Meteoritic Input of Amino Acids and Nucleobases: Methodology and Implications for the Origins of Life

The discoveries of amino acids of extraterrestrial origin in many meteorites over the last 40 years have revolutionized the Astrobiology field. A variety of non-terrestrial amino acids similar to those found in life on Earth have been detected in meteorites. A few amino acids have even been found with chiral excesses, suggesting that meteorites could have contributed to the origin of homochirality in life on Earth. In addition to amino acids, which have been productively studied for years, sugar-like molecules, activated phosphates, and nucleobases have also been determined to be indigenous to numerous meteorites. Because these molecules are essential for life as we know it, and meteorites have been delivering them to the Earth since accretion, it is plausible that the origin(s) of life on Earth were aided by extraterrestrially-synthesized molecules. Understanding the origins of life on Earth guides our search for life elsewhere, helping to answer the question of whether biology is unique to Earth. This tutorial review focuses on meteoritic amino acids and nucleobases, exploring modern analytical methods and possible formation mechanisms. We will also discuss the unique window that meteorites provide into the chemistry that preceded life on Earth, a chemical record we do not have access to on Earth due to geologic recycling of rocks and the pervasiveness of biology across the planet. Finally, we will address the future of meteorite research, including asteroid sample return mIssIons

Interventions for preventing delirium in older people in institutional long-term care

BACKGROUND: Delirium is a common and distressing mental disorder. It is often caused by a combination of stressor events in susceptible people, particularly older people living with frailty and dementia. Adults living in institutional long-term care (LTC) are at particularly high risk of delirium. An episode of delirium increases risks of admission to hospital, development or worsening of dementia and death. Multicomponent interventions can reduce the incidence of delirium by a third in the hospital setting. However, it is currently unclear whether interventions to prevent delirium in LTC are effective. This is an update of a Cochrane Review first published in 2014. OBJECTIVES: To assess the effectiveness of interventions for preventing delirium in older people in institutional long-term care settings. SEARCH METHODS: We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group (CDCIG) 's Specialised Register of dementia trials (dementia.cochrane.org/our-trials-register), to 27 February 2019. The search was sufficiently sensitive to identify all studies relating to delirium. We ran additional separate searches in the Cochrane Central Register of Controlled Trials (CENTRAL), major healthcare databases, trial registers and grey literature sources to ensure that the search was comprehensive. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster-randomised controlled trials (cluster-RCTs) of single and multicomponent, non-pharmacological and pharmacological interventions for preventing delirium in older people (aged 65 years and over) in permanent LTC residence. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes were prevalence, incidence and severity of delirium; and mortality. Secondary outcomes included falls, hospital admissions and other adverse events; cognitive function; new diagnoses of dementia; activities of daily living; quality of life; and cost-related outcomes. We used risk ratios (RRs) as measures of treatment effect for dichotomous outcomes, hazard ratios (HR) for time-to-event outcomes and mean difference (MD) for continuous outcomes. For each outcome, we assessed the overall certainty of the evidence using GRADE methods. MAIN RESULTS: We included three trials with 3851 participants. All three were cluster-RCTs. Two of the trials were of complex, single-component, non-pharmacological interventions and one trial was a feasibility trial of a complex, multicomponent, non-pharmacological intervention. Risk of bias ratings were mixed across the three trials. Due to the heterogeneous nature of the interventions, we did not combine the results statistically, but produced a narrative summary.It was not possible to determine the effect of a hydration-based intervention on delirium incidence (RR 0.85, 95% confidence interval (CI) 0.18 to 4.00; 1 study, 98 participants; very low-certainty evidence downgraded for risk of bias and very serious imprecision). This study did not assess delirium prevalence, severity or mortality.The introduction of a computerised system to identify medications that may contribute to delirium risk and trigger a medication review was probably associated with a reduction in delirium incidence (12-month HR 0.42, CI 0.34 to 0.51; 1 study, 7311 participant-months; moderate-certainty evidence downgraded for risk of bias) but probably had little or no effect on mortality (HR 0.88, CI 0.66 to 1.17; 1 study, 9412 participant-months; moderate-certainty evidence downgraded for imprecision), hospital admissions (HR 0.89, CI 0.72 to 1.10; 1 study, 7599 participant-months; moderate-certainty evidence downgraded for imprecision) or falls (HR 1.03, CI 0.92 to 1.15; 1 study, 2275 participant-months; low-certainty evidence downgraded for imprecision and risk of bias). Delirium prevalence and severity were not assessed.In the enhanced educational intervention study, aimed at changing practice to address key delirium risk factors, it was not possible to determine the effect of the intervention on delirium incidence (RR 0.62, 95% CI 0.16 to 2.39; 1 study, 137 resident months; very low-certainty evidence downgraded for risk of bias and serious imprecision) or delirium prevalence (RR 0.57, 95% CI 0.15 to 2.19; 1 study, 160 participants; very low-certainty evidence downgraded for risk of bias and serious imprecision). There was probably little or no effect on mortality (RR 0.82, CI 0.50 to 1.34; 1 study, 215 participants; moderate-certainty evidence downgraded for imprecision). The intervention was probably associated with a reduction in hospital admissions (RR 0.67, CI 0.57 to 0.79; 1 study, 494 participants; moderate-certainty evidence downgraded due to indirectness). AUTHORS' CONCLUSIONS: Our review identified limited evidence on interventions for preventing delirium in older people in LTC. A software-based intervention to identify medications that could contribute to delirium risk and trigger a pharmacist-led medication review, probably reduces incidence of delirium in older people in institutional LTC. This is based on one large RCT in the US and may not be practical in other countries or settings which do not have comparable information technology services available in care homes. In the educational intervention aimed at identifying risk factors for delirium and developing bespoke solutions within care homes, it was not possible to determine the effect of the intervention on delirium incidence, prevalence or mortality. This evidence is based on a small feasibility trial. Our review identified three ongoing trials of multicomponent delirium prevention interventions. We identified no trials of pharmacological agents. Future trials of multicomponent non-pharmacological delirium prevention interventions for older people in LTC are needed to help inform the provision of evidence-based care for this vulnerable group

Evaluation of Online Consumer Health Information for Idiopathic Scoliosis Identified by a Google Search

Introduction. This study sought to assess the quality of online consumerhealth information about idiopathic scoliosis. Previous studiesshowed that quality of online health information varies and oftenlacks adherence to expert recommendations and guidelines. Nevertheless,72% of internet users seek health information online. A 2005analysis of online scoliosis information found that the informationwas limited and of poor quality. Methods. Two reviewers vetted the top 10 websites resulting from aGoogleTM search for “scoliosis.” Content was organized into categoriesand rated by three physician evaluators using a 1 - 5 scale basedon quality, accuracy, completeness of information, readability, andwillingness to recommend. Additional information, such as numberof ads and Flesch-Kinkaid reading level, also was collected. Results. The average overall physician score was 47.6 (75 possible).All websites included content that was mostly accurate but varied incompleteness. Physicians unanimously recommended Mayo Clinic,MedicineNet, and Kids Health; none recommended the GoogleTMKnowledge Graph. The Scoliosis Research Society website reachedthe highest overall physician score. Readability ranged from 7th gradeto college level; only that of Kids Health was below 10th grade level. Conclusions. Most essential information provided by the websiteswas accurate and generally well rated by physicians. Website rankingby physicians was inconsistent with the ranking order by GoogleTM,indicating that health seekers reviewing the top GoogleTM-rankedwebsites may not be viewing the websites rated highest by physicians.Physicians should consider patient literacy in website recommendations,as many have an above average literacy level.Kans J Med 2018;11(4):95-101

Alteration of immune function in women collegiate soccer players and college students

The purpose of this study was to monitor the stress-induced alteration in concentrations of salivary immunoglobulin (S-IgA) and cortisol and the incidence of upper respiratory tract infections (URTI) over the course of a 9-week competitive season in college student-athletes and college students. The subjects consisted of 14 NCAA Division III collegiate female soccer athletes (19.8 ± 1.0 years, mean ± SD) and 14 female college students (22.5 ± 2.6 years). Salivary samples were collected for 9 weeks during a competitive soccer season. S-IgA and cortisol concentrations were determined by enzyme linked immunosorbent assay (ELISA). A training and performance questionnaire was given to the subjects every week, to record the subjects’ session rating of perceived exertion (RPE) for all the training, load, monotony and strain, as well as any injuries or illnesses experienced. The between groups ANOVA procedure for repeated measures showed no changes in salivary concentrations of IgA and cortisol. Chisquare analysis showed that during the 9-week training season injury and illness occurred at a higher rate among the soccer players. There was a significant difference at baseline between soccer and control SIgA levels (p ≤ 0.05). Decreased levels of SIgA and increases in the indices of training (load, strain and monotony) were associated with an increase in the incidence of illness during the 9-week competitive soccer season

The TREAT-NMD DMD global database: Analysis of more than 7,000 duchenne muscular dystrophy mutations

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations)

Field Performance of a Rapid Test to Detect Progressive, Regressive, and Abortive Feline Leukemia Virus Infections in Domestic Cats in Australia and Germany

Different feline leukemia virus (FeLV) infection outcomes are possible in cats following natural exposure, such as progressive infections (persistent viremia), regressive infections (transient or no viremia followed by proviral persistence) and abortive infections (presence of only antibodies). Laboratory-based testing is currently required for categorization of infection outcomes in cats. The aim of this study was to evaluate the field performance of a novel, rapid, combination point-of-care (PoC) test kit commercially available in Europe (v-RetroFel®Ag/Ab; 2020–2021 version) to determine different FeLV infection outcomes by concurrent detection of FeLV antigen (p27) and antibodies against FeLV transmembrane envelope protein (p15E). A secondary aim was to evaluate the performance of the same test kit (v-RetroFel®FIV) to determine positive/negative feline immunodeficiency virus (FIV) infection status by the detection of antibodies to FIV capsid protein (p24) and transmembrane glycoprotein (gp40). Two cohorts of domestic cats were recruited and tested with v-RetroFel® using plasma or serum, including cats in Australia (n = 200) and cats in Germany (n = 170). Results from p27 antigen PoC testing, proviral DNA PCR, and neutralizing antibody testing or testing for antibodies against non-glycosylated surface unit envelope protein (p45) were used to assign cats to groups according to different FeLV infection outcomes. Testing with a laboratory-based FeLV p15E antibody ELISA was also performed for comparison. In the first cohort, v-RetroFel®Ag/Ab correctly identified 89% (109/122) FeLV-unexposed cats and 91% (21/23) progressive infections, but no regressive (0/23) or abortive (0/32) infections. In the second cohort, v-RetroFel®Ag/Ab correctly identified 94% (148/158) FeLV-unexposed cats and 100% (4/4) progressive infections, but no regressive (0/2) and only 17% (1/6) abortive infections. There was test agreement between v-RetroFel®Ab and the p15E laboratory ELISA in 58.9% of samples. As a secondary outcome of this study, the sensitivity and specificity of v-RetroFel®FIV testing in cohort 1 were 94.7% (18/19) and 98.3% (178/181), and in cohort 2, 30.0% (3/10) and 100.0% (160/160), respectively. Prior history of FIV vaccination did not produce any false-positive FIV results. In conclusion, v-RetroFel®Ag/Ab (2020–2021 version) was unable to accurately determine different FeLV infection outcomes in the field. Improvements of the test prior to application to field samples are required

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

Predicting discharge to institutional long-term care after stroke: a systematic review & meta-analysis

Background/Objectives: Stroke is a leading cause of disability worldwide, and a significant proportion of stroke survivors require long-term institutional care. Understanding who cannot be discharged home is important for health and social care planning. Our aim was to establish predictive factors for discharge to institutional care after hospitalization for stroke. Design: We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42015023497) of observational studies. We searched MEDLINE, EMBASE, and CINAHL Plus to February 2017. Quantitative synthesis was performed where data allowed. Setting: Acute and rehabilitation hospitals. Participants: Adults hospitalized for stroke who were newly admitted directly to long-term institutional care at the time of hospital discharge. Measurements: Factors associated with new institutionalization. Results: From 10,420 records, we included 18 studies (n = 32,139 participants). The studies were heterogeneous and conducted in Europe, North America, and East Asia. Eight studies were at high risk of selection bias. The proportion of those surviving to discharge who were newly discharged to long-term care varied from 7% to 39% (median 17%, interquartile range 12%), and the model of care received in the long-term care setting was not defined. Older age and greater stroke severity had a consistently positive association with the need for long-term care admission. Individuals who had a severe stroke were 26 times as likely to be admitted to long-term care than those who had a minor stroke. Individuals aged 65 and older had a risk of stroke that was three times as great as that of younger individuals. Potentially modifiable factors were rarely examined. Conclusion: Age and stroke severity are important predictors of institutional long-term care admission directly from the hospital after an acute stroke. Potentially modifiable factors should be the target of future research. Stroke outcome studies should report discharge destination, defining the model of care provided in the long-term care setting

New horizons in the role of digital data in the healthcare of older people

There are national and global moves to improve effective digital data design and application in healthcare. This New Horizons commentary describes the role of digital data in healthcare of the ageing population. We outline how health and social care professionals can engage in the proactive design of digital systems that appropriately serve people as they age, carers and the workforce that supports them.// Key Points: //Healthcare improvements have resulted in increased population longevity and hence multimorbidity.// //Shared care records to improve communication and information continuity across care settings hold potential for older people.// Data structure and coding are key considerations.// A workforce with expertise in caring for older people with relevant knowledge and skills in digital healthcare is important./