Hepatic Oleate Regulates Insulin-like Growth Factor-Binding Protein 1 Partially through the mTORC1-FGF21 Axis during High-Carbohydrate Feeding.

Stearoyl-CoA desaturase-1 (SCD1) catalyzes the rate-liming step of monounsaturated fatty acid biosynthesis and is a key regulator of systemic glucose metabolism. Mice harboring either a global (GKO) or liver-specific deletion (LKO) of Scd1 display enhanced insulin signaling and whole-body glucose uptake. Additionally, GKO and LKO mice are protected from high-carbohydrate diet-induced obesity. Given that high-carbohydrate diets can lead to chronic metabolic diseases such as obesity, diabetes, and hepatic steatosis, it is critical to understand how Scd1 deficiency confers metabolically beneficial phenotypes. Here we show that insulin-like growth factor-binding protein 1 (IGFBP1), a hepatokine that has been reported to enhance insulin signaling, is significantly elevated in the liver and plasma of GKO and LKO mice fed a low-fat high-carbohydrate diet. We also observed that the expression of hepatic Igfbp1 is regulated by oleic acid (18:1n9), a product of SCD1, through the mTORC1-FGF21 axis both in vivo and in vitro.

Inositol-Requiring Enzyme 1α-Mediated Synthesis of Monounsaturated Fatty Acids as a Driver of B Cell Differentiation and Lupus-like Autoimmune Disease.

OBJECTIVE: To explore the molecular mechanisms underlying dysregulation of lipid metabolism in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: B cells in peripheral blood from patients with SLE and healthy controls were stained with BODIPY dye for detection of lipids. Mice with targeted knockout of genes for B cell-specific inositol-requiring enzyme 1α (IRE-1α) and stearoyl-coenzyme A desaturase 1 (SCD-1) were used for studying the influence of the IRE-1α/SCD-1/SCD-2 pathway on B cell differentiation and autoantibody production. The preclinical efficacy of IRE-1α suppression as a treatment for lupus was tested in MRL.Faslpr mice. RESULTS: In cultures with mouse IRE-1α-null B cells, supplementation with monounsaturated fatty acids largely rescued differentiation of plasma cells from B cells, indicating that the compromised capacity of B cell differentiation in the absence of IRE-1α may be attributable to a defect in monounsaturated fatty acid synthesis. Moreover, activation with IRE-1α/X-box binding protein 1 (XBP-1) was required to facilitate B cell expression of SCD-1 and SCD-2, which are 2 critical enzymes that catalyze monounsaturated fatty acid synthesis. Mice with targeted Scd1 gene deletion displayed a phenotype that was similar to that of IRE-1α-deficient mice, with diminished B cell differentiation into plasma cells. Importantly, in B cells from patients with lupus, both IRE-1α expression and Xbp1 messenger RNA splicing were significantly increased, and this was positively correlated with the expression of both Scd1 and Scd2 as well as with the amount of B cell lipid deposition. In MRL.Faslpr mice, both genetic and pharmacologic suppression of IRE-1α protected against the pathologic development and progression of lupus-like autoimmune disease. CONCLUSION: The results of this study reveal a molecular link in the dysregulation of lipid metabolism in the pathogenesis of lupus, demonstrating that the IRE-1α/XBP-1 pathway controls plasma cell differentiation through SCD-1/SCD-2-mediated monounsaturated fatty acid synthesis. These findings provide a rationale for targeting IRE-1α and monounsaturated fatty acid synthesis in the treatment of patients with SLE.

Designing tools to predict and mitigate impacts on water quality following the Australian 2019/2020 wildfires: Insights from Sydney's largest water supply catchment.

The 2019/2020 Australian bushfires (or wildfires) burned the largest forested area in Australia's recorded history, with major socio-economic and environmental consequences. Among the largest fires was the 280 000 ha Green Wattle Creek Fire, which burned large forested areas of the Warragamba catchment. This protected catchment provides critical ecosystem services for Lake Burragorang, one of Australia's largest urban supply reservoirs delivering ~85% of the water used in Greater Sydney. Water New South Wales (WaterNSW) is the utility responsible for managing water quality in Lake Burragorang. Its postfire risk assessment, done in collaboration with researchers in Australia, the UK, and United States, involved (i) identifying pyrogenic contaminants in ash and soil; (ii) quantifying ash loads and contaminant concentrations across the burned area; and (iii) estimating the probability and quantity of soil, ash, and associated contaminant entrainment for different rainfall scenarios. The work included refining the capabilities of the new WEPPcloud-WATAR-AU model (Water Erosion Prediction Project cloud-Wildfire Ash Transport And Risk-Australia) for predicting sediment, ash, and contaminant transport, aided by outcomes from previous collaborative postfire research in the catchment. Approximately two weeks after the Green Wattle Creek Fire was contained, an extreme rainfall event (~276 mm in 72 h) caused extensive ash and sediment delivery into the reservoir. The risk assessment informed on-ground monitoring and operational mitigation measures (deployment of debris-catching booms and adjustment of the water supply system configuration), ensuring the continuity of safe water supply to Sydney. WEPPcloud-WATAR-AU outputs can prioritize recovery interventions for managing water quality risks by quantifying contaminants on the hillslopes, anticipating water contamination risk, and identifying areas with high susceptibility to ash and sediment transport. This collaborative interaction among scientists and water managers, aimed also at refining model capabilities and outputs to meet managers' needs, exemplifies the successful outcomes that can be achieved at the interface of industry and science. Integr Environ Assess Manag 2021;17:1151-1161. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Hepatic stearoyl CoA desaturase 1 deficiency increases glucose uptake in adipose tissue partially through the PGC-1α-FGF21 axis in mice.

Increased carbohydrate consumption increases hepatic de novo lipogenesis, which has been linked to the development of chronic metabolic diseases, including obesity, hepatic steatosis, and insulin resistance. Stearoyl CoA desaturase 1 (SCD1) is a critical lipogenic enzyme that catalyzes the synthesis of two monounsaturated fatty acids, oleate and palmitoleate, from the saturated fatty acids stearate and palmitate, respectively. SCD1-deficient mouse models are protected against diet-induced adiposity, hepatic steatosis, and hyperglycemia. However, the mechanism of this protection by SCD1 deficiency is unclear. Using liver-specific SCD1 knockout (LKO) mice fed a high-carbohydrate, low-fat diet, we show that hepatic SCD1 deficiency increases systemic glucose uptake. Hepatic SCD1 deficiency enhanced glucose transporter type 1 (GLUT1) expression in the liver and also up-regulated GLUT4 and adiponectin expression in adipose tissue. The enhanced glucose uptake correlated with increased liver expression and elevated plasma levels of fibroblast growth factor 21 (FGF21), a hepatokine known to increase systemic insulin sensitivity and regulate whole-body lipid metabolism. Feeding LKO mice a triolein-supplemented but not tristearin-supplemented high-carbohydrate, low-fat diet reduced FGF21 expression and plasma levels. Consistently, SCD1 inhibition in primary hepatocytes induced FGF21 expression, which was repressed by treatment with oleate but not palmitoleate. Moreover, deletion of the transcriptional coactivator PPARγ coactivator 1α (PGC-1α) reduced hepatic and plasma FGF21 and white adipocyte tissue-specific GLUT4 expression and raised plasma glucose levels in LKO mice. These results suggest that hepatic oleate regulates glucose uptake in adipose tissue either directly or partially by modulating the hepatic PGC-1α-FGF21 axis.

Enhanced smoking cessation support for newly abstinent smokers discharged from hospital (the Hospital to Home trial): a randomized controlled trial.

BACKGROUND AND AIMS: The United Kingdom's National Institute for Health and Care Excellence guidance (NICE PH48) recommends that pharmacotherapy combined with behavioural support be provided for all smokers admitted to hospital; however, relapse to smoking after discharge remains common. This study aimed to assess the effect of adding home support for newly abstinent smokers to conventional NICE-recommended support in smokers discharged from hospital. DESIGN: Individually randomized parallel group trial. SETTING: One UK acute hospital. PARTICIPANTS: A total of 404 smokers aged > 18 admitted to acute medical wards between June 2016 and July 2017 were randomized in equal numbers to each treatment group. INTERVENTIONS AND COMPARATORS: The intervention provided 12 weeks of at-home cessation support, which included help in maintaining a smoke-free home, help in accessing and using medication, further behavioural support and personalized feedback on home air quality. The comparator was NICE PH48 care as usual. MEASURES: The primary outcome was self-reported continuous abstinence from smoking validated by an exhaled carbon monoxide level < 6 parts per million 4 weeks after discharge from hospital. FINDINGS: In an intention-to-treat analysis at the 4-week primary end-point, 38 participants (18.8%) in the usual care group and 43 (21.3%) in the intervention group reported continuous abstinence from smoking (odds ratio = 1.17, 95% confidence interval = 0.72 to 1.90, Bayes factor = 0.33). There were no significant differences in any secondary outcomes, including self-reported cessation at 3 months, having a smoke-free home or number of cigarettes smoked per day in those who did not quit. CONCLUSIONS: Provision of a home visit and continued support to prevent relapse to smoking after hospital discharge did not appear to increase subsequent abstinence rate above usual care in accordance with UK guidance from the National Institute of Health and Care Excellence.

The nature of mutations induced by replication­transcription collisions.

The DNA replication and transcription machineries share a common DNA template and thus can collide with each other co-directionally or head-on. Replication­transcription collisions can cause replication fork arrest, premature transcription termination, DNA breaks, and recombination intermediates threatening genome integrity. Collisions may also trigger mutations, which are major contributors to genetic disease and evolution. However, the nature and mechanisms of collision-induced mutagenesis remain poorly understood. Here we reveal the genetic consequences of replication­transcription collisions in actively dividing bacteria to be two classes of mutations: duplications/deletions and base substitutions in promoters. Both signatures are highly deleterious but are distinct from the previously well-characterized base substitutions in the coding sequence. Duplications/deletions are probably caused by replication stalling events that are triggered by collisions; their distribution patterns are consistent with where the fork first encounters a transcription complex upon entering a transcription unit. Promoter substitutions result mostly from head-on collisions and frequently occur at a nucleotide that is conserved in promoters recognized by the major σ factor in bacteria. This substitution is generated via adenine deamination on the template strand in the promoter open complex, as a consequence of head-on replication perturbing transcription initiation. We conclude that replication­transcription collisions induce distinct mutation signatures by antagonizing replication and transcription, not only in coding sequences but also in gene regulatory elements.

Care in specialist medical and mental health unit compared with standard care for older people with cognitive impairment admitted to general hospital: randomised controlled trial (NIHR TEAM trial).

OBJECTIVE: To develop and evaluate a best practice model of general hospital acute medical care for older people with cognitive impairment. DESIGN: Randomised controlled trial, adapted to take account of constraints imposed by a busy acute medical admission system. SETTING: Large acute general hospital in the United Kingdom. PARTICIPANTS: 600 patients aged over 65 admitted for acute medical care, identified as "confused" on admission. INTERVENTIONS: Participants were randomised to a specialist medical and mental health unit, designed to deliver best practice care for people with delirium or dementia, or to standard care (acute geriatric or general medical wards). Features of the specialist unit included joint staffing by medical and mental health professionals; enhanced staff training in delirium, dementia, and person centred dementia care; provision of organised purposeful activity; environmental modification to meet the needs of those with cognitive impairment; delirium prevention; and a proactive and inclusive approach to family carers. PRIMARY OUTCOME: number of days spent at home over the 90 days after randomisation. SECONDARY OUTCOMES: structured non-participant observations to ascertain patients' experiences; satisfaction of family carers with hospital care. When possible, outcome assessment was blind to allocation. RESULTS: There was no significant difference in days spent at home between the specialist unit and standard care groups (median 51 v 45 days, 95% confidence interval for difference -12 to 24; P=0.3). Median index hospital stay was 11 versus 11 days, mortality 22% versus 25% (-9% to 4%), readmission 32% versus 35% (-10% to 5%), and new admission to care home 20% versus 28% (-16% to 0) for the specialist unit and standard care groups, respectively. Patients returning home spent a median of 70.5 versus 71.0 days at home (-6.0 to 6.5). Patients on the specialist unit spent significantly more time with positive mood or engagement (79% v 68%, 2% to 20%; P=0.03) and experienced more staff interactions that met emotional and psychological needs (median 4 v 1 per observation; P<0.001). More family carers were satisfied with care (overall 91% v 83%, 2% to 15%; P=0.004), and severe dissatisfaction was reduced (5% v 10%, -10% to 0%; P=0.05). CONCLUSIONS: Specialist care for people with delirium and dementia improved the experience of patients and satisfaction of carers, but there were no convincing benefits in health status or service use. Patients' experience and carers' satisfaction might be more appropriate measures of success for frail older people approaching the end of life. TRIAL REGISTRATION: Clinical Trials NCT01136148.

Six-month outcomes following an emergency hospital admission for older adults with co-morbid mental health problems indicate complexity of care needs.

BACKGROUND: two-thirds of older patients admitted as an emergency to a general hospital have co-existing mental health problems including delirium, dementia and depression. This study describes the outcomes of older adults with co-morbid mental health problems after an acute hospital admission. METHODS: a follow-up study of 250 patients aged over 70 admitted to 1 of 12 wards (geriatric, medical or orthopaedic) of an English acute general hospital with a co-morbid mental health problem and followed up at 180 days. RESULTS: twenty-seven per cent did not return to their original place of residence after the hospital admission. After 180 days 31% had died, 42% had been readmitted and 24% of community residents had moved to a care home. Only 31% survived without being readmitted or moving to a care home. However, 16% spent >170 of the 180 days at home. Significant predictors for poor outcomes were co-morbidity, nutrition, cognitive function, reduction in activities of daily living ability prior to admission, behavioural and psychiatric problems and depression. Only 42% of survivors recovered to their pre-acute illness level of function. Clinically significant behavioural and psychiatric symptoms were present at follow-up in 71% of survivors with baseline cognitive impairment, and new symptoms developed frequently in this group. CONCLUSIONS: the variable, but often adverse, outcomes in this group implies a wide range of health and social care needs. Community and acute services to meet these needs should be anticipated and provided for.

Thin-filament length correlates with fiber type in human skeletal muscle.

Force production in skeletal muscle is proportional to the amount of overlap between the thin and thick filaments, which, in turn, depends on their lengths. Both thin- and thick-filament lengths are precisely regulated and uniform within a myofibril. While thick-filament lengths are essentially constant across muscles and species (∼1.65 µm), thin-filament lengths are highly variable both across species and across muscles of a single species. Here, we used a high-resolution immunofluorescence and image analysis technique (distributed deconvolution) to directly test the hypothesis that thin-filament lengths vary across human muscles. Using deltoid and pectoralis major muscle biopsies, we identified thin-filament lengths that ranged from 1.19 ± 0.08 to 1.37 ± 0.04 µm, based on tropomodulin localization with respect to the Z-line. Tropomodulin localized from 0.28 to 0.47 µm further from the Z-line than the NH(2)-terminus of nebulin in the various biopsies, indicating that human thin filaments have nebulin-free, pointed-end extensions that comprise up to 34% of total thin-filament length. Furthermore, thin-filament length was negatively correlated with the percentage of type 2X myosin heavy chain within the biopsy and shorter in type 2X myosin heavy chain-positive fibers, establishing the existence of a relationship between thin-filament lengths and fiber types in human muscle. Together, these data challenge the widely held assumption that human thin-filament lengths are constant. Our results also have broad relevance to musculoskeletal modeling, surgical reattachment of muscles, and orthopedic rehabilitation.

Can primary care data be used to monitor regional smoking prevalence? An analysis of The Health Improvement Network primary care data.

BACKGROUND: Accurate and timely regional data on smoking trends allow tobacco control interventions to be targeted at the areas most in need and facilitate the evaluation of such interventions. Electronic primary care databases have the potential to provide a valuable source of such data due to their size, continuity and the availability of socio-demographic data. UK electronic primary care data on smoking prevalence from The Health Improvement Network (THIN) have previously been validated at the national level, but may be less representative at the regional level due to reduced sample sizes. We investigated whether this database provides valid regional data and whether it can be used to compare smoking prevalence in different UK regions. METHODS: Annual estimates of smoking prevalence by government office region (GOR) from THIN were compared with estimates of smoking prevalence from the General Lifestyle Survey (GLF) from 2000 to 2008. RESULTS: For all regions, THIN prevalence data were generally found to be highly comparable with GLF data from 2006 onwards. CONCLUSIONS: THIN primary care data could be used to monitor regional smoking prevalence and highlight regional differences in smoking in the UK.

The association of two different measures of body habitus with lung function: a population-based study.

BACKGROUND: The relation between obesity and respiratory function is complex and may be confounded by other components of body habitus such as lean muscle mass. The present study aimed to explore the association between two different measures of body habitus (Body Mass Index - BMI, and lean muscle mass) with lung function. METHODS: We used data from 2663 adults who participated in a community-based survey and provided measures of lung function, BMI and 24-h urinary creatinine excretion to quantify lean muscle mass. RESULTS: There was a positive linear association between 24-h urinary creatinine excretion and lung function as measured by both Forced Expiratory Volume in 1 s (FEV(1)) and Forced Vital Capacity. A one standard deviation increment in 24-h urinary creatinine excretion was associated with a 45 ml increase in FEV(1) (95% confidence intervals CI: +16 to +73). There was no linear association between body mass index and lung function although those in the extreme categories of BMI had lower measures of lung function compared to a reference group with a BMI of 20-24.9 kg/m(2). For FEV(1), BMI less than 20 kg/m(2) was 122 ml lower (95% CI: -234 to -10); BMI greater than 30 kg/m(2) was 85 ml lower (95% CI: -160 to -9). CONCLUSIONS: Lean muscle mass and BMI have very different associations with lung function that have implications for understanding the relationship between body habitus and lung function.

Evaluation of a Medical and Mental Health Unit compared with standard care for older people whose emergency admission to an acute general hospital is complicated by concurrent 'confusion': a controlled clinical trial. Acronym: TEAM: Trial of an Elderly Acute care Medical and mental health unit.

BACKGROUND: Patients with delirium and dementia admitted to general hospitals have poor outcomes, and their carers report poor experiences. We developed an acute geriatric medical ward into a specialist Medical and Mental Health Unit over an eighteen month period. Additional specialist mental health staff were employed, other staff were trained in the 'person-centred' dementia care approach, a programme of meaningful activity was devised, the environment adapted to the needs of people with cognitive impairment, and attention given to communication with family carers. We hypothesise that patients managed on this ward will have better outcomes than those receiving standard care, and that such care will be cost-effective. METHODS/DESIGN: We will perform a controlled clinical trial comparing in-patient management on a specialist Medical and Mental Health Unit with standard care. Study participants are patients over the age of 65, admitted as an emergency to a single general hospital, and identified on the Acute Medical Admissions Unit as being 'confused'. Sample size is 300 per group. The evaluation design has been adapted to accommodate pressures on bed management and patient flows. If beds are available on the specialist Unit, the clinical service allocates patients at random between the Unit and standard care on general or geriatric medical wards. Once admitted, randomised patients and their carers are invited to take part in a follow up study, and baseline data are collected. Quality of care and patient experience are assessed in a non-participant observer study. Outcomes are ascertained at a follow up home visit 90 days after randomisation, by a researcher blind to allocation. The primary outcome is days spent at home (for those admitted from home), or days spent in the same care home (if admitted from a care home). Secondary outcomes include mortality, institutionalisation, resource use, and scaled outcome measures, including quality of life, cognitive function, disability, behavioural and psychological symptoms, carer strain and carer satisfaction with hospital care. Analyses will comprise comparisons of process, outcomes and costs between the specialist unit and standard care treatment groups. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01136148.

The motivators and barriers to a smoke-free home among disadvantaged caregivers: identifying the positive levers for change.

INTRODUCTION: The aims of this study were to explore home smoking behaviors and the motivators and barriers to smoke-free homes among a group of disadvantaged caregivers for young children and to identify the positive levers that health care professionals can utilize when supporting smoking behavior change. METHODS: In-depth qualitative interviews were conducted between July and September 2009, with 22 disadvantaged smoking caregivers, accessing Children's Centre Services in Nottingham, UK. Interviews were audiorecorded and transcribed verbatim. Data were coded and analyzed thematically to identify emergent main and subthemes. RESULTS: Caregivers had some general understanding of the dangers of secondhand smoke (SHS), but their knowledge appeared incomplete and confused. All interviewees described rules around smoking in the home; however, these tended to be transient and fluid and unlikely to be effective. Caregivers were often living in difficult and complex circumstances and experienced significant barriers to creating a smoke-free home. The motivators for change were more strongly linked to house decor and smell than children's health, suggesting that visible evidence of the harm done by SHS to children might help promote smoke-free homes. CONCLUSIONS: Findings suggest that further tailored information on the effect of SHS is required, but to instigate caregiver behavior change, providing demonstrable evidence of the impact that their smoking is having on their children's health is more likely to be effective.

The association between blood coagulation activity and lung function: a population-based study.

BACKGROUND: Increased in susceptibility to thrombotic disease may be associated with lower lung function. If causal, this association may suggest an area for development of new interventions for lung disease. The aim of this study was to investigate the association between blood coagulation activation as measured by plasma d-dimers and lung function. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional study on 2463 randomly selected adults in 1991 and followed up 1252 of these individuals in 2000. Plasma D-dimer levels, a marker of activity of blood coagulation pathways, were analysed in the baseline 1991 samples. There was an inverse cross-sectional association between plasma D-dimer and Forced Expiratory Volume in one second, with a decrease of 71 ml per µg FEU/ml increment in plasma D-dimer (95% confidence intervals CI: -135 to -6), and a decrease in Forced Vital Capacity (97 ml per µg FEU/ml increase in D-dimer, 95%CI: -170 to -24). These associations were attenuated after adjustment for serum highly sensitive CRP. No association was observed between plasma D-dimer and the decline in lung function between 1991 and 2000. CONCLUSIONS/SIGNIFICANCE: The cross-sectional findings are consistent with the hypothesis that activation of blood coagulation pathways is associated with decreased lung function, and that systemic inflammation may contribute to this relation. However, the lack of an association with decline in lung function suggests that clotting pathways that involve d-dimers may not be a promising therapeutic target for new interventions for respiratory disease.

Patterns of dietary intake and relation to respiratory disease, forced expiratory volume in 1 s, and decline in 5-y forced expiratory volume.

BACKGROUND: The independent effect of individual foods on the risk of respiratory disease is difficult to establish because intakes of specific foods are generally strongly correlated. To date, few studies have examined the relation between dietary food patterns and forced expiratory volume in 1 s (FEV(1)) or respiratory symptoms. OBJECTIVE: The objective was to investigate the relation between dietary patterns and FEV(1), FEV(1) decline, and respiratory health in a general population sample. DESIGN: Data were collected from the cross-sectional study in 12,648 adults from the Netherlands [MORGEN-EPIC (Monitoring Project on Risk Factors and Chronic Diseases in the Netherlands-European Prospective Investigation into Cancer and Nutrition)]. Principal components analysis was used to derive dietary patterns, and multivariate regression analyses were conducted to investigate these patterns with FEV(1) or respiratory health. We also investigated these dietary patterns in relation to lung function decline over 5 y in a subpopulation. RESULTS: A more traditional diet (high intake of meat and potatoes and lower intake of soy and cereal) was associated with a lower FEV(1) (fifth compared with first quintile: -94.4 mL; 95% CI: -123.4, -65.5 mL; P for trend < 0.001) and a higher prevalence of chronic obstructive pulmonary disease. An increased trend through quintiles was seen with a cosmopolitan diet (higher intakes of vegetables, fish, and chicken) for asthma and wheeze. CONCLUSIONS: The results suggest that a traditional diet has adverse effects on lung function and chronic obstructive pulmonary disease and that a more cosmopolitan diet was associated with increased risk of wheeze and asthma. However, none of the dietary patterns appear to be related to lung function decline.

Impact of adopting low sodium diet on biomarkers of inflammation and coagulation: a randomised controlled trial.

BACKGROUND: A low sodium diet is an established intervention in the treatment of impaired renal function and hypertension which may modulate cardiovascular risk independent of recognised antihypertensive effects. Epidemiological data suggest that dietary sodium intake may be associated with systemic inflammation: another potential pathophysiological mechanism by which sodium intake may modify vascular disease. METHODS: We tested the hypothesis that adopting a low sodium diet may decrease biomarkers of systemic inflammation or coagulation using data from a randomised double-blind placebo-controlled trial. Participants (n=171; aged 18-65 years) in a randomised double-blind placebo-controlled trial of a low sodium diet for 6 weeks provided paired serum samples for analysis to assess the impact of adopting a low sodium diet on biomarkers of systemic inflammation and coagulation. RESULTS: There was a significant difference in 24-hour sodium urinary excretion between the low sodium intake and the normal sodium intake groups of 43 mmol (p<0.001). In the primary analysis there was no effect of adopting a low sodium diet on serum D-dimers, but high-sensitivity C-reactive protein (hsCRP) was reduced by 1.13 mg/L (95% confidence interval [95% CI], 0.03 to 2.22). However, after elimination of outlying high values for baseline serum hsCRP (>10 mg/L), this effect was attenuated (-0.47 mg/L; 95% CI, -1.25 to 0.31). CONCLUSIONS: Using data from a randomised double-blind placebo-controlled trial in asthma with objective confirmation of adherence to the low sodium diet, we report that adopting a low sodium diet for 6 weeks has no effect on measures of systemic inflammation or coagulation.

Exhaled carbon monoxide in asthmatic adults with bronchial reactivity: a prospective study.

HYPOTHESIS: We hypothesized that eCO may permit non-invasive assessment of disease activity in adults with asthma and bronchial reactivity. METHODS: A total of 209 participants 18 to 65 years of age with a diagnosis of asthma and bronchial reactivity provided data for analysis. The association between eCO and bronchial reactivity, forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), peak expiratory flow rate measurements (PEFR), asthma symptoms score, and bronchodilator use cross-sectionally and within-subject change in eCO were analyzed in relation to change in these variables over 6 weeks. RESULTS: There was no difference in eCO in those who were taking inhaled corticosteroids and those who were not (p = 0.33). There was also no cross-sectional or within-in subject association between eCO and bronchial reactivity, FEV(1), FVC, PEFR, symptoms score, or bronchodilator use. CONCLUSIONS: In a population of adults with bronchial reactivity, eCO has no or very limited potential as a biomarker of asthma activity.

A population-based epidemiologic study of Helicobacter pylori infection and its association with systemic inflammation.

BACKGROUND: Infection with Helicobacter pylori is associated with a variety of non-gastrointestinal sequelae. These may be mediated by an increase in systemic inflammation. We assessed if serologic evidence of infection with H. pylori is associated with increased serum C-reactive protein (CRP) levels. METHODS: The study design consisted of a randomly selected, cross-sectional population-based study of 2633 individuals phenotyped in 1991, of whom 2361 participants provided serum samples to permit measurement of H. pylori's serologic status and CRP levels. RESULTS: Male gender (odds ratio (OR): 1.65; 95% confidence interval (CI): 1.23-2.21), age (OR per year: 1.05; 95% CI: 1.04-1.06), height (OR per meter: 0.05; 95% CI: 0.01-0.24), current smoking habit (compared with never smokers, OR: 1.46; 95% CI: 1.13-1.88), and less affluent socioeconomic status were associated with increased odds of being seropositive for H. pylori. Helicobacter pylori infection was associated with increased risk of having an elevated serum CRP (above 3 mg/L) after adjustment for gender, age, height, smoking status, and socioeconomic status (OR: 1.32; 95% CI: 1.05-1.67). Similar associations were seen using a threshold for elevated serum CRP of greater than 1 mg/L. CONCLUSIONS: Our data suggest that infection with H. pylori is associated with increased systemic inflammation. This suggests one potential mechanism to explain the extra-gastrointestinal conditions associated with H. pylori infection.

Unplanned attempts to quit smoking: missed opportunities for health promotion?

OBJECTIVES: To investigate the occurrence, determinants and reported success of unplanned and planned attempts to quit smoking, and sources of support used in these attempts. DESIGN: Cross-sectional questionnaire survey of 3512 current and ex-smokers. SETTING: Twenty-four general practices in Nottinghamshire, UK. PARTICIPANTS: Individuals who reported making a quit attempt within the last 6 months. MEASUREMENTS: Occurrence, triggers for, support used and success of planned and unplanned quit attempts. RESULTS: A total of 1805 (51.4%) participants returned completed questionnaires, reporting 394 quit attempts made within the previous 6 months of which 37% were unplanned. Males were significantly more likely to make an unplanned quit attempt [adjusted odds ratio (OR) 1.60, 95% confidence interval (CI) 1.04-2.46], but the occurrence of unplanned quit attempts did not differ significantly by socio-economic group or amount smoked. The most common triggers for unplanned quit attempts were advice from a general practitioner or health professional (27.9%) and health problems (24.5%). 5.4% and 4.1% of unplanned quit attempts used National Health Service cessation services on a one to one and group basis, respectively, and more than half (51.7%) were made without any support. Nevertheless, unplanned attempts were more likely to be reported to be successful (adjusted OR 2.01, 95% CI 1.23-3.27, P < 0.01). CONCLUSIONS: Unplanned quit attempts are common among smokers in all socio-demographic groups, are triggered commonly by advice from a health professional and are more likely to succeed; however, the majority of these unplanned attempts are unsupported. It is important to develop methods of providing behavioural and/or pharmacological support for these attempts, and determine whether these increase cessation rates still further.

An evaluation of the use of bronchoconstriction induced by deep inspiration as a new epidemiological measure for asthma.

RATIONALE: Bronchoconstriction after deep inhalation is associated with increased severity of asthma and is also a predictor of length of hospital stay in individuals admitted with asthma exacerbations. We hypothesized that this effect may represent a new non-invasive method to assess bronchial reactivity and other measures of asthma control. METHODS: We used a cross-sectional study design recruiting participants 18 to 65 years of age with a physician diagnosis of asthma. All participants were asked to provide three serial peak expiratory flow rate (PEFR) measurements in the morning, and bronchial reactivity was measured up to a maximum inhaled dose of 24.5 micromoL methacholine on the same day. Participants also recorded their asthma symptoms score and bronchodilator use during the 7 days before measuring bronchial reactivity. RESULTS: A total of 127 people provided data for analysis. There was no significant relationship between bronchoconstriction after deep inhalation (as measured by three serial PEFR measurements) and either bronchial reactivity to methacholine, asthma symptoms, or bronchodilator use. CONCLUSIONS: Bronchoconstriction induced by deep inspiration does not appear to be a valid marker of airway hyperresponsiveness or asthma severity in adults with mild to moderate asthma.