The hygiene hypothesis proposes that several chronic inflammatory disorders (allergies, autoimmunity, inflammatory bowel disease) are increasing in prevalence in developed countries because a ...changing microbial environment has perturbed immunoregulatory circuits which normally terminate inflammatory responses. Some stress-related psychiatric disorders, particularly depression and anxiety, are associated with markers of ongoing inflammation, even without any accompanying inflammatory disorder. Moreover, pro-inflammatory cytokines can induce depression, which is commonly seen in patients treated with interleukin-2 or interferon-α. Therefore, some psychiatric disorders in developed countries might be attributable to failure of immunoregulatory circuits to terminate ongoing inflammatory responses. This is discussed in relation to the effects of the immune system on a specific group of brain serotonergic neurons involved in the pathophysiology of mood disorders.
Patients who regularly take nonsteroidal anti-inflammatory drugs (NSAIDs) have an increased risk for small-intestinal mucosal ulceration and bleeding, which may present as anemia of undetermined ...gastrointestinal origin or protein loss. The prevalence and severity of small-intestinal lesions remains unclear. Our aim was to assess the frequency of NSAID-induced small-bowel injury among chronic NSAID users.
Ambulatory patients with various types of arthritides who took NSAIDs daily (>3 mo duration) or took either acetaminophen alone or nothing were enrolled in the study. All patients fasted overnight and underwent wireless video capsule endoscopy. Two investigators, blind to therapy, reviewed each video beginning after the pylorus. Lesions were scored as normal, red spots, small erosions, large erosions, or ulcers. An ulcer was defined as a larger lesion with apparent depth and a definite rim.
Forty-one patients, 36 men and 5 women, ages ranging from 22 to 66 years (mean age, 49.8 y) were analyzed including 21 chronic NSAID users and 20 control patients. Small-bowel injury was seen in 71% of NSAID users compared with 10% of controls (P < .001). Injury was mild (few or no erosions, absence of large erosions/ulcers) in 10 NSAID users compared with 2 controls. Five NSAID users had major (>4 erosions or large ulcers/ulcers) damage compared with none in the control group. There were no complications or problems with the capsule endoscopy procedure.
Endoscopically evident small-intestinal mucosal injury is very common among chronic NSAID users. The role of endoscopically evident injury in unexplained iron-deficiency anemia and hypoalbuminemia among chronic NSAID users remains undetermined.
Objective: To measure the prevalence of chronic obstructive pulmonary disease (COPD) among people aged 40 years or older in Australia.
Design, setting and participants: A cross‐sectional study of ...people in the community aged ≥ 40 years, selected at random using electoral rolls, in six sites chosen to reflect the sociodemographic and geographic diversity of Australia, conducted between 2006 and 2010. Standardised questionnaires were administered by interview. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the FEV1/FVC ratio were measured by spirometry, before and after bronchodilator administration.
Main outcome measure: Prevalence of COPD, classified according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2006 criteria.
Results: Complete data were available for 1620 men (participation rate, 26%) and 1737 women (participation rate, 28%). The prevalence of GOLD Stage II or higher COPD (defined as post‐bronchodilator FEV1/FVC ratio < 0.70 and FEV1 < 80% predicted) was 7.5% (95% CI, 5.7%–9.4%) among people aged ≥ 40 years, and 29.2% (95% CI, 18.1%–40.2%) among those aged ≥ 75 years. Among people aged ≥ 40 years, the prevalence of wheeze in the past 12 months was 30.0% (95% CI, 27.5%–32.5%), and prevalence of shortness of breath when hurrying on the level or climbing a slight hill was 25.2% (95% CI, 22.7%–27.6%).
Conclusions: Symptoms and spirometric evidence of COPD are common among people aged 40 years or older and increase with age. Further research is needed to better understand the diagnosis and management of COPD in Australia, along with continuing efforts to prevent the disease.
ABSTRACT
Tidal features in the outskirts of galaxies yield unique information about their past interactions and are a key prediction of the hierarchical structure formation paradigm. The Vera C. ...Rubin Observatory is poised to deliver deep observations for potentially millions of objects with visible tidal features, but the inference of galaxy interaction histories from such features is not straightforward. Utilizing automated techniques and human visual classification in conjunction with realistic mock images produced using the NewHorizon cosmological simulation, we investigate the nature, frequency, and visibility of tidal features and debris across a range of environments and stellar masses. In our simulated sample, around 80 per cent of the flux in the tidal features around Milky Way or greater mass galaxies is detected at the 10-yr depth of the Legacy Survey of Space and Time (30–31 mag arcsec−2), falling to 60 per cent assuming a shallower final depth of 29.5 mag arcsec−2. The fraction of total flux found in tidal features increases towards higher masses, rising to 10 per cent for the most massive objects in our sample (M⋆ ∼ 1011.5 M⊙). When observed at sufficient depth, such objects frequently exhibit many distinct tidal features with complex shapes. The interpretation and characterization of such features varies significantly with image depth and object orientation, introducing significant biases in their classification. Assuming the data reduction pipeline is properly optimized, we expect the Rubin Observatory to be capable of recovering much of the flux found in the outskirts of Milky Way mass galaxies, even at intermediate redshifts (z < 0.2).
Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, ...management of TB infection (TBI) and implementation of TPT.
A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.
Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.
This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.
The El Niño-Southern Oscillation (ENSO) is the most potent source of interannual climate variability. Uncertainty surrounding the impact of greenhouse warming on ENSO strength and frequency has ...stimulated efforts to develop a better understanding of the sensitivity of ENSO to climate change. Here we use annually banded corals from Papua New Guinea to show that ENSO has existed for the past 130,000 years, operating even during "glacial" times of substantially reduced regional and global temperature and changed solar forcing. However, we also find that during the 20th century ENSO has been strong compared with ENSO of previous cool (glacial) and warm (interglacial) times. The observed pattern of change in amplitude may be due to the combined effects of ENSO dampening during cool glacial conditions and ENSO forcing by precessional orbital variations.
Background
Developing a shared agenda is an important step in ensuring future research has the necessary relevance.
Objective
To characterise research priority setting partnerships (PSPs) relevant to ...women’s health.
Search strategy
Included studies were identified by searching MEDLINE and the James Lind Alliance (JLA) database.
Selection criteria
Priority setting partnerships using formal consensus methods.
Data collection and analysis
Descriptive narrative to describe the study characteristics, methods, and results.
Main results
Ten national and two international PSPs were identified. All PSPs used the JLA method to identify research priorities. Nine PSPs had published a protocol. Potential research uncertainties were gathered from guidelines (two studies), Cochrane reviews (five studies), and surveys (12 studies). The number of healthcare professionals (31–287), patients (44–932), and others (33–139) who responded to the survey, and the number of uncertainties submitted (52–4767) varied. All PSPs entered confirmed research uncertainties (39–104) into interim priority setting surveys and healthcare professionals (31–287), patients (44–932), and others (33–139) responded. All PSPs entered a short list of research uncertainties into a consensus development meeting, which enabled healthcare professionals (six to 21), patients (eight to 14), and others (two to 13) to identify research priorities (ten to 15). Four PSPs have published their results.
Conclusion
Future research priority setting studies should publish a protocol, use formal consensus development methods, and ensure their methods and results are comprehensively reported.
Tweetable
Research published in @BJOGtweets highlights future research priorities across women’s health, including @FertilityTop10, @jamesmnduffy.
Tweetable
Research published in @BJOGtweets highlights future research priorities across women’s health, including @FertilityTop10, @jamesmnduffy.
This paper includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights16150
Prescription of PCSK9-inhibitors has increased in recent years but not much is known about its off-target effects. PCSK9-expression is evident in non-hepatic tissues, notably the brain, and genetic ...variation in the PCSK9 locus has recently been shown to be associated with mood disorder-related traits. We investigated whether PCSK9 inhibition, proxied by a genetic reduction in expression of PCSK9 mRNA, might have a causal adverse effect on mood disorder-related traits. We used genetic variants in the PCSK9 locus associated with reduced PCSK9 expression (eQTLs) in the European population from GTEx v8 and examined the effect on PCSK9 protein levels and three mood disorder-related traits (major depressive disorder, mood instability, and neuroticism), using summary statistics from the largest European ancestry genome-wide association studies. We conducted summary-based Mendelian randomization analyses to estimate the causal effects, and attempted replication using data from eQTLGen, Brain-eMETA, and the CAGE consortium. We found that genetically reduced PCSK9 gene-expression levels were significantly associated with reduced PCSK9 protein levels but not with increased risk of mood disorder-related traits. Further investigation of nearby genes demonstrated that reduced USP24 gene-expression levels was significantly associated with increased risk of mood instability (p-value range = 5.2x10-5-0.03), and neuroticism score (p-value range = 2.9x10-5-0.02), but not with PCSK9 protein levels. Our results suggest that genetic variation in this region acts on mood disorders through a PCSK9-independent pathway, and therefore PCSK9-inhibitors are unlikely to have an adverse impact on mood disorder-related traits.
Rationale
Mycobacterium vaccae
(NCTC 11659) is an environmental saprophytic bacterium with anti-inflammatory, immunoregulatory, and stress resilience properties. Previous studies have shown that ...whole, heat-killed preparations of
M. vaccae
prevent allergic airway inflammation in a murine model of allergic asthma. Recent studies also demonstrate that immunization with
M. vaccae
prevents stress-induced exaggeration of proinflammatory cytokine secretion from mesenteric lymph node cells stimulated ex vivo, prevents stress-induced exaggeration of chemically induced colitis in a model of inflammatory bowel disease, and prevents stress-induced anxiety-like defensive behavioral responses. Furthermore, immunization with
M. vaccae
induces anti-inflammatory responses in the brain and prevents stress-induced exaggeration of microglial priming. However, the molecular mechanisms underlying anti-inflammatory effects of
M. vaccae
are not known.
Objectives
Our objective was to identify and characterize novel anti-inflammatory molecules from M. vaccae NCTC 11659.
Methods
We have purified and identified a unique anti-inflammatory triglyceride, 1,2,3-tri
Z
-10-hexadecenoyl glycerol, from
M. vaccae
and evaluated its effects in freshly isolated murine peritoneal macrophages.
Results
The free fatty acid form of 1,2,3-tri
Z
-10-hexadecenoyl glycerol, 10(
Z
)-hexadecenoic acid, decreased lipopolysaccharide-stimulated secretion of the proinflammatory cytokine IL-6 ex vivo. Meanwhile, next-generation RNA sequencing revealed that pretreatment with 10(
Z
)-hexadecenoic acid upregulated genes associated with peroxisome proliferator-activated receptor alpha (PPARα) signaling in lipopolysaccharide-stimulated macrophages, in association with a broad transcriptional repression of inflammatory markers. We confirmed using luciferase-based transfection assays that 10(
Z
)-hexadecenoic acid activated PPARα signaling, but not PPARγ, PPARδ, or retinoic acid receptor (RAR) α signaling. The effects of 10(
Z
)-hexadecenoic acid on lipopolysaccharide-stimulated secretion of IL-6 were prevented by PPARα antagonists and absent in PPARα-deficient mice.
Conclusion
Future studies should evaluate the effects of 10(
Z
)-hexadecenoic acid on stress-induced exaggeration of peripheral inflammatory signaling, central neuroinflammatory signaling, and anxiety- and fear-related defensive behavioral responses.
Accelerated lung function decline in individuals with cystic fibrosis (CF) starts in adolescence with respiratory complications being the most common cause of death in later life. Factors ...contributing to lung function decline are not well understood, in particular its relationship with structural lung disease in early childhood. Detection and management of structural lung disease could be an important step in improving outcomes in CF patients.
Annual chest computed tomography (CT) scans were available from 2005 to 2016 as a part of the AREST CF cohort for children aged 3 months to 6 years. Annual spirometry measurements were available for 89.77% of the cohort (167 children aged 5-6 years) from age 5 to 15 years through outpatient clinics at Perth Children's Hospital (Perth, Australia) and The Royal Children's Hospital in Melbourne (Melbourne, Australia) (697 measurements, mean±sd age 9.3±2.1 years).
Children with a total CT score above the median at age 5-6 years were more likely to have abnormal forced expiratory volume in 1 s (FEV
) (adjusted hazard ratio 2.67 (1.06-6.72), p=0.037) during the next 10 years compared to those below the median chest CT score. The extent of all structural abnormalities except bronchial wall thickening were associated with lower FEV
Z-scores. Mucus plugging and trapped air were the most predictive sub-score (adjusted mean change -0.17 (-0.26 - -0.07) p<0.001 and -0.09 (-0.14 - -0.04) p<0.001, respectively).
Chest CT identifies children at an early age who have adverse long-term outcomes. The prevention of structural lung damage should be a goal of early intervention and can be usefully assessed with chest CT. In an era of therapeutics that might alter disease trajectories, chest CT could provide an early readout of likely long-term success.
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