Cognitive Impairment among Older Adults in the Emergency Department

Background: Within the next 30 years, the number of visits older adults will make to emergency departments (EDs) is expected to double from 16 million, or 14% of all visits, to 34 million and comprise nearly a quarter of all visits.Objective: The objectives of this study were to determine prevalence rates of cognitive impairment among older adults in the ED and to identify associations, if any, between environmental factors unique to the ED and rates of cognitive impairment.Methods: A cross-sectional observational study of adults 65 and older admitted to the ED of a large, urban, tertiary academic health center was conducted between September 2007 and May 2008. Patients were screened for cognitive impairment in orientation, recall and executive function using the Six-Item Screen (SIS) and the CLOX1, clock drawing task. Cognitive impairment among this ED population was assessed and both patient demographics and ED characteristics (crowding, triage time, location of assessment, triage class) were compared through adjusted generalized linear models.Results: Forty-two percent (350/829) of elderly patients presented with deficits in orientation and recall as assessed by the SIS. An additional 36% of elderly patients with no impairment in orientation or recall had deficits in executive function as assessed by the CLOX1. In full model adjusted analyses patients were more likely to screen deficits in orientation and recall (SIS) if they were 85 years or older (Relative Risk [RR]=1.63, 95% Confidence Interval [95% CI]=1.3-2.07), black (RR=1.85, 95% CI=1.5-2.4) and male (RR=1.42, 95% CI=1.2-1.7). Only age was significantly associated with executive functioning deficits in the ED screened using the clock drawing task (CLOX1) (75-84 years: RR=1.35, 95% CI= 1.2-1.6; 85+ years: RR=1.69, 95% CI= 1.5-2.0).Conclusion: These findings have several implications for patients seen in the ED. The SIS coupled with a clock drawing task (CLOX1) provide a rapid and simple method for assessing and documenting cognition when lengthier assessment tools are not feasible and add to the literature on the use of these tools in the ED. Further research on provider use of these tools and potential implication for quality improvement is needed. [West J Emerg Med. 2011; 12(1):56-62.

The RCSB Protein Data Bank: views of structural biology for basic and applied research and education.

The RCSB Protein Data Bank (RCSB PDB, http://www.rcsb.org) provides access to 3D structures of biological macromolecules and is one of the leading resources in biology and biomedicine worldwide. Our efforts over the past 2 years focused on enabling a deeper understanding of structural biology and providing new structural views of biology that support both basic and applied research and education. Herein, we describe recently introduced data annotations including integration with external biological resources, such as gene and drug databases, new visualization tools and improved support for the mobile web. We also describe access to data files, web services and open access software components to enable software developers to more effectively mine the PDB archive and related annotations. Our efforts are aimed at expanding the role of 3D structure in understanding biology and medicine

How birds cope physiologically and behaviourally with extreme climatic events

As global climate change progresses, the occurrence of potentially disruptiveclimatic events such as storms are increasing in frequency, duration and inten-sity resulting in higher mortality and reduced reproductive success. Whatconstitutes an extreme climatic event? First we point out that extreme climaticevents in biological contexts can occur in any environment. Focusing on fieldand laboratory data on wild birds we propose a mechanistic approach to defin-ing and investigating what extreme climatic events are and how animals copewith them at physiological and behavioural levels. The life cycle of birds ismade up of life-history stages such as migration, breeding and moult thatevolved to match a range of environmental conditions an individual mightexpect during the year. When environmental conditions deteriorate anddeviate from the expected range then the individual must trigger copingmechanisms (emergency life-history stage) that will disrupt the temporal pro-gression of life-history stages, but enhance survival. Using the framework ofallostasis, we argue that an extreme climatic event in biological contexts canbe defined as when the cumulative resources available to an individual areexceeded by the sum of its energetic costs—a state called allostatic overload.This allostatic overload triggers the emergency life-history stage that tempor-arily allows the individual to cease regular activities in an attempt to surviveextreme conditions. We propose that glucocorticoid hormones play a majorrole in orchestrating coping mechanisms and are critical for enduring extremeclimatic events.This article is part of the themed issue ‘Behavioural, ecological andevolutionary responses to extreme climatic events’

Late-season snowfall is associated with decreased offspring survival in two migratory arctic-breeding songbird species

While the effect of weather on reproduction has been studied for many years in avian taxa, the rapid pace of climate change in arctic regions has added urgency to this question by changing the weather conditions species experience during breeding. Given this, it is important to understand how factors such as temperature, rain, snowfall, and wind affect reproduction both directly and indirectly (e.g. through their effects on food availability). In this study, we ask how weather factors and food availability influence daily survival rates of clutches in two arctic-breeding migratory songbirds: the Lapland longspur Calcarius lapponicus , a circumpolar breeder, and Gambel’s white-crowned sparrow Zonotrichia leucophrys gambelii , which breeds in shrubby habitats across tundra, boreal and continental climates. To do this, we monitored clutch survival in these two species from egg-lay through fledge at field sites located near Toolik Field Station (North Slope, Alaska) across 5 yr (2012–2016). Our results indicate that snowfall and cold temperatures decreased offspring survival rates in both species; although Lapland longspurs were more susceptible to snowfall. Food availability, quantified by pitfall sampling and sweep-net sampling methods, had minimal effects on offspring survival. Some climate models predict increased precipitation for the Arctic with global warming, and in the Toolik region, total snow accumulation may be increasing. Placed in this context, our results suggest that changes in snow storms with climate change could have substantial consequences for reproduction in migratory songbirds breeding in the North American Arctic

A manganese photosensitive tricarbonyl molecule [Mn(CO)3(tpa-κ(3)N)]Br enhances antibiotic efficacy in a multi-drug-resistant Escherichia coli

Carbon monoxide-releasing molecules (CORMs) are a promising class of new antimicrobials, with multiple modes of action that are distinct from those of standard antibiotics. The relentless increase in antimicrobial resistance, exacerbated by a lack of new antibiotics, necessitates a better understanding of how such novel agents act and might be used synergistically with established antibiotics. This work aimed to understand the mechanism(s) underlying synergy between a manganese-based photoactivated carbon monoxide-releasing molecule (PhotoCORM), [Mn(CO)3(tpa-κ(3)N)]Br [tpa=tris(2-pyridylmethyl)amine], and various classes of antibiotics in their activities towards Escherichia coli EC958, a multi-drug-resistant uropathogen. The title compound acts synergistically with polymyxins [polymyxin B and colistin (polymyxin E)] by damaging the bacterial cytoplasmic membrane. [Mn(CO)3(tpa-κ(3)N)]Br also potentiates the action of doxycycline, resulting in reduced expression of tetA, which encodes a tetracycline efflux pump. We show that, like tetracyclines, the breakdown products of [Mn(CO)3(tpa-κ(3)N)]Br activation chelate iron and trigger an iron starvation response, which we propose to be a further basis for the synergies observed. Conversely, media supplemented with excess iron abrogated the inhibition of growth by doxycycline and the title compound. In conclusion, multiple factors contribute to the ability of this PhotoCORM to increase the efficacy of antibiotics in the polymyxin and tetracycline families. We propose that light-activated carbon monoxide release is not the sole basis of the antimicrobial activities of [Mn(CO)3(tpa-κ(3)N)]Br

Eavesdropping on the Arctic: Automated bioacoustics reveal dynamics in songbird breeding phenology

Bioacoustic networks could vastly expand the coverage of wildlife monitoring to complement satellite observations of climate and vegetation. This approach would enable global-scale understanding of how climate change influences phenomena such as migratory timing of avian species. The enormous data sets that autonomous recorders typically generate demand automated analyses that remain largely undeveloped. We devised automated signal processing and machine learning approaches to estimate dates on which songbird communities arrived at arctic breeding grounds. Acoustically estimated dates agreed well with those determined via traditional surveys and were strongly related to the landscape’s snow-free dates. We found that environmental conditions heavily influenced daily variation in songbird vocal activity, especially before egg laying. Our novel approaches demonstrate that variation in avian migratory arrival can be detected autonomously. Large-scale deployment of this innovation in wildlife monitoring would enable the coverage necessary to assess and forecast changes in bird migration in the face of climate change

Carbon Monoxide Gas Is Not Inert, but Global, in Its Consequences for Bacterial Gene Expression, Iron Acquisition, and Antibiotic Resistance

Aims: Carbon monoxide is a respiratory poison and gaseous signaling molecule. Although CO-releasing molecules (CORMs) deliver CO with temporal and spatial specificity in mammals, and are proven antimicrobial agents, we do not understand the modes of CO toxicity. Our aim was to explore the impact of CO gas per se, without intervention of CORMs, on bacterial physiology and gene expression. Results: We used tightly controlled chemostat conditions and integrated transcriptomic datasets with statistical modeling to reveal the global effects of CO. CO is known to inhibit bacterial respiration, and we found expression of genes encoding energy-transducing pathways to be significantly affected via the global regulators, Fnr, Arc, and PdhR. Aerobically, ArcA—the response regulator—is transiently phosphorylated and pyruvate accumulates, mimicking anaerobiosis. Genes implicated in iron acquisition, and the metabolism of sulfur amino acids and arginine, are all perturbed. The global iron-related changes, confirmed by modulation of activity of the transcription factor Fur, may underlie enhanced siderophore excretion, diminished intracellular iron pools, and the sensitivity of COchallenged bacteria to metal chelators. Although CO gas (unlike H2S and NO) offers little protection from antibiotics, a ruthenium CORM is a potent adjuvant of antibiotic activity. Innovation: This is the first detailed exploration of global bacterial responses to CO, revealing unexpected targets with implications for employing CORMs therapeutically. Conclusion: This work reveals the complexity of bacterial responses to CO and provides a basis for understanding the impacts of CO from CORMs, heme oxygenase activity, or environmental sources

Mendelian gene identification through mouse embryo viability screening.

BACKGROUND: The diagnostic rate of Mendelian disorders in sequencing studies continues to increase, along with the pace of novel disease gene discovery. However, variant interpretation in novel genes not currently associated with disease is particularly challenging and strategies combining gene functional evidence with approaches that evaluate the phenotypic similarities between patients and model organisms have proven successful. A full spectrum of intolerance to loss-of-function variation has been previously described, providing evidence that gene essentiality should not be considered as a simple and fixed binary property. METHODS: Here we further dissected this spectrum by assessing the embryonic stage at which homozygous loss-of-function results in lethality in mice from the International Mouse Phenotyping Consortium, classifying the set of lethal genes into one of three windows of lethality: early, mid, or late gestation lethal. We studied the correlation between these windows of lethality and various gene features including expression across development, paralogy and constraint metrics together with human disease phenotypes. We explored a gene similarity approach for novel gene discovery and investigated unsolved cases from the 100,000 Genomes Project. RESULTS: We found that genes in the early gestation lethal category have distinct characteristics and are enriched for genes linked with recessive forms of inherited metabolic disease. We identified several genes sharing multiple features with known biallelic forms of inborn errors of the metabolism and found signs of enrichment of biallelic predicted pathogenic variants among early gestation lethal genes in patients recruited under this disease category. We highlight two novel gene candidates with phenotypic overlap between the patients and the mouse knockouts. CONCLUSIONS: Information on the developmental period at which embryonic lethality occurs in the knockout mouse may be used for novel disease gene discovery that helps to prioritise variants in unsolved rare disease cases

Robot Assisted Training for the Upper Limb after Stroke (RATULS): study protocol for a randomised controlled trial.

BACKGROUND: Loss of arm function is a common and distressing consequence of stroke. We describe the protocol for a pragmatic, multicentre randomised controlled trial to determine whether robot-assisted training improves upper limb function following stroke. METHODS/DESIGN: Study design: a pragmatic, three-arm, multicentre randomised controlled trial, economic analysis and process evaluation. SETTING: NHS stroke services. PARTICIPANTS: adults with acute or chronic first-ever stroke (1 week to 5 years post stroke) causing moderate to severe upper limb functional limitation. Randomisation groups: 1. Robot-assisted training using the InMotion robotic gym system for 45 min, three times/week for 12 weeks 2. Enhanced upper limb therapy for 45 min, three times/week for 12 weeks 3. Usual NHS care in accordance with local clinical practice Randomisation: individual participant randomisation stratified by centre, time since stroke, and severity of upper limb impairment. PRIMARY OUTCOME: upper limb function measured by the Action Research Arm Test (ARAT) at 3 months post randomisation. SECONDARY OUTCOMES: upper limb impairment (Fugl-Meyer Test), activities of daily living (Barthel ADL Index), quality of life (Stroke Impact Scale, EQ-5D-5L), resource use, cost per quality-adjusted life year and adverse events, at 3 and 6 months. Blinding: outcomes are undertaken by blinded assessors. Economic analysis: micro-costing and economic evaluation of interventions compared to usual NHS care. A within-trial analysis, with an economic model will be used to extrapolate longer-term costs and outcomes. Process evaluation: semi-structured interviews with participants and professionals to seek their views and experiences of the rehabilitation that they have received or provided, and factors affecting the implementation of the trial. SAMPLE SIZE: allowing for 10% attrition, 720 participants provide 80% power to detect a 15% difference in successful outcome between each of the treatment pairs. Successful outcome definition: baseline ARAT 0-7 must improve by 3 or more points; baseline ARAT 8-13 improve by 4 or more points; baseline ARAT 14-19 improve by 5 or more points; baseline ARAT 20-39 improve by 6 or more points. DISCUSSION: The results from this trial will determine whether robot-assisted training improves upper limb function post stroke. TRIAL REGISTRATION: ISRCTN, identifier: ISRCTN69371850 . Registered 4 October 2013