survey of obstetricians, before and following the first wave of the COVID-19 pandemic
No full textObjective
This study aimed to understand the views and practice of obstetricians regarding self-monitoring for hypertensive disorders of pregnancy (blood pressure (BP) and proteinuria), the potential for self-management (including actions taken on self-monitored parameters) and to understand the impact of the COVID-19 pandemic on such views.
Design
Cross-sectional online survey pre- and post- the first wave of the COVID-19 pandemic.
Setting and Sample
UK obstetricians recruited via an online portal.
Methods
A survey undertaken in two rounds: December 2019-January 2020 (pre-pandemic), and September-November 2020 (during pandemic)
Results
251 responses were received across rounds one (1 5 0) and two (1 0 1). Most obstetricians considered that self-monitoring of BP and home urinalysis had a role in guiding clinical decisions and this increased significantly following the first wave of the COVID-19 pandemic (88%, (132/150) 95%CI: 83–93% first round vs 96% (95%CI: 92–94%), (97/101), second round; p = 0.039). Following the pandemic, nearly half were agreeable to women self-managing their hypertension by using their own readings to make a pre-agreed medication change themselves (47%, 47/101 (95%CI: 37–57%)).
Conclusions
A substantial majority of UK obstetricians considered that self-monitoring had a role in the management of pregnancy hypertension and this increased following the pandemic. Around half are now supportive of women having a wider role in self-management of hypertensive treatment. Maximising the potential of such changes in pregnancy hypertension management requires further work to understand how to fully integrate women’s own measurements into clinical care
Examining the level and inequality in health insurance coverage in 36 sub-Saharan African countries
No full textIntroduction Low/middle-income countries (LMICs) in sub-Saharan Africa (SSA) are increasingly turning to public contributory health insurance as a mechanism for removing financial barriers to access and extending financial risk protection to the population. Against this backdrop, we assessed the level and inequality of population coverage of existing health insurance schemes in 36 SSA countries.
Methods Using secondary data from the most recent Demographic and Health Surveys, we computed mean population coverage for any type of health insurance, and for specific forms of health insurance schemes, by country. We developed concentration curves, computed concentration indices, and rich–poor differences and ratios to examine inequality in health insurance coverage. We decomposed the concentration index using a generalised linear model to examine the contribution of household and individual-level factors to the inequality in health insurance coverage.
Results Only four countries had coverage levels with any type of health insurance of above 20% (Rwanda—78.7% (95% CI 77.5% to 79.9%), Ghana—58.2% (95% CI 56.2% to 60.1%), Gabon—40.8% (95% CI 38.2% to 43.5%), and Burundi 22.0% (95% CI 20.7% to 23.2%)). Overall, health insurance coverage was low (7.9% (95% CI 7.8% to 7.9%)) and pro-rich; concentration index=0.4 (95% CI 0.3 to 0.4, p<0.001). Exposure to media made the greatest contribution to the pro-rich distribution of health insurance coverage (50.3%), followed by socioeconomic status (44.3%) and the level of education (41.6%).
Conclusion Coverage of health insurance in SSA is low and pro-rich. The four countries that had health insurance coverage levels greater than 20% were all characterised by substantial funding from tax revenues. The other study countries featured predominantly voluntary mechanisms. In a context of high informality of labour markets, SSA and other LMICs should rethink the role of voluntary contributory health insurance and instead embrace tax funding as a sustainable and feasible mechanism for mobilising resources for the health sector
ActiveDriverDB: Interpreting genetic variation in human and cancer genomes using post-translational modification sites and signaling networks (2021 Update)
No full textDeciphering the functional impact of genetic variation is required to understand phenotypic diversity and the molecular mechanisms of inherited disease and cancer. While millions of genetic variants are now mapped in genome sequencing projects, distinguishing functional variants remains a major challenge. Protein-coding variation can be interpreted using post-translational modification (PTM) sites that are core components of cellular signaling networks controlling molecular processes and pathways. ActiveDriverDB is an interactive proteo-genomics database that uses more than 260,000 experimentally detected PTM sites to predict the functional impact of genetic variation in disease, cancer and the human population. Using machine learning tools, we prioritize proteins and pathways with enriched PTM-specific amino acid substitutions that potentially rewire signaling networks via induced or disrupted short linear motifs of kinase binding. We then map these effects to site-specific protein interaction networks and drug targets. In the 2021 update, we increased the PTM datasets by nearly 50%, included glycosylation, sumoylation and succinylation as new types of PTMs, and updated the workflows to interpret inherited disease mutations. We added a recent phosphoproteomics dataset reflecting the cellular response to SARS-CoV-2 to predict the impact of human genetic variation on COVID-19 infection and disease course. Overall, we estimate that 16-21% of known amino acid substitutions affect PTM sites among pathogenic disease mutations, somatic mutations in cancer genomes and germline variants in the human population. These data underline the potential of interpreting genetic variation through the lens of PTMs and signaling networks. The open-source database is freely available at www.ActiveDriverDB.org
Soap operas won’t wash for wildlife
No full text1. Natural history documentaries are a globally important source of information about wildlife, conservation and environmental issues and they are the closest many will get to seeing featured animals and their behaviour in the wild. They are entertainment, certainly, but may also inform people’s knowledge of the natural world and influence their ideas on conservation of species and habitats. We locate our perspective in the existing literature analysing wildlife documentary making and its effects.
2. We argue that a conspicuous preoccupation with the ‘personalisation’ of individual animals and the injection of false jeopardy in recent wildlife documentaries leads to significant misinformation and creates problems for public understanding of wider conservation.
3. We illustrate our point by detailing episodes from the BBC natural history series Dynasties, discussing personalisation, anthropomorphism and the use of jeopardy to gain emotive impact and audience engagement. We find that narratives are framed around a single individual, that “stories” are framed as soap-operas, that jeopardy is emphasised throughout and that animals are endowed with the capacity to be aware of, and work towards, the dynasties of the title.
4. With conservation increasingly relying on public support, we argue that it is important that people are presented with factually correct information, and portraying wild animals as soap-opera style characters is neither honest nor helpful
E. coli Nickel-Iron Hydrogenase 1 catalyses non-native reduction of flavins: demonstration for alkene hydrogenation by old yellow enzyme ene-reductases
No full textA new activity for the [NiFe] uptake hydrogenase 1 of Escherichia coli (Hyd1) is presented. Direct reduction of biological flavin cofactors FMN and FAD is achieved using H2 as a simple, completely atom-economical reductant. The robust nature of Hyd1 is exploited for flavin reduction across a broad range of temperatures (25–70 °C) and extended reaction times. The utility of this system as a simple, easy to implement FMNH2 or FADH2 regenerating system is then demonstrated by supplying reduced flavin to Old Yellow Enzyme “ene-reductases” to support asymmetric alkene reductions with up to 100 % conversion. Hyd1 turnover frequencies up to 20.4 min−1 and total turnover numbers up to 20 200 were recorded during flavin recycling
Ebola virus antibody decay–stimulation in a high proportion of survivors
No full textNeutralizing antibody function provides a foundation for the efficacy of vaccines and therapies. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013–2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a ‘decay–stimulation–decay’ pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77–100 days and a doubling time of 46–86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5–2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak
An observational study of breakthrough SARS-CoV-2 Delta variant infections among vaccinated healthcare workers in Vietnam
No full textBackground
Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited.
Methods
We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing.
Findings
Between 11th–25th June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8–33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.043). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms.
Interpretation
Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals
Major genetic discontinuity and novel toxigenic species in Clostridioides difficile taxonomy
No full textClostridioides difficile infection (CDI) remains an urgent global One Health threat. The genetic heterogeneity seen across C. difficile underscores its wide ecological versatility and has driven the significant changes in CDI epidemiology seen in the last 20 years. We analysed an international collection of over 12,000 C. difficile genomes spanning the eight currently defined phylogenetic clades. Through whole-genome average nucleotide identity, and pangenomic and Bayesian analyses, we identified major taxonomic incoherence with clear species boundaries for each of the recently described cryptic clades CI–III. The emergence of these three novel genomospecies predates clades C1–5 by millions of years, rewriting the global population structure of C. difficile specifically and taxonomy of the Peptostreptococcaceae in general. These genomospecies all show unique and highly divergent toxin gene architecture, advancing our understanding of the evolution of C. difficile and close relatives. Beyond the taxonomic ramifications, this work may impact the diagnosis of CDI